HIV

The Food and Drug Administration’s Antimicrobial Drugs Advisory Committee backed the fixed dose combination of emtricitabine and tenofovir alafenamide (TAF; Descovy, Gilead) for pre-exposure prophylaxis (PrEP) against HIV for men and transgender women who have sex with men.

In a discussion after a 16-2 vote, committee members cited analysis by the study’s sponsor and the FDA showing efficacy and a generally good safety profile in the DISCOVER trial, the single new clinical trial conducted to support TAF’s use for pre-exposure prophylaxis (PrEP).

However, this trial included no cisgender women; the sponsor asked for approval based primarily on extrapolation from the DISCOVER results and previous results with tenofovir disoproxil fumarate (TDF) in cisgender women. Both formulations of tenofovir are prodrugs and converted to tenofovir diphosphate intracellularly in peripheral blood mononuclear cells, though many aspects of their pharmacokinetics differ.

The committee voted 10-8 against the proposition that these data supported an indication of TAF for PrEP in cisgender women, in a narrowly worded question from the FDA.

Many members who voted on either side of the question had strongly worded reservations about the lack of data for cisgender women. Said committee chair Lindsey R. Baden, MD, director of the infectious disease service at Dana-Farber Cancer Institute, Boston, who voted against the indication for cisgender women, “We’ve failed women. To be at this point and not have the data to guide decision-making is a shame on all of us.”

Ighovwerha Ofotokun, MD, who voted yes, concurred: “I agree it is a terrible failure that the agency, as well as the sponsor, would come to this committee with a lack of data on women.” But for Dr. Ofotokun, a professor of infectious diseases at Emory University, Atlanta, not including cisgender women in the approval was a distasteful proposition. “Creating a two-tier prevention and treatment hierarchy would not be helpful. We should remind ourselves that there are more women living with HIV in the world than there are men, and the risk of new HIV infection is higher among women than among men, if you look at this globally,” he said.

“I find it disrespectful and an issue of research equity. Women deserve the same quality of data about the safety and efficacy of the drugs they are exposed to that men get and that is not the situation we find ourselves in at the moment,” said Dawn K. Smith, MD, MPH, a lead scientist at the Centers for Disease Control and Prevention (CDC), Atlanta, who voted against approval for cisgender women.

Michael Green, MD, MPH, professor of pediatrics, surgery and clinical and translational science at the University of Pittsburgh, echoed the frustration of many committee members when he said, “I voted yes, almost abstained, then almost voted no.” He, along with all who voted yes, emphasized the importance of mandatory postmarketing studies in cisgender women to ensure efficacy data are obtained.

Transgender women made up only about 1% of the DISCOVER population, a fact that also gave many committee members pause.

If TAF is approved, labeling and package materials should be clear that the data support only noninferiority, not superiority, compared with TDF, said several advisory committee members who voted for approval for men and transgender women who have sex with men. “My expectation of this approval is that it should be marketed responsibly from the perspective of not creating these disparities and having Truvada be a drug for poor people and Descovy be a drug for rich people,” said Demetre Dasklalakis, MD, assistant commissioner of the Bureau of HIV/AIDS Prevention and Control at the city of New York’s Department of Health and Hygiene, and of the Icahn School of Medicine at Mount Sinai, N.Y. Truvada is slated to be offered as a generic drug in 2020, according to a Securities and Exchange Commission filing by Gilead Sciences.

The CDC reported earlier in 2019 that rates of new HIV infections have plateaued in recent years. Uptake of PrEP has been particularly low among at-risk members of minority populations, in rural areas, and in the South, according to a CDC report.

The DISCOVER trial is a 96-week ongoing trial to test TAF’s noninferiority to a fixed-drug combination of emcitrabine and tenofovir dimethyl fumarate (TDF; Truvada, Gilead) for PrEP. Both drugs are already approved to treat HIV infection, and TDF is approved for PrEP. Non-inferiority was preestablished at a rate ratio of HIV incidence of 1.62 (TAF:TDF) between the two study arms.

DISCOVER has enrolled 5,387 men and transgender women who have sex with men and are deemed at high risk for HIV, and found an incidence rate ratio of 0.47, with the upper bound of the confidence interval at 1.15. Since this figure was less than the prespecified noninferiority margin, both Gilead presenters and the FDA agreed, TAF’s noninferiority for efficacy was established.

Characteristics were similar between patients in the TAF arm (N = 2,694) and the TDF arm (N = 2,693). About 60% of patients in each arm reported having receptive anal sex with at least two partners in the previous 12 weeks, and recent rectal gonorrhea, syphilis, and chlamydia rates were 9-13% at baseline. Two thirds of participants reported recreational drug use, and about one in four reported binge drinking.

Sexual behavior and sexually transmitted infection rates continued generally unchanged from baseline during the study period.

The median age was 34 years, and most participants (84%) were white. Black participants made up 9% of the study population, and about 25% were of Hispanic or Latin ethnic origin.

Known decreases in bone mineral density occur with TDF; these were not seen with TAF, and bone mineral density increased while on TAF for the DISCOVER population aged 19-25 years.

Renal biomarkers of concern with TDF included two proteins linked with proximal tubule dysfunction, as well as estimated glomerular filtration rate. According to the sponsor’s analysis, eGFR fell by 2.3 mL/min for the TAF group, compared with a 1.8 mL/min rise while on TDF (P less than .001). Changes of similar statistical significance were seen for proximal tubular proteinuria. Also, improvements were seen in renal measures for the subset of patients enrolled who were on TDF PrEP at baseline but switched to TAF, in a prespecified subgroup analysis.

However, patients who were on TDF had a significant decrease in total cholesterol and both low- and high-density lipoprotein cholesterol compared with those on TAF, who had minimal changes or slight increases in lipids (P less than .001 for all). Triglycerides rose for those on TAF and remained unchanged for those on TDF (P = .002).

The PrEP indication sought by Gilead includes adults and adolescents, defined as those who weigh more than 35 kg. A nonvoting question put before the committee asked whether the totality of tenofovir data supported an indication of TAF for cisgender men who have insertive vaginal sex; though this extrapolation didn’t give the committee as much pause as the request for approval in cisgender women, they cited similar concerns and noted that cervicovaginal mucosa are different in many ways from rectal mucosa.

The study included no cisgender women, for a host of reasons cited by the sponsor and the FDA. These included high nonadherence rates among this population, relatively lower HIV infection rates among cisgender women in the United States, and mixed efficacy results in previous tenofovir clinical trials; the latter point made establishing a noninferiority margin problematic, according to the FDA.

For Dr. Baden, “The optics of approval for population A but not for population B are problematic.” Speaking to both the sponsor and the FDA, he said, “Everyone agrees there needs to be actual data. Please do the study as quickly as possible.” What’s needed is the collective will to make it happen, he added: “I don’t accept that it’s too big, too hard, too difficult.”

The FDA usually follows the recommendations of its advisory committees.

koakes@mdedge.com

This article was updated 8/8/19.

The Food and Drug Administration’s Antimicrobial Drugs Advisory Committee backed the fixed dose combination of emtricitabine and tenofovir alafenamide (TAF; Descovy, Gilead) for pre-exposure prophylaxis (PrEP) against HIV for men and transgender women who have sex with men.

In a discussion after a 16-2 vote, committee members cited analysis by the study’s sponsor and the FDA showing efficacy and a generally good safety profile in the DISCOVER trial, the single new clinical trial conducted to support TAF’s use for pre-exposure prophylaxis (PrEP).

However, this trial included no cisgender women; the sponsor asked for approval based primarily on extrapolation from the DISCOVER results and previous results with tenofovir disoproxil fumarate (TDF) in cisgender women. Both formulations of tenofovir are prodrugs and converted to tenofovir diphosphate intracellularly in peripheral blood mononuclear cells, though many aspects of their pharmacokinetics differ.

The committee voted 10-8 against the proposition that these data supported an indication of TAF for PrEP in cisgender women, in a narrowly worded question from the FDA.

Many members who voted on either side of the question had strongly worded reservations about the lack of data for cisgender women. Said committee chair Lindsey R. Baden, MD, director of the infectious disease service at Dana-Farber Cancer Institute, Boston, who voted against the indication for cisgender women, “We’ve failed women. To be at this point and not have the data to guide decision-making is a shame on all of us.”

Ighovwerha Ofotokun, MD, who voted yes, concurred: “I agree it is a terrible failure that the agency, as well as the sponsor, would come to this committee with a lack of data on women.” But for Dr. Ofotokun, a professor of infectious diseases at Emory University, Atlanta, not including cisgender women in the approval was a distasteful proposition. “Creating a two-tier prevention and treatment hierarchy would not be helpful. We should remind ourselves that there are more women living with HIV in the world than there are men, and the risk of new HIV infection is higher among women than among men, if you look at this globally,” he said.

“I find it disrespectful and an issue of research equity. Women deserve the same quality of data about the safety and efficacy of the drugs they are exposed to that men get and that is not the situation we find ourselves in at the moment,” said Dawn K. Smith, MD, MPH, a lead scientist at the Centers for Disease Control and Prevention (CDC), Atlanta, who voted against approval for cisgender women.

Michael Green, MD, MPH, professor of pediatrics, surgery and clinical and translational science at the University of Pittsburgh, echoed the frustration of many committee members when he said, “I voted yes, almost abstained, then almost voted no.” He, along with all who voted yes, emphasized the importance of mandatory postmarketing studies in cisgender women to ensure efficacy data are obtained.

Transgender women made up only about 1% of the DISCOVER population, a fact that also gave many committee members pause.

If TAF is approved, labeling and package materials should be clear that the data support only noninferiority, not superiority, compared with TDF, said several advisory committee members who voted for approval for men and transgender women who have sex with men. “My expectation of this approval is that it should be marketed responsibly from the perspective of not creating these disparities and having Truvada be a drug for poor people and Descovy be a drug for rich people,” said Demetre Dasklalakis, MD, assistant commissioner of the Bureau of HIV/AIDS Prevention and Control at the city of New York’s Department of Health and Hygiene, and of the Icahn School of Medicine at Mount Sinai, N.Y. Truvada is slated to be offered as a generic drug in 2020, according to a Securities and Exchange Commission filing by Gilead Sciences.

The CDC reported earlier in 2019 that rates of new HIV infections have plateaued in recent years. Uptake of PrEP has been particularly low among at-risk members of minority populations, in rural areas, and in the South, according to a CDC report.

The DISCOVER trial is a 96-week ongoing trial to test TAF’s noninferiority to a fixed-drug combination of emcitrabine and tenofovir dimethyl fumarate (TDF; Truvada, Gilead) for PrEP. Both drugs are already approved to treat HIV infection, and TDF is approved for PrEP. Non-inferiority was preestablished at a rate ratio of HIV incidence of 1.62 (TAF:TDF) between the two study arms.

DISCOVER has enrolled 5,387 men and transgender women who have sex with men and are deemed at high risk for HIV, and found an incidence rate ratio of 0.47, with the upper bound of the confidence interval at 1.15. Since this figure was less than the prespecified noninferiority margin, both Gilead presenters and the FDA agreed, TAF’s noninferiority for efficacy was established.

Characteristics were similar between patients in the TAF arm (N = 2,694) and the TDF arm (N = 2,693). About 60% of patients in each arm reported having receptive anal sex with at least two partners in the previous 12 weeks, and recent rectal gonorrhea, syphilis, and chlamydia rates were 9-13% at baseline. Two thirds of participants reported recreational drug use, and about one in four reported binge drinking.

Sexual behavior and sexually transmitted infection rates continued generally unchanged from baseline during the study period.

The median age was 34 years, and most participants (84%) were white. Black participants made up 9% of the study population, and about 25% were of Hispanic or Latin ethnic origin.

Known decreases in bone mineral density occur with TDF; these were not seen with TAF, and bone mineral density increased while on TAF for the DISCOVER population aged 19-25 years.

Renal biomarkers of concern with TDF included two proteins linked with proximal tubule dysfunction, as well as estimated glomerular filtration rate. According to the sponsor’s analysis, eGFR fell by 2.3 mL/min for the TAF group, compared with a 1.8 mL/min rise while on TDF (P less than .001). Changes of similar statistical significance were seen for proximal tubular proteinuria. Also, improvements were seen in renal measures for the subset of patients enrolled who were on TDF PrEP at baseline but switched to TAF, in a prespecified subgroup analysis.

However, patients who were on TDF had a significant decrease in total cholesterol and both low- and high-density lipoprotein cholesterol compared with those on TAF, who had minimal changes or slight increases in lipids (P less than .001 for all). Triglycerides rose for those on TAF and remained unchanged for those on TDF (P = .002).

The PrEP indication sought by Gilead includes adults and adolescents, defined as those who weigh more than 35 kg. A nonvoting question put before the committee asked whether the totality of tenofovir data supported an indication of TAF for cisgender men who have insertive vaginal sex; though this extrapolation didn’t give the committee as much pause as the request for approval in cisgender women, they cited similar concerns and noted that cervicovaginal mucosa are different in many ways from rectal mucosa.

The study included no cisgender women, for a host of reasons cited by the sponsor and the FDA. These included high nonadherence rates among this population, relatively lower HIV infection rates among cisgender women in the United States, and mixed efficacy results in previous tenofovir clinical trials; the latter point made establishing a noninferiority margin problematic, according to the FDA.

For Dr. Baden, “The optics of approval for population A but not for population B are problematic.” Speaking to both the sponsor and the FDA, he said, “Everyone agrees there needs to be actual data. Please do the study as quickly as possible.” What’s needed is the collective will to make it happen, he added: “I don’t accept that it’s too big, too hard, too difficult.”

The FDA usually follows the recommendations of its advisory committees.

koakes@mdedge.com

This article was updated 8/8/19.

The Food and Drug Administration’s Antimicrobial Drugs Advisory Committee backed the fixed dose combination of emtricitabine and tenofovir alafenamide (TAF; Descovy, Gilead) for pre-exposure prophylaxis (PrEP) against HIV for men and transgender women who have sex with men.

In a discussion after a 16-2 vote, committee members cited analysis by the study’s sponsor and the FDA showing efficacy and a generally good safety profile in the DISCOVER trial, the single new clinical trial conducted to support TAF’s use for pre-exposure prophylaxis (PrEP).

However, this trial included no cisgender women; the sponsor asked for approval based primarily on extrapolation from the DISCOVER results and previous results with tenofovir disoproxil fumarate (TDF) in cisgender women. Both formulations of tenofovir are prodrugs and converted to tenofovir diphosphate intracellularly in peripheral blood mononuclear cells, though many aspects of their pharmacokinetics differ.

The committee voted 10-8 against the proposition that these data supported an indication of TAF for PrEP in cisgender women, in a narrowly worded question from the FDA.

Many members who voted on either side of the question had strongly worded reservations about the lack of data for cisgender women. Said committee chair Lindsey R. Baden, MD, director of the infectious disease service at Dana-Farber Cancer Institute, Boston, who voted against the indication for cisgender women, “We’ve failed women. To be at this point and not have the data to guide decision-making is a shame on all of us.”

Ighovwerha Ofotokun, MD, who voted yes, concurred: “I agree it is a terrible failure that the agency, as well as the sponsor, would come to this committee with a lack of data on women.” But for Dr. Ofotokun, a professor of infectious diseases at Emory University, Atlanta, not including cisgender women in the approval was a distasteful proposition. “Creating a two-tier prevention and treatment hierarchy would not be helpful. We should remind ourselves that there are more women living with HIV in the world than there are men, and the risk of new HIV infection is higher among women than among men, if you look at this globally,” he said.

“I find it disrespectful and an issue of research equity. Women deserve the same quality of data about the safety and efficacy of the drugs they are exposed to that men get and that is not the situation we find ourselves in at the moment,” said Dawn K. Smith, MD, MPH, a lead scientist at the Centers for Disease Control and Prevention (CDC), Atlanta, who voted against approval for cisgender women.

Michael Green, MD, MPH, professor of pediatrics, surgery and clinical and translational science at the University of Pittsburgh, echoed the frustration of many committee members when he said, “I voted yes, almost abstained, then almost voted no.” He, along with all who voted yes, emphasized the importance of mandatory postmarketing studies in cisgender women to ensure efficacy data are obtained.

Transgender women made up only about 1% of the DISCOVER population, a fact that also gave many committee members pause.

If TAF is approved, labeling and package materials should be clear that the data support only noninferiority, not superiority, compared with TDF, said several advisory committee members who voted for approval for men and transgender women who have sex with men. “My expectation of this approval is that it should be marketed responsibly from the perspective of not creating these disparities and having Truvada be a drug for poor people and Descovy be a drug for rich people,” said Demetre Dasklalakis, MD, assistant commissioner of the Bureau of HIV/AIDS Prevention and Control at the city of New York’s Department of Health and Hygiene, and of the Icahn School of Medicine at Mount Sinai, N.Y. Truvada is slated to be offered as a generic drug in 2020, according to a Securities and Exchange Commission filing by Gilead Sciences.

The CDC reported earlier in 2019 that rates of new HIV infections have plateaued in recent years. Uptake of PrEP has been particularly low among at-risk members of minority populations, in rural areas, and in the South, according to a CDC report.

The DISCOVER trial is a 96-week ongoing trial to test TAF’s noninferiority to a fixed-drug combination of emcitrabine and tenofovir dimethyl fumarate (TDF; Truvada, Gilead) for PrEP. Both drugs are already approved to treat HIV infection, and TDF is approved for PrEP. Non-inferiority was preestablished at a rate ratio of HIV incidence of 1.62 (TAF:TDF) between the two study arms.

DISCOVER has enrolled 5,387 men and transgender women who have sex with men and are deemed at high risk for HIV, and found an incidence rate ratio of 0.47, with the upper bound of the confidence interval at 1.15. Since this figure was less than the prespecified noninferiority margin, both Gilead presenters and the FDA agreed, TAF’s noninferiority for efficacy was established.

Characteristics were similar between patients in the TAF arm (N = 2,694) and the TDF arm (N = 2,693). About 60% of patients in each arm reported having receptive anal sex with at least two partners in the previous 12 weeks, and recent rectal gonorrhea, syphilis, and chlamydia rates were 9-13% at baseline. Two thirds of participants reported recreational drug use, and about one in four reported binge drinking.

Sexual behavior and sexually transmitted infection rates continued generally unchanged from baseline during the study period.

The median age was 34 years, and most participants (84%) were white. Black participants made up 9% of the study population, and about 25% were of Hispanic or Latin ethnic origin.

Known decreases in bone mineral density occur with TDF; these were not seen with TAF, and bone mineral density increased while on TAF for the DISCOVER population aged 19-25 years.

Renal biomarkers of concern with TDF included two proteins linked with proximal tubule dysfunction, as well as estimated glomerular filtration rate. According to the sponsor’s analysis, eGFR fell by 2.3 mL/min for the TAF group, compared with a 1.8 mL/min rise while on TDF (P less than .001). Changes of similar statistical significance were seen for proximal tubular proteinuria. Also, improvements were seen in renal measures for the subset of patients enrolled who were on TDF PrEP at baseline but switched to TAF, in a prespecified subgroup analysis.

However, patients who were on TDF had a significant decrease in total cholesterol and both low- and high-density lipoprotein cholesterol compared with those on TAF, who had minimal changes or slight increases in lipids (P less than .001 for all). Triglycerides rose for those on TAF and remained unchanged for those on TDF (P = .002).

The PrEP indication sought by Gilead includes adults and adolescents, defined as those who weigh more than 35 kg. A nonvoting question put before the committee asked whether the totality of tenofovir data supported an indication of TAF for cisgender men who have insertive vaginal sex; though this extrapolation didn’t give the committee as much pause as the request for approval in cisgender women, they cited similar concerns and noted that cervicovaginal mucosa are different in many ways from rectal mucosa.

The study included no cisgender women, for a host of reasons cited by the sponsor and the FDA. These included high nonadherence rates among this population, relatively lower HIV infection rates among cisgender women in the United States, and mixed efficacy results in previous tenofovir clinical trials; the latter point made establishing a noninferiority margin problematic, according to the FDA.

For Dr. Baden, “The optics of approval for population A but not for population B are problematic.” Speaking to both the sponsor and the FDA, he said, “Everyone agrees there needs to be actual data. Please do the study as quickly as possible.” What’s needed is the collective will to make it happen, he added: “I don’t accept that it’s too big, too hard, too difficult.”

The FDA usually follows the recommendations of its advisory committees.

koakes@mdedge.com

This article was updated 8/8/19.

Even when a standard HIV RNA test is negative, some patients may still have viral DNA in their cerebrospinal fluid (CSF)—and that could be a predictor of later memory and concentration problems, say researchers who conducted a National Institute of Health (NIH)-funded study of patients on long-term antiretroviral therapy (ART).

The 69 participants, enrolled in the AIDS Clinical Trials Group HIV Reservoirs Cohort Study, had infections controlled with ART for a median of 9 years. Calling it a “striking observation,” the researchers found nearly half of the patients had viral DNA in CSF cells, although the standard viral load tests of the cell-free CSF fluid were positive in only 4% of the patients.

Of the 30 patients with persistent HIV, 9 (30%) experienced neurocognitive difficulties in a 7-domain neuropsychological test battery. Among 35 participants with no detectable HIV DNA in CSF, 4 (11%) were clinically impaired.

The low rates of detectable HIV RNA in the cell-free CSF fraction and within CSF cell pellets suggest low levels of HIV transcription within cells and infrequent release into the extracellular space during systemically suppressive ART, the researchers say.

The brain is one of the first targets of the virus, and CNS manifestations are common. Neurocognitive impairment in HIV-positive patients is probably related to multiple factors, including HIV infection, age, neuroinflammation, and comorbid conditions, including substance abuse, the researchers say. There also may be a “legacy effect,” in which processes associated with long-term exposure to HIV before ART leads to irreversible neurologic injury and more extensive infection of CSF cells. Lack of an association with inflammatory biomarkers in this study suggested that current inflammation does not lead to present neurocognitive dysfunction, the researchers say, but does not rule out prior inflammation as the underlying cause of neuronal injury.

Still, given that brain tissue in living individuals is “inaccessible” (as the researchers put it), CSF offers a window into neuropathogenesis of HIV. Studies have found a range between 15% and 55% of participants develop an HIV-associated neurocognitive disorder (HAND). The new findings may support a role of persistent HIV-infected cells, but the researchers emphasize that the association does not confirm that HIV DNA causes HAND. However, they add, persistent HIV in “sanctuary sites” despite ART presents a barrier to curing the infection. Their study, they say, indicates that examination of CSF cells is important in assessing residual HIV in compartments during ART.

Even when a standard HIV RNA test is negative, some patients may still have viral DNA in their cerebrospinal fluid (CSF)—and that could be a predictor of later memory and concentration problems, say researchers who conducted a National Institute of Health (NIH)-funded study of patients on long-term antiretroviral therapy (ART).

The 69 participants, enrolled in the AIDS Clinical Trials Group HIV Reservoirs Cohort Study, had infections controlled with ART for a median of 9 years. Calling it a “striking observation,” the researchers found nearly half of the patients had viral DNA in CSF cells, although the standard viral load tests of the cell-free CSF fluid were positive in only 4% of the patients.

Of the 30 patients with persistent HIV, 9 (30%) experienced neurocognitive difficulties in a 7-domain neuropsychological test battery. Among 35 participants with no detectable HIV DNA in CSF, 4 (11%) were clinically impaired.

The low rates of detectable HIV RNA in the cell-free CSF fraction and within CSF cell pellets suggest low levels of HIV transcription within cells and infrequent release into the extracellular space during systemically suppressive ART, the researchers say.

The brain is one of the first targets of the virus, and CNS manifestations are common. Neurocognitive impairment in HIV-positive patients is probably related to multiple factors, including HIV infection, age, neuroinflammation, and comorbid conditions, including substance abuse, the researchers say. There also may be a “legacy effect,” in which processes associated with long-term exposure to HIV before ART leads to irreversible neurologic injury and more extensive infection of CSF cells. Lack of an association with inflammatory biomarkers in this study suggested that current inflammation does not lead to present neurocognitive dysfunction, the researchers say, but does not rule out prior inflammation as the underlying cause of neuronal injury.

Still, given that brain tissue in living individuals is “inaccessible” (as the researchers put it), CSF offers a window into neuropathogenesis of HIV. Studies have found a range between 15% and 55% of participants develop an HIV-associated neurocognitive disorder (HAND). The new findings may support a role of persistent HIV-infected cells, but the researchers emphasize that the association does not confirm that HIV DNA causes HAND. However, they add, persistent HIV in “sanctuary sites” despite ART presents a barrier to curing the infection. Their study, they say, indicates that examination of CSF cells is important in assessing residual HIV in compartments during ART.

Even when a standard HIV RNA test is negative, some patients may still have viral DNA in their cerebrospinal fluid (CSF)—and that could be a predictor of later memory and concentration problems, say researchers who conducted a National Institute of Health (NIH)-funded study of patients on long-term antiretroviral therapy (ART).

The 69 participants, enrolled in the AIDS Clinical Trials Group HIV Reservoirs Cohort Study, had infections controlled with ART for a median of 9 years. Calling it a “striking observation,” the researchers found nearly half of the patients had viral DNA in CSF cells, although the standard viral load tests of the cell-free CSF fluid were positive in only 4% of the patients.

Of the 30 patients with persistent HIV, 9 (30%) experienced neurocognitive difficulties in a 7-domain neuropsychological test battery. Among 35 participants with no detectable HIV DNA in CSF, 4 (11%) were clinically impaired.

The low rates of detectable HIV RNA in the cell-free CSF fraction and within CSF cell pellets suggest low levels of HIV transcription within cells and infrequent release into the extracellular space during systemically suppressive ART, the researchers say.

The brain is one of the first targets of the virus, and CNS manifestations are common. Neurocognitive impairment in HIV-positive patients is probably related to multiple factors, including HIV infection, age, neuroinflammation, and comorbid conditions, including substance abuse, the researchers say. There also may be a “legacy effect,” in which processes associated with long-term exposure to HIV before ART leads to irreversible neurologic injury and more extensive infection of CSF cells. Lack of an association with inflammatory biomarkers in this study suggested that current inflammation does not lead to present neurocognitive dysfunction, the researchers say, but does not rule out prior inflammation as the underlying cause of neuronal injury.

Still, given that brain tissue in living individuals is “inaccessible” (as the researchers put it), CSF offers a window into neuropathogenesis of HIV. Studies have found a range between 15% and 55% of participants develop an HIV-associated neurocognitive disorder (HAND). The new findings may support a role of persistent HIV-infected cells, but the researchers emphasize that the association does not confirm that HIV DNA causes HAND. However, they add, persistent HIV in “sanctuary sites” despite ART presents a barrier to curing the infection. Their study, they say, indicates that examination of CSF cells is important in assessing residual HIV in compartments during ART.

The first-in-class antiretroviral therapy islatravir (Merck) was well tolerated and had promising efficacy in a phase 2B study including treatment-naive adults with HIV-1 infection, supporting plans to initiate a phase 3 trial, an investigator said at the International AIDS Society Conference on HIV Science.

MattZ90/Thinkstock.com

The proportion of patients achieving viral suppression at week 48 with combinations including the nucleoside transcriptase translocation inhibitor (NRTTI) was comparable to what was achieved with a standard triple regimen, said investigator Jean-Michel Molina, MD, professor of infectious diseases at the University of Paris Diderot, and head of the infectious diseases department at the Saint-Louis Hospital in Paris

The treatment was effective not only as part of a three-drug combination of islatravir, doravirine, and lamivudine over 24 weeks, but also over an additional 24 weeks in patients who achieved viral suppression and were switched to dual therapy with islatravir and doravirine, according to Dr. Molina.

“These are promising data that will encourage the company to move to a phase 3 trial to see how these results can be confirmed in a larger study set, and also to assess the potency of the dual combination for maintenance therapy in the future, providing also novel options for people with a drug that has a high genetic barrier to resistance and efficacy that seems to be quite interesting,” Dr. Molina said in an IAS press conference in Mexico City.

This drug has very potent activity not only against wild-type HIV-1 viruses, but also multiresistant viruses, according to Dr. Molina.

“It has a high inhibitory quotient at a very low dose, so you give people a tiny amount of drug – in the range of 1 milligram per day, instead of a few hundred milligrams with other, regular drugs,” he said.

Another attribute of islatravir is its long half-life of approximately 120 hours, allowing not only for once-daily dosing, but potentially for evaluation as once-weekly or once-monthly dosing in the future, he said, adding that a subdermal islatravir-eluting implant under investigation for preexposure prophylaxis has potential as a once-yearly option.

The international, multicenter, 121-patient clinical trial that Dr. Molina described included adults with HIV-1 infection naive to antiretroviral therapy randomized to islatravir (in one of three doses) plus doravirine and lamivudine, or to the combination of doravirine, lamivudine, and tenofovir (Delstrigo, Merck).

After at least 24 weeks of treatment, subjects in the islatravir treatment groups were transitioned to the two-drug combination of islatravir and doravirine if they had HIV-1 RNA levels less than 50 copies/mL and did not meet any protocol-defined criteria for virologic failure.

Those participants in the islatravir arms who received 48 weeks of treatment had “very good response” and safety that was comparable to the control arm, according to Dr. Molina.

At 48 weeks, the proportion of patients with HIV-1 RNA less than 50 copies/mL were 89.7%, 90%, and 77.4% for regimens containing islatravir 0.25 mg, 0.75 mg, and 2.25 mg, respectively, and 83.9% for those receiving the standard triple therapy, according to reported data.

All patients with protocol-defined virologic failure (greater than or equal to 50 copies/mL) in the study actually had very low viral load, below 80 copies/mL, Dr. Molina said.

The study was supported by Merck. Dr. Molina has been on the Merck advisory board and speaker’s bureau.

SOURCE: Molina J-M et al. IAS 2019, Abstract WEAB0402LB.

The first-in-class antiretroviral therapy islatravir (Merck) was well tolerated and had promising efficacy in a phase 2B study including treatment-naive adults with HIV-1 infection, supporting plans to initiate a phase 3 trial, an investigator said at the International AIDS Society Conference on HIV Science.

MattZ90/Thinkstock.com

The proportion of patients achieving viral suppression at week 48 with combinations including the nucleoside transcriptase translocation inhibitor (NRTTI) was comparable to what was achieved with a standard triple regimen, said investigator Jean-Michel Molina, MD, professor of infectious diseases at the University of Paris Diderot, and head of the infectious diseases department at the Saint-Louis Hospital in Paris

The treatment was effective not only as part of a three-drug combination of islatravir, doravirine, and lamivudine over 24 weeks, but also over an additional 24 weeks in patients who achieved viral suppression and were switched to dual therapy with islatravir and doravirine, according to Dr. Molina.

“These are promising data that will encourage the company to move to a phase 3 trial to see how these results can be confirmed in a larger study set, and also to assess the potency of the dual combination for maintenance therapy in the future, providing also novel options for people with a drug that has a high genetic barrier to resistance and efficacy that seems to be quite interesting,” Dr. Molina said in an IAS press conference in Mexico City.

This drug has very potent activity not only against wild-type HIV-1 viruses, but also multiresistant viruses, according to Dr. Molina.

“It has a high inhibitory quotient at a very low dose, so you give people a tiny amount of drug – in the range of 1 milligram per day, instead of a few hundred milligrams with other, regular drugs,” he said.

Another attribute of islatravir is its long half-life of approximately 120 hours, allowing not only for once-daily dosing, but potentially for evaluation as once-weekly or once-monthly dosing in the future, he said, adding that a subdermal islatravir-eluting implant under investigation for preexposure prophylaxis has potential as a once-yearly option.

The international, multicenter, 121-patient clinical trial that Dr. Molina described included adults with HIV-1 infection naive to antiretroviral therapy randomized to islatravir (in one of three doses) plus doravirine and lamivudine, or to the combination of doravirine, lamivudine, and tenofovir (Delstrigo, Merck).

After at least 24 weeks of treatment, subjects in the islatravir treatment groups were transitioned to the two-drug combination of islatravir and doravirine if they had HIV-1 RNA levels less than 50 copies/mL and did not meet any protocol-defined criteria for virologic failure.

Those participants in the islatravir arms who received 48 weeks of treatment had “very good response” and safety that was comparable to the control arm, according to Dr. Molina.

At 48 weeks, the proportion of patients with HIV-1 RNA less than 50 copies/mL were 89.7%, 90%, and 77.4% for regimens containing islatravir 0.25 mg, 0.75 mg, and 2.25 mg, respectively, and 83.9% for those receiving the standard triple therapy, according to reported data.

All patients with protocol-defined virologic failure (greater than or equal to 50 copies/mL) in the study actually had very low viral load, below 80 copies/mL, Dr. Molina said.

The study was supported by Merck. Dr. Molina has been on the Merck advisory board and speaker’s bureau.

SOURCE: Molina J-M et al. IAS 2019, Abstract WEAB0402LB.

The first-in-class antiretroviral therapy islatravir (Merck) was well tolerated and had promising efficacy in a phase 2B study including treatment-naive adults with HIV-1 infection, supporting plans to initiate a phase 3 trial, an investigator said at the International AIDS Society Conference on HIV Science.

MattZ90/Thinkstock.com

The proportion of patients achieving viral suppression at week 48 with combinations including the nucleoside transcriptase translocation inhibitor (NRTTI) was comparable to what was achieved with a standard triple regimen, said investigator Jean-Michel Molina, MD, professor of infectious diseases at the University of Paris Diderot, and head of the infectious diseases department at the Saint-Louis Hospital in Paris

The treatment was effective not only as part of a three-drug combination of islatravir, doravirine, and lamivudine over 24 weeks, but also over an additional 24 weeks in patients who achieved viral suppression and were switched to dual therapy with islatravir and doravirine, according to Dr. Molina.

“These are promising data that will encourage the company to move to a phase 3 trial to see how these results can be confirmed in a larger study set, and also to assess the potency of the dual combination for maintenance therapy in the future, providing also novel options for people with a drug that has a high genetic barrier to resistance and efficacy that seems to be quite interesting,” Dr. Molina said in an IAS press conference in Mexico City.

This drug has very potent activity not only against wild-type HIV-1 viruses, but also multiresistant viruses, according to Dr. Molina.

“It has a high inhibitory quotient at a very low dose, so you give people a tiny amount of drug – in the range of 1 milligram per day, instead of a few hundred milligrams with other, regular drugs,” he said.

Another attribute of islatravir is its long half-life of approximately 120 hours, allowing not only for once-daily dosing, but potentially for evaluation as once-weekly or once-monthly dosing in the future, he said, adding that a subdermal islatravir-eluting implant under investigation for preexposure prophylaxis has potential as a once-yearly option.

The international, multicenter, 121-patient clinical trial that Dr. Molina described included adults with HIV-1 infection naive to antiretroviral therapy randomized to islatravir (in one of three doses) plus doravirine and lamivudine, or to the combination of doravirine, lamivudine, and tenofovir (Delstrigo, Merck).

After at least 24 weeks of treatment, subjects in the islatravir treatment groups were transitioned to the two-drug combination of islatravir and doravirine if they had HIV-1 RNA levels less than 50 copies/mL and did not meet any protocol-defined criteria for virologic failure.

Those participants in the islatravir arms who received 48 weeks of treatment had “very good response” and safety that was comparable to the control arm, according to Dr. Molina.

At 48 weeks, the proportion of patients with HIV-1 RNA less than 50 copies/mL were 89.7%, 90%, and 77.4% for regimens containing islatravir 0.25 mg, 0.75 mg, and 2.25 mg, respectively, and 83.9% for those receiving the standard triple therapy, according to reported data.

All patients with protocol-defined virologic failure (greater than or equal to 50 copies/mL) in the study actually had very low viral load, below 80 copies/mL, Dr. Molina said.

The study was supported by Merck. Dr. Molina has been on the Merck advisory board and speaker’s bureau.

SOURCE: Molina J-M et al. IAS 2019, Abstract WEAB0402LB.

An implant that elutes an investigational antiretroviral agent provided drug release that should be sufficient for HIV prophylaxis for 12 months or more, according to results of a phase 1 clinical trial just presented here at the International AIDS Society Conference on HIV Science.

grandeduc/Thinkstock

The islatravir-eluting arm implant was safe and generally well tolerated, with drug concentrations that remained above the target level needed for protection throughout the randomized, placebo-controlled study, said investigator Randolph P. Matthews, MD, PhD, senior principal scientist at Merck, Kenilworth, N.J.

“Based on this study, the islatravir-eluting implant appears to be a potentially important option for preexposure prophylaxis (PrEP) as an agent that could be effective with yearly dosing,” Dr. Matthews said in an IAS press conference.

This drug-eluting implant, inserted subdermally in the skin of the upper arm, could represent a “meaningful option” for many individuals at high risk of HIV infection, particularly those who have adherence challenges, said Dr. Matthews.

“Many at-risk individuals face adherence challenges with the existing daily oral PrEP therapy,” he added. “A high degree of adherence is required for it to be effective, and daily adherence is challenging for many, particularly for women.”

Islatravir, formerly known as MK-8591, is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) being evaluated in clinical trials not only for PrEP, but also for treatment of HIV-1 infection in combination with other antiretrovirals.

In preclinical trials, islatravir demonstrated high potency, a high barrier to resistance, and a long half-life, according to Dr. Matthews.

The phase 1, single-site, double-blind study included a total of 16 healthy adult volunteers who received implants of islatravir at one of two doses (54 mg and 62 mg) or placebo for 12 weeks.

Both active doses of islatravir led to concentrations above the target level at 12 weeks, and based on data modeling, the higher-dose implant would still be above the target level for at least a year, Dr. Matthews said in the press conference.

The projected duration above the target ranged from 12 to 16 months for the 62-mg dose of islatravir, and from 8 to 10 months for the 54-mg dose, according to the reported data.

All drug-related adverse events were mild or moderate in severity, and none of the volunteers discontinued the study because of an adverse event, Dr. Matthews said.

Taken together, these data support the continued progression of the implant clinical development program, said Dr. Matthews, who is an employee of Merck, which sponsored the study.

SOURCE: Matthews RP et al. IAS 2019, Abstract TUAC0401LB.

An implant that elutes an investigational antiretroviral agent provided drug release that should be sufficient for HIV prophylaxis for 12 months or more, according to results of a phase 1 clinical trial just presented here at the International AIDS Society Conference on HIV Science.

grandeduc/Thinkstock

The islatravir-eluting arm implant was safe and generally well tolerated, with drug concentrations that remained above the target level needed for protection throughout the randomized, placebo-controlled study, said investigator Randolph P. Matthews, MD, PhD, senior principal scientist at Merck, Kenilworth, N.J.

“Based on this study, the islatravir-eluting implant appears to be a potentially important option for preexposure prophylaxis (PrEP) as an agent that could be effective with yearly dosing,” Dr. Matthews said in an IAS press conference.

This drug-eluting implant, inserted subdermally in the skin of the upper arm, could represent a “meaningful option” for many individuals at high risk of HIV infection, particularly those who have adherence challenges, said Dr. Matthews.

“Many at-risk individuals face adherence challenges with the existing daily oral PrEP therapy,” he added. “A high degree of adherence is required for it to be effective, and daily adherence is challenging for many, particularly for women.”

Islatravir, formerly known as MK-8591, is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) being evaluated in clinical trials not only for PrEP, but also for treatment of HIV-1 infection in combination with other antiretrovirals.

In preclinical trials, islatravir demonstrated high potency, a high barrier to resistance, and a long half-life, according to Dr. Matthews.

The phase 1, single-site, double-blind study included a total of 16 healthy adult volunteers who received implants of islatravir at one of two doses (54 mg and 62 mg) or placebo for 12 weeks.

Both active doses of islatravir led to concentrations above the target level at 12 weeks, and based on data modeling, the higher-dose implant would still be above the target level for at least a year, Dr. Matthews said in the press conference.

The projected duration above the target ranged from 12 to 16 months for the 62-mg dose of islatravir, and from 8 to 10 months for the 54-mg dose, according to the reported data.

All drug-related adverse events were mild or moderate in severity, and none of the volunteers discontinued the study because of an adverse event, Dr. Matthews said.

Taken together, these data support the continued progression of the implant clinical development program, said Dr. Matthews, who is an employee of Merck, which sponsored the study.

SOURCE: Matthews RP et al. IAS 2019, Abstract TUAC0401LB.

An implant that elutes an investigational antiretroviral agent provided drug release that should be sufficient for HIV prophylaxis for 12 months or more, according to results of a phase 1 clinical trial just presented here at the International AIDS Society Conference on HIV Science.

grandeduc/Thinkstock

The islatravir-eluting arm implant was safe and generally well tolerated, with drug concentrations that remained above the target level needed for protection throughout the randomized, placebo-controlled study, said investigator Randolph P. Matthews, MD, PhD, senior principal scientist at Merck, Kenilworth, N.J.

“Based on this study, the islatravir-eluting implant appears to be a potentially important option for preexposure prophylaxis (PrEP) as an agent that could be effective with yearly dosing,” Dr. Matthews said in an IAS press conference.

This drug-eluting implant, inserted subdermally in the skin of the upper arm, could represent a “meaningful option” for many individuals at high risk of HIV infection, particularly those who have adherence challenges, said Dr. Matthews.

“Many at-risk individuals face adherence challenges with the existing daily oral PrEP therapy,” he added. “A high degree of adherence is required for it to be effective, and daily adherence is challenging for many, particularly for women.”

Islatravir, formerly known as MK-8591, is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) being evaluated in clinical trials not only for PrEP, but also for treatment of HIV-1 infection in combination with other antiretrovirals.

In preclinical trials, islatravir demonstrated high potency, a high barrier to resistance, and a long half-life, according to Dr. Matthews.

The phase 1, single-site, double-blind study included a total of 16 healthy adult volunteers who received implants of islatravir at one of two doses (54 mg and 62 mg) or placebo for 12 weeks.

Both active doses of islatravir led to concentrations above the target level at 12 weeks, and based on data modeling, the higher-dose implant would still be above the target level for at least a year, Dr. Matthews said in the press conference.

The projected duration above the target ranged from 12 to 16 months for the 62-mg dose of islatravir, and from 8 to 10 months for the 54-mg dose, according to the reported data.

All drug-related adverse events were mild or moderate in severity, and none of the volunteers discontinued the study because of an adverse event, Dr. Matthews said.

Taken together, these data support the continued progression of the implant clinical development program, said Dr. Matthews, who is an employee of Merck, which sponsored the study.

SOURCE: Matthews RP et al. IAS 2019, Abstract TUAC0401LB.

New studies of a two-drug, integrase inhibitor–based regimen, presented at the International AIDS Society Conference on HIV Science, provide additional data to challenge the three-drug HIV treatment paradigm.

In the results of one study, known as TANGO (NCT03446573), switching to the fixed-dose combination of dolutegravir (DTG) plus lamivudine (3TC) from a tenofovir alafenamide (TAF)–based three- or four-drug regimen maintained virologic suppression at 48 weeks in HIV-1 infected adults, an investigator said, and was noninferior to continuing TAF-based therapy.

In another presentation, updating results of the GEMINI-1 (NCT02831673) and GEMINI-2 studies (NCT02831764), a researcher said the DTG+3TC combination remained noninferior to DTG plus tenofovir/emtricitabine (TDF/FTC) at week 96 in antiretroviral (ART) treatment-naive adults with HIV-1 infection, with no treatment-emergent resistance and no increase in risk of virologic failure.

In light of these findings and encouraging findings from studies of other two-drug regimens, it may be time to “rethink the position of dual therapy in the international guidelines,” according to IAS Past President Pedro Cahn, MD, PhD, of Fundación Huésped, Buenos Aires, who presented the updated GEMINI study results.

“We don’t mean to say now everything should be dual therapy, and we are going to wipe out all other options, but I think we have another strong option for initiating therapy, and probably also for switch therapy,” Dr. Cahn said in a press conference.

Dr. Cahn presented an updated analysis of GEMINI-1 and GEMINI-2, two identically designed phase 3 randomized clinical trials including a total of 1,400 patients.

The 48-week results from those trials, presented in 2018, showed for the first time that a dual-therapy combination of an integrase inhibitor with 3TC was noninferior to the triple-drug regimen of DTG+TDF/FTC, Dr. Cahn said.

In the updated analysis, including 96 weeks of data, the two-drug regimen remained noninferior to the three-drug regimen, according to the investigator.

A total of 11 patients on DTG+3TC and 7 on DTG+TDF/FTC met virologic withdrawal criteria through week 96, with no treatment-emergent resistance mutations seen in either arm, according to results reported in the study abstract.

The proportion of subjects with plasma HIV-1 RNA below 50 c/mL at week 96 was 86% for the two-drug regimen and 90% for the three-drug regimen (adjusted difference, –3.4; 95% confidence interval, –6.7 to 0.0), the reported data showed.

Drug-related adverse events were numerically more common in the three-drug arm, though rates of adverse event–related withdrawal were low in both arms, according to investigators.

The strategy of switching to DTG+3TC was evaluated in the randomized, phase 3 TANGO trial, which included 741 subjects who were already virally suppressed on a TAF-based three- or four-drug regimen. After 48 weeks of therapy, the two-drug regimen was noninferior to remaining on TAF-based therapy in terms of achieving and maintaining viral suppression, according to investigator Jean van Wyk, MB, ChB, Global Medical Lead for dolutegravir at ViiV Healthcare.

Safety outcomes were similar between the arms, though the absolute number of treatment-related adverse events was higher in the DTG+3TC arm “as expected in a switch study,” Dr. van Wyk said.

The percentage of subjects withdrawing from the study because of adverse events was 4% in the DTG+3TC arm and less than 1% in the TAF-based treatment arm, according to reported data.

And with regard to safety there were similar outcomes between the two arms, with regard to overall adverse events, “but as expected in a switch study, we did see more treatment-related adverse events in the dolutegravir plus lamivudine arm, and that’s because the majority of patients were on two new agents in the form of dolutegravir plus lamivudine, so it’s completely expected,” Dr. van Wyk said.

The study met its primary endpoint for noninferiority at week 48, based on the Food and Drug Administration snapshot algorithm. Results showed that switching to DTG+3TC was noninferior to continuing the TAF-containing regimen at week 48, with virologic failure per snapshot criteria seen in less than 1% of subjects in either arm, according to reported data. The proportion of subjects with plasma HIV-1 RNA less than 50 c/mL was 93.2% and 93.0% for the DTG+3TC and TAF-based treatment arms, respectively.

Longer-term follow-up will be important to confirm the noninferiority of the two-drug approach, Dr. van Wyk and Dr. Cahn said in the press conference. The TANGO study of the switch strategy will continue through 148 weeks, while an additional year of follow-up is ongoing for the GEMINI studies of the initial therapy approach.

TANGO and both GEMINI 1 and GEMINI 2 were sponsored by ViiV Healthcare. Dr. van Wyk is an employee of ViiV Healthcare. Dr. Cahn has received research support grants, and fees as consultant and speaker from ViiV Healthcare.

SOURCE: Cahn P et al. IAS 2019, Abstract WEAB0404LB; van Wyk J et al. IAS 2019, Abstract WEAB0403LB.

New studies of a two-drug, integrase inhibitor–based regimen, presented at the International AIDS Society Conference on HIV Science, provide additional data to challenge the three-drug HIV treatment paradigm.

In the results of one study, known as TANGO (NCT03446573), switching to the fixed-dose combination of dolutegravir (DTG) plus lamivudine (3TC) from a tenofovir alafenamide (TAF)–based three- or four-drug regimen maintained virologic suppression at 48 weeks in HIV-1 infected adults, an investigator said, and was noninferior to continuing TAF-based therapy.

In another presentation, updating results of the GEMINI-1 (NCT02831673) and GEMINI-2 studies (NCT02831764), a researcher said the DTG+3TC combination remained noninferior to DTG plus tenofovir/emtricitabine (TDF/FTC) at week 96 in antiretroviral (ART) treatment-naive adults with HIV-1 infection, with no treatment-emergent resistance and no increase in risk of virologic failure.

In light of these findings and encouraging findings from studies of other two-drug regimens, it may be time to “rethink the position of dual therapy in the international guidelines,” according to IAS Past President Pedro Cahn, MD, PhD, of Fundación Huésped, Buenos Aires, who presented the updated GEMINI study results.

“We don’t mean to say now everything should be dual therapy, and we are going to wipe out all other options, but I think we have another strong option for initiating therapy, and probably also for switch therapy,” Dr. Cahn said in a press conference.

Dr. Cahn presented an updated analysis of GEMINI-1 and GEMINI-2, two identically designed phase 3 randomized clinical trials including a total of 1,400 patients.

The 48-week results from those trials, presented in 2018, showed for the first time that a dual-therapy combination of an integrase inhibitor with 3TC was noninferior to the triple-drug regimen of DTG+TDF/FTC, Dr. Cahn said.

In the updated analysis, including 96 weeks of data, the two-drug regimen remained noninferior to the three-drug regimen, according to the investigator.

A total of 11 patients on DTG+3TC and 7 on DTG+TDF/FTC met virologic withdrawal criteria through week 96, with no treatment-emergent resistance mutations seen in either arm, according to results reported in the study abstract.

The proportion of subjects with plasma HIV-1 RNA below 50 c/mL at week 96 was 86% for the two-drug regimen and 90% for the three-drug regimen (adjusted difference, –3.4; 95% confidence interval, –6.7 to 0.0), the reported data showed.

Drug-related adverse events were numerically more common in the three-drug arm, though rates of adverse event–related withdrawal were low in both arms, according to investigators.

The strategy of switching to DTG+3TC was evaluated in the randomized, phase 3 TANGO trial, which included 741 subjects who were already virally suppressed on a TAF-based three- or four-drug regimen. After 48 weeks of therapy, the two-drug regimen was noninferior to remaining on TAF-based therapy in terms of achieving and maintaining viral suppression, according to investigator Jean van Wyk, MB, ChB, Global Medical Lead for dolutegravir at ViiV Healthcare.

Safety outcomes were similar between the arms, though the absolute number of treatment-related adverse events was higher in the DTG+3TC arm “as expected in a switch study,” Dr. van Wyk said.

The percentage of subjects withdrawing from the study because of adverse events was 4% in the DTG+3TC arm and less than 1% in the TAF-based treatment arm, according to reported data.

And with regard to safety there were similar outcomes between the two arms, with regard to overall adverse events, “but as expected in a switch study, we did see more treatment-related adverse events in the dolutegravir plus lamivudine arm, and that’s because the majority of patients were on two new agents in the form of dolutegravir plus lamivudine, so it’s completely expected,” Dr. van Wyk said.

The study met its primary endpoint for noninferiority at week 48, based on the Food and Drug Administration snapshot algorithm. Results showed that switching to DTG+3TC was noninferior to continuing the TAF-containing regimen at week 48, with virologic failure per snapshot criteria seen in less than 1% of subjects in either arm, according to reported data. The proportion of subjects with plasma HIV-1 RNA less than 50 c/mL was 93.2% and 93.0% for the DTG+3TC and TAF-based treatment arms, respectively.

Longer-term follow-up will be important to confirm the noninferiority of the two-drug approach, Dr. van Wyk and Dr. Cahn said in the press conference. The TANGO study of the switch strategy will continue through 148 weeks, while an additional year of follow-up is ongoing for the GEMINI studies of the initial therapy approach.

TANGO and both GEMINI 1 and GEMINI 2 were sponsored by ViiV Healthcare. Dr. van Wyk is an employee of ViiV Healthcare. Dr. Cahn has received research support grants, and fees as consultant and speaker from ViiV Healthcare.

SOURCE: Cahn P et al. IAS 2019, Abstract WEAB0404LB; van Wyk J et al. IAS 2019, Abstract WEAB0403LB.

New studies of a two-drug, integrase inhibitor–based regimen, presented at the International AIDS Society Conference on HIV Science, provide additional data to challenge the three-drug HIV treatment paradigm.

In the results of one study, known as TANGO (NCT03446573), switching to the fixed-dose combination of dolutegravir (DTG) plus lamivudine (3TC) from a tenofovir alafenamide (TAF)–based three- or four-drug regimen maintained virologic suppression at 48 weeks in HIV-1 infected adults, an investigator said, and was noninferior to continuing TAF-based therapy.

In another presentation, updating results of the GEMINI-1 (NCT02831673) and GEMINI-2 studies (NCT02831764), a researcher said the DTG+3TC combination remained noninferior to DTG plus tenofovir/emtricitabine (TDF/FTC) at week 96 in antiretroviral (ART) treatment-naive adults with HIV-1 infection, with no treatment-emergent resistance and no increase in risk of virologic failure.

In light of these findings and encouraging findings from studies of other two-drug regimens, it may be time to “rethink the position of dual therapy in the international guidelines,” according to IAS Past President Pedro Cahn, MD, PhD, of Fundación Huésped, Buenos Aires, who presented the updated GEMINI study results.

“We don’t mean to say now everything should be dual therapy, and we are going to wipe out all other options, but I think we have another strong option for initiating therapy, and probably also for switch therapy,” Dr. Cahn said in a press conference.

Dr. Cahn presented an updated analysis of GEMINI-1 and GEMINI-2, two identically designed phase 3 randomized clinical trials including a total of 1,400 patients.

The 48-week results from those trials, presented in 2018, showed for the first time that a dual-therapy combination of an integrase inhibitor with 3TC was noninferior to the triple-drug regimen of DTG+TDF/FTC, Dr. Cahn said.

In the updated analysis, including 96 weeks of data, the two-drug regimen remained noninferior to the three-drug regimen, according to the investigator.

A total of 11 patients on DTG+3TC and 7 on DTG+TDF/FTC met virologic withdrawal criteria through week 96, with no treatment-emergent resistance mutations seen in either arm, according to results reported in the study abstract.

The proportion of subjects with plasma HIV-1 RNA below 50 c/mL at week 96 was 86% for the two-drug regimen and 90% for the three-drug regimen (adjusted difference, –3.4; 95% confidence interval, –6.7 to 0.0), the reported data showed.

Drug-related adverse events were numerically more common in the three-drug arm, though rates of adverse event–related withdrawal were low in both arms, according to investigators.

The strategy of switching to DTG+3TC was evaluated in the randomized, phase 3 TANGO trial, which included 741 subjects who were already virally suppressed on a TAF-based three- or four-drug regimen. After 48 weeks of therapy, the two-drug regimen was noninferior to remaining on TAF-based therapy in terms of achieving and maintaining viral suppression, according to investigator Jean van Wyk, MB, ChB, Global Medical Lead for dolutegravir at ViiV Healthcare.

Safety outcomes were similar between the arms, though the absolute number of treatment-related adverse events was higher in the DTG+3TC arm “as expected in a switch study,” Dr. van Wyk said.

The percentage of subjects withdrawing from the study because of adverse events was 4% in the DTG+3TC arm and less than 1% in the TAF-based treatment arm, according to reported data.

And with regard to safety there were similar outcomes between the two arms, with regard to overall adverse events, “but as expected in a switch study, we did see more treatment-related adverse events in the dolutegravir plus lamivudine arm, and that’s because the majority of patients were on two new agents in the form of dolutegravir plus lamivudine, so it’s completely expected,” Dr. van Wyk said.

The study met its primary endpoint for noninferiority at week 48, based on the Food and Drug Administration snapshot algorithm. Results showed that switching to DTG+3TC was noninferior to continuing the TAF-containing regimen at week 48, with virologic failure per snapshot criteria seen in less than 1% of subjects in either arm, according to reported data. The proportion of subjects with plasma HIV-1 RNA less than 50 c/mL was 93.2% and 93.0% for the DTG+3TC and TAF-based treatment arms, respectively.

Longer-term follow-up will be important to confirm the noninferiority of the two-drug approach, Dr. van Wyk and Dr. Cahn said in the press conference. The TANGO study of the switch strategy will continue through 148 weeks, while an additional year of follow-up is ongoing for the GEMINI studies of the initial therapy approach.

TANGO and both GEMINI 1 and GEMINI 2 were sponsored by ViiV Healthcare. Dr. van Wyk is an employee of ViiV Healthcare. Dr. Cahn has received research support grants, and fees as consultant and speaker from ViiV Healthcare.

SOURCE: Cahn P et al. IAS 2019, Abstract WEAB0404LB; van Wyk J et al. IAS 2019, Abstract WEAB0403LB.

Health care providers who do not have the time or tools to screen patients for HIV risk also may not be prescribing preexposure prophylaxis (PrEP). But help is on the way: NIH-funded researchers have come up with novel computerized methods to identify the patients PrEP could benefit.

In 2 separate studies, the researchers developed and validated algorithms that analyze electronic health records (EHR). In the first study, Harvard researchers used machine learning to create an HIV prediction algorithm using 2007 to 2015 data from > 1 million patients in Massachusetts. The model included variables such as diagnosis codes for HIV counseling or sexually transmitted infections (STIs), laboratory tests for HIV or STIs, and prescriptions for medications related to treating STIs.

The model was validated using data from nearly 600,000 other patients treated between 2011 and 2016. The prediction algorithm successfully distinguished with high precision between patients who did or did not acquire HIV and between those who did or did not receive a PrEP prescription.

The researchers found hundreds of potential missed opportunities. They point to > 9,500 people in the 2016 dataset with particularly high-risk scores who were not prescribed PrEP. A “striking outcome,” the researchers say, is that their analysis suggests that nearly 40% of new HIV cases might have been averted had clinicians received alerts to discuss and offer PrEP to patients with the highest 2% of risk scores.

In the second study, researchers used the EHRs of > 3.7 million patients who entered the Kaiser Permanente System Northern California between 2007 and 2014 to develop a model to predict HIV incidence, then validated the model with data from between 2015 and 2017. Of the original patient group, 784 developed HIV within 3 years of baseline. The study found that the model identified nearly half of the incident HIV cases among males by flagging only 2% of the general patient population.

Embedding the algorithm into the EHR, the lead investigator says, “could prompt providers to discuss PrEP with patients who are most likely to benefit.”

Health care providers who do not have the time or tools to screen patients for HIV risk also may not be prescribing preexposure prophylaxis (PrEP). But help is on the way: NIH-funded researchers have come up with novel computerized methods to identify the patients PrEP could benefit.

In 2 separate studies, the researchers developed and validated algorithms that analyze electronic health records (EHR). In the first study, Harvard researchers used machine learning to create an HIV prediction algorithm using 2007 to 2015 data from > 1 million patients in Massachusetts. The model included variables such as diagnosis codes for HIV counseling or sexually transmitted infections (STIs), laboratory tests for HIV or STIs, and prescriptions for medications related to treating STIs.

The model was validated using data from nearly 600,000 other patients treated between 2011 and 2016. The prediction algorithm successfully distinguished with high precision between patients who did or did not acquire HIV and between those who did or did not receive a PrEP prescription.

The researchers found hundreds of potential missed opportunities. They point to > 9,500 people in the 2016 dataset with particularly high-risk scores who were not prescribed PrEP. A “striking outcome,” the researchers say, is that their analysis suggests that nearly 40% of new HIV cases might have been averted had clinicians received alerts to discuss and offer PrEP to patients with the highest 2% of risk scores.

In the second study, researchers used the EHRs of > 3.7 million patients who entered the Kaiser Permanente System Northern California between 2007 and 2014 to develop a model to predict HIV incidence, then validated the model with data from between 2015 and 2017. Of the original patient group, 784 developed HIV within 3 years of baseline. The study found that the model identified nearly half of the incident HIV cases among males by flagging only 2% of the general patient population.

Embedding the algorithm into the EHR, the lead investigator says, “could prompt providers to discuss PrEP with patients who are most likely to benefit.”

Health care providers who do not have the time or tools to screen patients for HIV risk also may not be prescribing preexposure prophylaxis (PrEP). But help is on the way: NIH-funded researchers have come up with novel computerized methods to identify the patients PrEP could benefit.

In 2 separate studies, the researchers developed and validated algorithms that analyze electronic health records (EHR). In the first study, Harvard researchers used machine learning to create an HIV prediction algorithm using 2007 to 2015 data from > 1 million patients in Massachusetts. The model included variables such as diagnosis codes for HIV counseling or sexually transmitted infections (STIs), laboratory tests for HIV or STIs, and prescriptions for medications related to treating STIs.

The model was validated using data from nearly 600,000 other patients treated between 2011 and 2016. The prediction algorithm successfully distinguished with high precision between patients who did or did not acquire HIV and between those who did or did not receive a PrEP prescription.

The researchers found hundreds of potential missed opportunities. They point to > 9,500 people in the 2016 dataset with particularly high-risk scores who were not prescribed PrEP. A “striking outcome,” the researchers say, is that their analysis suggests that nearly 40% of new HIV cases might have been averted had clinicians received alerts to discuss and offer PrEP to patients with the highest 2% of risk scores.

In the second study, researchers used the EHRs of > 3.7 million patients who entered the Kaiser Permanente System Northern California between 2007 and 2014 to develop a model to predict HIV incidence, then validated the model with data from between 2015 and 2017. Of the original patient group, 784 developed HIV within 3 years of baseline. The study found that the model identified nearly half of the incident HIV cases among males by flagging only 2% of the general patient population.

Embedding the algorithm into the EHR, the lead investigator says, “could prompt providers to discuss PrEP with patients who are most likely to benefit.”

The risk of neural tube defects linked to dolutegravir exposure during pregnancy is lower than previously signaled, according to new reports that have prompted the World Health Organization (WHO) to confirm that this antiviral medication should be the preferred option across all populations.

alexskopje/Thinkstock

The use of dolutegravir (DTG) during pregnancy has been a pressing global health question since May 2018, when an unplanned interim analysis of the Tsepamo surveillance study of birth outcomes in Botswana showed four neural tube defects associated with dolutegravir exposure among 426 infants born to HIV-positive women (0.94%).

With follow-up for additional births, however, just one more neural tube defect was identified out of 1,683 deliveries among women who had taken DTG around the time of conception (0.30%), according to a report just presented here at the at the International AIDS Society Conference on HIV Science.

By comparison, prevalence rates of neural tube defects were 0.10% for mothers taking other antiretroviral therapies at conception, 0.04% for those specifically taking efavirenz at conception, and 0.08% in HIV-uninfected mothers, according to the report, which was simultaneously published in the New England Journal of Medicine.

“While there may be a risk for neural tube defects, this risk is small, and really importantly, needs to be weighed against the large potential benefits of dolutegravir,” investigator Rebecca M. Zash, MD, of Beth Israel Deaconess Medical Center, Boston, said here in Mexico City during an IAS 2019 video press conference.

The WHO had previously sounded a note of caution, saying that DTG could be “considered” in women of childbearing age if other first‐line antiretroviral agents such as efavirenz could not be used.

However, following release of new evidence, including the study by Dr. Zash and colleagues, the WHO has come out with a clear recommendation for HIV drug as “the preferred first-line and second-line treatment for all populations, including pregnant women and those of childbearing potential.”

The updated scientific reports and guidelines have important implications for global health. “Many countries have been working to make dolutegravir-based treatment their preferred first-line regimen, as it’s got several advantages over efavirenz, which people have been using for many years now, including its tolerability and resistance profiles, and its impact on morbidity and mortality,” IAS president Anton Pozniak, MD, said in the press conference.

Some countries paused their plans to roll out dolutegravir-based regimens after the preliminary safety signal from the Tsepamo study was reported, Dr. Pozniak added.

In another study presented at IAS looking at dolutegravir use at conception, investigators described an additional surveillance study in Botswana, conducted independently from the Tsepamo study. One neural tube defect was found among 152 deliveries in mothers who had been taking DTG at conception (0.66%), and two neural tube defects among 2,326 deliveries to HIV-negative mothers (0.09%).

Although the number of deliveries are small in this study, the results suggest a risk of neural tube defects with DTG exposure at conception of less than 1%, said Mmakgomo Mimi Raesima, MD, MPH, public health specialist, Ministry of Health and Wellness, Botswana.

Because neural-tube defects might be related to low folate levels, Dr. Raesima said “conversations are continuing” with regard to folate food fortification in Botswana, a country that does not mandate folate-fortified grains.

“We want to capitalize on the momentum from these results,” Dr. Raesima said in the press conference.

The Tsepamo study was funded by the National Institutes of Health. Dr. Zash reported grants during the conduct of the study from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

SOURCE: Zash R et al. N Engl J Med. 2019 Jul 22. doi: 10.1056/NEJMoa1905230.

The risk of neural tube defects linked to dolutegravir exposure during pregnancy is lower than previously signaled, according to new reports that have prompted the World Health Organization (WHO) to confirm that this antiviral medication should be the preferred option across all populations.

alexskopje/Thinkstock

The use of dolutegravir (DTG) during pregnancy has been a pressing global health question since May 2018, when an unplanned interim analysis of the Tsepamo surveillance study of birth outcomes in Botswana showed four neural tube defects associated with dolutegravir exposure among 426 infants born to HIV-positive women (0.94%).

With follow-up for additional births, however, just one more neural tube defect was identified out of 1,683 deliveries among women who had taken DTG around the time of conception (0.30%), according to a report just presented here at the at the International AIDS Society Conference on HIV Science.

By comparison, prevalence rates of neural tube defects were 0.10% for mothers taking other antiretroviral therapies at conception, 0.04% for those specifically taking efavirenz at conception, and 0.08% in HIV-uninfected mothers, according to the report, which was simultaneously published in the New England Journal of Medicine.

“While there may be a risk for neural tube defects, this risk is small, and really importantly, needs to be weighed against the large potential benefits of dolutegravir,” investigator Rebecca M. Zash, MD, of Beth Israel Deaconess Medical Center, Boston, said here in Mexico City during an IAS 2019 video press conference.

The WHO had previously sounded a note of caution, saying that DTG could be “considered” in women of childbearing age if other first‐line antiretroviral agents such as efavirenz could not be used.

However, following release of new evidence, including the study by Dr. Zash and colleagues, the WHO has come out with a clear recommendation for HIV drug as “the preferred first-line and second-line treatment for all populations, including pregnant women and those of childbearing potential.”

The updated scientific reports and guidelines have important implications for global health. “Many countries have been working to make dolutegravir-based treatment their preferred first-line regimen, as it’s got several advantages over efavirenz, which people have been using for many years now, including its tolerability and resistance profiles, and its impact on morbidity and mortality,” IAS president Anton Pozniak, MD, said in the press conference.

Some countries paused their plans to roll out dolutegravir-based regimens after the preliminary safety signal from the Tsepamo study was reported, Dr. Pozniak added.

In another study presented at IAS looking at dolutegravir use at conception, investigators described an additional surveillance study in Botswana, conducted independently from the Tsepamo study. One neural tube defect was found among 152 deliveries in mothers who had been taking DTG at conception (0.66%), and two neural tube defects among 2,326 deliveries to HIV-negative mothers (0.09%).

Although the number of deliveries are small in this study, the results suggest a risk of neural tube defects with DTG exposure at conception of less than 1%, said Mmakgomo Mimi Raesima, MD, MPH, public health specialist, Ministry of Health and Wellness, Botswana.

Because neural-tube defects might be related to low folate levels, Dr. Raesima said “conversations are continuing” with regard to folate food fortification in Botswana, a country that does not mandate folate-fortified grains.

“We want to capitalize on the momentum from these results,” Dr. Raesima said in the press conference.

The Tsepamo study was funded by the National Institutes of Health. Dr. Zash reported grants during the conduct of the study from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

SOURCE: Zash R et al. N Engl J Med. 2019 Jul 22. doi: 10.1056/NEJMoa1905230.

The risk of neural tube defects linked to dolutegravir exposure during pregnancy is lower than previously signaled, according to new reports that have prompted the World Health Organization (WHO) to confirm that this antiviral medication should be the preferred option across all populations.

alexskopje/Thinkstock

The use of dolutegravir (DTG) during pregnancy has been a pressing global health question since May 2018, when an unplanned interim analysis of the Tsepamo surveillance study of birth outcomes in Botswana showed four neural tube defects associated with dolutegravir exposure among 426 infants born to HIV-positive women (0.94%).

With follow-up for additional births, however, just one more neural tube defect was identified out of 1,683 deliveries among women who had taken DTG around the time of conception (0.30%), according to a report just presented here at the at the International AIDS Society Conference on HIV Science.

By comparison, prevalence rates of neural tube defects were 0.10% for mothers taking other antiretroviral therapies at conception, 0.04% for those specifically taking efavirenz at conception, and 0.08% in HIV-uninfected mothers, according to the report, which was simultaneously published in the New England Journal of Medicine.

“While there may be a risk for neural tube defects, this risk is small, and really importantly, needs to be weighed against the large potential benefits of dolutegravir,” investigator Rebecca M. Zash, MD, of Beth Israel Deaconess Medical Center, Boston, said here in Mexico City during an IAS 2019 video press conference.

The WHO had previously sounded a note of caution, saying that DTG could be “considered” in women of childbearing age if other first‐line antiretroviral agents such as efavirenz could not be used.

However, following release of new evidence, including the study by Dr. Zash and colleagues, the WHO has come out with a clear recommendation for HIV drug as “the preferred first-line and second-line treatment for all populations, including pregnant women and those of childbearing potential.”

The updated scientific reports and guidelines have important implications for global health. “Many countries have been working to make dolutegravir-based treatment their preferred first-line regimen, as it’s got several advantages over efavirenz, which people have been using for many years now, including its tolerability and resistance profiles, and its impact on morbidity and mortality,” IAS president Anton Pozniak, MD, said in the press conference.

Some countries paused their plans to roll out dolutegravir-based regimens after the preliminary safety signal from the Tsepamo study was reported, Dr. Pozniak added.

In another study presented at IAS looking at dolutegravir use at conception, investigators described an additional surveillance study in Botswana, conducted independently from the Tsepamo study. One neural tube defect was found among 152 deliveries in mothers who had been taking DTG at conception (0.66%), and two neural tube defects among 2,326 deliveries to HIV-negative mothers (0.09%).

Although the number of deliveries are small in this study, the results suggest a risk of neural tube defects with DTG exposure at conception of less than 1%, said Mmakgomo Mimi Raesima, MD, MPH, public health specialist, Ministry of Health and Wellness, Botswana.

Because neural-tube defects might be related to low folate levels, Dr. Raesima said “conversations are continuing” with regard to folate food fortification in Botswana, a country that does not mandate folate-fortified grains.

“We want to capitalize on the momentum from these results,” Dr. Raesima said in the press conference.

The Tsepamo study was funded by the National Institutes of Health. Dr. Zash reported grants during the conduct of the study from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

SOURCE: Zash R et al. N Engl J Med. 2019 Jul 22. doi: 10.1056/NEJMoa1905230.

The US Department of Veterans Affairs (VA) has a well-established National HIV Program, says Dr. Richard Stone, executive in charge of the VHA. In fact, he notes, the VA is the single largest provider of HIV care in America and has treated 31,000 veterans for HIV.

Thus, the VA plays a critical role in the effort to establish tools and resources to eradicate HIV in the US, Stone says, “one veteran at a time.” To realize this “ambitious but achievable target,” the VA is:

• Offering HIV testing at least once to every veteran and more often to those at risk;
• Rapidly linking those who are diagnosed to effective treatment;
• Deploying an HIV health force to hard-hit areas of the country, expanding timely access to high-quality HIV care and prevention across the VA’s integrated network, with both face-to-face encounters and telehealth; and
• Offering pre-exposure prophylaxis (PrEP) when clinically appropriate.

The primary goal, Stone says, is for veterans with HIV or at risk for HIV to be able to access the best care “safely and free from stigma and discrimination.”

Resources and educational tools are available at www.hiv.va.gov, including recently updated fact sheets and videos for patients about PrEP

The US Department of Veterans Affairs (VA) has a well-established National HIV Program, says Dr. Richard Stone, executive in charge of the VHA. In fact, he notes, the VA is the single largest provider of HIV care in America and has treated 31,000 veterans for HIV.

Thus, the VA plays a critical role in the effort to establish tools and resources to eradicate HIV in the US, Stone says, “one veteran at a time.” To realize this “ambitious but achievable target,” the VA is:

• Offering HIV testing at least once to every veteran and more often to those at risk;
• Rapidly linking those who are diagnosed to effective treatment;
• Deploying an HIV health force to hard-hit areas of the country, expanding timely access to high-quality HIV care and prevention across the VA’s integrated network, with both face-to-face encounters and telehealth; and
• Offering pre-exposure prophylaxis (PrEP) when clinically appropriate.

The primary goal, Stone says, is for veterans with HIV or at risk for HIV to be able to access the best care “safely and free from stigma and discrimination.”

Resources and educational tools are available at www.hiv.va.gov, including recently updated fact sheets and videos for patients about PrEP

The US Department of Veterans Affairs (VA) has a well-established National HIV Program, says Dr. Richard Stone, executive in charge of the VHA. In fact, he notes, the VA is the single largest provider of HIV care in America and has treated 31,000 veterans for HIV.

Thus, the VA plays a critical role in the effort to establish tools and resources to eradicate HIV in the US, Stone says, “one veteran at a time.” To realize this “ambitious but achievable target,” the VA is:

• Offering HIV testing at least once to every veteran and more often to those at risk;
• Rapidly linking those who are diagnosed to effective treatment;
• Deploying an HIV health force to hard-hit areas of the country, expanding timely access to high-quality HIV care and prevention across the VA’s integrated network, with both face-to-face encounters and telehealth; and
• Offering pre-exposure prophylaxis (PrEP) when clinically appropriate.

The primary goal, Stone says, is for veterans with HIV or at risk for HIV to be able to access the best care “safely and free from stigma and discrimination.”

Resources and educational tools are available at www.hiv.va.gov, including recently updated fact sheets and videos for patients about PrEP

The Indian Health Service (IHS) and the Cherokee Nation Health Service are launching a new pilot project to help “accelerate progress” toward ending the HIV epidemic in native communities.

The project, which will investigate the most effective prevention strategies and share the findings locally, is part of the initiative Ending the HIV Epidemic: A Plan for America. That plan focuses prevention and treatment efforts on 48 counties and 7 southern states with a higher proportion of HIV diagnosis in rural areas. The Cherokee Nation is in Oklahoma, which has the highest American Indian population among the 7 southern states.

Recent data show new HIV infections at the lowest level yet, but progress in prevention has slowed, in part due to new threats such as the opioid crisis: 10% of new HIV infections are among injectable-drug users.

The Cherokee Nation’s proven track record in hepatitis C prevention and treatment makes it a valuable partner in the project. Half of its health services patients have been screened, and among the 3.2% testing positive, 90% have been cured. The pilot project will use a similar model, IHS says. Current statistics show that 35% of Cherokee National patients using the tribe’s health centers have been screened for HIV, with < 1% testing positive. Of the patients diagnosed with HIV, 90% are receiving care and 90% of those are virally suppressed. The pilot project is aimed at boosting the screening numbers.

The pilot is one of several HHS efforts to jumpstart key activities in select communities using resources from the Minority HIV/AIDS fund. The CDC also is launching projects in select communities.

“Improved health care over multiple generations is our top priority,” said Cherokee Nation Principal Chief Bill John Baker. “If we can collaborate with our federal partners at IHS to raise awareness, increase education, and actively work to prevent new cases of HIV, then we will be creating a healthier future for northeast Oklahoma.”

The Indian Health Service (IHS) and the Cherokee Nation Health Service are launching a new pilot project to help “accelerate progress” toward ending the HIV epidemic in native communities.

The project, which will investigate the most effective prevention strategies and share the findings locally, is part of the initiative Ending the HIV Epidemic: A Plan for America. That plan focuses prevention and treatment efforts on 48 counties and 7 southern states with a higher proportion of HIV diagnosis in rural areas. The Cherokee Nation is in Oklahoma, which has the highest American Indian population among the 7 southern states.

Recent data show new HIV infections at the lowest level yet, but progress in prevention has slowed, in part due to new threats such as the opioid crisis: 10% of new HIV infections are among injectable-drug users.

The Cherokee Nation’s proven track record in hepatitis C prevention and treatment makes it a valuable partner in the project. Half of its health services patients have been screened, and among the 3.2% testing positive, 90% have been cured. The pilot project will use a similar model, IHS says. Current statistics show that 35% of Cherokee National patients using the tribe’s health centers have been screened for HIV, with < 1% testing positive. Of the patients diagnosed with HIV, 90% are receiving care and 90% of those are virally suppressed. The pilot project is aimed at boosting the screening numbers.

The pilot is one of several HHS efforts to jumpstart key activities in select communities using resources from the Minority HIV/AIDS fund. The CDC also is launching projects in select communities.

“Improved health care over multiple generations is our top priority,” said Cherokee Nation Principal Chief Bill John Baker. “If we can collaborate with our federal partners at IHS to raise awareness, increase education, and actively work to prevent new cases of HIV, then we will be creating a healthier future for northeast Oklahoma.”

The Indian Health Service (IHS) and the Cherokee Nation Health Service are launching a new pilot project to help “accelerate progress” toward ending the HIV epidemic in native communities.

The project, which will investigate the most effective prevention strategies and share the findings locally, is part of the initiative Ending the HIV Epidemic: A Plan for America. That plan focuses prevention and treatment efforts on 48 counties and 7 southern states with a higher proportion of HIV diagnosis in rural areas. The Cherokee Nation is in Oklahoma, which has the highest American Indian population among the 7 southern states.

Recent data show new HIV infections at the lowest level yet, but progress in prevention has slowed, in part due to new threats such as the opioid crisis: 10% of new HIV infections are among injectable-drug users.

The Cherokee Nation’s proven track record in hepatitis C prevention and treatment makes it a valuable partner in the project. Half of its health services patients have been screened, and among the 3.2% testing positive, 90% have been cured. The pilot project will use a similar model, IHS says. Current statistics show that 35% of Cherokee National patients using the tribe’s health centers have been screened for HIV, with < 1% testing positive. Of the patients diagnosed with HIV, 90% are receiving care and 90% of those are virally suppressed. The pilot project is aimed at boosting the screening numbers.

The pilot is one of several HHS efforts to jumpstart key activities in select communities using resources from the Minority HIV/AIDS fund. The CDC also is launching projects in select communities.

“Improved health care over multiple generations is our top priority,” said Cherokee Nation Principal Chief Bill John Baker. “If we can collaborate with our federal partners at IHS to raise awareness, increase education, and actively work to prevent new cases of HIV, then we will be creating a healthier future for northeast Oklahoma.”

Here are 5 articles from the July issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Cloud of inconsistency hangs over cannabis data

To take the posttest, go to: https://bit.ly/2NfjaDS
Expires February 6, 2020

2. Roux-en-Y achieves diabetes remission in majority of patients

To take the posttest, go to: https://bit.ly/2x9hLnE
Expires February 6, 2020

3. Socioeconomic status, race found to impact CPAP compliance

To take the posttest, go to: https://bit.ly/2RBpLa9
Expires February 8, 2020

4. Exercise type matters for fall prevention among elderly

To take the posttest, go to: https://bit.ly/2X26OUh
Expires February 12, 2020

5. Adult HIV patients should receive standard vaccinations, with caveats

To take the posttest, go to: https://bit.ly/2X1S7LV
Expires February 12, 2020

Here are 5 articles from the July issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Cloud of inconsistency hangs over cannabis data

To take the posttest, go to: https://bit.ly/2NfjaDS
Expires February 6, 2020

2. Roux-en-Y achieves diabetes remission in majority of patients

To take the posttest, go to: https://bit.ly/2x9hLnE
Expires February 6, 2020

3. Socioeconomic status, race found to impact CPAP compliance

To take the posttest, go to: https://bit.ly/2RBpLa9
Expires February 8, 2020

4. Exercise type matters for fall prevention among elderly

To take the posttest, go to: https://bit.ly/2X26OUh
Expires February 12, 2020

5. Adult HIV patients should receive standard vaccinations, with caveats

To take the posttest, go to: https://bit.ly/2X1S7LV
Expires February 12, 2020

Here are 5 articles from the July issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Cloud of inconsistency hangs over cannabis data

To take the posttest, go to: https://bit.ly/2NfjaDS
Expires February 6, 2020

2. Roux-en-Y achieves diabetes remission in majority of patients

To take the posttest, go to: https://bit.ly/2x9hLnE
Expires February 6, 2020

3. Socioeconomic status, race found to impact CPAP compliance

To take the posttest, go to: https://bit.ly/2RBpLa9
Expires February 8, 2020

4. Exercise type matters for fall prevention among elderly

To take the posttest, go to: https://bit.ly/2X26OUh
Expires February 12, 2020

5. Adult HIV patients should receive standard vaccinations, with caveats

To take the posttest, go to: https://bit.ly/2X1S7LV
Expires February 12, 2020