CMV viremia not culprit in high mortality of TB/HIV coinfection

DURBAN, SOUTH AFRICA – Cytomegalovirus viremia is common among patients hospitalized for HIV-associated tuberculosis, but it appears to be a bystander rather than a contributor to the high mortality seen in this population, Amy Ward, MD, said at the 21st International AIDS Conference.

“CMV [cytomegalovirus] viremia is likely a marker of more severe immunodeficiency rather than a direct contributor to mortality,” she concluded based upon the findings of her prospective cohort study. The finding means therapies for CMV viremia will not open up a new avenue of potentially life-saving treatments for these patients.

Courtesy CDC/ Dr. Haraszti

In other severe immunodeficiency conditions, such as after organ transplant, CMV viremia is directly related to increased mortality, and ganciclovir therapy can prevent progression to clinical disease and death, explained Dr. Ward of the University of Cape Town, South Africa.

She presented a prospective cohort study of 256 HIV-infected South African adults, median age 36 years, who were hospitalized with a new diagnosis of TB. At enrollment, their median CD4 count was 64 cells/mm³. Only 35% were on antiretroviral therapy (ART); 44% had previously been on ART, 21% were ART-naive, and 41% had a positive TB blood culture.

CMV viremia was present in 31%, and CMV viral load was 1,000 copies/mL or more in half of them. None had CMV retinitis, based on panoptic fundoscopy at enrollment. HIV-related retinal pathologies at enrollment included disseminated cryptococcal disease, ocular TB granules, and HIV retinitis.

The primary endpoint of the study was mortality at 12 weeks on anti-TB therapy. The mortality rate was 38% in the CMV viremic group, significantly higher than the 17.8% mortality rate seen in the CMV-negative patients.

In a univariate Cox proportional hazards regression analysis, CMV viremia was associated with a 2.1-fold increased risk for 12-week mortality. But advancing age, a low CD4 count, and decreasing serum albumin were also risk factors.

When these variables were incorporated in a multivariate regression analysis along with HIV viral load, tuberculosis blood culture results, and gender, CMV viremia was no longer a significant risk factor for 12-week mortality. Age was the sole significant predictor of death. Patients who were at least 36 years old had a 32.8% mortality rate, compared with a 14.1% rate in those who were younger. The CD4 count didn’t differ significantly by age; however, the prevalence of CMV viremia was 38% in the older group and 26.3% in patients under age 36.

“Those patients who were 36 years old and above had a higher mortality and were more likely to have CMV viremia, both findings perhaps reflecting premature aging of the immune system,” Dr. Ward said.

Also, no dose-response was seen between CMV viral load and mortality risk. The 12-week mortality rate was 33.3% in patients with a CMV viral load below 1,000 copies/mL and similar at 34.1% in those with a viral load above that cutpoint, she noted.

The study was funded by the Wellcome Trust and the South African Medical Research Council. Dr. Ward reported having no financial conflicts of interest.

bjancin@frontlinemedcom.com

DURBAN, SOUTH AFRICA – Cytomegalovirus viremia is common among patients hospitalized for HIV-associated tuberculosis, but it appears to be a bystander rather than a contributor to the high mortality seen in this population, Amy Ward, MD, said at the 21st International AIDS Conference.

“CMV [cytomegalovirus] viremia is likely a marker of more severe immunodeficiency rather than a direct contributor to mortality,” she concluded based upon the findings of her prospective cohort study. The finding means therapies for CMV viremia will not open up a new avenue of potentially life-saving treatments for these patients.

Courtesy CDC/ Dr. Haraszti

In other severe immunodeficiency conditions, such as after organ transplant, CMV viremia is directly related to increased mortality, and ganciclovir therapy can prevent progression to clinical disease and death, explained Dr. Ward of the University of Cape Town, South Africa.

She presented a prospective cohort study of 256 HIV-infected South African adults, median age 36 years, who were hospitalized with a new diagnosis of TB. At enrollment, their median CD4 count was 64 cells/mm³. Only 35% were on antiretroviral therapy (ART); 44% had previously been on ART, 21% were ART-naive, and 41% had a positive TB blood culture.

CMV viremia was present in 31%, and CMV viral load was 1,000 copies/mL or more in half of them. None had CMV retinitis, based on panoptic fundoscopy at enrollment. HIV-related retinal pathologies at enrollment included disseminated cryptococcal disease, ocular TB granules, and HIV retinitis.

The primary endpoint of the study was mortality at 12 weeks on anti-TB therapy. The mortality rate was 38% in the CMV viremic group, significantly higher than the 17.8% mortality rate seen in the CMV-negative patients.

In a univariate Cox proportional hazards regression analysis, CMV viremia was associated with a 2.1-fold increased risk for 12-week mortality. But advancing age, a low CD4 count, and decreasing serum albumin were also risk factors.

When these variables were incorporated in a multivariate regression analysis along with HIV viral load, tuberculosis blood culture results, and gender, CMV viremia was no longer a significant risk factor for 12-week mortality. Age was the sole significant predictor of death. Patients who were at least 36 years old had a 32.8% mortality rate, compared with a 14.1% rate in those who were younger. The CD4 count didn’t differ significantly by age; however, the prevalence of CMV viremia was 38% in the older group and 26.3% in patients under age 36.

“Those patients who were 36 years old and above had a higher mortality and were more likely to have CMV viremia, both findings perhaps reflecting premature aging of the immune system,” Dr. Ward said.

Also, no dose-response was seen between CMV viral load and mortality risk. The 12-week mortality rate was 33.3% in patients with a CMV viral load below 1,000 copies/mL and similar at 34.1% in those with a viral load above that cutpoint, she noted.

The study was funded by the Wellcome Trust and the South African Medical Research Council. Dr. Ward reported having no financial conflicts of interest.

bjancin@frontlinemedcom.com

DURBAN, SOUTH AFRICA – Cytomegalovirus viremia is common among patients hospitalized for HIV-associated tuberculosis, but it appears to be a bystander rather than a contributor to the high mortality seen in this population, Amy Ward, MD, said at the 21st International AIDS Conference.

“CMV [cytomegalovirus] viremia is likely a marker of more severe immunodeficiency rather than a direct contributor to mortality,” she concluded based upon the findings of her prospective cohort study. The finding means therapies for CMV viremia will not open up a new avenue of potentially life-saving treatments for these patients.

Courtesy CDC/ Dr. Haraszti

In other severe immunodeficiency conditions, such as after organ transplant, CMV viremia is directly related to increased mortality, and ganciclovir therapy can prevent progression to clinical disease and death, explained Dr. Ward of the University of Cape Town, South Africa.

She presented a prospective cohort study of 256 HIV-infected South African adults, median age 36 years, who were hospitalized with a new diagnosis of TB. At enrollment, their median CD4 count was 64 cells/mm³. Only 35% were on antiretroviral therapy (ART); 44% had previously been on ART, 21% were ART-naive, and 41% had a positive TB blood culture.

CMV viremia was present in 31%, and CMV viral load was 1,000 copies/mL or more in half of them. None had CMV retinitis, based on panoptic fundoscopy at enrollment. HIV-related retinal pathologies at enrollment included disseminated cryptococcal disease, ocular TB granules, and HIV retinitis.

The primary endpoint of the study was mortality at 12 weeks on anti-TB therapy. The mortality rate was 38% in the CMV viremic group, significantly higher than the 17.8% mortality rate seen in the CMV-negative patients.

In a univariate Cox proportional hazards regression analysis, CMV viremia was associated with a 2.1-fold increased risk for 12-week mortality. But advancing age, a low CD4 count, and decreasing serum albumin were also risk factors.

When these variables were incorporated in a multivariate regression analysis along with HIV viral load, tuberculosis blood culture results, and gender, CMV viremia was no longer a significant risk factor for 12-week mortality. Age was the sole significant predictor of death. Patients who were at least 36 years old had a 32.8% mortality rate, compared with a 14.1% rate in those who were younger. The CD4 count didn’t differ significantly by age; however, the prevalence of CMV viremia was 38% in the older group and 26.3% in patients under age 36.

“Those patients who were 36 years old and above had a higher mortality and were more likely to have CMV viremia, both findings perhaps reflecting premature aging of the immune system,” Dr. Ward said.

Also, no dose-response was seen between CMV viral load and mortality risk. The 12-week mortality rate was 33.3% in patients with a CMV viral load below 1,000 copies/mL and similar at 34.1% in those with a viral load above that cutpoint, she noted.

The study was funded by the Wellcome Trust and the South African Medical Research Council. Dr. Ward reported having no financial conflicts of interest.

bjancin@frontlinemedcom.com