T-Cell Levels Determine Mortality Risk for HIV, HBV Positive Patients

CD4⁺ levels could help determine the mortality risk for patients with co-infections of HIV and hepatitis B virus (HBV).

A team, led by Gérard M Kouamé, University of Bordeaux, determined whether HIV-HBV co-infections influences changes in CD4⁺ cell counts both prior and during antiretroviral therapy (ART) and whether it impacts mortality risk levels of CD4⁺.

Co-Infections

Co-infections of HBV and HIV often lead to increased risk of overall mortality, particularly when HBV DNA levels are high. However, the role of CD4^­+, which are crucial cells on the adaptive immune system that use T cell antigen receptors to recognize peptides generated in endosomes or phagosomes, is not well defined.

“HIV-positive individuals with both resolved and chronic HBV-infection have been shown to have an increased risk in progression to AIDS-defining illnesses in the absence of effective treatment,” the authors wrote.

However, potent antiretroviral therapy has shown the ability to prevent the progression to AIDs in HIV-HBV positive individuals. Co-infections can still be linked to slower immunoreconstittiion, which leads to lower CD4⁺ cell counts during long-term antiretroviral therapy.

The Study

In the randomized, controlled study, the investigators examined 2052 HIV-positive patients from the Côte d’Ivoire from the Temprano ANRS 12,126 trial between March 2008 and July 2012.

Included in the study were HIV positive adults with CD4⁺ counts of less than 800/mm³, and the absence of active tuberculosis or severe liver disease.

The team determined HBV status using hepatitis B surface antigen (HBsAg) and estimated changes in CD4⁺ cell levels using a mixed-effect linear model.

They also estimated the incidence rates of all-cause mortality at CD4⁺ counts ≤350, 351–500, >500/mm³. The counts were compared between HBV-status groups as incidence rate ratios (IRR).

The patient population included 190 (9%) HBsAg-positive patients at baseline, 71% (n = 135) of which with HBV DNA <2000 IU/mL and 29% (n = 55) of which with HBV DNA ≥2000 IU/mL. There was a median follow-up period of 58 months.

Results

Overall, there was no differences in CD4⁺ increase following antiretroviral therapy initiation.

After the investigators adjusted for sex, age, baseline HIV RNA level, and early or deferred antiretroviral therapy arm, they found mortality rates were not significantly different between HBsAg-positive compared to HBsAg-negative participants across strata of CD4⁺ levels.

On the other hand, patients were HBsAg-positive with HBV-DNA ≥2000 IU/mL had increased mortality rates at ≤350/mm³ (adjusted-IRR, 3.82; 95% CI, 1.11–9.70) and 351–500/mm³ (adjusted-IRR, 4.37; 95% CI, 0.98–13.02) compared to individuals HBsAg-negative.

However, this was not true for >500/mm³ (adjusted-IRR, 1.07; 95% CI, 0.01–4.91).

“In conclusion, we observed that HIV–HBV co-infected and HIV mono-infected patients did not have differences in CD4⁺ decline while not receiving ART or in immunorestoration after initiating ART,” the authors wrote. “Importantly, the risk of mortality associated with HIV–HBV co-infection at high HBV DNA levels was only evident when CD4⁺ counts were below 500/mm³.”

Co-infections of HBV occur in about 8% of HIV positive individuals, which is known to increase the risk of progression to AIDS-defining illnesses in the absence of an effective therapeutic option.

The study, “Higher risk of mortality in HIV-HBV co-infected patients from sub-Saharan Africa is observed at lower CD4+ cell counts,” was published online in Antiviral Therapy.