HIV/HBV co-infection linked to worse immune recovery and death, but tenofovir improves outcomes

HIV-positive people with hepatitis B virus (HBV) co-infection had impaired CD4 cell recovery after starting antiretroviral therapy (ART) and a higher risk of death than those without hepatitis B, but use of ART regimens containing tenofovir significantly reduced mortality, according to a study presented at the recent Conference on Retroviruses and Opportunistic Infections (CROI 2016) in Boston.

Hepatitis B co-infection is common among people with HIV in sub-Saharan Africa. HIV/HBV co-infection is associated with impaired immunological recovery and worse clinical outcomes, even among people on effective ART, but the association between co-infection and mortality, and the effect of regimens containing tenofovir (Viread, also in Truvada and single-tablet regimens such as Atripla) is not fully understood.

Murithi Mbae from the London School of Hygiene and Tropical Medicine and colleagues conducted a retrospective analysis of data from the African Infectious Disease Village Clinics in the Rift Valley province of Kenya to determine the prevalence of hepatitis B among HIV-positive patients enrolling in ART programmes between 2003 and 2012. The clinic serves a predominantly rural Maasai population of approximately 200,000 people. This cohort enrolled 7155 patients, followed for a total of 12,408 person years.

All participants were screened for hepatitis B surface antigen (HBsAg) at baseline, which indicates current hepatitis B virus infection.

ART was prescribed according to World Health Organization (WHO) and Kenyan guidelines, with an initiation threshold of < 200 cells/mm³ until 2007, increased to 250 during 2007-2010 and 350 thereafter. First-line ART regimens consisted of stavudine (d4T, Zerit) or zidovudine (AZT, Retrovir) plus lamivudine (3TC, Epivir), with efavirenz (Sustiva or Stocrin) or nevirapine (Viramune) until 2010, when tenofovir was introduced. A total of 6214 people started ART, of whom 3125 used tenofovir-containing regimens.

Patients were monitored every three months for a mean duration of approximately 1.75 years. The researchers compared clinical outcomes and immunological and virological response to ART between HIV mono-infected and HIV/HBV co-infected participants. The impact of tenofovir-containing ART was determined in an analysis adjusting for confounding factors including age, sex, baseline CD4 count, calendar year and baseline creatinine level.

HBsAg was detected in 451 patients, for a prevalence of 6.3% (95% CI 5.8-6.9%). HBsAg prevalence was significantly higher among men than among women (9.2 vs 5.0%, respectively) and increased with age.

HBsAg-positive patients had significantly impaired immunological recovery compared to HBsAg-negative patients, with median CD4 count increases of 110 vs 135 cells/mm³ during the first year on treatment despite similar rates of HIV viral suppression (90 vs 89%, respectively).

Baseline ALT levels – an indicator of liver inflammation – were higher among HBsAg-positive patients (27 vs 23 IU/L), but the difference was not clinically significant. There was no evidence of severe liver disease among HBsAg-positive people during the first year on ART.

The death rate during the first year on ART was significantly higher among HBsAg-positive compared to HBsAg-negative participants (9.3% vs 5.3%, respectively). Being HBsAg positive was associated with a significantly increased risk of death in an adjusted analysis (hazard ratio [HR] 1.84; 95% CI 1.3-2.6).

However, among people who started tenofovir-containing regimens, HBsAg positivity was no longer significantly associated with increased mortality (adjusted HR 1.45; 95% CI 0.9-2.2). Among people who used regimens without tenofovir, in contrast, those who were HBsAg-positive had "markedly increased" mortality, with a threefold higher risk of death (adjusted HR 3.32; 95% CI 1.8-6.2).

"Hepatitis B co-infection was associated with impaired immunological responses to ART and increased risk of mortality in this large cohort of Kenyans initiating ART, despite adequate HIV virological suppression and no evidence for severe liver disease," the researchers concluded. "Use of tenofovir-containing regimens significantly reduced mortality risk in HIV/HBV co-infected patients."

Based on these findings, they cautioned, "Any move away from tenofovir-containing first-line ART in sub-Saharan Africa must be combined with hepatitis B surface antigen screening to enable effective treatment of individuals with HIV/HBV co-infection."