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 and 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
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 people with HIV 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
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 people with HIV mono-infection and those with HIV and HBV co-infection. 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 participants, 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 –
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."