The inclusion of lamivudine (3TC)
in antiretroviral therapy had few additional benefits for South African HIV-positive
patients co-infected with hepatitis B, South African investigators report in
the online edition of AIDS.
Hepatitis B virus
(HBV) outcomes were not significantly better in patients treated with lamivudine than in patients taking an alternative antiretroviral drug.
“Overall the efficacy
of 3TC on markers of HBV disease in this HIV/HBV co-infected population was
poor,” comment the investigators. They believe their results support the World
Health Organization (WHO) recommendation that co-infected patients should
receive antiretroviral therapy that includes tenofovir (Viread).
A protein made in the liver, needed to maintain a balance of the fluids in the body. In a blood test, lower than normal levels of albumin and total protein may indicate liver damage or disease. If there is not enough albumin, fluid may accumulate in the abdomen (ascites).
Rates of HIV and
hepatitis B co-infection are high in many resource-limited settings, and liver
disease caused by hepatitis B is a major cause of serious illness and death in
A number of anti-HIV
drugs are also active against hepatitis B. These include 3TC, FTC
(emtricitabine), and tenofovir. In resource-rich countries, antiretroviral
therapy for co-infected patients is recommended to include tenofovir and 3TC or FTC in order to provide two antiretroviral drugs that are also active against hepatitis B.
In poorer countries,
however, 3TC is the only one of these drugs which is widely available.
Investigators from the
South African military wanted to see if the inclusion of 3TC, rather than
alternative anti-HIV drugs, in first-line antiretroviral regimens was
associated with improved HIV and hepatitis B treatment outcomes in co-infected
retrospectively analysed results from the PHIDISA II study. Its participants
included 1771 patients, 6% of whom had chronic hepatitis B infection.
The patients were
starting HIV therapy because of a fall in their CD4 cell count to below 200
cells/mm3 or because they had developed an AIDS-defining illness.
HIV therapy was based
on NRTI pairs of either 3TC combined with d4T (stavudine) or ddI (didadosine)
with AZT (zidovudine).
compared four outcomes in the co-infected patients according to the use of 3TC
or non-3TC regimens. These were:
HIV viral load and CD4 cell count.
hepatitis B flares.
Compared to patients
with HIV-mono-infection, those with co-infection were significantly more likely
to be male (86% vs. 64%, p < 0.0001).
At baseline, a number
of laboratory markers associated with poorer long-term outcomes were
significantly more unfavourable in co-infected patients than in individuals
only infected with HIV. These included higher liver enzyme levels (ALTs) (p
< 0.0001), lower albumin (p < 0.0001), and lower platelet counts (p =
After starting HIV
therapy, changes in CD4 cell count and HIV viral load were similar between
mono- and co-infected patients. Moreover, for co-infected patients, these
HIV-related outcomes were comparable regardless of the use of 3TC.
Overall, only 2% in
patients experienced a hepatitis flare after initiating therapy. But rates were
much higher in the co-infected patients than among patients only infected with
HIV (9% vs. 0.02%, p < 0.0001).
When analysis was
restricted to the co-infected patients, rates of hepatitis flares were
comparable between the 3TC-treated patients and individuals who were not taking
After a year of
therapy, 33% of co-infected patients who were taking 3TC had an undetectable
hepatitis B viral load (below 55 iu/m). This compared to 13% of co-infected
patients who were taking an alternative anti-HIV drug – a non-significant
Mortality rates were
significantly higher among co-infected patients than mono-infected individuals
(17% vs. 11%, p = 0.04). The investigators urge “urgent” action to improve the
management and care of co-infected patients in resource-limited settings.
However, the risk of
mortality was comparable for co-infected patients regardless of whether they
were treated with 3TC. Baseline albumin (p = 0.001) and platelet count (p =
0.001) were the only significant risk factors for mortality.
“There is little
benefit from the use of 3TC,” write the authors.
They conclude that
their findings support the WHO recommendation for tenofovir therapy for all
HIV/hepatitis B-co-infected patients.
Matthews GV et al. Impact of 3TC on HIV and HBV related
outcomes in HIV/HBV individuals in a randomized controlled trial of
antiretroviral therapy in South
Africa. AIDS 25, online edition, doi: