HIV/hepatitis B coinfection in Africa posing dilemma for 3TC-based ART

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Over 10% of infants in Cote D'Ivoire are coinfected with HIV and hepatitis B virus, according to the findings of a study published in the February 1st edition of Clinical Infectious Diseases. Furthermore, 40% of coinfected infants have chronic hepatitis B.

Hepatitis B virus management in these HIV-infected patients using current front line antiretroviral therapy containing 3TC (lamivudine) must be urgently revisited, according to an accompanying editorial.

Approximately 350 million people have chronic hepatitis B virus infection with 600,000 annual deaths directly related to hepatitis B liver disease and cancer. By contrast, 40 million people live with HIV/AIDS and about 3 million die of HIV-related causes annually. There has therefore been a greater emphasis on the treatment of HIV than the treatment of hepatitis B virus.

Glossary

hepatitis B virus (HBV)

The hepatitis B virus can be spread through sexual contact, sharing of contaminated needles and syringes, needlestick injuries and during childbirth. Hepatitis B infection may be either short-lived and rapidly cleared in less than six months by the immune system (acute infection) or lifelong (chronic). The infection can lead to serious illnesses such as cirrhosis and liver cancer. A vaccine is available to prevent the infection.

strain

A variant characterised by a specific genotype.

 

deoxyribonucleic acid (DNA)

The material in the nucleus of a cell where genetic information is stored.

seroconversion

The transition period from infection with HIV to the detectable presence of HIV antibodies in the blood. When seroconversion occurs (usually within a few weeks of infection), the result of an HIV antibody test changes from HIV negative to HIV positive. Seroconversion may be accompanied with flu-like symptoms.

 

mother-to-child transmission (MTCT)

Transmission of HIV from a mother to her unborn child in the womb or during birth, or to infants via breast milk. Also known as vertical transmission.

The population prevalence of HIV/hepatitis B coinfections in Africa is estimated to be about 8%. However, the prevalence of HIV/hepatitis B coinfections in infants remains unknown but is thought to be high because of mother-to-child transmission of HIV and the fact that the highest burden of hepatitis B infection occurs in the first five years of life.

Although antiretroviral therapy has reduced the incidence of opportunistic infections in both developed and developing countries, there has been an increase in chronic hepatitis B infection in developed countries. There is concern that with the increasing access to antiretroviral therapy in resource-poor countries, liver disease due to chronic hepatitis B virus might become a public health problem due to HIV/hepatitis B coinfections.

There is another concern. Four out of the 7 drugs currently used for treating chronic hepatitis B including 3TC and tenofovir have dual anti-HIV and anti-hepatitis B activity. Almost all front line antiretorviral therapy in Africa contains 3TC. However, treatment with 3TC is constrained by problems such as increased prevalence of HBeAg seroconversion and selection for 3TC-resistant HBV strains.

The effect of antiretroviral therapy, with or without 3TC, on HBeAg seroconversion rates in HIV/hepatitis B coinfected African children is not known. In order to address this question, a team of French, Burkinabe, and Cote D’Ivoirian researchers investigated the prevalence of hepatitis B and C and chronic hepatitis B in children with HIV in Abidjan, Cote D’Ivoire.

The study was part of the ANRS 1244/1278 cohort which has already been published. The study included 280 HIV-infected children with a median age of a little under six years of whom 128 (45.7 %) were females. Among these infants, 173 (61.8%) received antiretroviral therapy and 122 (43.6 %) received therapy containing 3TC during follow up, respectively.

Hepatitis B virus and hepatitis C virus markers were retrospectively and longitudinally assessed in the children. Detection of the HBsAg was performed on specimens collected at baseline and six months later. If results of both time points were positive, HBeAg, hepatitis B e antibody (HBeAb) and hepatitis B DNA levels were measured at baseline and during follow-up. A fourth-generation hepatitis C virus enzyme immunoassay was used for baseline hepatitis C virus screening.

At baseline, 34/280 children (12.1%) were positive for HbsAg while none was positive for hepatitis C virus (HCV) antibody. Among the HIV/HBV–coinfected children, a high rate of positive HBeAg chronic hepatitis B (CHB) was observed at baseline (82.4%) and after a median follow-up of 18 months (78.3%), with no significant difference between children treated with HAART (with or without 3TC) and untreated ones.

These HIV/hepatitis B–coinfected children had high hepatitis B DNA levels (usually 18.0 log10 copies/ml) and a viral population consisting of almost exclusively wild-type, or drug-sensitive, HBeAg-positive hepatitis B strains. These data strongly suggest that most of the children were in the initial immunotolerant phase of chronic hepatitis B.

The data of Rouet et al constitute a significant contribution to our understanding of HIV/hepatitis B coinfection in African infants and the high prevalence of chronic hepatitis B in these children. With such a high prevalence of chronic hepatitis B in these children, what is the best treatment regime for managing both HIV and hepatitis B, considering the known disadvantages of 3TC treatments?

The authors recommend that antiretroviral therapy without 3TC is the best option. The implementation of this recommendation is almost impossible in Africa since practically all first line antiretroviral therapy contain 3TC. This highlights the conundrum of treating HIV/hepatitis B in both adults and children. First, as already mentioned, 3TC selects for drug resistant hepatitis B strains. Second, other drugs such as tenofovir, which can be safely combined with 3TC, are not available or licensed.

The study demonstrates the enormity of HIV/hepatitis B coinfection in Africa. The authors sound an alarm about the risk of 3TC treatment in these infants and the need for additional studies to guide policy on better management of HIV/hepatitis B coinfections in Africa. The editorial highlights several key issues which must be urgently addressed in this regard.

References

Rouet F et al. Frequent occurrence of chronic Hepatitis B Virus Infection among West African HIV type-1–infected children. Clinical Infectious Diseases 46: 361-366, 2008.

Puoti M et al. Hepatitis B virus and HIV coinfection in low income countries: unmet needs. Clinical Infectious Diseases 46: 367-369, 2008.