A recent study published on the Web site PloS One implicates Combivir (zidovudine/lamivudine) in “limb fat loss,” a common side effect of treatment for HIV infection. In a clinical trial conducted by researchers in the Netherlands, Combivir-containing therapy was associated with localized loss of fat tissue and build up of internal fat tissue in the stomach. These findings support using alternatives to Combivir as preferred components of antiretroviral treatment.

Combivir (zidovudine/lamivudine) is a combination therapy that includes zidovudine (Retrovir) and Epivir (lamivudine). Both zidovudine and Epivir are nucleoside reverse transcriptase inhibitors (NRTIs), which act as fake versions of the building blocks HIV needs to replicate. Zidovudine used in combination with Epivir is often part of the first line of antiretroviral therapy for HIV patients.

Lipodystrophy, abnormal growth or change in fat tissue, is one of the most common and potentially serious side effects associated with HIV treatment. Two different types of lipodystrophy are often present in HIV patients, lipoatrophy and lipohypertrophy. Lipoatrophy, or limb fat loss, is a decrease in fat tissue in a localized area such as the legs, arms, buttocks, or face. Some other signs of lipoatrophy could include veins protruding in those areas and sunken cheeks in the face. Lipohypertrophy, in contrast, is an abnormal increase in fat. In patients receiving treatment for HIV, lipohypertrophy commonly occurs around the stomach, and can also lead to increased fat tissue in the breasts and in the back of the neck or shoulders.

Previous studies have shown that lipodystrophy is associated with HIV treatment with stavudine (Zerit), another NRTI. This study suggests that other NRTIs may also be associated with lipodystrophy.

The study was conducted with 50 HIV-infected men who were undergoing antiretroviral treatment for the first time. Each participant was randomly assigned one of two different therapy treatments. The Combivir-containing therapy included Combivir and Kaletra (lopinavir/ritonavir). Kaletra is a combination therapy using two protease inhibitors (PIs) that disable a protein necessary for HIV replication. The Combivir-free treatment included Kaletra and Viramune (nevirapine), a non-nucleoside reverse transcriptase inhibitor (NNRTI), which works by blocking the action of reverse transcriptase, an essential protein for HIV replication.

The study was conducted for 24 months, and results showed that the Combivir-containing therapy led to increased lipoatrophy and lipohypertrophy compared to the Combivir-free therapy. Since no differences in effectiveness or safety were found between the two treatments, the researchers recommend that Combivir no longer be considered as a first-line antiretroviral therapy for treatment of HIV infections.

For more information about the study, see the original article at the PLoS Hub Web site.