The exact mechanism of HIV-associated
lipodystrophy is not fully elucidated. There is evidence indicating both that it can be caused by
anti-retroviral medications and that it can be caused by HIV infection in the absence of anti-retroviral medication.
Evidence implicating anti-retroviral medications The development of lipoatrophy in people living with HIV has been historically linked to specific classes of early antiretroviral therapy (ART). Initial treatment regimens typically combined a
protease inhibitor (PI) with two
nucleoside reverse transcriptase inhibitors (NRTIs), specifically
thymidine analogs like
stavudine (d4T) and
zidovudine (AZT). While these drugs helped maintain CD4 T-cell levels, they were strongly associated with changes in
lipid metabolism and significant subcutaneous fat loss, often resulting in a 30% reduction of fat in the extremities and noticeable facial wasting. Other older drugs, such as the non-nucleoside reverse transcriptase inhibitor (NNRTI)
efavirenz, have also been implicated in fat loss. The incidence of the condition dropped dramatically following the transition to newer, less toxic medications. By the late 2000s, clinical guidelines recommended replacing zidovudine with
tenofovir disoproxil fumarate (TDF), which exhibited significantly lower lipoatrophic effects. This was further improved by the introduction of
tenofovir alafenamide (TAF), which is largely devoid of lipodystrophy. ==Management==