HIV-associated lipodystrophy has been strongly associated with which antiretroviral therapy?

HIV-associated lipodystrophy has been strongly associated with which antiretroviral therapy?

• A. Non-nucleoside reverse transcriptase inhibitors
• B. Protease inhibitors
• C. Integrase inhibitors
• D. First-generation nucleoside reverse transcriptase inhibitors

Answer: (D)

HIV-associated lipodystrophy is most strongly linked to older, first-generation nucleoside reverse transcriptase inhibitors because of their mitochondrial toxicity, which damages adipocytes and leads to subcutaneous fat loss. This lipoatrophy primarily affects the face, arms, and legs and can be accompanied by fat redistribution in other areas, such as increased central fat. Mechanistically, these thymidine analogue NRTIs impair mitochondrial DNA replication in adipose tissue, triggering adipocyte dysfunction and loss. While other antiretroviral classes can contribute to fat changes or metabolic abnormalities, the classic and most reproducible pattern of lipodystrophy (notably lipoatrophy) is associated with these older NRTIs. Protease inhibitors, for example, are more commonly linked to central fat gain and metabolic syndrome features, rather than the pronounced peripheral fat loss seen with first-generation NRTIs. Integrase inhibitors and newer regimens tend to have a lower risk of lipodystrophy. Thus, the regimen most strongly associated with HIV-related lipodystrophy, particularly the lipoatrophy phenotype, is first-generation NRTIs.

HIV-associated lipodystrophy is most strongly linked to older, first-generation nucleoside reverse transcriptase inhibitors because of their mitochondrial toxicity, which damages adipocytes and leads to subcutaneous fat loss. This lipoatrophy primarily affects the face, arms, and legs and can be accompanied by fat redistribution in other areas, such as increased central fat. Mechanistically, these thymidine analogue NRTIs impair mitochondrial DNA replication in adipose tissue, triggering adipocyte dysfunction and loss.

While other antiretroviral classes can contribute to fat changes or metabolic abnormalities, the classic and most reproducible pattern of lipodystrophy (notably lipoatrophy) is associated with these older NRTIs. Protease inhibitors, for example, are more commonly linked to central fat gain and metabolic syndrome features, rather than the pronounced peripheral fat loss seen with first-generation NRTIs. Integrase inhibitors and newer regimens tend to have a lower risk of lipodystrophy.

Thus, the regimen most strongly associated with HIV-related lipodystrophy, particularly the lipoatrophy phenotype, is first-generation NRTIs.