What long-term treatment complications have been associated with antiretroviral therapy?

Long-term treatment complications associated with combination antiretroviral therapy include lipodystrophy syndrome, hepatotoxicity, peripheral neuropathy, lactic acidosis, premature bone loss, and avascular necrosis of the hips. Lipodystrophy syndrome consists of body morphology changes (deposition of fat in abdomen, breasts, and neck; loss of fat in face and extremities), metabolic complications (hyperlipidemia, glucose intolerance/diabetes mellitus), or both. Its epidemiology and pathogenesis are not fully understood, and its optimal management is unknown. An evolving literature suggests that patients on antiretroviral therapy may be at increased risk for coronary artery disease. Hepatotoxicity may occur with any antiretroviral drug but most often has been described with NNRTIs-especially nevirapine. Peripheral neuropathy has been reported in association with certain drugs (ddI, d4T, ddC) and HIV infection itself. Asymptomatic mild-to-moderate lactic acidemia is common in patients on NRTI-based regimens. Symptomatic lactic acidosis with a variety of manifestations (peripheral neuropathy, pancreatitis, myopathy, steatosis with liver failure) has less commonly been described. The mechanism of action is NRTI interference with DNA polymerase in mitochondria. A venous lactate level is recommended in patients on NRTI-based regimens who have unexplained constitutional or gastrointestinal symptoms. Premature bone loss (osteopenia/osteoporosis) and avascular necrosis of the hips also have been reported in HIV-infected patients on antiretroviral therapy. The etiology of these bone abnormalities is uncertain.