infectious diseases
Antiretroviral Treatment of HIV Infection
Adverse effects of antiretrovirals
Antiretrovirals can have serious adverse effects. Some of these effects, notably anemia, hepatitis, renal insufficiency, pancreatitis, and glucose intolerance, can be detected by blood tests before they cause symptoms. Patients should be screened regularly, both clinically and with appropriate laboratory testing (complete blood count; blood tests for hyperglycemia, hyperlidemia, hepatic and pancreatic damage, and renal function; urinalysis), especially after new drugs are started or unexplained symptoms develop. Metabolic effectsconsist of interrelated syndromes of fat redistribution, hyperlipidemia, andinsulinresistance. Subcutaneous fat is commonly redistributed from the face and extremities to the trunk, neck, breasts, and abdomen—a cosmetic effect that can stigmatize and distress patients called lipodystrophy. Treating the resulting deep facial grooves with injected collagen or polylactic acid can be beneficial. resistance, which together constitute the Metabolic Syndrome , increase the risk of myocardial infarction, stroke, and dementia. Antivirals from all classes appear to contribute to these metabolic effects, but PIs are the most clearly involved. Some older ART drugs, such asritonaviror d4T, commonly have metabolic effects. Others, such astenofovir disoproxil fumarate,etravirine,atazanavirordarunavir(even when combined with low-doseritonavir),raltegravir, andmaraviroc, appear to have small to minimal effects on lipid levels. Mechanisms for metabolic effects appear to be multiple; one is mitochondrial toxicity. Risk of metabolic effects (highest with PIs) and mitochondrial toxicity (highest with NRTIs) varies by drug class and within drug classes (eg, among NRTIs, highest with d4T). Metabolic effects are dose-dependent and often begin in the first 1 to 2 years of treatment. Lactic acidosis is uncommon but can be lethal. Metabolic Dysfunction–Associated Liver Disease (MASLD) is being increasingly recognized among patients living with HIV. Certain early-generation ART drugs caused steatosis, and as their use decreased, incidence of steatosis decreased. Nonetheless, even with newer-generation ART drugs, there appears to be a risk of steatosis. Long-term effects and optimal management of metabolic effects are unclear. Lipid-lowering drugs (statins) andinsulin-sensitizing drugs (glitazones) may help. Patients should be counseled about maintaining a healthy diet and regular physical activity as ways to help promote health. (See also the recommendations of the HIV Medicine Association of the Infectious Diseases Society of America and the Adult AIDS Clinical Trials Group:Guidelines for the evaluation and management of dyslipidemia in HIV-infected adults receiving antiretroviral therapy.) Bone complicationsof ART include asymptomatic osteopenia and osteoporosis, which are common. Uncommonly, osteonecrosis of large joints such as the hip and shoulder causes severe joint pain and dysfunction. Mechanisms of bone complications are poorly understood. These images show clinical signs of lipodystrophy and lipoatrophy. The left panel shows the accumulation of fat tissue in the posterior cervical areas known as “buffalo hump” (red arrow). The right panel shows increased abdominal fat. The abdominal fat gains that people living with HIV experience are deep inside the organ cavity (visceral fat). The right panel also shows the loss of fat under the skin in the arms and legs, known as lipoatrophy. Image courtesy of Dr. Edward R. Cachay. With use of antiretroviral drugs, body fat can be redistributed from the face and extremities (left panel) to the trunk, breasts, and abdomen (center panel) and neck (right panel). © Springer Science+Business Media 