This table focuses on antiretroviral (ARV)-associated adverse effects that a person may experience as a result of taking an ARV regimen. The attribution of adverse effects to individual ARVs is inherently limited by the absence of long-term monotherapy trials, making it difficult to delineate the specific contribution of each medication within the combination regimens. These limitations should be considered carefully when assessing causality, as adverse effects may be related to the ARV regimen as a whole rather than to any single component.
Adverse effects for ARV medications that are no longer on the market or are not commonly used in clinical practice (didanosine [ddI], fosamprenavir/ritonavir, indinavir, lopinavir/ritonavir, nelfinavir, nevirapine, saquinavir/ritonavir, stavudine [d4T], tipranavir/ritonavir, zidovudine [ZDV]), with few exceptions, have been removed from this table. Clinicians should refer to the product labels or to the archived July 10, 2019, version of the Guidelines for information regarding the adverse effects associated with select older ARVs. Because some adverse effects may persist long after discontinuation of the older ARVs—such as d4T, ddI, zalcitabine, and ZDV—and people with HIV may still present with these long-lasting toxicities, these medications remain listed among the ARVs associated with adverse effects such as lipodystrophy and peripheral neuropathy.
For information regarding potential adverse effects of ARVs on fetuses and newborns when certain ARVs are taken around the time of conception or during pregnancy, refer to the Perinatal Guidelines.
This table highlights the common and/or severe adverse effects by ARV class and for individual ARVs, when appropriate. For ARV class–specific adverse effects, the table provides relative comparisons among individual ARVs for each class effect. In some cases, the terms “no known effect,” “rarely observed” (for select severe effects), “not common or severe,” or “no or limited data” are used, especially for the entry inhibitor and capsid inhibitor classes, where the evaluation of safety is based mostly on uncontrolled and nonrandomized clinical trials. See Appendix A, Tables 3, 4, 5, 6, 7, 8, 9, and 10 for additional information listed by ARV medication.
Adverse Effect Type | Adverse Effect | NRTIs | NNRTIs | PIs | INSTIs | EIs | CI |
|---|---|---|---|---|---|---|---|
| Cardiovascular Effects | Cardiac Conduction Effects | No known effects | RPV and EFV: QTc prolongation RPV: QTc prolongation occurred at 3 and 12 times the recommended dose. Consider alternatives when coadministered with drugs with known risk of Torsade de Pointes. | ATV: PR prolongation. Risk factors include pre-existing heart disease and concomitant use of medications that may cause PR prolongation. | No known effect | FTR: QTc prolongation was seen at 4 times the recommended dose. Consider alternatives when coadministered with drugs with a known risk of Torsade de Pointes. | No known effect |
| Cardiovascular Disease | ABC: Associated with an increased risk of MI in some cohort studies. Absolute risk greatest in people with traditional CVD risk factors. | No known effect | DRV/r: Associated with cardiovascular events in some cohorts. | Not common or severe | No or limited data | No or limited data | |
| Dermatologic Effects, Not Including Systemic Hypersensitivity Reaction | Rash | FTC: Skin hyperpigmentation | All NNRTIs | ATV, DRV | All INSTIs | MVC, IBA, FTR | Not common or severe |
| Stevens-Johnson Syndrome/Toxic Epidermal Necrosis | No known effect | EFV, ETR > DOR, RPV | Rarely observed with DRV and ATV | Rarely observed with BIC, CAB, and RAL | No or limited data | Not common or severe | |
| Gastrointestinal Effects | Cholelithiasis | No known effect | No or limited data | ATV: Cholelithiasis and kidney stones may present concurrently. Median onset is 42 months after ARV initiation. | No known effect | No known effect | No known effect |
| Gastrointestinal Effects | ZDV > other NRTIs: Nausea and vomiting | Not common or severe | GI intolerance (e.g., diarrhea, nausea, vomiting) | EVG/c: Nausea and diarrhea | No known effect | Not common or severe | |
| Hepatic Effects | Hepatic Effects | When TAF, TDF, 3TC, and FTC are withdrawn in people with HBV/HIV coinfection or when HBV resistance develops: People with HBV/HIV coinfection may develop severe hepatic flares. | EFV: Most cases relate to an increase in transaminases. Fulminant hepatitis leading to death or hepatic failure requiring transplantation have been reported. RPV: Risk may be further increased in people with HBV or HCV coinfection. | All PIs: Drug-induced hepatitis and hepatic decompensation have been reported. ATV: Jaundice due to indirect hyperbilirubinemia | DTG: Rarely observed, but risk may be further increased in people with HBV or HCV coinfection. BIC, CAB, EVG/c, RAL: Not common or severe | MVC: Hepatotoxicity with or without rash or HSRs has been reported. FTR: Transaminase elevation was seen more commonly in patients with HBV/HCV. Transient elevation of bilirubin observed in clinical trials. | Not common or severe |
| Hypersensitivity Reactions, Not Including Rash Alone or Stevens-Johnson Syndrome | Hypersensitivity Reaction | ABC: Contraindicated if person is HLA-B*5701 positive. Median onset for HSR is 9 days after treatment initiation; 90% of reactions occur within 6 weeks. HSR symptoms (in order of descending frequency): Fever, rash, malaise, nausea, headache, myalgia, chills, diarrhea, vomiting, abdominal pain, dyspnea, arthralgia, and respiratory symptoms Symptoms worsen with continuation of ABC. People should not be rechallenged with ABC if HSR is suspected, regardless of their HLA-B*5701 status. | Rarely observed | No known effect | Rarely observed | MVC: HSR reported as part of a syndrome related to hepatotoxicity. IBA: HSR, including infusion-related reactions and anaphylactic reactions, were reported. | No known effect |
| Injection Site Reactions | Injection Site Reaction | Not applicable | RPV IM injection: Reported in >80% of patients; reactions may include localized pain/discomfort (most common), nodules, induration, swelling, erythema, hematoma. When given with CAB IM, injection site pain: RPV > CAB. | Not applicable | CAB IM injection: Reported in >80% of patients; reactions may include localized pain/discomfort (most common), nodules, induration, swelling, erythema, hematoma. When given with RPV IM, injection site pain: RPV > CAB.
| Not applicable | LEN SQ injection: Reported in 47–65% of people; reactions may include swelling, erythema, pain, nodules, inflammation, and induration. Nodules and induration may persist for months in some people. Injection site necrosis has been reported. |
| Metabolic Effects | Bone Density Effects | TDF: Associated with greater loss of BMD than other NRTIs, especially when given with a PK booster. Osteomalacia may be associated with proximal tubulopathy and urine phosphate wasting. TAF: Associated with smaller declines in BMD than those seen with TDF. | No known effect | No known effect | Not common or severe | No known effect | No known effect |
| Diabetes Mellitus and Insulin Resistance | ZDV | No known effect | Rarely observed | No known effect | No or limited data | No or limited data | |
| Dyslipidemia | ABC: ↑ TG and ↑ LDL TAF: ↑ TG, ↑ LDL, and ↑ HDL (no change in TC:HDL ratio) TDF: Associated with lower lipid levels than ABC or TAF. | EFV: ↑ TG, ↑ LDL, ↑ HDL | All RTV- or COBI-boosted PIs: ↑ TG, ↑ LDL, ↑ HDL | EVG/c: ↑ TG, ↑ LDL, ↑ HDL | No known effect | No known effect | |
| Lactic Acidosis | Reported with older NRTIs (e.g., d4T, ZDV, ddI), but not with ABC, 3TC, FTC, TAF, or TDF. | No known effect | No known effect | No known effect | No known effect | No known effect | |
| Lipodystrophy | Lipoatrophy: Associated with history of exposure to d4T or ZDV (d4T > ZDV). Not reported with ABC, 3TC or FTC, or TAF or TDF. | Lipohypertrophy: Trunk fat increase is observed with EFV-containing regimens; however, a causal relationship has not been established. | Lipohypertrophy: Trunk fat increase is observed with PI-containing regimens; however, a causal relationship has not been established. | Lipohypertrophy: Trunk fat increase is observed with RAL-containing regimens; however, a causal relationship has not been established. | No known effect | No known effect | |
| Weight Gain | Weight gain has been associated with initiation of ART and subsequent viral suppression. The increase appears to be greater with INSTIs, especially BIC and DTG, than with other drug classes. Greater weight increase has also been reported with TAF than with TDF and with DOR than with EFV. | No known effect | No known effect | ||||
| Musculoskeletal Effects | Myopathy/ Rhabdomyolysis | ddI, D4T Rarely observed with ABC, TAF, or TDF. | No known effect | No known effect | Rarely observed | No known effect | No known effect |
| Neuropsychiatric Effects | Nervous System/Psychiatric Effects | Peripheral neuropathy (can be irreversible): Associated with history of exposure to ddI, ddC, or d4T. | Neuropsychiatric events: EFV > DOR, RPV > ETR EFV: Somnolence, insomnia, abnormal dreams, dizziness, impaired concentration, depression, psychosis, suicidal ideation, ataxia, encephalopathy. Some symptoms may subside or diminish after 2–4 weeks. Bedtime dosing and taking without food may reduce symptoms. RPV: Depression, suicidality, sleep disturbances DOR: Sleep disorders and disturbances, dizziness, altered sensorium; depression, suicidality, and self-harm | No known effect | Insomnia, depression, and suicidality have been reported with INSTI use, primarily in people with pre-existing psychiatric conditions. | Not common or severe | Not common or severe |
| Renal Effects | Renal Effects/Nephrolithiasis/ Urolithiasis | TDF: ↑ SCr, proteinuria, hypophosphatemia, urinary phosphate wasting, glycosuria, hypokalemia, and non-anion gap metabolic acidosis. Concurrent use of TDF with COBI- or RTV-containing regimens appears to increase risk. TAF: Less renal effect than TDF. | RPV: Inhibits Cr secretion without reducing renal glomerular function | ATV: Associated with increased risk of chronic kidney disease in a large cohort study. ATV: Stone or crystal formation; adequate hydration may reduce risk COBI (as a pharmacokinetic booster for DRV or ATV): Inhibits Cr secretion without reducing renal glomerular function | DTG, COBI (as a pharmacokinetic booster for EVG), and BIC: Inhibits Cr secretion without reducing renal glomerular function | No or limited data | No or limited data |
| Key: 3TC = lamivudine; ABC = abacavir; ART= antiretroviral therapy; ARV = antiretroviral; ATV = atazanavir; BIC = bictegravir; BMD = bone mineral density; CAB = cabotegravir; CI = capsid inhibitor; COBI = cobicistat; Cr = creatinine; CVD = cardiovascular disease; d4T = stavudine; ddC = zalcitabine; ddI = didanosine; DOR = doravirine; DRV = darunavir; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EFV = efavirenz; EI = entry inhibitor; ETR = etravirine; EVG = elvitegravir; EVG/c = elvitegravir/cobicistat; FTC = emtricitabine; FTR = fostemsavir; GI = gastrointestinal; HBV = hepatitis B virus; HCV = hepatitis C virus; HDL = high-density lipoprotein; HSR = hypersensitivity reaction; IBA = ibalizumab; IDV = indinavir; IM = intramuscular; INSTI = integrase strand transfer inhibitor; LDL = low-density lipoprotein; LEN = lenacapavir; MI = myocardial infarction; MVC = maraviroc; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; QTc = QT corrected for heart rate; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SCr = serum creatinine; SQ = subcutaneous; TAF = tenofovir alafenamide; TC = total cholesterol; TDF = tenofovir disoproxil fumarate; TG = triglycerides; ZDV = zidovudine | |||||||