skip navigation

Skip Nav

Clinical Guidelines Portal

Clinical Guidelines Portal

Table of Contents

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents

Limitations to Treatment Safety and Efficacy

Adverse Effects of Antiretroviral Agents

(Last updated:May 01, 2014; last reviewed:May 01, 2014)

Adverse effects have been reported with the use of all antiretroviral (ARV) drugs and are among the most common reasons cited for switching or discontinuing therapy and for medication non-adherence.1 However, with the use of newer ARV regimens, rates of treatment-limiting adverse events in antiretroviral therapy (ART)-naive patients enrolled in randomized trials appear to be declining and are generally now occurring in less than 10% of study participants. However, because most clinical trials have a relatively short follow-up duration, the longer term complications of ART can be underestimated. In the Swiss Cohort study during 6 years of follow-up, the presence of laboratory adverse events was associated with higher rates of mortality, which highlights the importance of adverse events in overall patient management.2

Several factors may predispose individuals to adverse effects of ARV medications. For example, compared with men, women (especially ART-naive women with CD4 counts >250 cells/mm3) seem to have a higher propensity to develop Stevens-Johnson syndrome, rashes, and hepatotoxicity from nevirapine (NVP)3-5 and have higher rates of lactic acidosis due to nucleoside reverse transcriptase inhibitors.6-8 Other factors may also contribute to the development of adverse events: 

  • Concomitant use of medications with overlapping and additive toxicities;
  • Comorbid conditions that may increase the risk of or exacerbate adverse effects (e.g., alcoholism9 or coinfection with viral hepatitis10-12 may increase the risk of hepatotoxicity);
  • Drug-drug interactions that may lead to an increase in drug toxicities (e.g., interactions that result from concomitant use of statins with protease inhibitors); or
  • Genetic factors that predispose patients to abacavir (ABC) hypersensitivity reaction.10,11
The therapeutic goals of ART include achieving and maintaining viral suppression and improving immune function, but an overarching goal of treatment should be to select a regimen that is not only effective but also safe. To accomplish this goal, the clinician must consider the toxicity potential of an ARV regimen, as well as the individual patient’s underlying conditions, concomitant medications, and prior history of drug intolerances. 

In addition, it should be appreciated that, in general, the overall benefits of ART outweigh its risks and that some conditions (e.g., anemia, cardiovascular disease, renal impairment), may be more likely in the absence of ART.12,13 

Information on the adverse events of ARVs is outlined in several tables in the guidelines. Table 14 provides clinicians with a list of the most common and/or severe known ARV-associated adverse events by drug class. The most common adverse effects of individual ARV agents are summarized in Appendix B, Tables 1–6

(See Appendix B for additional information listed by drug. Empty spaces in the table may mean no reported cases for the particular side effect or no data are available for the specific ARV drug class)

Click here to view this table as an image

Table 14. Antiretroviral Therapy-Associated Common and/or Severe Adverse Effects
 Adverse Effects  NRTIs  NNRTIs  PIs  INSTI  EI
Bleeding events  N/A N/A PIs: Increased spontaneous bleeding, hematuria in patients with hemophilia reported with some PIs

TPV: Reports of intracranial hemorrhage. Risks include CNS lesions, trauma, surgery, hypertension, alcohol abuse, coagulopathy, and concomitant use of anti-coagulant or anti-platelet agents, including vitamin E
 N/A N/A
Bone Density Effects  TDF: Associated with greater loss of BMD than ZDV, d4T, and ABC.

Osteomalacia reported in association with proximal renal tubulopathy.
Decreases in BMD observed in studies of regimens containing different NRTIs combined with NNRTIs, PIs, or INSTIs. N/A
Bone marrow suppression ZDV: Anemia, neutropenia  N/A N/A N/A N/A
Cardiovascular disease (CVD) ABC and ddI: Associated with an increased risk of MI in some, but not all, cohort studies. Absolute risk is greatest in patients with traditional CVD risk factors.  N/A PIs: Associated with MI and stroke in some cohort studies. Data on newer PIs (ATV, DRV, and TPV) are limited.

SQV/r, ATV/r, and LPV/r: PR interval prolongation. Risks include structural heart disease, conduction system abnormalities, cardiomyopathy, ischemic heart disease, and co-administration with drugs that prolong PR interval.

SQV/r: QT interval prolongation in patients in a healthy volunteer study. Risks include underlying heart conditions, pre-existing prolonged QT or arrhythmia, or use with other QT-prolonging drugs. ECG is recommended before SQV initiation and should be considered during therapy.
 N/A N/A
Cholelithiasis  N/A N/A ATV:
  • History of kidney stones increases risk.
  • Patients may present with cholelithiasis and kidney stones concurrently.
  • Typically presents as abdominal pain.
  • Reported complications include cholecystitis, pancreatitis, choledocholithiasis, and cholangitis.
  • Median time to onset is 42 months (range 1–90 months).
 N/A N/A
Diabetes mellitus (DM)/insulin resistance  ZDV, d4T, and ddI  N/A

Reported for some PIs (IDV, LPV/r), but not all PIs

 N/A N/A
Dyslipidemia d4T > ZDV > ABC:

↑ LDL and TG

 EFV:↑ TG, ↑  LDL, ↑ HDL LDL, ↑ TG, ↑ HDL: All RTV-boosted PIs

TG:
LPV/r = FPV/r and LPV/r > DRV/r and ATV/r
 EVG/cobi/TDF/FTC: ↑ TG, ↑  LDL, ↑ HDL  N/A
Gastrointestinal (GI) effects Nausea and vomiting:
ddI
and ZDV > other NRTIs
Pancreatitis: ddI
  GI intolerance (e.g., diarrhea, nausea, vomiting) Diarrhea:
Common with NFV;
LPV/r > DRV/r and
ATV/r
Nausea and diarrhea:
EVG/COBI/TDF/FTC

 
Hepatic effects Reported with most NRTIs

ddI: Prolonged exposure has been linked to non-cirrhotic portal hypertension, including some cases with esophageal varices.

Steatosis: Most commonly seen with ZDV, d4T, or ddI

Flares: HIV/HBV-co-infected patients may develop severe hepatic flares when TDF, 3TC, and FTC are withdrawn or when HBV resistance develops

 
NVP > other NNRTIs

NVP:
  • Severe hepatic toxicity with NVP is often associated with skin rash or symptoms of hypersensitivity.
  • In ARV-naive patients, risk is greater for women with pre-NVP CD4 count >250 cells/mm3 and men with pre-NVP CD4 count >400 cells/mm3. Overall risk is higher for women than men.
  • Risk is greatest in the first few months of treatment.
  • 2-week dose escalation of NVP reduces risk of rash and possibly hepatotoxicity if related to hypersensitivity.
  • NVP is contraindicated in patients with moderate to severe hepatic insufficiency (Child-Pugh classification B or C).
  • Liver failure observed in HIV-uninfected individuals receiving NVP for post-exposure prophylaxis. NVP should never be used for this indication.
All PIs: Drug-induced hepatitis and hepatic decompensation (and rare cases of fatalities) have been reported with all PIs. The frequency of hepatic events is higher with TPV/r than with other PIs.

IDV, ATV: Jaundice due to indirect hyperbilirubinemia

TPV/r: Contraindicated in patients with moderate to severe hepatic insufficiency (Child Pugh classification B or C)
 
 N/A MVC: Hepatotoxicity with or without rash or HSRs reported
HSR

Excluding rash alone or SJS
 
ABC:
  • HLA-B*5701 screening should be performed before initiation of ABC. ABC should not be started if the HLA-B*5701 test result is positive.
  • Symptoms of HSR include (in descending frequency): fever, skin rash, malaise, nausea, headache, myalgia, chills, diarrhea, vomiting, abdominal pain, dyspnea, arthralgia, and respiratory symptoms.
  • Symptoms worsen with continuation of ABC.
  • Median onset of reactions is 9 days; approximately 90% of reactions occur within the first 6 weeks of treatment.
  • Patients, regardless of HLA-B*5701 status, should not be re-challenged with ABC if HSR is suspected.
NVP:
  • Hypersensitivity syndrome of hepatic toxicity and rash that may be accompanied by fever, general malaise, fatigue, myalgias, arthralgias, blisters, oral lesions, conjunctivitis, facial edema, eosinophilia, granulocytopenia, lymphadenopathy, or renal dysfunction.
  • In ARV-naive patients, risk is greater for women with pre-NVP CD4 count >250 cells/mm3 and men with pre-NVP CD4 count >400 cells/mm3. Overall, risk is higher for women than men.
  • 2-week dose escalation of NVP reduces risk.
 N/A RAL: HSR reported when RAL given in combination with other drugs known to cause HSR. All ARVs should be stopped if HSR occurs.

DTG: Reported in <1% of patients in clinical development program 
 
MVC: Reported as part of a syndrome related to hepatotoxicity
Lactic acidosis NRTIs, especially d4T, ZDV, and ddI:
  • Insidious onset with GI prodrome, weight loss, and fatigue. May be rapidly progressive with tachycardia, tachypnea, jaundice, muscular weakness, mental status changes, respiratory distress, pancreatitis, and organ failure.
  • Mortality up to 50% in some case series, especially in patients with serum lactate >10 mmol/L
  • Females and obese patients at increased risk
Laboratory findings:
  • ↑ lactate (often >5 mmol/L), anion gap, AST, ALT, PT, bilirubin
  • ↑ amylase and lipase in patients with pancreatitis
  • ↓ arterial pH, serum bicarbonate, serum albumin
 N/A N/A N/A N/A
Lipodystrophy Lipoatrophy: Thymidine analogs (d4T > ZDV). May be more likely when NRTIs combined with EFV than with a RTV-boosted PI. Lipohypertophy: Trunk fat increase observed with EFV-, PI-, and RAL-containing regimens; however, causal relationship has not been established.  N/A
Myopathy/elevated CPK ZDV: Myopathy  N/A N/A RAL: ↑ CPK

Muscle weakness and rhabdomyolysis

 N/A
Nervous System/Psychiatric Effects Peripheral neuropathy (pain and/or paresthesia, lower extremities > upper extremities): d4T > ddI and ddC (can be irreversible)

d4T: Associated with rapidly progressive, ascending neuromuscular weakness resembling Guillain-Barré syndrome (rare)

 
EFV: Somnolence, insomnia, abnormal dreams, dizziness, impaired concentration, depression, psychosis, and suicidal ideation. Symptoms usually subside or diminish after 2–4 weeks. Bedtime dosing may reduce symptoms. Risks include history of psychiatric illness, concomitant use of agents with neuropsychiatric effects, and increased plasma EFV concentrations because of genetic factors or increased absorption with food. An association between EFV and suicidal ideation, suicide, and attempted suicide (especially among younger patients and those with history of mental illness or substance abuse) was found in one retrospective analysis of several comparative trials.
N/A All INSTIs: insomnia

RAL: Depression and suicidal ideation (uncommon)



N/A
Rash FTC: Hyperpigmentation 
All NNRTIs
ATV, DRV, FPV, LPV/r, TPV
RAL, EVG/cobi/TDF/FTC: Uncommon
MVC
Renal Effects/
Urolithiasis

TDF: ↑ SCr, proteinuria, hypophosphatemia, urinary phosphate wasting, glycosuria, hypokalemia, non-anion gap metabolic acidosis

Concurrent use with PI appears to increase risk.
N/A ATV and LPV/r: Associated with increased risk of chronic kidney disease in a large cohort study.

IDV: ↑ SCr, pyuria; hydronephrosis or renal atrophy

IDV, ATV: Stone, crystal formation; adequate hydration may reduce risk.

cobi (a component of EVG/cobi/TDF/FTC) and DTG: Can increase SCr by reducing tubular secretion of Cr without reducing renal glomerular function; however, assess for renal dysfunction, especially if SCr increase by >0.4 mg/dL.  N/A
SJS/TEN ddI, ZDV: Reported cases NVP > DLV, EFV, ETR, RPV FPV, DRV, IDV, LPV/r, ATV: Reported cases  RAL N/A
Key to Abbreviations: 3TC = lamivudine; ABC = abacavir; ALT = alanine aminotransferase; ARV = antiretroviral; AST = aspartate aminotransferase; ATV = atazanavir; ATV/r = ritonavir-boosted atazanavir; BMD = bone mineral density; CrCl = creatinine clearance; CNS = central nervous system; cobi= cobicistat; CPK = creatine phosphokinase; CVD = cardiovascular disease; d4T = stavudine; ddC = zalcitabine; ddI = didanosine; DLV = delavirdine; DM = diabetes mellitus; DRV = darunavir; DRV/r = ritonavir-boosted darunavir; DTG = dolutegravir; ECG = electrocardiogram; EFV = efavirenz; EI = entry inhibitor; ETR = etravirine; EVG = elvitegravir; FPV = fosamprenavir; FPV/r = ritonavir-boosted fosamprenavir; FTC = emtricitabine; GI = gastrointestinal; HBV = hepatitis B virus; HDL = high-density lipoprotein; HSR = hypersensitivity reaction; IDV = indinavir; INSTI = integrase strand transfer inhibitor; LDL = low-density lipoprotein; LPV/r = ritonavir-boosted lopinavir; MI = myocardial infarction; MVC = maraviroc; NFV = nelfinavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PT = prothrombin time; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SCr. = serum creatinine; SJS = Stevens-Johnson syndrome; SQV = saquinavir; SQV/r = ritonavir-boosted saquinavir; TDF = tenofovir disoproxil fumarate; TEN = toxic epidermal necrosis; TG = triglyceride; TPV = tipranavir; TPV/r = ritonavir-boosted tipranavir; ZDV = zidovudine

Switching Antiretroviral Therapy Because of Adverse Effects

Most patients do not experience treatment-limiting ART-associated toxicities; however, some patients do, and in these cases, ART must be modified. ART-associated adverse events can range from acute and potentially life threatening to chronic and insidious. Acute life-threatening events (e.g., acute hypersensitivity reaction due to ABC, lactic acidosis due to stavudine [d4T] and didanosine [ddI], liver and/or severe cutaneous toxicities due to NVP) usually require the immediate discontinuation of all ARV drugs and re-initiation of an alternative regimen without overlapping toxicity. Non-life threatening toxicities (e.g., urolithiasis with atazanavir [ATV], renal tubulopathy with tenofovir [TDF]) can usually be handled by substituting another ARV agent for the presumed causative agent without interruption of ART. Other, more chronic, non-life threatening adverse events (e.g., dyslipidemia) can be addressed either by switching the potentially causative agent for another agent or by managing the adverse event with additional pharmacological or non-pharmacological interventions. Management strategies must be individualized for each patient. 

Switching from an effective ARV regimen to a new regimen must be done carefully and only when the potential benefits of the change outweigh the potential complications of altering treatment. The fundamental principle of regimen switching is to maintain viral suppression. When selecting a new agent or regimen, providers should be aware that resistance mutations selected for, regardless of whether previously or currently identified by genotypic resistance testing, are archived in HIV reservoirs and even if absent from subsequent resistance test results, may reappear under selective pressure. It is critical that providers review the following before implementing any treatment switch: the patient’s medical and complete ARV history including prior virologic responses to ART; resistance test results; viral tropism (when maraviroc [MVC] is being considered); HLA B*5701 status (when ABC is being considered); co-morbidities; adherence history; prior intolerances to any medications; and concomitant medications and supplements and their potential for drug interactions with ARVs. Patient acceptance of new food or dosing requirements must also be assessed. In some cases, medication costs may also be a factor to consider before switching treatment. Signs and symptoms of ART-associated adverse events may mimic those of comorbidities, other concomitant medications, or HIV infection itself. Therefore, concurrent with ascribing a particular clinical event to ART, alternative causes for the event should be investigated. In the case of a severe adverse event, it may be necessary to discontinue or switching ARVs pending the outcome of such an investigation. For the first few months after a switch in ART is made, the patient should be closely monitored for any new adverse events, and viral load should be monitored to assure continued viral suppression.

Table 15 lists several major ART-associated adverse events and potential options to appropriately switch agents in an ARV regimen. The table focuses on the ARVs most commonly used in the United States and lists substitutions that are supported by ARV switch studies, findings of comparative ARV trials and observational cohort studies, or expert opinion.

Table 15. Antiretroviral Therapy-Associated Adverse Events That Can Be Managed with Substitution of Alternative Antiretroviral Agent

Switching a successful ARV regimen should be done carefully and only when the potential benefits of the change outweigh the potential complications of altering treatment. The fundamental principle of regimen switching is to maintain viral suppression. Before any treatment switch is implemented, it is critical to review the patient’s medical and full ARV history including the patient’s prior virologic responses, resistance test results, viral tropism (when MVC is being considered), HLA B*5701 status (when ABC is being considered), co-morbidities, adherence history, concomitant medications and supplements and their potential for drug interactions, and prior intolerances to any ARV drugs.

Table 15. Antiretroviral Therapy-Associated Adverse Events That Can Be Managed with Substitution of Alternative Antiretroviral Agent
Adverse Event  ARV Agent(s)/Drug Class Comments
 Switch from Switch to
Bone Density Effects
 TDFa  ABCb Declines in BMD have been observed with the start of most ART. Modification of ART because of reduced BMD should be predicated on the clinical significance of the decline. Switching from TDF to alternative ARV agents has been shown to increase bone density, but the clinical significance of this increase remains uncertain.
Bone Marrow Suppression

Anemia, leukopenia

 

 ZDV TDF or ABCb N/A
CNS/Neuropsychiatric Side Effects 

Dizziness, suicidal ideation, sleep disturbance, abnormal dreams, depression


EFV Alternative NNRTI (RPV, ETR, NVP), a PI, or an INSTI
In most patients, EFV-related CNS effects subside within 4 weeks after initiation of the drug. Persistent or intolerable effects should prompt substitution of EFV with an alternate ARV agent.
Dyslipidemia

Hypertriglyceridemia (with or without high low-density LDL level)
 
RTV- or cobi-boosted regimens or EFV
RAL, DTG, RPV, NVP, or unboosted ATVc
Elevated TG and LDL levels are more common with LPV/r and FPV/r than with other RTV-boosted PIs. Improved TG and LDL levels have been seen following a switch from LPV/r to RTV-boosted and -unboosted ATV.c 
GI Effects

Nausea, diarrhea
 
LPV/r ATV/r, DRV/r, RAL, DTG, EVG/cobi/TDF/FTC
GI intolerance is relatively common with boosted PIs and is linked to the total dose of RTV. More GI toxicity is seen with LPV/r than with ATV/r or DRV/r. GI effects are often transient in nature, and do not warrant switching therapy. If GI adverse effects are persistent or intolerable, consider drug substitution.
Other RTV-boosted regimens or EVG/cobi/TDF/FTC
RAL, DTG, unboosted ATV,c NNRTIs
In a trial of treatment-naive patients, rates of diarrhea and nausea were similar for boosted EVG/cobi/TDF/FTC and ATV/r plus TDF/FTC.
HSR ABC TDF Never re-challenge with ABC following a suspected HSR, regardless of the patient’s HLA B*5701 status.
NVP, EFV, ETR, RPV
Non-NNRTI ART
Risk of HSR with NVP is higher for women and those with high CD4 cell counts.
DTG, RAL

MVC
 
Non-INSTI ART

Suitable alternative ART
 
Reactions to NVP, ETR, RAL, DTG and MVC may be accompanied by elevated liver transaminases.
Insulin Resistance
LPV/r, FPV/r 
NNRTI (NVP or RPV), INSTI, unboosted ATVc
Results of switch studies have been inconsistent. Studies in HIV-negative patients given short courses of a PI suggest a direct causal effect of LPV/r (and IDV) on insulin resistance. However, traditional risk factors, such as obesity and family history of diabetes, may be stronger risk factors for insulin resistance than use of any PIs.
Jaundice and Icterus
ATV, ATV/r
DRV/r, INSTI, or NNRTI
Increases in unconjugated bilirubin are commonly seen with ATV and generally do not require modification of therapy unless jaundice/icterus is distressing to the patient.
Lipoatrophy

Subcutaneous fat wasting of limbs, face, buttocks
 
d4T, ZDV
TDF or ABCb
Peripheral lipoatrophy is a legacy of prior thymidine analog (d4T and ZDV) use. Switching from these ARVs prevents worsening lipoatrophy, but fat recovery is typically slow, incomplete, and may take years.
Lipohypertrophy 

Accumulation of visceral abdominal, truncal, dorsocervical, and breast fat
 
Lipohypertrophy has been observed during ART, particularly during use of older PI-based regimens (e.g., IDV), but whether ART directly causes increases in fat depots remains unclear. There is no clinical evidence that switching to any currently recommended first line regimen will reverse weight or visceral fat gain.
Rash NNRTIs (especially NVP and EFV)
PI- or INSTI- based regimen
Rash can be seen with any NNRTI but occurs more frequently and is more severe with use of NVP, followed by EFV. Mild rashes developing after initiation of NNRTIs other than NVP rarely require treatment switch. When serious rash develops with use of any NNRTI, a switch to an agent from another ARV drug class is recommended.
DRV/r
ATV/r or another class, such as INSTI
Mild rashes following DRV/r initiation do not necessarily require treatment switch. Close follow-up until the rash subsides is recommended. For more severe reactions, therapy can be changed to an alternative RTV-boosted PI or an agent from another drug class.
Renal Effects

Including proximal renal tubulopathy, elevated creatinine
 
TDFa
ABCb Phosphate wasting as a consequence of TDF nephrotoxicity may lead to osteomalacia.
ATV/r, LPV/r
DTG, RAL, or NNRTI
cobi and DTG, and to a lesser extent RTV, RPV, and RAL, can increase SCr soon after treatment initiation because of inhibition of tubular secretion of creatinine. This effect does not affect glomerular filtration. However, assess for renal dysfunction, especially if SCr increases by >0.4 mg/dL.
Stones 

Nephrolithiasis and cholelithiasis
 
ATV, ATV/r
DRV/r, INSTI, or NNRTI
Nephrolithiasis (a frequent complication of IDV) has been observed with ATV. Cholelithiasis is also reported with ATV.
a For patients with chronic active HBV infection, another agent active against HBV should be added to substitute for TDF.
b ABC should be used only in patients known to be HLA-B*5701 negative.
c TDF reduces ATV levels; therefore, unboosted ATV should not be co-administered with TDF. Long term data for unboosted ATV are unavailable.

Key to Abbreviations: ABC = abacavir; ART = antiretroviral therapy; ARV = antiretroviral; ATV = atazanavir; ATV/r = ritonavir-boosted atazanavir; BMD = bone mineral density; CNS = central nervous system; cobi = cobicistat; d4T = stavudine; ddI = didanosine; DRV/r = ritonavir-boosted darunavir; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; EVG = elvitegravir; FPV/r = ritonavir-boosted fosamprenavir; FTC = emtricitabine; GI = gastrointestinal; HBV = hepatitis B virus; HSR = hypersensitivity reaction; IDV = indinavir; INSTI = integrase strand transfer inhibitor; LDL = low-density lipoprotein; LPV/r = ritonavir-boosted lopinavir; MVC = maraviroc; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SCr = serum creatinine; TDF = tenofovir disoproxil fumarate; TG = triglycerides; ZDV = zidovudine

 

References

  1. O'Brien ME, Clark RA, Besch CL, et al. Patterns and correlates of discontinuation of the initial HAART regimen in an urban outpatient cohort. J Acquir Immune Defic Syndr. 2003;34(4):407-414. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14615659.
  2. Keiser O, Fellay J, Opravil M, et al. Adverse events to antiretrovirals in the Swiss HIV Cohort Study: effect on mortality and treatment modification. Antivir Ther. 2007;12(8):1157-1164. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18240856.
  3. Baylor MS, Johann-Liang R. Hepatotoxicity associated with nevirapine use. J Acquir Immune Defic Syndr. 2004;35(5):538-539. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15021321.
  4. Bersoff-Matcha SJ, Miller WC, Aberg JA, et al. Sex differences in nevirapine rash. Clin Infect Dis. 2001;32(1):124-129. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11118391&dopt=Abstract.
  5. Fagot JP, Mockenhaupt M, Bouwes-Bavinck JN,  for the EuroSCAR study group. Nevirapine and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. AIDS. 2001;15(14):1843-1848. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11579247&dopt=Abstract.
  6. Moyle GJ, Datta D, Mandalia S, et al. Hyperlactataemia and lactic acidosis during antiretroviral therapy: relevance, reproducibility and possible risk factors. AIDS. 2002;16(10):1341-1349. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12131210&dopt=Abstract.
  7. Bolhaar MG, Karstaedt AS. A high incidence of lactic acidosis and symptomatic hyperlactatemia in women receiving highly active antiretroviral therapy in Soweto, South Africa. Clin Infect Dis. 2007;45(2):254-260. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17578788.
  8. Geddes R, Knight S, Moosa MY, Reddi A, Uebel K, H S. A high incidence of nucleoside reverse transcriptase inhibitor (NRTI)-induced lactic acidosis in HIV-infected patients in a South African context. S Afr Med J. 2006;96(8):722-724. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17019496.
  9. Dieterich DT, Robinson PA, Love J, Stern JO. Drug-induced liver injury associated with the use of nonnucleoside reverse-transcriptase inhibitors. Clin Infect Dis. 2004;38(Suppl 2):S80-89. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14986279.
  10. Mallal S, Phillips E, Carosi G, et al. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med. 2008;358(6):568-579. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18256392.
  11. Saag M, Balu R, Phillips E, et al. High sensitivity of human leukocyte antigen-b*5701 as a marker for immunologically confirmed abacavir hypersensitivity in white and black patients. Clin Infect Dis. 2008;46(7):1111-1118. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18444831.
  12. El-Sadr WM, Lundgren JD, Neaton JD, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355(22):2283-2296. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17135583.
  13. Lichtenstein KA, Armon C, Buchacz K, et al. Initiation of antiretroviral therapy at CD4 cell counts >/=350 cells/mm3 does not increase incidence or risk of peripheral neuropathy, anemia, or renal insufficiency. J Acquir Immune Defic Syndr. 2008;47(1):27-35. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17971714.

Back to Top