Lab Monitoring of ART Side Effects and Allergic Reactions

Lab Monitoring of ART Side Effects and Allergic Reactions

Bone Marrow Suppression

Medical Care Criteria Committee, March 2006 

RECOMMENDATION
Bone Marrow Suppression (March 2006)
  • Complete blood counts should be measured before initiation of ART therapy and at least every 4 months thereafter. For patients at high risk for bone marrow toxicity (e.g., those with advanced HIV infection, those with pre-treatment cytopenias, or those who are receiving zidovudine), blood counts may have to be monitored more frequently because significant cytopenias may occur. (III)

Bone marrow suppression is most often associated with zidovudine therapy. Significant drug-induced cytopenias become more common in the later stages of symptomatic HIV infection but occasionally develop abruptly in patients at earlier stages.

Pancreatitis

Medical Care Criteria Committee, March 2006

RECOMMENDATIONS
Pancreatitis (March 2006)
  • When patients receiving ART present with signs or symptoms suggestive of pancreatitis, clinicians should obtain serum amylase and lipase levels. (III)
  • If signs or symptoms of pancreatitis occur in patients taking antiretroviral medications, the clinician should temporarily suspend the entire ART regimen. A new ART regimen may be initiated when enzymes are normalized but should not include antiretroviral medications that are most likely linked to pancreatitis, such as didanosine or stavudine.
  • An elevated serum amylase level should be confirmed with a serum lipase level. (III)
  • Clinicians should not prescribe didanosine for patients who have a history of pancreatitis. (III)

The incidence of pancreatitis is higher in patients infected with HIV and may be associated with opportunistic infections as well as ART. Didanosine has been the agent most often associated with this complication; however, cases of pancreatitis also have been reported with other antiretroviral agents since the advent of triple combination therapy. Tenofovir increases the levels of didanosine, thereby increasing the theoretical risk of pancreatitis. Thus, when these antiretroviral medications are used in combination, the dose of didanosine should be reduced.

Pancreatitis should be considered in any patient receiving ART who presents with signs or symptoms of pancreatitis (e.g., abdominal pain, persistent nausea, and vomiting), and serum amylase and lipase should be obtained in this setting. Significant hypertriglyceridemia (>500 mg/dL) is associated with an increased risk of pancreatitis, particularly in patients with other risk factors for pancreatitis (e.g., alcohol or didanosine use). Other causes linked to pancreatitis in the general population should be included in the differential diagnosis.

Hyperamylasemia of non-pancreatic (e.g., parotid) origin may occur in HIV-infected patients. Serum lipase levels should be obtained to delineate the source of the increased amylase. Asymptomatic patients with modest elevations in amylase and lipase levels (<3-fold) may be monitored closely without change in therapy.

Lactic Acidosis/Hepatic Steatosis

Medical Care Criteria Committee, March 2006

RECOMMENDATIONS
Lactic Acidosis/Hepatic Steatosis (March 2006)
  • When patients develop symptoms consistent with lactic acidosis syndrome in conjunction with an elevated lactate level (>2 mmol/L) and decreased serum bicarbonate (<20 mmol/L), the clinician should temporarily discontinue the entire ART regimen while an evaluation is conducted. (II)
  • Routine monitoring of serum lactate levels is not indicated in asymptomatic patients. (I)
  • Patients who are asymptomatic and have an unexplained decrease in serum bicarbonate level (<20 mmol/L) should be promptly re-evaluated with a repeat test and a venous or arterial lactate. (II) If a venous lactate is mildly elevated (2.1 to 5.0 mmol/L), an arterial lactate should be obtained, and re-assessment for the presence of symptoms associated with lactic acidosis should be performed. (I) If the lactate is persistently elevated, the arterial pH is abnormal, or the patient has become symptomatic, ART should be discontinued. (III)

The syndrome of lactic acidosis/hepatic steatosis is rare but associated with a high mortality rate and has been most often associated with the use of NRTIs. Groups at higher risk for this complication include African Americans, obese patients, female patients, and patients with chronic hepatitis C virus (HCV). The syndrome is marked by constitutional complaints, such as abdominal pain, anorexia, nausea/vomiting, hyperventilation, and/or myalgias associated with elevations in serum lactate levels and decreased serum bicarbonate levels. Blood sampling for venous lactate levels should avoid the use of prolonged tourniquetting, and samples should be transported on ice and processed promptly. Lactic acidosis is believed to manifest only at lactate levels >5 mmol/L with an accompanying decreased bicarbonate level.

Patients taking NRTIs who present with constitutional symptoms should be evaluated for lactic acidosis, including lactate (arterial or venous) and bicarbonate level, arterial blood gas determination, serum amylase and lipase, and serum liver enzymes. In conjunction with the evaluation, ART should be discontinued. If the evaluation does not support the diagnosis of lactic acidosis, ART may be restarted.

Patients with mildly elevated lactate levels (2.1 to 5.0 mmol/L) and a normal bicarbonate level are usually asymptomatic. The clinical significance of mildly elevated lactate levels is still unknown. In the absence of decreased bicarbonate levels, lactic acidosis is uncommon.

Hepatotoxicity

Medical Care Criteria Committee,  January 2007

RECOMMENDATIONS
Hepatotoxicity (January 2007)
  • Clinicians should obtain serum liver enzyme levels at baseline and every 3 to 4 months thereafter in patients receiving ART. (III)
  • Clinicians should screen for alcohol use in patients with abnormal serum liver enzyme levels. (III)
Use of Nevirapine (January 2007)
  • Clinicians should not use nevirapine as part of the initial regimen in women with CD4 counts >250 cells/mm3 or men with CD4 counts >400 cells/mm3 because of an increased incidence of hepatotoxicity. (I)
  • When initiating an ART regimen that includes nevirapine, clinicians should obtain serum liver enzymes at baseline, at the time of dose escalation (14 days), and 2 weeks after dose escalation. (III)
  • Clinicians should counsel patients to seek medical evaluation when signs and symptoms of hepatitis, severe skin reactions, or hypersensitivity reactions related to nevirapine occur. Serum liver enzymes should be obtained whenever patients develop a rash during nevirapine therapy, particularly during the first 18 weeks of therapy. (II)
  • In the setting of hepatotoxicity related to nevirapine, patients should not be re-challenged with nevirapine. (I)

All antiretroviral agents have the potential to cause abnormalities in liver function, especially in patients with preexisting liver disease. Serum liver enzyme levels should be obtained at baseline and every 3 to 4 months in patients receiving ART. More frequent monitoring may be necessary for patients with preexisting liver disease or serum liver enzyme abnormalities. The use of full-dose ritonavir (600 mg twice daily) has been associated with worsening transaminases in patients with preexisting liver disease and should be avoided. Patients who develop serum liver enzyme abnormalities greater than five times the upper limit of normal should be promptly assessed. Any potentially hepatotoxic medication, including all antiretroviral agents, should be discontinued.

A higher incidence of significant hepatotoxicity associated with nevirapine therapy has recently been reported, especially in women with CD4 counts >250 cells/mm3, men with CD4 counts >400 cells/mm3, and in the setting of HCV coinfection. The greatest risk of severe and potentially fatal hepatotoxicity occurs in the first 6 weeks of treatment; however, the FDA and the manufacturer strongly recommend intensive monitoring during the first 18 weeks of nevirapine therapy, with discontinuation of the drug if moderate or severe abnormalities occur. In the absence of definitive clinical evidence, monitoring serum liver enzymes every 2 weeks for the first month of nevirapine therapy, then monthly for the first 12 weeks, and every 1 to 3 months thereafter is a reasonable approach, given the potential severity of adverse events. It is essential that the 14-day lead-in period be strictly followed. In some cases, the hepatic injury progresses even after discontinuation of nevirapine. In the setting of hepatotoxicity related to nevirapine, the patient should not be re-challenged with nevirapine.

Some clinicians would avoid using efavirenz after severe nevirapine-related hepatotoxicity (LFTs >5x ULN) with or without Grade 4 rash (Stevens-Johnson syndrome); however, there is no clear evidence to support an association between nevirapine-related hepatotoxicity and efavirenz-related hepatotoxicity [Sulkowski et al 2002]. For mild to moderate nevirapine-related hepatotoxicity (LFTs >3-5 x ULN), switching to efavirenz after complete resolution of hepatotoxicity is an option if there are no other contraindications to efavirenz. Contraindications to efavirenz include known adverse reactions to efavirenz, first-trimester pregnancy, or strong likelihood of becoming pregnant.

For pregnant women with nevirapine-related hepatotoxicity, the clinician should switch the regimen to 2 NRTIs + PI. Efavirenz should only be considered after the first 8 weeks of pregnancy if there are no other options and the benefits outweigh the risks. For additional information, see the DHHS Recommendations for the Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States.

In the setting of severe nevirapine-related hepatotoxicity, all antiretroviral agents and any other possible offending agents should be discontinued. The risk of severe hepatotoxicity outweighs the risk of possible emergence of resistance. 

Reference

Sulkowski MS, Thomas DL, Mehta SH, et al. Hepatotoxicity associated with nevirapine or efavirenz-containing antiretroviral therapy: Role of hepatitis C and B infections. Hepatology 2002;35;182-189. [PubMed

Renal Toxicity

Medical Care Criteria Committee, September 2012

RECOMMENDATIONS
Assessing Kidney Function in All Patients Taking ART (September 2012)
  • Clinicians should routinely assess kidney function in all HIV-infected patients. A renal assessment should include:
    • Glomerular filtration rate estimated from serum creatinine (baseline and at least every 6 months) (A2)
    • Blood urea nitrogen (baseline and at least every 6 months) (A3)
    • Urinalysis (baseline and at least annually) (A3)
    • For patients with diabetes and no known proteinuria: calculation of urine albumin-to-creatinine ratio to detect microalbuminuria (baseline and at least annually) (A1)
Patients Taking Tenofovir (September 2012)
  • For patients initiating a tenofovir-containing regimen, clinicians should calculate glomerular filtration rates at initiation of therapy, 1 month after initiation of therapy, and then at least every 4 months thereafter.
  • Clinicians should adjust tenofovir dosing when glomerular filtration rate approaches 50 mL/min or discontinue tenofovir according to clinical status. (A2)
Patients Taking Indinavir (September 2012)
  • Clinicians should counsel patients receiving indinavir to drink at least 48 ounces of fluid per day.

HIV infection has been associated with several renal complications that may lead to renal insufficiency or failure [Miro et al. 2012; Zaidan et al 2013]. Renal impairment necessitates dose adjustment or discontinuation of many antiretroviral agents.

Clinicians should routinely obtain urinalysis and serum creatinine levels as well as calculate glomerular filtration rates (GFR) to assess renal function. When calculating GFR, the clinician should consistently use the same method. GFR can be calculated by using one of the following equations:

Tenofovir is excreted by glomerular filtration and tubular secretion. Renal impairment has been reported in patients receiving tenofovir [Zaidan et al 2013; Laprise et al 2013]. The extent of this toxicity is unclear. Additional risk factors include low body weight, older age, use of boosted regimens, hypertension, diabetes, and use of other nephrotoxic drugs. Hypophosphatemia may be an early indicator of renal failure. Clinicians may want to use a lower threshold for dose adjustment in patients receiving tenofovir. Clinicians should discontinue tenofovir when patients present with symptoms suggestive of Fanconi syndrome, such as declining renal function with associated metabolic acidosis, hypophosphatemia, hypokalemia, glycosuria, and uricosuria. The decision to rechallenge with tenofovir should be made on a case-by-case basis.

Indinavir (especially when used with ritonavir) and agents used to prevent and/or treat opportunistic infections may cause hematuria, pyuria, or crystalluria. Patients receiving indinavir should be counseled to drink at least 48 ounces of fluid per day. Clinicians should consider urinalysis every 3 to 4 months for patients receiving indinavir-containing regimens.

For additional information regarding renal assessment and management of kidney disease in HIV-infected patients, see NYSDOH AI Kidney Disease Guideline.

References

Laprise C, Baril JG, Dufresne S, et al. Association between tenofovir exposure and reduced kidney function in a cohort of HIV-positive patients: Results from 10 years of follow-up. Clin Infect Dis 2013;56:567-575. [PubMed

Miro JM, Cofan F, Trullas JC, et al. Renal dysfunction in the setting of HIV/AIDS. Curr HIV/AIDS Rep 2012;9:187-199. [PubMed

Zaidan M, Lescure FX, Brochériou I, et al. Tubulointerstitial nephropathies in HIV-infected patients over the past 15 years: A clinico-pathological study. Clin J Am Soc Nephrol 2013;8:930-938. [PubMed]

Monitoring for ART-Associated Allergic Reactions

Medical Care Criteria Committee, June 2010

RECOMMENDATIONS
ART-Associated Allergic Reactions (June 2010)
  • When patients receive any new antiretroviral drugs, clinicians should educate them about the possibility of ART-associated allergic reactions, including a hypersensitivity reaction, and the range of possible symptoms (see Table 4). (III)
  • Clinicians should discontinue offending drugs when there is a moderate to severe skin reaction, mucous membrane involvement, systemic toxicity, or fever. (I)
  • Clinicians should perform HLA-B*5701 testing before initiating abacavir-based therapy.
  • Clinicians should avoid re-challenging patients with a medication that has been associated with a hypersensitivity reaction, especially in the setting of abacavir reactions and severe NNRTI reactions. (I)
  • In patients who develop mild rash in response to nevirapine, clinicians should avoid escalating the nevirapine dose to twice daily until after the rash has resolved. For patients with moderate to severe cutaneous toxicity, nevirapine should be discontinued and should not be re-challenged. Use of an alternate NNRTI should be avoided. (III)
Table 4: Antiretroviral Drugs Typically Associated with Allergic Reactions
ARV Drug (usual timing of symptoms) Most Frequent Symptoms  Action
Abacavir* (first 4 to 6 weeks after initiation) Hypersensitivity reaction: Fever, headache, gastrointestinal symptoms, malaise, arthralgias, myalgias, and respiratory problems. Skin involvement, with rash and pruritus may be mild or absent.
  • Prompt discontinuation of abacavir
  • Do not re-challenge
Delavirdine (first 4 weeks after initiation)  Mild to moderate cutaneous allergy
  • Consider systemic antihistamines while continuing delavirdine for mild rashes
  • Discontinue when there is a moderate to severe skin reaction, mucous membrane involvement, systemic toxicity, or fever
Efavirenz (first 4 weeks after initiation)  Mild to moderate cutaneous allergy
  • Consider systemic antihistamines while continuing efavirenz for mild rashes
  • Discontinue when there is a moderate to severe skin reaction, mucous membrane involvement, systemic toxicity, or fever
Enfuvirtide In the phase 3 trials of enfuvirtide, three cases of probable hypersensitivity were identified. These included, either individually or in combination: rash, fever, nausea and vomiting, chills, rigors, hypotension, and elevated LFTs.  —
Etravirine (generally occurs in the 2nd week of treatment; infrequent after week 4)

Severe reaction: Cutaneous, involving the mucocutaneous surfaces (Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme)

Mild reaction: mild skin rash

 Severe reaction:

  • Discontinue etravirine promptly
  • Discontinue if rash accompanied by fever, hepatitis, and other systemic symptoms.
  • Obtain serum liver enzyme levels
  • Grade 3 and 4 rashes reported in 1.3% of patients
  • Rash more common in women

Mild reaction: Manage with antihistamines and close monitoring

Fosamprenavir, tipranavir,and darunavir  Mild to moderate cutaneous allergy
  • Patients with sulfa allergy may be at increased risk of developing an allergic reaction
  • For mild rashes, consider using systemic antihistamines while continuing protease inhibitors with sulfa moiety
  • Discontinue when there is a moderate to severe skin reaction, mucous membrane involvement, systemic toxicity, or fever
Nevirapine (first 2 to 18 weeks after initiation)

Severe reaction: Cutaneous, involving the mucocutaneous surfaces (Stevens-Johnson syndrome), often accompanied by fever and severe hepatitis

Mild reaction: mild skin rash

 Severe reaction:

  • Discontinue nevirapine promptly
  • Obtain serum liver enzyme levels
  • Do not re-challenge
  • Do not use alternate NNRTI (however, patients with NNRTI rash did not have a higher incidence of rash when given etravirine)

Mild reaction:

  • Close monitoring recommended, but most clinicians would switch to an alternative antiretroviral
  • Obtain serum liver enzyme levels
  • Do not escalate dose to twice daily until the rash has resolved
Raltegravir Rashes, including severe skin rashes and cases of Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported Discontinue if rash is accompanied by constitutional symptoms (i.e., fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema)
*HLA-B*5701 is a pharmacogenetic test (HLA-B*5701) used to identify patients who are predisposed to abacavir hypersensitivity. Clinicians should perform HLA-B*5701 testing before initiating abacavir-based therapy.

Many medications pose the risk of causing various types of allergic reactions, typically presenting as maculopapular rash, with or without fever. Occasionally, a more severe hypersensitivity reaction occurs, consisting of rash and fever, with a combination of other symptoms, such as headache, arthralgias, hepatitis, eosinophilia, and GI or respiratory symptoms. The hypersensitivity reaction usually occurs within 2 to 6 weeks after the drug is started.

Although trimethoprim/sulfamethoxazole is the drug most frequently implicated in common allergic reactions in HIV-infected patients, abacavir, darunavir, tipranavir, fosamprenavir, all of the NNRTIs (nevirapine, delavirdine, efavirenz, etravirine), and enfuvirtide (less commonly) have been associated with a hypersensitivity reaction or syndrome (see Table 4). These reactions are for the most part idiosyncratic and unanticipated. The reactions to darunavir, fosamprenavir, tipranavir (all have a sulfa moiety), delavirdine, and efavirenz are generally mild to moderate cutaneous allergy (drug rash). Patients may rarely develop severe mucous membrane involvement with systemic toxicity. Occasionally, patients will only have a fever. Clinicians should discuss the possibility of these reactions with patients initiating ART because they are most commonly seen in the first 4 weeks of treatment; clinicians should educate patients about the symptoms of hypersensitivity.

Systemic antihistamines may be useful in treating mild cases while patients continue to receive the offending drug. The offending drug should be discontinued when there is a moderate to severe skin reaction, mucous membrane involvement, systemic toxicity, or fever.

Individuals with human leukocyte Ag (HLA)-B*5701, HLA-DR7, and HLA-DQ3 have a genetic predisposition to development of abacavir hypersensitivity. HLA-B*5701 testing is the most thoroughly documented method for assessing for abacavir hypersensitivity and should be determined prior to treatment with this agent [Mallal et al. 2002; Hetherington et al. 2001]. Unlike virus-specific tests (HIV genotype, phenotype, co-receptor tropism assays), HLA genotyping is necessary only once during an individual’s lifetime, because it will not change over time.

Hypersensitivity to abacavir occurred in as many as 5% of patients before routine HLA-B*5701 testing was recommended. The reaction usually occurs within the first 10 to 14 days of therapy and rarely occurs after the first 6 weeks. Fever, headache, GI symptoms, malaise, arthralgias, myalgias, and respiratory problems are the most frequent manifestations of the abacavir hypersensitivity reaction. Skin involvement, with rash and pruritus, may be mild or absent. HLA-B*5701 is a pharmacogenetic test (HLA-B*5701) used to identify patients who are predisposed to abacavir hypersensitivity. Clinicians should perform HLA-B*5701 testing before initiating abacavir-based therapy.

Prompt discontinuation of abacavir when a hypersensitivity reaction is suspected is necessary because symptoms will worsen over time. Once abacavir has been discontinued because of a possible or definite hypersensitivity reaction, abacavir should never be administered again. Re-challenge may result in an anaphylactic reaction with associated hypotension or death.

Nevirapine, an NNRTI, has been associated with severe hypersensitivity reactions in the first 2 to 12 weeks of use. Graduated dosing of nevirapine at initiation with 200 mg daily for the first 2 weeks followed by 200 mg twice daily thereafter has reduced the incidence of hypersensitivity reactions. Systemic antihistamines or corticosteroids given at the time of nevirapine initiation have not been proven useful. Such reactions manifest as severe cutaneous reaction involving the mucocutaneous surfaces (Stevens-Johnson syndrome), often with accompanying fever and severe hepatitis. Deaths associated with these reactions have been reported. Patients who develop mild rashes without systemic toxicity may be managed with antihistamines and close monitoring. The nevirapine dose should not be escalated to twice daily until the rash has resolved. However, those with moderate to severe cutaneous toxicity should discontinue nevirapine promptly and should not be re-challenged with this drug. Because of potential cross-reactivity, use of an alternate NNRTI should be avoided in patients who have a severe reaction to nevirapine; however, the incidence of etravirine rash is not high in patients with a history of NNRTI rash.

Etravirine, an NNRTI, has been associated with hypersensitivity reaction. Up to 10% of patients in clinical trials reported rashes. Most reported mild to moderate rashes. Grade 3 and 4 rashes reported in 1.3% of patients, and up to 2.2% of patients required etravirine discontinuation. Rashes generally occur in the second week of treatment and are infrequent after week 4. Etravirine should be discontinued for severe rash or if rash is accompanied by fever, hepatitis, and other systemic symptoms.

In the phase 3 trials of enfuvirtide, three cases of probable hypersensitivity to the drug were identified. These have included, either individually or in combination, rash, fever, nausea and vomiting, chills, rigors, hypotension, and elevated serum liver enzymes.

References

Hetherington S, Hughes AR, Mosteller M, et al. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet 2002;359:1121-1122. [PubMed]

Mallal S, Nolan D, Witt C, et al. Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse transcriptase inhibitor abacavir. Lancet 2002;359:727-732. [PubMed]

All Recommendations

Medical Care Criteria Committee, dates of most recent updates listed by topic below

ALL RECOMMENDATIONS: LAB MONITORING OF ART SIDE EFFECTS AND ALLERGIC REACTIONS GUIDELINE
Bone Marrow Suppression (March 2006)
  • Complete blood counts should be measured before initiation of ART therapy and at least every 4 months thereafter. For patients at high risk for bone marrow toxicity (e.g., those with advanced HIV infection, those with pre-treatment cytopenias, or those who are receiving zidovudine), blood counts may have to be monitored more frequently because significant cytopenias may occur. (III)
Pancreatitis (March 2006)
  • When patients receiving ART present with signs or symptoms suggestive of pancreatitis, clinicians should obtain serum amylase and lipase levels. (III)
  • If signs or symptoms of pancreatitis occur in patients taking antiretroviral medications, the clinician should temporarily suspend the entire ART regimen. A new ART regimen may be initiated when enzymes are normalized but should not include antiretroviral medications that are most likely linked to pancreatitis, such as didanosine or stavudine.
  • An elevated serum amylase level should be confirmed with a serum lipase level. (III)
  • Clinicians should not prescribe didanosine for patients who have a history of pancreatitis. (III)
Lactic Acidosis/Hepatic Steatosis (March 2006)
  • When patients develop symptoms consistent with lactic acidosis syndrome in conjunction with an elevated lactate level (>2 mmol/L) and decreased serum bicarbonate (<20 mmol/L), the clinician should temporarily discontinue the entire ART regimen while an evaluation is conducted. (II)
  • Routine monitoring of serum lactate levels is not indicated in asymptomatic patients. (I)
  • Patients who are asymptomatic and have an unexplained decrease in serum bicarbonate level (<20 mmol/L) should be promptly re-evaluated with a repeat test and a venous or arterial lactate. (II) If a venous lactate is mildly elevated (2.1 to 5.0 mmol/L), an arterial lactate should be obtained, and re-assessment for the presence of symptoms associated with lactic acidosis should be performed. (I) If the lactate is persistently elevated, the arterial pH is abnormal, or the patient has become symptomatic, ART should be discontinued. (III)
Hepatotoxicity (January 2007)
  • Clinicians should obtain serum liver enzyme levels at baseline and every 3 to 4 months thereafter in patients receiving ART. (III)
  • Clinicians should screen for alcohol use in patients with abnormal serum liver enzyme levels. (III)
Use of Nevirapine (January 2007)
  • Clinicians should not use nevirapine as part of the initial regimen in women with CD4 counts >250 cells/mm3 or men with CD4 counts >400 cells/mm3 because of an increased incidence of hepatotoxicity. (I)
  • When initiating an ART regimen that includes nevirapine, clinicians should obtain serum liver enzymes at baseline, at the time of dose escalation (14 days), and 2 weeks after dose escalation. (III)
  • Clinicians should counsel patients to seek medical evaluation when signs and symptoms of hepatitis, severe skin reactions, or hypersensitivity reactions related to nevirapine occur. Serum liver enzymes should be obtained whenever patients develop a rash during nevirapine therapy, particularly during the first 18 weeks of therapy. (II)
  • In the setting of hepatotoxicity related to nevirapine, patients should not be re-challenged with nevirapine. (I)
Assessing Kidney Function in All Patients Taking ART (September 2012)
  • Clinicians should routinely assess kidney function in all HIV-infected patients. A renal assessment should include:
    • Glomerular filtration rate estimated from serum creatinine (baseline and at least every 6 months) (A2)
    • Blood urea nitrogen (baseline and at least every 6 months) (A3)
    • Urinalysis (baseline and at least annually) (A3)
    • For patients with diabetes and no known proteinuria: calculation of urine albumin-to-creatinine ratio to detect microalbuminuria (baseline and at least annually) (A1)
Patients Taking Tenofovir (September 2012)
  • For patients initiating a tenofovir-containing regimen, clinicians should calculate glomerular filtration rates at initiation of therapy, 1 month after initiation of therapy, and then at least every 4 months thereafter.
  • Clinicians should adjust tenofovir dosing when glomerular filtration rate approaches 50 mL/min or discontinue tenofovir according to clinical status. (A2)
Patients Taking Indinavir (September 2012)
  • Clinicians should counsel patients receiving indinavir to drink at least 48 ounces of fluid per day.
ART-Associated Allergic Reactions (June 2010)
  • When patients receive any new antiretroviral drugs, clinicians should educate them about the possibility of ART-associated allergic reactions, including a hypersensitivity reaction, and the range of possible symptoms (see Table 4). (III)
  • Clinicians should discontinue offending drugs when there is a moderate to severe skin reaction, mucous membrane involvement, systemic toxicity, or fever. (I)
  • Clinicians should perform HLA-B*5701 testing before initiating abacavir-based therapy.
  • Clinicians should avoid re-challenging patients with a medication that has been associated with a hypersensitivity reaction, especially in the setting of abacavir reactions and severe NNRTI reactions. (I)
  • In patients who develop mild rash in response to nevirapine, clinicians should avoid escalating the nevirapine dose to twice daily until after the rash has resolved. For patients with moderate to severe cutaneous toxicity, nevirapine should be discontinued and should not be re-challenged. Use of an alternate NNRTI should be avoided. (III)