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Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

Management of Medication Toxicity or Intolerance

Gastrointestinal Effects

(Last updated: March 1, 2016; last reviewed: March 1, 2016)

Table 12c. Antiretroviral-Therapy-Associated Adverse Effects and Management Recommendations—Gastrointestinal Effects
Adverse Effects Associated ARVs Onset/Clinical Manifestations Estimated Frequency Risk Factors Prevention/
Nausea/Vomiting Principally ZDV and PIs (e.g., LPV/r, RTV), but can occur with all ARVs and COBI
  • Early
  • Nausea, emesis—may be associated with anorexia and/or abdominal pain.
Varies with ARV agent; 10% to 30% in some series
Unknown Instruct patient to take PIs with food.

Generally improves with time; monitor for weight loss, ARV adherence.
Reassure patient/caretaker that nausea and vomiting will likely decrease over time.

Provide supportive care, including instruction on dietary modification.

Although antiemetics are not generally indicated, they may be useful in extreme or persistent cases.
Diarrhea PIs (particularly NFV, LPV/r, FPV/r), buffered ddI, INSTI (mild)
  • Early
  • Generally soft, more frequent stools
Varies with ARV agent; 10% to 30% in some series Unknown Generally improves with time (usually over 6–8 weeks); monitor for weight loss, dehydration. Exclude infectious causes of diarrhea.

Although data in children on treatment of ARV-associated diarrhea are lacking, dietary modification, use of calcium carbonate (should not be used with DTG), bulk-forming agents (psyllium), or antimotility agents (loperamide) may be helpful. 

While there are few published data on its use, crofelemer is FDA-approved for treatment of ART-associated diarrhea in adults but not in children.
ddI, d4T (especially concurrently or with TDF), boosted PIs 

Reported, albeit rarely, with most ARVs
  • Any time, usually after months of therapy
  • Emesis, abdominal pain, elevated amylase and lipase (asymptomatic hyperamylasemia or elevated lipase do not in and of themselves indicate pancreatitis).
<2% in recent series

Frequency was higher in the past with higher dosing of ddI.
Concomitant treatment with other medications associated with pancreatitis (e.g., TMP-SMX, pentamidine, ribavirin)


Advanced disease

Previous episode of pancreatitis
Avoid use of ddI in patients with a history of pancreatitis. Discontinue offending agent—avoid reintroduction.

Manage symptoms of acute episode.

If associated with hypertriglyceridemia, consider interventions to lower TG levels.
Key to Acronyms: ART = antiretroviral therapy; ARV = antiretroviral; COBI = cobicistat; d4T = stavudine; ddI = didanosine; DTG = dolutegravir; FDA = Food and Drug Administration; FPV/r = fosamprenavir/ritonavir; INSTI = integrase strand transfer inhibitor; LPV/r = lopinavir/ritonavir; NFV = nelfinavir; PI = protease inhibitor; RTV = ritonavir; TDF = tenofovir disoproxil fumarate; TG = triglyceride; TMP-SMX = trimethoprim sulfamethoxazole; ZDV = zidovudine


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