Antiretroviral Associated Adverse Effects and Management Recommendations for Gastrointestinal Effects

Adverse Effects	Associated ARVs	Onset/Clinical Manifestations	Estimated Frequency	Risk Factors	Prevention/ Monitoring	Management
Nausea/‌Vomiting	All ARV drugs, but most notably RTV-boosted PIs	Onset Early Presentation Nausea and emesis, both of which may be associated with anorexia and/or abdominal pain	Varies by ARV agent; generally <15%	Unknown	Instruct patient to take PIs with food. Monitor for weight loss and ARV adherence.	Reassure the patient that these adverse effects generally improve over time (usually in 6–8 weeks). Consider switching to ARV drugs with smaller tablet sizes (see Appendix A, Table 2. Antiretroviral Fixed-Dose Combination Tablets and Co-packaged Formulations: Minimum Body Weights and Considerations for Use in Children and Adolescents). Provide supportive care. In extreme or persistent cases, use antiemetics or switch to another ARV regimen.
Diarrhea	All ARV drugs, but most notably RTV-boosted PIs	Onset Early Presentation More frequent bowel movements and stools that are generally soft	Varies by ARV agent; generally <15%	Unknown	Monitor for weight loss and dehydration.	In prolonged or severe cases, exclude infectious or noninfectious (e.g., lactose intolerance) causes of diarrhea. Reassure patient that this adverse effect generally improves over time (usually in 6–8 weeks). Consider switching to another ARV regimen in persistent and severe cases. Treatment data in children are lacking; however, the following strategies may be useful when the ARV regimen cannot be changed: Modifying the diet Using bulk-forming agents (e.g., psyllium) Using antimotility agents (e.g., loperamide) Using crofelemer, which is approved by the FDA to treat ART-associated diarrhea in adults aged ≥18 years; no pediatric data are available.
Pancreatitis	Rare, but may occur with NRTIs or RTV-boosted PIs	Onset Any time, usually after months of therapy Presentation Emesis, abdominal pain, elevated amylase and lipase levels (asymptomatic hyperamylasemia or elevated lipase do not in and of themselves indicate pancreatitis)	<2%	Use of concomitant medications that are associated with pancreatitis (e.g., TMP-SMX, pentamidine, ribavirin) Hypertriglyceridemia Advanced HIV infection Previous episode of pancreatitis Alcohol use	Measure serum amylase and lipase concentrations if persistent abdominal pain develops.	Discontinue offending agent and avoid reintroduction. Manage symptoms of acute episodes. If pancreatitis is associated with hypertriglyceridemia, consider using interventions to lower TG levels.
Key: ART = antiretroviral therapy; ARV = antiretroviral; FDA = U.S. Food and Drug Administration; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; RTV = ritonavir; TG = triglyceride; TMP-SMX = trimethoprim sulfamethoxazole

References

Table 17c. Antiretroviral Therapy–Associated Adverse Effects and Management Recommendations—Gastrointestinal Effects