Opportunistic infections continue to cause a significant amount of morbidity and mortality worldwide in patients infected with HIV. Trimethoprim-sulfamethoxazole (cotrimoxazole) is used in the treatment and prophylaxis of several opportunistic infections. In patients with HIV/AIDS, cotrimoxazole use can cause a higher rate of adverse drug reactions than in the general population. Given the cost-effectiveness of cotrimoxazole, the management of these adverse reactions has included continuing the drug (treating-through) and reintroducing the drug at a later date, either using dose-escalation (desensitization), or rechallenge at full dose. This systematic review is the first to examine the differences in patient outcomes between these strategies.