Combinations of drugs may result in greater toxicity than would be seen with single drugs. For example, either AZT or ganciclovir (Cymevene) used on its own has a suppressive effect on the bone marrow that decreases its ability to form red and white blood cells and platelets. If these drugs are taken at the same time, the toxic effects on the bone marrow are increased and anaemia or neutropenia may develop.

Other drugs that can cause serious bone marrow inhibition when taken with AZT include cotrimoxazole (Bactrim/Septrin), interferon, dapsone, pyrimethamine (Daraprim), pentamidine, and cytotoxic chemotherapy drugs such as doxorubicin (Caelyx/Myocet).

Pancreatitis can occur with ddI and ddC (zalcitabine, Hivid) and alcohol use increases this risk.

The other notable additive toxicity in persons with HIV is peripheral neuropathy. Neuropathy is most often associated with the NRTIs, notably ddI, ddC, and d4T. When used together, the likelihood of peripheral neuropathy occurring is greater so the combined use of these agents is generally contraindicated.