DHFR and AIDS: It thus appears that a significant proportion of isolates carried pfdhfr mutations prior to 1998, and use of SP as the first-line anti-malarial in Kenya resulted in the development of highly mutant pfdhps. Pre-existing mutations in pfdhfr may have derived from a combination of two sources: the use of SP as a second-line anti-malarial in Kenya prior to 1998 and the ongoing treatment of persons with HIV/AIDS with co-trimoxazole, a bacterial DHFR/DHPS inhibitor used to treat respiratory tract infections and prevent opportunistic infections.