This study is designed to elucidate the relationship between virologic risk factors and immunologic and clinical progression in HIV+ subjects receiving ZDV or ddI, and to compare new treatment regimens with combinations of reverse transcriptase inhibitors in long-term recipients of monotherapy. This is a randomized, partially blinded trial for ACTG 175 participants who are on ZDV or ddI monotherapy at the time of enrollment into ACTG 302. Treatment goals are: to define the best nucleoside analog sequence and combination, to determine the reason for disease progression in the face of therapy, and to compare strategies for maintaining suppression of viral replication. Since ddI and ZDV induce different drug resistance mutations and may exert different effects on HIV, the treatment regimens offered in this trial depend on prior therapy in ACTG 175. For those participants unblinded to long term ZDV monotherapy, the study seeks to investigate two therapeutic strategies: 1) the addition of a new reverse transcriptase inhibitor, lamivudine (3TC) with ZDV, and 2) switching to monotherapy with stavudine (d4T). For those participants unblinded to long term ddI monotherapy, the addition of ZDV and 3TC may provide additional drug resistance. The addition of ZDV to subjects on long term ddI will provide a test of the hypothesis that the 215 and 74 mutations are incompatible within the same virus/subject when both drugs are sued. The interaction between 3TC and ddI could place even more selective pressure on the virus, resulting in either more virus suppression, or more rapid development of codon 184 and escape from both ddI and 3TC suppressive effects. This study is closed to enrollment as of 1/31/96.

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