Prevalence of drug resistant mutants and virological response to combination therapy in patients with primary HIV-1 infection

Baseline genotype resistance analysis was carried out in 48 adults with pri mary HIV-1 infection between 1995 and 1998 before starting early combinatio n therapy. Seventeen percent (8/48) of the isolates displayed key mutations conferring resistance to reverse transcriptase (RT) inhibitors such as ami no acid substitutions 215Y/F 15/48,10%), 70R (3/48, 6%), 184V (2%). Two per cent (1/48) had a major mutation associated with resistance to protease inh ibitors (D30N). Other mutations at positions 10, 15, 20, 33, 36, 46, 63, 71 ,77, 82, 93 of the protease gene were frequent (73%). Among the 46 patients who were given antiretroviral combination therapy and who responded durabl y to treatment after 6 and 12 months, there was no significant difference b etween those harboring RT muta nt strains (Group I) and those with wild-typ e isolates (Group II). No significant difference was found at months 6 and 12 between the two groups in terms of CD4+ cell counts. These findings sugg est that the presence of drug-resistant strains at the time of primary HIV- 1 infection does not necessarily predict drug failure. Other factors, such as adherence to treatment, tolerance and pharmacokinetics parameters are pr obably major determinants of virological response in patients with early th erapeutic intervention. (C) 2000 Wiley-Liss, Inc.