Primary genotypic and phenotypic HIV-1 drug resistance in recent seroconverters in Madrid

Objective: Transmission of drug-resistant HIV-1 strains is increasing with widespread use of antiretroviral drugs in developed countries. This study e xamined the prevalence of resistant viruses in recent seroconverters in Mad rid, Spain. Design: HIV isolates from 30 consecutive participants with positive or inde terminate HIV antibody test results and a negative test result at a mean of 6.6 months earlier were examined for HIV drug resistance. All study subjec ts admitted to having Very recently engaged in high-risk practices. All wer e therapeutically naive and were recruited between 1997 and 1999 in a refer ring health care facility for sexually transmitted diseases. Methods: Population-based sequencing of the viral reverse transcriptase (RT ) and protease (PR) regions derived From plasma viral RNA was performed. Ph enotypic resistance was assessed by a recombinant virus assay. Results: Overall prevalence of genotypes associated with reduced susceptibi lity was 26.7% (8 of 30 participants), Resistance mutations were seen again st nucleoside analogues in 7 (23.3%), nonnucleoside reverse transcriptase i nhibitors in 1 (3.3%) and protease inhibitors in 2 (6.7%). Zidovudine-resis tance mutations M41L and/or T215Y were the commonest, found in 20% (6 of 30 participants). Resistance mutations to at least two antiretroviral familie s (multidrug-resistance) were detected in 2 (6.7%) study subjects. A median infectious dose (IC50) increase of fourfold for any drug was found in 7 pa tients, and in 2 was > tenfold for zidovudine (genotype M41L + T215Y) and l amivudine (genotype M184V), respectively. Conclusions: Drug-resistant HIV variants were present ill over one quarter of individuals recently diagnosed as infected in Madrid, Spain. Therefore, resistance testing at baseline should be considered for the optimal design of first-line antiretroviral combinations.