Primary Genotypic and Phenotypic HIV-1 Drug Resistance in Recent Seroconverters in Madrid

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Abstract
Transmission of drug-resistant HIV-1 strains is increasing with widespread use of antiretroviral drugs in developed countries. This study examined the prevalence of resistant viruses in recent seroconverters in Madrid, Spain. HIV isolates from 30 consecutive participants with positive or indeterminate 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 subjects admitted to having very recently engaged in high-risk practices. All were therapeutically naive and were recruited between 1997 and 1999 in a referring health care facility for sexually transmitted diseases. Population-based sequencing of the viral reverse transcriptase (RT) and protease (PR) regions derived from plasma viral RNA was performed. Phenotypic resistance was assessed by a recombinant virus assay. Overall prevalence of genotypes associated with reduced susceptibility was 26.7% (8 of 30 participants). Resistance mutations were seen against nucleoside analogues in 7 (23.3%), nonnucleoside reverse transcriptase inhibitors in 1 (3.3%), and protease inhibitors in 2 (6.7%). Zidovudine-resistance mutations M41L and/or T215Y were the commonest, found in 20% (6 of 30 participants). Resistance mutations to at least two antiretroviral families (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 patients, and in 2 was > tenfold for zidovudine (genotype M41L + T215Y) and lamivudine (genotype M184V), respectively. Drug-resistant HIV variants were present in 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.