Background:  The transmission of drug-resistant HIV-1 can impair the virological response to first-line regimens. The detection of minor resistant variants has been reported in acute seroconverters. We wished to investigate the clinical relevance of the detection of minor resistant variants in antiretroviral naïve, recently infected patients.

Methods:  We included patients from the Aquitaine Cohort with a date of seroconversion between 1996 and 2005, a plasma sample obtained less than 18 months after seroconversion and prior starting ART. Reverse transcriptase (RT) and protease sequences were determined by direct population sequencing from plasma samples. Minor populations of drug-resistant variants were detected by real-time, allele-specific polymerase chain reaction (PCR) for the RT mutations K103N and M184V and the protease mutation L90M. Resistance to at least 1 drug of the first-line regimen was defined using the ANRS 2006 algorithm. The association between resistance and plasma viral load/CD4 levels at treatment initiation and change during the first 12 months were estimated by using a piecewise linear mixed model taking into account left-censoring of undetectable viral loads.

Results:  Among 172 included patients, 16 (9.3%) presented a resistance to at least 1 drug of the initiated therapy, by using population sequencing (group 1). We found minority resistant variants in 18 (9.9%) additional patients (group 2), with a detection of 184V in 16 patients, K103N in 3 patients, and 90M in none. At ART initiation, mean plasma viral load was significantly (p = 0.002) lower in group 1 (3.76 log₁₀ copies/mL) compared to those without any resistance (4.59 log₁₀ copies/mL), reflecting a lower viral fitness. Baseline CD4 count differed as well (557 cells/µL in group 1 vs 425, p = 0.03). The presence of minority variants did not modify baseline plasma viral load (4.84 log₁₀ copies/mL, p = 0.33) and baseline CD4 cell count (519 cells/µL, p = 0.09). The change in plasma viral load during the first month on ART did not differed between groups (group 1, p = 0.48; group 2, p = 0.66). However, the decrease in plasma viral load after 1 month was significantly more pronounced in patients without resistance compared to the gGroup 1 (–0.24 log₁₀ copies/mL/month vs –0.04, p = 0.02), but was similar in group 2 (–0.17 log₁₀ copies/mL/month). Change in CD4 cell count was similar in all groups.

Conclusion: The transmission of majority resistant variants, but not of minority resistant variants, did influence the response to ART in this prospective cohort study.