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Background:  A5077 is a 96-week, multi-center, longitudinal study designed to assess HIV characteristics in blood and non-blood compartments in men and women who were starting antiretroviral (ARV) drug therapy or changing from a failing regimen. An evaluation of the baseline plasma drug susceptibility was performed to study sex-differences in drug resistance and genital viral shedding.

Methods:  We enrolled 87 men and 86 women. Genital specimens (64 semen and 80 cervical fluid) were matched with blood plasma. Sequencing of pol from plasma virus was performed with valid results for 58 men and 79 women. A mutational score (HIVDB.stanford.edu) was used to estimate the number of ARV to which each subject was resistant. Within 90 days of study entry, 53 subjects were on ARV therapy of which 29 subjects were on therapy within 10 days of obtaining genotypic susceptibility scores. Resistance by ARV drug class and individual genotypic susceptibility scores were compared between men and women to identify the association with genital HIV shedding.

Results:  Subjects had a median age of 41 years, number of ARV ever taken (5), years of prior therapy (5.6), CD4 cells/µL (208); blood plasma HIV RNA log₁₀ copies/mL (4.7), semen HIV RNA (3.8), and cervical fluid HIV RNA was below the limit of detection in 86%. For those on ARV within 90 days of study entry, 21 men and 29 women had a similar mean (SD) number of resistant ARV:  nucleoside reverse transcriptase inhibitors (NRTI) 2.57 (2.96) vs 1.86 (2.60) and protease inhibitors (PI) 2.05 (3.04) vs 1.45 (2.75), respectively, but men trended toward less non-NRTI (NNRTI) resistance 0.90 (1.34) vs 1.62 (1.42) (Wilcoxon rank-sum test, p = 0.08), and more than half of the women had resistance to > 2 NNRTI drugs. Genital HIV shedding was markedly greater among men who received ARV therapy within 10 days of sampling compared to women, which persisted after controlling for plasma HIV RNA (p < 0.001). Genital HIV shedding for GSS ≤ 2 and > 2 was: 5 of 9 men vs 1 of 10 women and 3 of 3 men vs 0 of 5 women, respectively. Shedding for those on ARV within 10 days (8 of 13 men vs 1 of 16 women, RR 9.8 [95% CI 2.2 to 171]) with those not on ARV (41 of 51 men vs 28 of 64 women, RR 1.8 [1.4 to 2.6]) suggested a greater effect on the genital viral load of women (p = 0.03).

Conclusions:  Among highly ARV drug-experienced subjects receiving therapy within 10 days of study entry, there was markedly more genital HIV shedding among men than women. Shedding of genital HIV among men with drug resistance, despite therapy, suggests that seminal HIV may contribute to transmission of drug-resistant virus.

Keywords: Drug resistance; semen; cervical secretions