Changes in HIV-1 Subtypes B and C Genital Tract RNA in Women and Men after Initiation of Antiretroviral Therapy

Background. Combination antiretroviral therapy ( cART) reduces genital tract human immunodeficiency virus type 1 (HIV-1) load and reduces the risk of sexual transmission, but little is known about the efficacy of cARTfor decreasing genital tract viral load(GTVL) and differences in sex or HIV-1 subtype. Methods.  HIV-1 RNA from blood plasma, seminal plasma, or cervical wicks was quantified at baseline and at weeks 48 and 96 after entry in a randomized clinical trial of 3 cARTregimens. Results. One hundred fifty-eight men and 170 women from 7 countries were studied (men: 55% subtypeB and 45% subtypeC; women: 24% subtypeB and 76% subtypeC). Despite similar baseline CD4+ cell counts and blood plasma viral loads, women with subtypeC had the highest GTVL (median, 5.1 log10 copies/mL) compared to women with subtypeB and men with subtypeC or B (4.0, 4.0, and 3.8 log10 copies/mL, respectively; P < .001). The proportion of participants with a GTVL below the lower limit of quantification (LLQ) at week 48 (90%) and week 96 (90%) was increased compared to baseline (16%; P < .001 at both times). Women were significantly less likely to have GTVL below the LLQ compared to men (84% vs 94% at week 48, P = .006; 84% vs 97% at week 96, P = .002), despite a more sensitive assay for seminal plasma than for cervical wicks. No difference in GTVL response across the 3 cARTregimens was detected. Conclusions. The female genitaltract may serve as a reservoir of persistent HIV-1 replication during cARTand affect the use of cARTto prevent sexual and perinatal transmission of HIV-1.