HIV-1-RNA levels vary with the menstrual cycle in the female genital tract but not the blood compartment. HIV-1-RNA levels are higher in endocervical canal fluid than in blood plasma. These findings may have important implications for sex-specific pathogenesis, heterosexual transmission, and contraceptive hormone interventions in HIV-1-infected women.

To understand the impact of the menstrual cycle on immunologic parameters, we measured the level of cytokines and chemokines from plasma, cervicovaginal lavage (CVL), and saliva samples of 6 premenopausal women during the follicular and luteal phases of the ovulatory cycle. We demonstrate that the level of plasma interleukin-8 (IL-8) was 4-fold higher during the follicular phase than the luteal phase (p = 0.004), whereas plasma IL-1beta, IL-4, IL-6, IL-10, interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-1alpha (MIP-1alpha), and TNF receptor II (TNFR II) were not altered during the ovulatory cycle. In the vaginal compartment, as measured from CVL samples, the levels of IL-6 and IL-1beta were both 5-fold higher in the follicular than the luteal phase (p = 0.0002 and 0.03, respectively). Salivary cytokine and chemokine samples were similar when measured during the luteal and the follicular phases. Additional analysis of lymphocyte subsets for phenotypic and functional markers indicated that they were not influenced by the ovulatory cycle. Collectively, these data suggest that IL-6, IL-8, and IL-1beta are differentially regulated during the ovulatory cycle.

We provide evidence of elevated vaginal cytokine levels during menses, which appear to regulate vaginal and not plasma HIV shedding, suggesting that a menstrual cycle pattern exists for cytokine production in HIV-positive women impacting vaginal shedding of HIV.

The short-term detection and variability of human immunodeficiency virus type 1 (HIV-1) RNA level was assessed in the blood plasma and genital tracts of 55 HIV-1-infected women. Specimens were collected weekly for 8 weeks from the endocervical canal with wicks and cytobrushes and from the ectocervix and vagina with cervicovaginal lavage. In all, 48 women (87.3%) had detectable genital tract HIV-1 RNA at > or =1 collection times. HIV-1 RNA levels varied least in specimens from endocervical canal wick and most in cervicovaginal lavage samples. The within-subject variation for genital-tract virus level was greater than that for blood. Overall, the odds for viral RNA detection in the genital tract approximately tripled for each 10-fold increase in plasma viral RNA concentration (P<.001) or with concomitant genital tract infection (P=.003). Endocervical canal wicks should be considered as an adjunct to cervicovaginal lavage, to improve the sensitivity and precision of HIV-1 RNA detection.

No abstract