ArticlesDeterminants of HIV-1 shedding in the genital tract of women
Introduction
There is evidence that HIV-1 transmission from mother to child and between sexual partners may be related to plasma viral load.1, 2, 3, 4, 5, 6 Furthermore, female to male transmission could occur as frequently as male to female transmission.4 However, heterosexual, and in many cases perinatal transmission, most probably occurs through direct contact with virus present in the genital tract.7, 8 Therefore, it is critical to understand both systemic and local factors that affect shedding of HIV-1 there.
Past studies of HIV-1 in the female genital tract have been done either in small cohorts or among women from Africa.9, 10, 11, 12, 13, 14, 15 Factors associated with genital tract shedding have included CD4 cell count, concentration of plasma HIV RNA, cervical mucus and ectopy, inflammation, use of hormonal contraceptives, pregnancy, vitamin A deficiency, and co-infection with other sexually transitted diseases (STDs).
Previous research, primarily among men, or female prostitutes in Africa, where non-clade B subtypes of HIV-1 predominate, has shown that the genital tract has a distinct microenvironment that permits viral replication independent from the systemic circulation.16, 17, 18 Therefore, the study of potential sanctuaries where HIV-1 can replicate is of paramount importance.
We did a cross-sectional study involving a large cohort of HIV-1 infected women to comprehensively assess HIV-1 shedding in the genital tract.
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Study population
The Division of AIDS Treatment Research Initiative Study 009 (DATRI 009) is a cross-sectional study nested within the Women's Interagency HIV-1 Study (WIHS), a multicentre, prospective study of the natural history of HIV-1 infection and associated diseases in women. The methods and baseline cohort characteristics of WIHS women have been described previously.19 WIHS women were eligible for this study if they were 18–45 years of age, were not pregnant, with an intact uterus and cervix, and were
Results
In general, the women in this study were similar to women reported to have AIDS in the USA. Most were black, between the ages of 19 and 45 years, infected heterosexually, and had had two or more pregnancies (table 1). Over half of women had had 11 or more lifetime partners and a small percentage had over 1 000 sexual partners. Almost half were not receiving any antiretroviral therapy and a third were receiving combination therapy with a protease inhibitor. Over a third of women had 500 CD4
Discussion
Assessment for determinants of genital tract HIV-1 shedding can assist in our understanding of HIV-1 transmission, potential reservoirs, and possible interventions. We have comprehensively assessed both systemic and local factors affecting genital tract shedding of HIV-1 in women in the USA. Plasma RNA concentration, both qualitatively and quantitatively, was the most important factor in predicting genital HIV-1 shedding, even among women receiving potent antiretroviral therapy. No other
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