Elsevier

The Lancet

Volume 358, Issue 9293, 10 November 2001, Pages 1593-1601
The Lancet

Articles
Determinants of HIV-1 shedding in the genital tract of women

https://doi.org/10.1016/S0140-6736(01)06653-3Get rights and content

Summary

Background

Plasma HIV-1 RNA concentration has been the best predictor for risk of heterosexual and perinatal transmission. However, direct contact with HIV-1 present locally in the genital tract might be necessary for transmission. We aimed to assess the relation between HIV-1 shedding (RNA or culturable virus) in female genital secretions and other factors that might affect HIV-1 shedding.

Methods

This was a cross-sectional study within the Women's Interagency HIV Study (WIHS), a prospective longitudinal cohort study of HIV-infected women. We enrolled 311 HIV positive women from Jan 30, 1997 to July 1, 1998. We did clinical assesments, cultured HIV-1, and measured RNA in peripheral blood mononuclear cells (PBMC) and genital secretions. We compared the results with univariate and multivariate analyses. Presence of HIV-1 RNA or culturable virus in genital secretions was defined as HIV-1 shedding.

Findings

HIV-1 RNA was present in genital secretions of 57% (152/268) of women whereas infectious virus was detected only in 6% (17/271). Genital tract HIV-1 shedding was found in 80% (130/163) of women with detectable plasma RNA and 78% (116/148) of women with positive PBMC cultures. 33% (27/83) of women with less than 500 copies/mL plasma RNA and 39% (35/90) of those with negative PBMC cultures also had genital tract shedding.

Interpretation

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. However, HIV-1 shedding did occur in women with less than 500 copies/mL plasma HIV-1 RNA. This finding suggests that a separate reservoir of HIV-1 replication may exist in some 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.

Section snippets

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

References (40)

  • RA Royce et al.

    Sexual transmission of HIV

    N Engl J Med

    (1997)
  • R Chuachoowong et al.

    Short-course antenatal zidovudine reduces both cervicovaginal human immunodeficiency virus type 1 RNA levels and risk of perinatal transmission: Bangkok Collaborative Perinatal HIV Transmission Study Group

    J Infect Dis

    (2000)
  • S Cu-Uvin et al.

    Cervicovaginal human immunodeficiency virus secretion and plasma viral load in human immunodeficiency virus-seropositive women

    Obstet Gynecol

    (1997)
  • CE Hart et al.

    Correlation of human immunodeficiency virus type 1 RNA levels in blood and the female genital tract

    J Infect Dis

    (1999)
  • AK Iversen et al.

    Distinct determinants of human immunodeficiency virus type 1 RNA and DNA loads in vaginal and cervical secretions

    J Infect Dis

    (1998)
  • S Rasheed et al.

    Presence of cell-free human immunodeficiency virus in cervicovaginal secretions is independent of viral load in the blood of human immunodeficiency virus-infected women

    Am J Obstet Gynecol

    (1996)
  • A Kovacs et al.

    HIV-1 RNA in plasma and genital tract secretions in women infected with HIV-1

    J Acquir Immun Defic Syndr

    (1999)
  • C Goulston et al.

    Human immunodeficiency virus type 1 RNA shedding in the female genital tract

    J Infect Dis

    (1998)
  • J Overbaugh et al.

    Distinct but related human immunodeficiency virus type 1 variant populations in genital secretions and blood

    AIDS Res Hum Retroviruses

    (1996)
  • H Zhang et al.

    Human immunodeficiency virus type 1 in the semen of men receiving highly active antiretroviral therapy

    N Engl J Med

    (1998)
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