Human Immunodeficiency Virus Type 1 RNA Shedding in the Female Genital Tract

Goulston, Claudia; McFarland, William; Katzenstein, David

doi:10.1086/517404

Cited by 59 publications

(30 citation statements)

References 13 publications

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“…[44][45][46] There is less consensus on the association between plasma viremia and male genital tract HIV-1 levels, where modest or no correlations have been reported. [47][48][49][50] Our data indicate that there are gender differences in the relationship between plasma viral load and transmission.…”

Section: Discussionmentioning

confidence: 99%

Virologic and Immunologic Determinants of Heterosexual Transmission of Human Immunodeficiency Virus Type 1 in Africa

Fideli

Allen

Musonda

et al. 2001

AIDS Research and Human Retroviruses

332

281

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More than 80% of the world's HIV-infected adults live in sub-Saharan Africa, where heterosexual transmission is the predominant mode of spread. The virologic and immunologic correlates of femaleto-male (FTM) and male-to-female (MTF) transmission are not well understood. A total of 1022 heterosexual couples with discordant HIV-1 serology results (one partner HIV infected, the other HIV uninfected) were enrolled in a prospective study in Lusaka, Zambia and monitored at 3-month intervals. A nested case-control design was used to compare 109 transmitters and 208 nontransmitting controls with respect to plasma HIV-1 RNA (viral load, VL), virus isolation, and CD4 + cell levels. Median plasma VL was significantly higher in transmitters than nontransmitters (123,507 vs. 51,310 copies/ml, p < 0.001). In stratified multivariate Cox regression analyses, the risk ratio (RR) for FTM transmission was 7.6 (95% CI: 2.3, 25.5) for VL ≥ 100,000 copies/ ml and 4.1 (95% CI: 1.2, 14.1) for VL between 10,000 and 100,000 copies/ml compared with the reference group of <10,000 copies/ ml. Corresponding RRs for MTF transmission were 2.1 and 1.2, respectively, with 95% CI both bounding 1. Only 3 of 41 (7%) female transmitters had VL < 10,000 copies/ml compared with 32 of 93 (34%) of female nontransmitters (p < 0.001). The transmission rate within couples was 7.7/100 person-years and did not differ from FTM (61/862 person-years) and MTF (81/978 person-years) transmission. We conclude that the association between increasing plasma viral load was strong for female to male transmission, but was only weakly predictive of male to female transmission in Zambian heterosexual couples. FTM and MTF transmission rates were similar. These data suggest gender-specific differences in the biology of heterosexual transmission.Address reprint requests to: Grace M. Aldrovandi,

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Section: Discussionmentioning

confidence: 99%

Virologic and Immunologic Determinants of Heterosexual Transmission of Human Immunodeficiency Virus Type 1 in Africa

Fideli

Allen

Musonda

et al. 2001

AIDS Research and Human Retroviruses

332

281

View full text Add to dashboard Cite

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“…Reports that show an association between a woman's CD4 ϩ cell level in blood and her virus loads in BP and VS also indicate that cellular immune activity affects the HIV-1 populations in these two compartments in a similar manner (26,30,55). In addition, a previous report of correlated HIV-1 envspecific immunoglobulin G titers in BP and cervicovaginal secretions of infected women (10) suggests that humoral anti-HIV-1 titers in VS and BP also could have contributed to the associations in viral diversities and divergences we observed.…”

Section: Vol 79 2005 Hiv Quasispecies Shed In the Female Genital Trmentioning

confidence: 95%

“…Several studies found that cell-free virus levels in vaginal secretions are inversely correlated with CD4 ϩ cell levels in the blood of infected women (26,30,55), suggesting that a functioning immune system is associated with controlling viral replication in genital tissues. More recent evidence indicates that women with higher CD4 ϩ cell levels are more likely to have compartmentalized cell-free virus shed in their genital tract secretions (31).…”

mentioning

confidence: 99%

Diversity, Divergence, and Evolution of Cell-Free Human Immunodeficiency Virus Type 1 in Vaginal Secretions and Blood of Chronically Infected Women: Associations with Immune Status

Sullivan

Mandava

Evans-Strickfaden

et al. 2005

J Virol

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Most human immunodeficiency virus type 1 (HIV-1) infections are believed to be the result of exposure to the virus in genital secretions. However, prevention and therapeutic strategies are usually based on characterizations of HIV-1 in blood. To understand better the dynamics between HIV-1 quasispecies in the genital tract and blood, we performed heteroduplex assays on amplified env products from cell-free viral RNA in paired vaginal secretion (VS) and blood plasma (BP) samples of 14 women followed for 1.5 to 3.5 years. Diversity and divergence were less in VS than in BP (P ‫؍‬ 0.03 and P < 0.01, respectively), and divergence at both sites was correlated with blood CD4 ؉ cell levels (VS, P ‫؍‬ 0.05; BP, P ‫؍‬ 0.01). Evolution of quasispecies was observed in 58% of the women; the loss or gain of quasispecies in VS or BP was always accompanied by such changes at the other site. In addition, sustained compartmentalization of quasispecies in VS was found for four women, even as CD4 ؉ cell levels decreased to low levels (<50 cells/l). Quasispecies changes over time were associated with fluctuations in CD4 ؉ cell levels; concordant increases or decreases in VS and BP divergence had greater CD4 ؉ cell level changes than intervals with discordant changes (P ‫؍‬ 0.05), and women with evolving quasispecies had greater decreases in CD4؉ cell levels compared to that for women who maintained the same quasispecies (P < 0.05). Thus, diversity, divergence, and evolution of cell-free HIV-1 in VS can be different from that in BP, and dynamics between their respective quasispecies are associated with changes in CD4 ؉ cell levels.

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“…Factors that influence the amount of HIV-1 in vaginal secretions are important risk determinants for this mode of transmission. It is reported that the amount of HIV-1 RNA in vaginal secretions is correlated with that in plasma (8,13,17,20) and that an increase in plasma viral load in infected persons is associated with an increase in HIV-1 transmission to their sex partners (15,30,35). In addition, localized cervical inflammation and ulceration, without affecting the plasma viral load, can increase HIV-1 shedding in the female genital tract and thus influence HIV-1 transmission (3,22,24,47).…”

Section: Detection Of Infectious Hiv-1 In Vaginal Lavages Was Not Assmentioning

confidence: 99%

Detection of Infectious Human Immunodeficiency Virus Type 1 in Female Genital Secretions by a Short-Term Culture Method

et al. 2003

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Infectious human immunodeficiency virus type 1 (HIV-1) is difficult to detect in female genital secretions by standard virus culture techniques. To improve detection of cell-free HIV-1 in female genital secretions, we adapted a short-term assay that uses the multinuclear-activation galactosidase indicator (MAGI) assay. When vaginal lavages from HIV-1-infected women were tested with the adapted MAGI assay, 25 (64%) of 39 lavages with detectable, cell-free HIV-1 RNA were shown to have infectious virus. No infectious virus was found in 10 vaginal lavages from HIV-1-infected women with undetectable vaginal viral loads. Significantly (P < 0.01) more lavages from HIV-1-infected women tested positive for infectious virus by the MAGI assay than by standard peripheral blood mononuclear cell (PBMC) coculture, which detected infectious virus in only 6 (17%) of 35 vaginal lavages. Lavages with viral loads of >10,000 copies per lavage yielded significantly (P < 0.01) more positive cultures than those with <10,000 copies by using the MAGI assay. Detection of infectious HIV-1 in vaginal lavages was not associated with the presence of genital tract infections or CD4؉ -T-cell counts. However, although the results were not significant (P ‫؍‬ 0.08), the MAGI assay detected infectious virus from more vaginal lavages at a vaginal pH of >4.5 than at a pH of <4.5. These results indicate that the MAGI assay is more sensitive than PBMC culture methods for detecting infectious virus in female genital secretions. Accurate measurements of infectious virus in genital secretions will improve studies that evaluate sexual transmission of HIV-1.The majority of human immunodeficiency virus type 1 (HIV-1) infections worldwide continue to occur through heterosexual transmission (7,27). Factors that influence the amount of HIV-1 in vaginal secretions are important risk determinants for this mode of transmission. It is reported that the amount of HIV-1 RNA in vaginal secretions is correlated with that in plasma (8,13,17,20) and that an increase in plasma viral load in infected persons is associated with an increase in HIV-1 transmission to their sex partners (15,30,35). In addition, localized cervical inflammation and ulceration, without affecting the plasma viral load, can increase HIV-1 shedding in the female genital tract and thus influence HIV-1 transmission (3,22,24,47). Altogether, these studies suggest that increased HIV-1 shedding in mucosal secretions would lead to increased transmission; however, little information is available regarding the presence of infectious virus in cervicovaginal secretions.Several studies have attempted to evaluate infectious HIV-1 in genital secretions by using virus culture methods that are highly successful for propagating virus from an infected person's peripheral blood mononuclear cells (PBMCs). However, use of these methods to culture infectious virus from female genital tract cells has had an overall low success rate (ϳ30%) (18,29,(44)(45)(46). Moreover, recovery of infectious cell-free virus from genital s...

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Human Immunodeficiency Virus Type 1 RNA Shedding in the Female Genital Tract

Cited by 59 publications

References 13 publications

Virologic and Immunologic Determinants of Heterosexual Transmission of Human Immunodeficiency Virus Type 1 in Africa

Virologic and Immunologic Determinants of Heterosexual Transmission of Human Immunodeficiency Virus Type 1 in Africa

Diversity, Divergence, and Evolution of Cell-Free Human Immunodeficiency Virus Type 1 in Vaginal Secretions and Blood of Chronically Infected Women: Associations with Immune Status

Detection of Infectious Human Immunodeficiency Virus Type 1 in Female Genital Secretions by a Short-Term Culture Method

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