Lactobacillus-Deficient Cervicovaginal Bacterial Communities Are Associated with Increased HIV Acquisition in Young South African Women

Gosmann, Christina; Anahtar, Melis N.; Handley, Scott A.; Fărcăşanu, M; Abu-Ali, Galeb; Bowman, Brittany A.; Padavattan, Nikita; Desai, Chandni; Droit, Lindsay; Moodley, Amber; Dong, Mary; Chen, Yuezhou; Ismail, Nasreen; Ndung’u, Thumbi; Ghebremichael, Musie; Wesemann, Duane R.; Mitchell, Caroline; Dong, Krista; Huttenhower, Curtis; Walker, Bruce D.; Virgin, Herbert W.; Kwon, Douglas S.

doi:10.1016/j.immuni.2016.12.013

Cited by 513 publications

(801 citation statements)

References 33 publications

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“…Studies of the TFV film will need to assess whether the film delivery mechanism is capable of altering innate HIV immunity through changes to the mucin expression and the quantity of high mannose glycoproteins in the vaginal environment, as has also been suggested for the 1% TFV gel (41). Additionally, the TFV gel was shown to alter local microbial communities in the vagina, making women using these products more susceptible to bacterial dysbiosis and HIV acquisition through inflammatory pathways, and it will be important to explore similar associations for other topically applied HIV prevention products (15,18 ■ ,42). …”

Section: Text Of Reviewmentioning

confidence: 99%

“…However, it has recently been hypothesized that the efficacy of topically-applied PrEP products may be moderated by vaginosis dysbiosis, a general term indicating that vaginal microbiota are sub-optimal (13 ■■ ). This is a significant public health concern given that bacterial vaginosis (a condition diagnosed using microscopy and/or clinical criteria) is common in settings where HIV is highly prevalent and has been shown to significantly influence risk of HIV acquisition through inflammatory pathways (14,15,16 ■ ,17,18 ■ ,19 ■■ ). Specifically, vaginal dysbiosis can result in higher vaginal pH (due to lower concentrations of Lactobacillus species) and increased activated CCR5+ CD4+ T-cells in vaginal mucosa and pro-inflammatory cytokines in cervical secretions (15,16 ■ ,18 ■ ,19 ■■ ,20,21 ■ ).…”

Section: Introductionmentioning

confidence: 99%

“…Specific bacteria (e.g. Gardnerella vaginalis, Prevotella, Atopobium ), and/or microbial diversity may play a significant role in increased HIV risk, with four-fold increases in HIV risk observed among women with non- Lactobacillus dominant genital bacterial communities compared with those with less diverse microbiota (18 ■ ,21 ■ ). These women need PrEP products that will work effectively in an environment of vaginal dysbiosis (18 ■ ,21 ■ ).…”

Section: Introductionmentioning

confidence: 99%

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The Vaginal Microbiome and its Potential to Impact Efficacy of HIV Pre-exposure Prophylaxis for Women

Velloza

Heffron

2017

Curr HIV/AIDS Rep

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Purpose of review This review describes existing evidence addressing the potential modulation of PrEP products, specifically 1% tenofovir (TFV) gel and oral tenofovir-based PrEP, by vaginal dysbiosis and discusses future considerations for delivering novel, long-acting PrEP products to women at high-risk for vaginal dysbiosis and HIV. Recent findings We describe results from analyses investigating the modification of PrEP efficacy by vaginal dysbiosis and studies of biological mechanisms that could render PrEP ineffective in the presence of specific microbiota. A secondary analysis from the CAPRISA-004 cohort demonstrated that there is no effect of the 1% TFV gel in the presence of non-Lactobacillus dominant microbiota. Another recent analysis comparing oral tenofovir-based PrEP efficacy among women with and without bacterial vaginosis in the Partners PrEP Study found that oral PrEP efficacy is not modified by bacterial vaginosis. Gardnerella vaginalis, commonly present in women with vaginal dysbiosis, can rapidly metabolize TFV particularly when it is locally applied and thereby prevent TFV integration into cells. Given that vaginal dysbiosis appears to modulate efficacy for 1% TFV gel but not for oral tenofovir-based PrEP, vaginal dysbiosis is potentially less consequential to HIV protection from TFV in the context of systemic drug delivery and high product adherence. Summary Vaginal dysbiosis may undermine the efficacy of 1% TFV gel to protect women from HIV but not the efficacy of oral PrEP. Ongoing development of novel ring, injectable, and film-based PrEP products should investigate whether vaginal dysbiosis can reduce efficacy of these products, even in the presence of high adherence.

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Section: Text Of Reviewmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Vaginal Microbiome and its Potential to Impact Efficacy of HIV Pre-exposure Prophylaxis for Women

Velloza

Heffron

2017

Curr HIV/AIDS Rep

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“…Both P. amnii and P. bivia have been associated with genital inflammation (Anahtar et al 2015;Gosmann et al 2017;Lennard et al 2017) and BV, yet in this study P. bivia levels did not differ by BV status or inflammation (Lennard et al 2017). Fettweis et al (2014) previously reported that P. amnii is more prevalent in African American women, compared to women of European ancestry, which may explain the high rates of P. amnii colonisation seen here.…”

Section: Bvmentioning

confidence: 51%

High rates of bacterial vaginosis and Chlamydia in a low-income, high-population-density community in Cape Town

Lennard

Dabee

Barnabas

et al. 2017

Suid-Afrikaanse Tydskr Natuurwetenskap Tegnol

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Young South African women, from resource-poor communities, face several sexual and reproductive health challenges. Here we describe the vaginal microbiota and sexually transmitted infection (STI) prevalence of 102; 16-22-year-old, HIV-negative South African women from a low-income, highpopulation-density community in Cape Town (CPT). Vaginal microbiota were profiled using 16S rRNA amplicon sequencing; bacterial vaginosis (BV) status was established using Nugent scoring and STIs were determined by multiplex polymerase chain reaction. STIs were common, with 55% of women having at least one STI; 41% were infected with high-risk human papilloma virus (HPV) and a further 28% with low-risk HPV; 44% were infected with Chlamydia, 16% of whom had at least one additional STI. Similarly, BV rates were very high, with 55% of women classified as BV-positive (Nugent score ≥7), 7% as BV-intermediate (Nugent score 3-6) and 38% as BV-negative (Nugent 0-2). Group B Streptococcus (Streptococcus agalactiae), the leading cause of neonatal sepsis, was present in 25% of BV-positive women and 28% of BV-negative women, and was significantly more abundant among BV-negative women. Both Chlamydia infection and BV may adversely affect reproductive health and place these women at additional risk for HIV acquisition. The high abundance of Prevotella amnii, in particular, may increase HIV risk, given its inflammatory capacity. Laboratorybased testing for STIs (Chlamydia and Gonorrhoeae in particular) appear to be warranted in this community, together with further monitoring or treatment of BV. Hoë voorkomskoers van bakteriële vaginose en Chlamydia in 'n lae-inkomste, hoë-bevolkingsdigtheid gemeenskap in Kaapstad. Jong Suid-Afrikaanse vroue uit hulpbron-arm gemeenskappe staar verskeie uitdagings in die gesig in terme van hul seksuele en reproduktiewe gesondheid. Hier beskryf ons die voorkoms van vaginale mikrobiota en seksueel oordraagbare infeksies (SOI's) onder 102; 16-22-jarige MIV-negatiewe Suid-Afrikaanse vroue uit 'n lae-inkomste, hoë-bevolkingsdigtheid gemeenskap in Kaapstad. Vaginale mikrobiota is met behulp van 16S rRNA amplikon volgorde-bepaling geprofileer; bakteriese vaginose (BV) status is met behulp van 'n Nugent-telling vasgestel; en SOI's is deur middel van 'n multipleks polimerase kettingreaksie bepaal. SOI's was algemeen, met 55% van die vroue wat ten minste een SOI gehad het; 41% wat met hoë-risiko menslike papillomavirus (MPV) besmet was, en 'n verdere 28% wat met laerisiko-MPV besmet was; 44% van die vroue was met Chlamydia besmet, waarvan 16% een of meer addisionele SOI gehad het. BV persentasies was ook baie hoog, met 55% van die vroue wat as BV-positief (Nugent-telling ≥7) geklassifiseer is, 7% as BV-intermediêr (Nugent-telling 3-6), en 38% as BVnegatief (Nugent-telling 0-2). Streptococcus (Streptococcus agalactiae), die grootste oorsaak van neonatale sepsis, was teenwoordig in 25% van die BV-positiewe vroue en 28% van die BV-negatiewe vroue, en was dus meer onder BV-negatiewe vroue. Beide Chlamydia-infeksie en BV kan re...

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“…P. amnii sowel as P. bivia is met genitale inflammasie (Anahtar et al 2015;Gosmann et al 2017;Lennard et al 2017) en BV geassosieer. In hierdie studie het P. bivia-vlakke egter nie volgens BV-status of inflammasie verskil nie.…”

Section: Soi-voorkomssyfers (55%)unclassified

Hoë voorkomskoers van bakteriële vaginose en Chlamydia in ’n lae-inkomste, hoë-bevolkingsdigtheid gemeenskap in Kaapstad

Lennard

Dabee

Barnabas

et al. 2017

Suid-Afrikaanse Tydskr Natuurwetenskap Tegnol

View full text Add to dashboard Cite

Jong Suid-Afrikaanse vroue uit hulpbron-arm gemeenskappe staar verskeie uitdagings in die gesig in terme van hulle seksuele en reproduktiewe gesondheid. Hier beskryf ons die voorkoms van vaginale mikrobiota en seksueel oordraagbare infeksies (SOI's) onder 102; 16-22-jarige MIVnegatiewe Suid-Afrikaanse vroue uit 'n lae-inkomste, hoë-bevolkingsdigtheid gemeenskap in Kaapstad. Vaginale mikrobiota is met behulp van 16S rRNA amplikon volgorde-bepaling geprofileer; bakteriese vaginose (BV) status is met behulp van 'n Nugent-telling vasgestel; en SOI's is deur middel van 'n multipleks polimerase kettingreaksie bepaal. SOI's was algemeen, met 55% van die vroue wat ten minste een SOI gehad het; 41% wat met hoë-risiko menslike papillomavirus (MPV) besmet was, en 'n verdere 28% wat met laerisiko-MPV besmet was; 44% van die vroue was met Chlamydia besmet waarvan 16% een of meer addisionele SOI gehad het. BV persentasies was ook baie hoog met 55% van die vroue wat as BV-positief (Nugent-telling ≥7) geklassifiseer is, 7% as BVintermediêr (Nugent-telling 3-6), en 38% as BV-negatief (Nugent-telling 0-2). Streptococcus (Streptococcus agalactiae), die grootste oorsaak van neonatale sepsis, was teenwoordig in 25% van die BV-positiewe vroue en 28% van die BV-negatiewe vroue, en was dus meer onder BV-negatiewe vroue. Chlamydia-infeksie sowel as BV kan reproduktiewe gesondheid nadelig beïnvloed en verhoog hierdie vroue se risiko vir die verkryging van MIV. Die voorkoms van veral Prevotella amnii kan die MIV-risiko verhoog as gevolg van sy inflammatoriese kapasiteit. Laboratoriumgebaseerde toetsing vir SOI's (veral Chlamydia en Gonorrhoeae) blyk in hierdie gemeenskap geregverdig te wees, tesame met verdere monitering en/of behandeling van BV. High rates of bacterial vaginosis and Chlamydia in a low-income, high-population-density community in Cape Town. Young South African women, from resource-poor communities, face several sexual and reproductive health challenges. Here we describe the vaginal microbiota and sexually transmitted infection (STI) prevalence of 102; 16-22-year-old, HIV-negative South African women from a low-income, high-population-density community in Cape Town (CPT). Vaginal microbiota were profiled using 16S rRNA amplicon sequencing; bacterial vaginosis (BV) status was established using Nugent scoring; and STIs were determined by multiplex polymerase chain reaction. STIs were common, with 55% of women having at least one STI; 41% were infected with high-risk human papilloma virus (HPV) and a further 28% with low-risk HPV; 44% were infected with Chlamydia, 16% of whom had at least one additional STI. Similarly, BV rates were very high, with 55% of women classified as BV-positive (Nugent score ≥7); 7% as BV-intermediate (Nugent score 3-6) and 38% as BV-negative (Nugent 0-2). Group B Streptococcus (Streptococcus agalactiae), the leading cause of neonatal sepsis, was present in 25% of BV-positive women and 28% of BV-negative women, and was significantly more abundant among BV-negative women. Both Chlamydia infection and ...

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Lactobacillus-Deficient Cervicovaginal Bacterial Communities Are Associated with Increased HIV Acquisition in Young South African Women

Cited by 513 publications

References 33 publications

The Vaginal Microbiome and its Potential to Impact Efficacy of HIV Pre-exposure Prophylaxis for Women

The Vaginal Microbiome and its Potential to Impact Efficacy of HIV Pre-exposure Prophylaxis for Women

High rates of bacterial vaginosis and Chlamydia in a low-income, high-population-density community in Cape Town

Hoë voorkomskoers van bakteriële vaginose en Chlamydia in ’n lae-inkomste, hoë-bevolkingsdigtheid gemeenskap in Kaapstad

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