Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women

Klatt, Nichole R.; Cheu, Ryan; Birse, Kenzie; Zevin, Alexander S.; Perner, Michelle; Noël‐Romas, Laura; Grobler, Anneke; Westmacott, Garrett; Xie, Irene Y.; Butler, Jennifer; Mansoor, Leila E.; McKinnon, Lyle R.; Passmore, Jo‐Ann S.; Karim, Quarraisha Abdool; Burgener, Adam

doi:10.1126/science.aai9383

Cited by 332 publications

(372 citation statements)

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“…In the trials of 1% TFV gel, approximately 40% of all participants had bacterial vaginosis at enrollment (determined by Nugent score) and researchers have recently speculated that specific bacteria or vaginal microbial diversity may reduce PrEP effectiveness when it is topically, but not orally, administered (13 ■■ ,28 ■ ,29,30). Two analyses have since been conducted using data from topical gel and oral PrEP trials to explore the potential association between vaginal dysbiosis and PrEP efficacy (Table 1).…”

Section: Text Of Reviewmentioning

confidence: 99%

“…A secondary analysis with 688 women from the CAPRISA-004 study used mass spectrometry-based proteomics to classify women as having either Lactobacillus dominant or non- Lactobacillus dominant vaginal microbiota at baseline (13 ■■ ). In women with non- Lactobacillus dominant microbiota at baseline, of which Gardnerella vaginalis was the most common, the 1% TFV gel-based PrEP was not efficacious (efficacy: 18%; 95% CI: −77–63%) (13 ■■ ).…”

Section: Text Of Reviewmentioning

confidence: 99%

“…In women with non- Lactobacillus dominant microbiota at baseline, of which Gardnerella vaginalis was the most common, the 1% TFV gel-based PrEP was not efficacious (efficacy: 18%; 95% CI: −77–63%) (13 ■■ ). This is in contrast to women with Lactobacillus dominant microbiota at baseline, where efficacy was 61% (95% CI: 11–84%).…”

Section: Text Of Reviewmentioning

confidence: 99%

“…dapivirine, tenofovir alafenamide (TAF), and maraviroc rings, biodegradable tenofovir (TFV) films, cabotegravir injections, TAF or maraviroc pills, TFV implants), are at various stages of the research and development process and are promising, longer-acting HIV prevention options (9 ■ ,10 ■ ,11 ■ ,12). 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 ■■ ).…”

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: Text Of Reviewmentioning

confidence: 99%

Section: Text Of Reviewmentioning

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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“…Presenters will discuss new insights regarding how different mucosal microbiomes may affect HIV-STI spread, including the mechanisms of how STI-mediated chronic inflammation potentiates HIV transmission and susceptibility. As new prevention technologies are developed, one recent example of the need to focus on the mucosa was the finding that bacterial vaginosis attenuated the effectiveness of topical tenofovir gel to prevent HIV transmission [22].Presenters at STI 2018 will discuss how the advent of innovative technologies, including self-and point-of-care HIV and STI testing, and new service delivery models (e.g. express clinics using computer interfaces), home sample collection, rapid nucleic amplification testing, and SMS texting to deliver test results in an expedited manner) to more effectively deliver Mayer KH and de Vries H…”

mentioning

confidence: 99%

HIV and sexually transmitted infections: responding to the “newest normal”

Mayer

Vries

2018

J Intern AIDS Soc

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Although the first case reports of AIDS were in men who had sex with men (MSM) [1] and HIV is most commonly spread heterosexually [2], the epidemic has usually been addressed differently than other sexually transmitted infections (STI). Initially, this was because it emerged as a lethal, untreatable, rapidly spreading epidemic. Focused AIDS research, palliative patient care programmes, and community activism evolved to deal with the mounting morbidity, and to speed the development of highly active antiretroviral therapy (HAART). In contrast, "classical" STI care and research were already embedded in well-established settings. Thus, from the beginning, HIV and STI were often addressed through separate programmes.However, subsequent research demonstrated STI and HIV synergism [3]. The co-occurence of STI, particularly genital herpes, was shown to facilitate the spread of HIV [4]. Because of the effects of STI in potentiating HIV acquisition and transmission, several randomized controlled trials were undertaken to determine whether STI treatment and/or prophylaxis could decrease HIV incidence [5][6][7]. Only the Mwanza trial that treated symptomatic STI demonstrated a modest impact of STI treatment in HIV incidence [5]. The other studies did not find that mass treatment and/or syndromic management were sufficient to arrest HIV spread. STI management as a primary HIV prevention strategy was superseded once safe and effective HAART became widely accessible, since it was shown that suppressive treatment significantly decreased HIV transmission [8,9].The proof that HAART could decrease HIV transmission [10,11], and that pre-exposure prophylaxis (PrEP) could decrease HIV acquisition [12], uncoupled epidemiologic synergy between STI and HIV [13]. HIV-infected individuals who adhered to their medication, whose virus was suppressed, would not transmit HIV to partners [14], and PrEP adherence provided substantial protection against HIV acquisition for high risk uninfected people [15]. Although condoms remain highly effective in preventing STI transmission [16], their decreased use in this era of antiretroviral optimism has been associated with bacterial STI increasing globally. At present, there are more than 1 million new curable STI occurring daily globally [17], and although HIV incidence is slowly declining in several settings, there still are close to 2 million new HIV infections annually, and nearly 40 million people living with the virus [18].The "new normal" of HIV and STI spread becoming unlinked offers unique opportunities to control both epidemics [19], particularly in the light of increasing sophistication in understanding mucosal biology, as well as the behavioural and sociological factors potentiating HIV and STI spread [20]. At the 22nd International AIDS Conference in Amsterdam in July 2018, for the first time, there will be a two-day pre-conference focusing exclusively on HIV and STIs: "STI 2018: Understanding and Addressing the HIV and STI Syndemics. " This meeting is designed to review the contemporary ep...

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