Meeting NewsPerspective

Oral PrEP protective in women with bacterial vaginosis

Oral pre-exposure prophylaxis, or PrEP, for HIV prevention has a similar efficacy in women with “abnormal” vs. “normal” vaginal microbiota, according to recent findings.

Renee Heffron, PhD, MPH, assistant professor of global health and epidemiology at the University of Washington, and colleagues used data from the Partners PrEP study to evaluate the efficacy of daily oral Truvada (emtricitabine/tenofovir disoproxil fumarate, Gilead Sciences; FTC/TDF) among women with bacterial vaginosis (BV) after recent data suggested that a vaginal gel containing tenofovir (TFV) may not adequately protect this population from HIV infection.

“In that study, women with abnormal vaginal microbiota did not have any protection from the tenofovir gel whereas women with normal microbiota did have protection,” Heffron said during a news conference. “This is important because BV is common, affecting more than 25% — even up to 50% — of African women at risk for HIV.”

BV testing not needed for PrEP

The Partners PrEP study was a placebo-controlled trial of daily oral FTC/TDF conducted in Kenya and Uganda that had high adherence and efficacy rates among women. Heffron and colleagues conducted a substudy of 1,470 participants who were defined by BV status. Nugent scores were used to indicate “normal” and “intermediate” vaginal microbiota and BV.

The median age of the women was 33 years and 24% had BV at enrollment. According to Heffron and colleagues, the efficacy of FTC/TDF in women with “normal” and “intermediate” vaginal microbiota was 77% and 63%, respectively, compared with 73% in women with BV, showing “comparable” protectivity.   They found that PrEP efficacy also was not different among women with detected vs. undetected Gardnerella/Bacteroides (69% vs. 77%) and Lactobacillus (74% vs. 70%).

“PrEP works in women when it is taken, including in those with abnormal vaginal microbiota, and our results provide reassurance that oral PrEP delivery to women does not need to be accompanied by testing for BV,” Heffron said.

Microbiota may impact efficacy of TFV gel

A separate study by Sharon Hillier, PhD, professor of reproductive infectious diseases at the University of Pittsburgh School of Medicine, and colleagues suggests that BV may decrease the efficacy of TFV gel in women. Their findings support data presented at the International AIDS Conference last year showing that women with “healthy” vaginal bacteria benefitted from TFV gel while women with BV did not.

Hillier and colleagues found that women with microbiota associated with BV had lower levels of TDF, while those with Lactobacillus-dominant microbiota, considered beneficial to vaginal health, had significantly higher levels of TFV in plasma and TFV diphosphate in cervical tissue.

Hillier presented the findings at CROI 2017 and discussed what they mean for the treatment of patients.

“It does not have any implication for oral PrEP effectiveness, but I think it does mean that in the future, as we evaluate products for use vaginally, we need to ensure that there isn’t any impact of microbiota on the drugs for delivery,” Hillier said. by Gerard Gallagher

References:

Abdool Karim SS, et al. Session: New evidence: Why do women in Africa have higher rates of HIV infection? Presented at: The 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa.

Heffron R, et al. Abstract 85. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 13-16, 2017; Seattle.

Hillier SL, et al. Abstract 86LB. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 13-16, 2017; Seattle.

Disclosures: Heffron reports no relevant financial disclosures. Hillier reports being a consultant for Cepheid, Merck and Symbiomix.

Oral pre-exposure prophylaxis, or PrEP, for HIV prevention has a similar efficacy in women with “abnormal” vs. “normal” vaginal microbiota, according to recent findings.

Renee Heffron, PhD, MPH, assistant professor of global health and epidemiology at the University of Washington, and colleagues used data from the Partners PrEP study to evaluate the efficacy of daily oral Truvada (emtricitabine/tenofovir disoproxil fumarate, Gilead Sciences; FTC/TDF) among women with bacterial vaginosis (BV) after recent data suggested that a vaginal gel containing tenofovir (TFV) may not adequately protect this population from HIV infection.

“In that study, women with abnormal vaginal microbiota did not have any protection from the tenofovir gel whereas women with normal microbiota did have protection,” Heffron said during a news conference. “This is important because BV is common, affecting more than 25% — even up to 50% — of African women at risk for HIV.”

BV testing not needed for PrEP

The Partners PrEP study was a placebo-controlled trial of daily oral FTC/TDF conducted in Kenya and Uganda that had high adherence and efficacy rates among women. Heffron and colleagues conducted a substudy of 1,470 participants who were defined by BV status. Nugent scores were used to indicate “normal” and “intermediate” vaginal microbiota and BV.

The median age of the women was 33 years and 24% had BV at enrollment. According to Heffron and colleagues, the efficacy of FTC/TDF in women with “normal” and “intermediate” vaginal microbiota was 77% and 63%, respectively, compared with 73% in women with BV, showing “comparable” protectivity.   They found that PrEP efficacy also was not different among women with detected vs. undetected Gardnerella/Bacteroides (69% vs. 77%) and Lactobacillus (74% vs. 70%).

“PrEP works in women when it is taken, including in those with abnormal vaginal microbiota, and our results provide reassurance that oral PrEP delivery to women does not need to be accompanied by testing for BV,” Heffron said.

Microbiota may impact efficacy of TFV gel

A separate study by Sharon Hillier, PhD, professor of reproductive infectious diseases at the University of Pittsburgh School of Medicine, and colleagues suggests that BV may decrease the efficacy of TFV gel in women. Their findings support data presented at the International AIDS Conference last year showing that women with “healthy” vaginal bacteria benefitted from TFV gel while women with BV did not.

Hillier and colleagues found that women with microbiota associated with BV had lower levels of TDF, while those with Lactobacillus-dominant microbiota, considered beneficial to vaginal health, had significantly higher levels of TFV in plasma and TFV diphosphate in cervical tissue.

Hillier presented the findings at CROI 2017 and discussed what they mean for the treatment of patients.

“It does not have any implication for oral PrEP effectiveness, but I think it does mean that in the future, as we evaluate products for use vaginally, we need to ensure that there isn’t any impact of microbiota on the drugs for delivery,” Hillier said. by Gerard Gallagher

References:

Abdool Karim SS, et al. Session: New evidence: Why do women in Africa have higher rates of HIV infection? Presented at: The 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa.

Heffron R, et al. Abstract 85. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 13-16, 2017; Seattle.

Hillier SL, et al. Abstract 86LB. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 13-16, 2017; Seattle.

Disclosures: Heffron reports no relevant financial disclosures. Hillier reports being a consultant for Cepheid, Merck and Symbiomix.

    Perspective
    Jeanne Marrazzo

    Jeanne Marrazzo

    It is really good to have some focus on the complex vaginal environment. When you have billions of bacteria there, I think it is naive to think they are not having some immune-modifying effect or that they might interact with drugs. It is a welcome opportunity to look at some other reasons why topical PrEP might not have worked in young women. I do not think it is the whole story. I think that adherence is probably still the major player, but I do not think we can discount some of these other modifiers, which might turn out to be important, certainly for some groups of women.

    • Jeanne Marrazzo, MD, MPH
    • Director, division of infectious diseases University of Alabama at Birmingham School of Medicine

    Disclosures: Marrazzo reports being a consultant for Cepheid and the primary investigator in an NIH trial on an investigational treatment for bacterial vaginosis.

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