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Periodic Presumptive Treatment for Women With Prevalent Vaginal Infections: Secondary Analysis of Data From a Randomized Controlled Trial

Mochache, Vernon MBChB, MPH; McClelland, Raymond Scott MD, MPH; Balkus, Jennifer E. PhD, MPH

Sexually Transmitted Diseases: July 2014 - Volume 41 - Issue 7 - p 453
doi: 10.1097/OLQ.0000000000000152
Letter to the Editor

Department of Epidemiology, University of Washington, Seattle, WA

Departments of Epidemiology, Global Health, and Medicine, University of Washington, Seattle, WA

Institute of Tropical and Infectious Diseases, University of Nairobi, Nairobi, Kenya

Vaccine and Infectious Disease Division, Fred Hutchison Cancer Research Center, Seattle, WA

Department of Global Health, University of Washington, Seattle, WA

Conflicts of interest and sources of funding: Dr R. Scott McClelland has been a consultant and received donated study product from Embil Pharmaceuticals. He has also received research funding from Hologic/GenProbe. He received support for the original trial from the National Institutes of Health Research Grant K23-AI52480. Dr Vernon Mochache was a scholar in the University of Washington, International AIDS Research and Training Program supported by the Fogarty International Center, National Institutes of Health Research Grant D43 TW000007. Infrastructure and logistical support for the Mombasa Field Site was received from the University of Washington and Fred Hutchinson Cancer Research Center’s Center for AIDS Research (Grant No. P30-AI27757).

Dr. Vernon Mochache’s current affiliation: International Centre for Reproductive Health; Mombasa, Kenya.

To the Editor:

Bacterial vaginosis (BV), vulvovaginal candidiasis (VVC) and Trichomonas vaginalis (TV) are common vaginal infections associated with adverse reproductive health outcomes, including sexually transmitted infections.1–6 Their treatment is hindered by frequent recurrences and reinfection. Periodic presumptive treatment (PPT) has been evaluated as an alternative approach that involves providing antimicrobials to asymptomatic women to treat and potentially prevent these infections.7,8

We previously conducted a randomized trial to assess the effect of monthly oral PPT (2 g metronidazole plus 150 mg fluconazole) versus placebo administered for 12 months on the incidence of BV, VVC, and TV among Kenyan female sex workers.7 The intervention reduced the incidence of BV by Nugent’s score (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.49–0.63). Because women with prevalent vaginal infections are likely to experience recurrences/reinfection,8,9 we sought to test the hypothesis that the PPT effect would be greater among participants with a prevalent infection at enrollment. We used Andersen-Gill proportional hazards models to assess the intervention’s effect on BV incidence stratified by baseline infection status. Each visit with BV was considered a “new” event. We evaluated effect modification by baseline infection status using an interaction term and likelihood ratio test.

Among 310 women enrolled, 302 returned for at least 1 follow-up visit and 137 (45%) had 1 or more vaginal infections at enrollment: 105 (77%) BV, 32 (23%) VVC, and 6 (4%) TV. There were 62 (41%) of 151 participants with a baseline infection in the intervention arm versus 75 (50%) of 151 in the placebo arm. Bacterial vaginosis incidence among participants with a baseline infection was 294/100 person-years (py) in the intervention arm versus 522/100 py in the placebo arm (HR, 0.55; 95% CI, 0.41–0.76). Among those without a baseline infection, BV incidence was 141/100 py in the intervention arm versus 202/100 py in the placebo arm (HR, 0.71; 95% CI, 0.47–1.09). There was no evidence of effect modification by baseline infection status (likelihood ratio test: P = 0.11).

The reduction in BV episodes with the intervention versus placebo was greater among participants with a baseline infection (228/100 py) compared with those without (61/100 py). For participants without a baseline infection, the number needed to treat was 16.7 compared with 4.4 among those with a baseline infection. This approximately 4-fold difference in the number needed to treat suggests that although the intervention was similarly effective in both subgroups, more BV episodes could be averted if PPT were targeted toward women with a prevalent infection. Findings were similar when stratified by baseline BV status.

Data for this secondary analysis were collected as part of a randomized trial that had high retention and regularly measured biological outcomes, enabling a more precise assessment of the vaginal environment. Generalizability of our findings may be limited by behavioral characteristics unique to female sex workers, including differences in sexual activity, condom use, and intravaginal practices. Our findings suggest that targeting PPT to women with prevalent vaginal infections is the most efficient approach to reducing BV incidence. These results will be useful in designing future trials to improve vaginal health.

Vernon Mochache, MBChB, MPH

Department of Epidemiology

University of Washington

Seattle, WA

Raymond Scott McClelland, MD, MPH

Departments of Epidemiology

Global Health, and Medicine

University of Washington

Seattle, WA

Institute of Tropical and Infectious Diseases

University of Nairobi

Nairobi, Kenya

Jennifer E. Balkus, PhD, MPH

Vaccine and Infectious Disease Division

Fred Hutchison Cancer Research Center

Seattle, WA

Department of Global Health

University of Washington

Seattle, WA

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