Cotrimoxazole Prophylaxis Discontinuation among Antiretroviral-Treated HIV-1-Infected Adults in Kenya: A Randomized Non-inferiority Trial

<div><p>Background</p><p>Cotrimoxazole (CTX) prophylaxis is recommended by the World Health Organization (WHO) for HIV-1-infected individuals in settings with high infectious disease prevalence. The WHO 2006 guidelines were developed prior to the scale-up of antiretroviral therapy (ART). The threshold for CTX discontinuation following ART is undefined in resource-limited settings.</p><p>Methods and Findings</p><p>Between 1 February 2012 and 30 September 2013, we conducted an unblinded non-inferiority randomized controlled trial of CTX prophylaxis cessation versus continuation among HIV-1-infected adults on ART for ≥18 mo with CD4 count > 350 cells/mm³ in a malaria-endemic region in Kenya. Participants were randomized and followed up at 3-mo intervals for 12 mo. The primary endpoint was a composite of morbidity (malaria, pneumonia, and diarrhea) and mortality. Incidence rate ratios (IRRs) were estimated using Poisson regression.</p><p>Among 538 ART-treated adults screened, 500 were enrolled and randomized, 250 per arm. Median age was 40 y, 361 (72%) were women, and 442 (88%) reported insecticide-treated bednet use. Combined morbidity/mortality was significantly higher in the CTX discontinuation arm (IRR = 2.27, 95% CI 1.52–3.38; <i>p <</i> 0.001), driven by malaria morbidity. There were 34 cases of malaria, with 33 in the CTX discontinuation arm (IRR = 33.02, 95% CI 4.52–241.02; <i>p</i> = 0.001). Diarrhea and pneumonia rates did not differ significantly between arms (IRR = 1.36, 95% CI 0.82–2.27, and IRR = 1.43, 95% CI 0.54–3.75, respectively). Study limitations include a lack of placebo and a lower incidence of morbidity events than expected.</p><p>Conclusions</p><p>CTX discontinuation among ART-treated, immune-reconstituted adults in a malaria-endemic region resulted in increased incidence of malaria but not pneumonia or diarrhea. Malaria endemicity may be the most relevant factor to consider in the decision to stop CTX after ART-induced immune reconstitution in regions with high infectious disease prevalence. These data support the 2014 WHO CTX guidelines.</p><p>Trial registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01425073" target="_blank">NCT01425073</a></p></div

Subgroup analyses by enrollment CD4 count: comparing CTX discontinuation to CTX continuation arms.

<p>Subgroup analyses by enrollment CD4 count: comparing CTX discontinuation to CTX continuation arms.</p

Subgroup analyses by ART duration: comparing CTX discontinuation to CTX continuation arms.

<p>Subgroup analyses by ART duration: comparing CTX discontinuation to CTX continuation arms.</p

Characteristics of the study participants at baseline by study arm.

<p>Characteristics of the study participants at baseline by study arm.</p

Association between non-barrier modern contraceptive use and condomless sex among HIV-positive female sex workers in Mombasa, Kenya: A prospective cohort analysis

<div><p>Background</p><p>As access to antiretroviral therapy in sub-Saharan Africa continues to expand, more women with HIV can expect to survive through their reproductive years. Modern contraceptives can help women choose the timing and spacing of childbearing. However, concerns remain that women with HIV who use non-barrier forms of modern contraception may engage in more condomless sex because of their decreased risk of unintended pregnancy. We examined whether non-barrier modern contraceptive use by HIV-positive female sex workers was associated with increased frequency of recent condomless sex, measured by detection of prostate-specific antigen (PSA) in vaginal secretions.</p><p>Methods</p><p>Women who were HIV-positive and reported transactional sex were included in this analysis. Pregnant and post-menopausal follow-up time was excluded, as were visits at which women reported trying to get pregnant. At enrollment and quarterly follow-up visits, a pelvic speculum examination with collection of vaginal secretions was conducted for detection of PSA. In addition, women completed a structured face-to-face interview about their current contraceptive methods and sexual risk behavior at enrollment and monthly follow-up visits. Log-binomial generalized estimating equations regression was used to test for associations between non-barrier modern contraceptive use and detection of PSA in vaginal secretions and self-reported condomless sex. Data from October 2012 through September 2014 were included in this analysis.</p><p>Results</p><p>Overall, 314 women contributed 1,583 quarterly examination visits. There was minimal difference in PSA detection at contraceptive-exposed versus contraceptive-unexposed visits (adjusted relative risk [aRR] 1.28, 95% confidence interval [95% CI] 0.93–1.76). There was a higher rate of self-reported condomless sex at visits where women reported using modern contraceptives, but this difference was not statistically significant after adjustment for potential confounding factors (aRR 1.59, 95% CI 0.98–2.58).</p><p>Conclusion</p><p>Non-barrier methods of modern contraception were not associated with increased risk of objective evidence of condomless sex.</p></div

Trial profile.

<p>Trial profile.</p

Morbidity and mortality and adverse event incidence rates by study arm—intention-to-treat analysis.

<p>Morbidity and mortality and adverse event incidence rates by study arm—intention-to-treat analysis.</p

CD4 count by arm at 0, 6, and 12 mo.

<p>CD4 count by arm at 0, 6, and 12 mo.</p

Timing of last visit in 12 months after ART start.

<p>*Among 2,166 Option B+ clients. **Among 850 Option B+ clients with known pregnancy and HIV testing dates. Rapid ART start = ART start within 7 days of registration in HIV care; No rapid ART start = ART start >7 days after registration in HIV care. ǂp<0.001 for Chi2 test of equality of proportions between Rapid ART start vs. No rapid ART start and between HIV test before vs. after start of pregnancy.</p

Prevalent helminth infections.

<p>Prevalent helminth infections.</p