Explore the vast range of titles available.

Background: Although PrEP discontinuation rates in clinical trials and demonstration projects have been well characterized, little is known about it in routine public health settings. Understanding discontinuation decisions in non-study settings is important for calibrating expectations of PrEP persistence in national programs and strengthening public health approaches to HIV prevention. Methods: In-depth interviews were conducted with 47 individuals who initiated PrEP at 25 different HIV comprehensive care centers (CCCs) in Central and Western Kenya, whose clinic record indicated had not returned for scheduled refills. We explored decisions around initiation, discontinuation, and restarting PrEP. An inductive, thematic, content-analytic approach was used to analyze the data. Results: Clients initiated PrEP because they had one or more sexual partners who were either HIV positive or of unknown status. Many discontinued PrEP when their perceived risk decreased (i.e. because those relationships ended, because they were living apart from a primary partner, or when a known HIV positive partner became virally suppressed). These participants expressed willingness to re-start PrEP if their partnership situation changed. Others reported discontinuation due to side effects (dizziness, nausea, weight gain) or found daily pill-taking too burdensome, and preferred condoms for prevention purposes. Some participants (mostly women) discontinued PrEP due to their partner's insistence and wished for additional PrEP education and counselling to foster partner support. Though relatively few participants identified facility level factors as primary reasons for discontinuing PrEP, many described stigma-related discomfort with accessing PrEP at CCCs, inconvenient clinic location and/or operating hours, long wait times, and short refill dates as barriers. Most individuals reported multiple reasons for deciding to discontinue PrEP and did not inform health facilities of their decision to stop. Conclusions: Clients make intentional decisions to discontinue PrEP as they weigh different prevention options and navigate fluid and sometimes challenging relationships. Many clients will decide to discontinue PrEP when perceiving themselves to be at reduced risk and PrEP counseling approaches must include provisions for addressing 'seasonal risk.' PrEP will not be the right prevention method for everyone. However, expanding PrEP access points and increasing sex-positive messaging may facilitate PrEP being a better option for many.

Background. Antiretroviral (ARV) prophylaxis effectively reduces mother-to-child transmission of human immunodeficiency virus type 1 (HIV). However, it is unclear whether stopping ARVs after breastfeeding cessation affects maternal HIV disease progression. We assessed 18-24-month postpartum disease progression risk among women in a randomized trial assessing efficacy and safety of prophylactic maternal ARVs. Methods. From 2005 to 2008, HIV—infected pregnant women with CD4 + counts of 200-500/mm 3 were randomized to receive either triple ARV (zidovudine, lamivudine, and lopinavir/ritonavir during pregnancy and breastfeeding) or AZT/sdNVP (zidovudine until delivery with single-dose nevirapine without postpartum prophylaxis). Maternal disease progression was defined as the combined endpoint of death, World Health Organization clinical stage 4 disease, or CD4 + counts of <200/mm 3 . Results. Among 824 randomized women, 789 had at least 1 study visit after cessation of ARV prophylaxis. Following delivery, progression risk up to 24 months postpartum in the triple ARV arm was significantly lower than in the AZT/sdNVP arm (15.7% vs 28.3%; P = .001), but the risks of progression after cessation of ARV prophylaxis (rather than after delivery) were not different (15.0% vs 13.8% 18 months after ARV cessation). Among women with CD4 + counts of 200-349/mm 3 at enrollment, 24.0% (95% confidence interval [CI], 15.7-35.5) progressed with triple ARV, and 23.0% (95% CI, 17.8-29.5) progressed with AZT/sdNVP, whereas few women in either arm (<5%) with initial CD4 + counts of ≥350/mm 3 progressed. Conclusions. Interrupting prolonged triple ARV prophylaxis had no effect on HIV progression following cessation (compared with AZT/sdNVP). However, women on triple ARV prophylaxis had lower progression risk during the time on triple ARV. Given the high rate of progression among women with CD4 + cells of <350/mm 3 , ARVs should not be discontinued in this group. Clinical Trials Registration. ISRCTN71468410.

Background For successful implementation of PrEP as a HIV prevention strategy, participant’s adherence to the intervention is vital. Frequent interruption of study product, impacts its effectiveness negatively. We documented the frequency and causes of study drug interruptions among participants enrolled in the Partners PrEP Study, Thika-Kenya Methods Between October 2008 and November 2010, we enrolled 496 HIV serodiscordant couples who were followed up to 36 months. We categorised time off study drug into two; protocol-defined, in which the parameters of withholding study drug was clearly outlined in the study protocol and participant-initiated interruption where the participant opted to stop taking study drug. Data on study drug interruptions were captured on monthly basis and documented on specific case report forms in pharmacy. Results We reported 152 cases of study drug interruptions, these were contributed by 128 participants. Sixty four per cent of HIV-1 uninfected participants who recorded study drug interruption were male, median age for both gender was 31.8 (IQR 26.5, 37.4) years. Sixty five (43%) of reported drug interruptions were participant initiated, cited due to marital disharmony 34 (22%), fatigue and loss of interest 24 (16%), perceived side effects in 7 (5%). The median time off study product was 90 (IQR 28, 268) days. Age, gender and education were not associated with participant-initiated interruptions. Pregnancy and possible seroconversion were some of protocol defined reasons to stop study drug. Conclusions Marital disharmony and loss of interest were two of the most common reasons for participant initiated interruption of study drug. Going forward, psychosocial support and continuous adherence counselling should be part of the package for successful implementation of PrEP for HIV prevention.

Background Women in biomedical HIV prevention clinical trials are frequently counselled to use effective contraceptive methods in order to avoid pregnancy during the study and consequent withholding of study products. Moreover, research study participants often have access to medical care at research clinics that might not otherwise be as readily available in their communities. We evaluated change in contraceptive use among women after exiting from a biomedical HIV prevention clinical trial in Kenya. Methods The Partners in Prevention HSV/HIV Transmission Study enrolled HIV serodiscordant couples at 14 sites in East Africa and Southern Africa, including a site in Thika, Kenya. Participants were offered contraception free-of-charge at the research site during the clinical trial. Unblinding visits, at which the results of the trial were conveyed to participants, were conducted after the trial results were reported. Contraceptive use data were collected at the trial exit visit and at the later study unblinding visit. Results Among 213 women from Thika in the trial, 114 returned for the unblinding visit, of whom 80 (70.2%) were HIV positive. The median time between exit and the unblinding visit was 1.11 years (ranging from 0.84—to 2.13 years). Non-barrier contraceptive prevalence (ie, use of oral, injectable, implantable contraceptives, intrauterine devices [IUD] or surgical) dropped from 62.3% to 47.4% (p=0.01) between exit and unblinding visits: from 70.0% to 53.8%, (p=0.03) among HIV positive women and from 44.1% to 32.4%, (p=0.31) among HIV negative women. However, the prevalence of IUD use among the HIV positive women increased from 3.8% to 20%, (p=0.002) during this period. Additionally, the proportion of women who were using condoms as their sole contraceptive method decreased, from 29% at study exit to 1.8% at the unblinding visit (p<0.0001), resulting in greater numbers of women who were not using any contraceptive method. Conclusions There was a high rate of contraceptive discontinuation, both hormonal and barrier methods, after women exited from a biomedical HIV prevention trial. Discontinuation of contraception may reflect participant fertility desires after trial procedures are completed, or may reflect loss of clinical and counselling services available during the study. Innovative strategies to support the contraceptive needs of women after exiting HIV prevention trials are urgently needed.

The vaginal microbiome plays a critical role in maintaining immune and epithelial homeostasis in the female reproductive tract. Bacterial Vaginosis (BV) is deleterious to female health, causing the loss of beneficial species, overgrowth of anaerobic taxa, changes in vaginal pH, breakdown of protective mucins and epithelial barriers, and activation of the immune system. Treatment with gel-based antibiotics (Metronidazole or Clindamycin) resolves BV for 85% of patients, but 50% of those cases recur, indicating a need to identify strategies for overcoming antibiotic resistance and achieving a more durable response. Here, we developed a systems biology approach termed to characterize the antibiotic potential of vaginal microbes, their metabolites and functions, via computational fusion of human cohort multi-omics and post-drug perturbation transcriptomic profiles. We focused on Clindamycin and Metronidazole as candidate drugs and screened 780 vaginal microbiome-drug mimicry candidates to identify candidate taxa and metabolites with antibiotic potential. We demonstrate experimentally that -derived Hydroxyisocaproate (HICA) selectively kills and that HICA enhances epithelial barrier integrity in a human vagina-on-a-chip system. Our work demonstrates the first use of , for discovering novel, selective antibiotic metabolites for BV with implications for charting the full pharmacologic potential of the vaginal microbiome.

The vaginal microbiome's role in risk, progression, and treatment of female cancers has been widely explored. Yet, there remains a need to develop methods to understand the interaction of microbiome factors with host cells and to characterize their potential therapeutic functions. To address this challenge, we developed a systems biology framework we term the Pharmacobiome for microbiome pharmacology analysis. The Pharmacobiome framework evaluates similarities between microbes and microbial byproducts and known drugs based on their impact on host transcriptomic cellular signatures. Here, we apply our framework to characterization of the Anti-Gynecologic Cancer Vaginal Pharmacobiome. Using published vaginal microbiome multi-omics data from the Partners PrEP clinical trial, we constructed vaginal epithelial gene signatures associated with each profiled vaginal microbe and metabolite. We compared these microbiome-associated host gene signatures to post-drug perturbation host gene signatures associated with 35 FDA-approved anti-cancer drugs from the Library of Integrated Network-based Cellular Signatures database to identify vaginal microbes and metabolites with high statistical and functional similarity to these drugs. We found that and their metabolites can regulate host gene expression in ways similar to many anti-cancer drugs. Additionally, we experimentally tested our model prediction that taurine, a metabolite produced by kills cancerous breast and endometrial cancer cells. Our study shows that the Pharmacobiome is a powerful framework for characterizing the anti-cancer therapeutic potential of vaginal microbiome factors with generalizability to other cancers, microbiomes, and diseases.

Background The introduction of pre-exposure prophylaxis (PrEP) for human immunodeficiency virus-1 (HIV-1) prevention in Africa presents new challenges for health systems that are already overburdened because PrEP delivery requires frequent clinic visits (generally every 3 months) for HIV-1 testing and PrEP refills. HIV-1 self-testing (HIVST) has the potential to improve the efficiency of PrEP delivery by decreasing the number of clinic visits. Here, we describe the rationale and design of a randomized, noninferiority trial designed to test the effectiveness and safety of using HIVST to support PrEP delivery in Kenya. Methods The JiPime-JiPrEP (Kiswahili for ‘Test Yourself, PrEP Yourself’) study is a three-arm randomized trial taking place in Thika, Kenya. Participants ( n  = 495) are eligible for enrollment if they are at least 18 years old, HIV-1 seronegative, and have been taking PrEP for 1 month. Three distinct participant types will be enrolled: men ( n  = 165) and women ( n  = 165) who are in mutually disclosed HIV-1 serodiscordant relationships, and women ( n  = 165) who are at HIV-1 risk and not in a known serodiscordant relationship. Participants in each of these subpopulations will be 1:1:1 randomized to: 1) the standard of care, with quarterly clinic visits; 2) oral HIVST, with biannual clinic visits plus oral HIVSTs to use at the quarters between those visits; or 3) blood-based HIVST, with biannual clinic visits plus blood-based HIVSTs. All participants will complete quantitative surveys and provide blood samples for the objective measurement of PrEP adherence at baseline, 6 months, and 12 months. The primary outcomes are PrEP adherence, PrEP continuation, and HIV-1 testing, measured at 6 months and secondarily at 12 months. Discussion The findings from this trial can help to understand how HIVST—a new HIV-1 testing technology—can support health systems in sub-Saharan Africa. Additionally, the findings can inform policy aimed at improving the efficiency of PrEP implementation and scale-up in Kenya. Trial registration ClinicalTrials.gov, NCT03593629 . Retrospectively registered on 20 July 2018.

Data are sparse on the epidemiological picture of Taenia saginata taeniasis in Kenya. Infections are underreported, and their persistence nonetheless negatively impacts the beef industry. Populations vulnerable to taeniasis in the developing world are commonly burdened with other intestinal parasites, ubiquitous in unsanitary environments. This study aimed to estimate the occurrence of human taeniasis in Narok County, Kenya, and screen for the presence of other intestinal parasitic infections. A community‐based survey was conducted in five pastoral wards, and stool samples, mainly from adults, subjected to multiple diagnostic tests. One sample tested positive for Taenia spp. by coproantigen enzyme‐linked immunosorbent assay (0.3%, 95% CI, 0–1.6, n = 360), and all samples tested negative on multiplex copro‐polymerase chain reaction targeting the cytochrome c oxidase subunit 1 gene and copromicroscopy. Microscopy ( n = 361) additionally identified Entamoeba histolytica / dispar / moshkovskii at a prevalence of 15.5% (95% CI, 12.1–19.6), Giardia spp. at 5.3% (95% CI, 3.4–8.1), Hymenolepis spp. at 1.1% (95% CI, 0.4–2.8), and hookworm at 0.3% (95% CI, 0–1.6). Grazing livestock near the homestead (< 2 km) and a formal education background were associated with a reduced likelihood of Giardia spp. infection (AOR 0.07, 95% CI 0–0.36, p = 0.011, and AOR 0.06, 95% CI 0.01–0.50, p = 0.014, respectively). Our findings suggest a very low prevalence of human taeniasis in the population. The occurrence of other pathogenic zoonotic intestinal parasites highlights a public health concern and calls for a One Health approach in the enhancement of hygiene initiatives.

Most human immunodeficiency virus (HIV) infections occur in cisgender women in resource-limited settings. In women, self-protection with emtricitabine/tenofovir disoproxil fumarate pre-exposure prophylaxis (FTC/TDF-PrEP) constitutes a major pillar of HIV prevention. However, clinical trials in women had inconsistent outcomes, sparking uncertainty about adherence requirements and reluctance in evaluating on-demand regimens. We analyzed data from published FTC/TDF-PrEP trials to establish efficacy ranges in cisgender women. In a ‘bottom-up’ approach, we modeled hypotheses in the context of risk-group-specific, adherence–efficacy profiles and challenged those hypotheses with clinical data. We found that different clinical outcomes were related to the proportion of women taking the product, allowing coherent interpretation of the data. Our analysis showed that 90% protection was achieved when women took some product. We found that hypotheses of putative male/female differences were either not impactful or statistically inconsistent with clinical data. We propose that differing clinical outcomes could arise from pill-taking behavior rather than biological factors driving specific adherence requirements in cisgender women. Modeling shows that antiretroviral treatment as pre-exposure prophylaxis (PrEP) can be highly effective in cisgender women at preventing HIV-1 acquisition, but underscores the need to understand the barriers that limit PrEP adherence in women.