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AbstractIntroductionQuestions remain whether HIV pre‐exposure prophylaxis (PrEP) can be translated into a successful public health intervention, leading to a decrease in population‐level HIV incidence. We use examples from HIV treatment and contraceptives to discuss expectations for PrEP uptake, adherence, and persistence and their combined impact on the epidemic.DiscussionTargets for PrEP uptake must be based on the local HIV epidemic and will depend on appropriate estimates of the key populations at risk for HIV. However, there is evidence that targets, once established, can successfully be met and that uptake may increase with awareness. Messaging around adherence should include that daily adherence is the goal (except for those MSM for whom event‐driven dosing is a good fit), but perfect adherence should not be a barrier. Ideally, clients persist on PrEP for as long as they are at risk for HIV. While PrEP will be most effective when coverage is focused on high‐risk populations, normalizing rather than stigmatizing PrEP will be highly beneficial.ConclusionsWhile many challenges to PrEP implementation exist, we focused on the three key steps of uptake, adherence and persistence as measurable processes that can lead to improved coverage and decreased HIV incidence.

AbstractIntroduction: For HIV serodiscordant couples in resource‐limited settings, pregnancy is common despite the risk of sexual and/or perinatal HIV transmission. Some safer conception strategies to reduce HIV transmission during pregnancy attempts are available but often not used for reasons including knowledge, accessibility, preference and others. We sought to understand Kenyan health providers' and HIV serodiscordant couples' perspectives and experiences with safer conception.Methods: Between August 2015 and March 2016, we conducted key informant interviews (KIIs) with health providers from public and private HIV care and fertility clinics and in‐depth interviews (IDIs) and focus group discussions (FGDs) with HIV serodiscordant couples participating in an open‐label study of integrated pre‐exposure prophylaxis (PrEP) and antiretroviral therapy (ART) for HIV prevention (the Partners Demonstration Project). An inductive analytic approach identified a number of themes related to experiences with and perceptions of safer conception strategies.Results: We conducted 20 KIIs with health providers, and 21 IDIs and 4 FGDs with HIV serodiscordant couples. HIV clinic providers frequently discussed timed condomless sex and antiretroviral medications while providers at private fertility care centres were more comfortable recommending medically assisted reproduction. Couples experienced with ART and PrEP reported that they were comfortable using these strategies to reduce HIV risk when attempting pregnancy. Timed condomless sex in conjunction with ART and PrEP was a preferred strategy, often owing to them being available for free in public and research clinics, as well as most widely known; however, couples often held inaccurate knowledge of how to identify days with peak fertility in the upcoming menstrual cycle.Conclusions: Antiretroviral‐based HIV prevention is acceptable and accessible to meet the growing demand for safer conception services in Kenya, since medically assisted interventions are currently cost prohibitive. Cross‐disciplinary training for health providers would expand confidence in all prevention options and foster the tailoring of counselling to couples' preferences.

AbstractIntroduction: HIV testing is key to the delivery of pre‐exposure prophylaxis (PrEP): testing HIV‐uninfected at‐risk persons is the first step for PrEP initiation and ongoing HIV testing is an essential part of PrEP delivery. Thus, novel and cost‐effective HIV‐testing approaches to streamline delivery of PrEP are urgently needed. Within a demonstration project of PrEP for HIV prevention among high‐risk HIV serodiscordant couples in Kenya (the Partners Demonstration Project), we conducted a pilot evaluation of HIV self‐testing.Methods: Clinic visits were scheduled quarterly and included in‐clinic HIV testing using fingerstick rapid HIV tests and refills of PrEP prescriptions. HIV oral fluid self‐test kits were provided for participants to use in the two‐month interval between scheduled quarterly clinic visits. Acceptability of HIV self‐testing was assessed using both quantitative and qualitative methods.Results: We found that 222 of 226 (98%) HIV‐uninfected persons who were offered accepted self‐testing. Nearly all (96.8%) reported that using the self‐testing kit was easy. More than half (54.5%) reportedly did not share the HIV results from self‐testing with anyone and almost all (98.7%) the participants did not share the HIV self‐testing kits with anyone. Many participants reported that HIV self‐testing was empowering and reduced anxiety associated with waiting between clinic HIV tests.Conclusions: HIV self‐testing was highly acceptable and may therefore be a feasible strategy to efficiently permit routine HIV testing between PrEP refills.

IntroductionAntiretroviral therapy (ART) prevents HIV transmission within HIV serodiscordant couples (SDCs), but slow implementation and low uptake has limited its impact on population‐level HIV incidence. Home HIV testing and counselling (HTC) campaigns could increase ART uptake among SDCs by incorporating couples' testing and ART referral. We estimated the reduction in adult HIV incidence achieved by incorporating universal ART for SDCs into home HTC campaigns in KwaZulu‐Natal (KZN), South Africa, and southwestern (SW) Uganda.MethodsWe constructed dynamic, stochastic, agent‐based network models for each region. We compared adult HIV incidence after 10 years under three scenarios: (1) "Current Practice," (2) "Home HTC" with linkage to ART for eligible persons (CD4 <350) and (3) "ART for SDCs" regardless of CD4, delivered alongside home HTC.ResultsART for SDCs reduced HIV incidence by 38% versus Home HTC: from 1.12 (95% CI: 0.98–1.26) to 0.68 (0.54–0.82) cases per 100 person‐years (py) in KZN, and from 0.56 (0.50–0.62) to 0.35 (0.30–0.39) cases per 100 py in SW Uganda. A quarter of incident HIV infections were averted over 10 years, and the proportion of virally suppressed HIV‐positive persons increased approximately 15%.ConclusionsUsing home HTC to identify SDCs and deliver universal ART could avert substantially more new HIV infections than home HTC alone, with a smaller number needed to treat to prevent new HIV infections. Scale‐up of home HTC will not diminish the effectiveness of targeting SDCs for treatment. Increasing rates of couples' testing, disclosure, and linkage to care is an efficient way to increase the impact of home HTC interventions on HIV incidence.

IntroductionDespite scale‐up of antiretroviral therapy (ART) for treating HIV‐positive persons, HIV incidence remains elevated among those at high risk such as persons in serodiscordant partnerships. Antiretrovirals taken by HIV‐negative persons as pre‐exposure prophylaxis (PrEP) has the potential to avert infections in individuals in serodiscordant partnerships. Evaluating the cost‐effectiveness of implementing time‐limited PrEP as a short‐term bridge during the first six months of ART for the HIV‐positive partner to prevent HIV transmission compared to increasing ART coverage is crucial to informing policy‐makers considering PrEP implementation.MethodsTo estimate the real world delivery costs of PrEP, we conducted micro‐costing and time and motion analyses in an open‐label prospective study of PrEP and ART delivery targeted to high‐risk serodiscordant couples in Uganda (the Partners Demonstration Project). The cost (in USD, in 2012) of PrEP and ART for serodiscordant couples was assessed, with and without research components, in the study setting. Using Ministry of Health costs, the cost of PrEP and ART provision within a government programme was estimated, as was the cost of providing PrEP in addition to ART. We parameterized an HIV transmission model to estimate the health and economic impacts of 1) PrEP and ART targeted to high‐risk serodiscordant couples in the context of current ART use and 2) increasing ART coverage to 55% of HIV‐positive persons with CD4 ≤500 cells/µL without PrEP. The incremental cost‐effectiveness ratios (ICERs) per HIV infection and disability‐adjusted life year (DALY) averted were calculated over 10 years.ResultsThe annual cost of PrEP and ART delivery for serodiscordant couples was $1058 per couple in the study setting and $453 in the government setting. The portion of the programme cost due to PrEP was $408 and $92 per couple per year in the study and government settings, respectively. Over 10 years, a programme of PrEP and ART for high‐risk serodiscordant couples was projected to avert 43% of HIV infections compared to current practice with an ICER of $1340 per infection averted. This was comparable to ART expansion alone, which would avert 37% of infections with an ICER of $1452.ConclusionsUsing Uganda's gross domestic product per capita of $1681 as a threshold, PrEP and ART for high‐risk persons have the potential for synergistic action and are cost‐effective in preventing HIV infections in high prevalence settings. The annual cost of PrEP in this programme is less than $100 per serodiscordant couple if implemented in public clinics.

AbstractIntroductionRandomized trials of new agents for HIV pre‐exposure prophylaxis (PrEP) compare against emtricitabine and tenofovir disoproxil fumarate (F/TDF), without a placebo group. We used the well‐characterized adherence‐efficacy relationship for F/TDF to back‐calculate the (non‐PrEP) counterfactual background HIV incidence (bHIV) in a randomized trial of a novel PrEP agent and estimate comparative efficacy (to counterfactual bHIV).MethodsThe DISCOVER trial (ClinicalTrials.gov: NCT02842086) randomized 5387 men who have sex with men (MSM) and transgender women who have sex with men and demonstrated non‐inferiority of emtricitabine and tenofovir alafenamide (F/TAF) to F/TDF (HIV incidence rate ratio [IRR] 0·47, 95% CI: 0·19 to 1.15). Tenofovir diphosphate (TFV‐DP) levels in dried blood spots (DBS) were assessed for all diagnosed with HIV and in a random 10% of the cohort. We used a Bayesian model with a diffuse prior distribution, derived from established data relating tenofovir diphosphate levels to HIV prevention efficacy. This prior, combined with the F/TDF seroconversion rate and tenofovir diphosphate levels in DISCOVER, yielded Bayesian inferences on the counterfactual bHIV.ResultsThere were six versus 11 postbaseline HIV infections (0.14 vs. 0.25/100 person‐years [PY]) on F/TAF and F/TDF respectively. Of the 11 on F/TDF, 10 had low, none had medium and one had high tenofovir diphosphate levels; among HIV‐negative controls, 5% of the person‐time years had low, 9% had medium and 86% had high TFV‐DP levels. A non‐informative prior distribution for counterfactual bHIV, combined with the prior for TFV‐DP level‐efficacy relationship, yielded a posterior counterfactual bHIV of 3·4 infections/100 PY (0.80 Bayesian credible interval [CrI] 1·9 to 5·9), which suggests a median HIV efficacy of 96% (0.95 CrI [88% to 99%]) for F/TAF and 93% (0.95 CrI [87% to 96%]) for F/TDF compared to bHIV.ConclusionsBased on the established connection of drug concentrations to PrEP prevention efficacy, a Bayesian framework can be used to estimate a synthetic non‐PrEP control group in randomized, active‐controlled PrEP trials that include a F/TDF‐comparator group.

IntroductionSince 2015, the World Health Organization recommends pre‐exposure prophylaxis (PrEP) for all persons at substantial risk for HIV, including HIV‐uninfected partners in serodiscordant relationships in resource‐limited settings. As PrEP moves from clinical trials to real‐world use, understanding facilitators of and barriers to PrEP initiation and adherence is critical to successful PrEP implementation and rollout.MethodsWe conducted 44 in‐depth individual or couple interviews with 63 participants (30 without HIV and 33 with HIV) enrolled in the Partners Demonstration Project in Kisumu, Kenya, between August and September 2014. The semi‐structured interviews discussed the following: 1) perceived advantages and disadvantages of antiretroviral therapy (ART)/PrEP; 2) reasons for accepting or declining ART/PrEP and 3) influence of prevention of transmission to partner or infant on ART/PrEP use. Transcripts from the interviews were iteratively analyzed using inductive content analysis.ResultsOur study identified three key factors that may facilitate initiation of PrEP in this population. First, participants using PrEP felt reduced stress and increased trust in their HIV serodiscordant relationships. Second, greater community‐wide knowledge of PrEP was thought to likely increase PrEP acceptance. Third, greater education and counselling by providers on PrEP use was also considered to likely increase the adoption of PrEP. We also identified three key barriers to initiation of and adherence to PrEP. First, most participants who declined PrEP expressed doubts about the relative additional effectiveness of PrEP in combination with other prevention tools. Second, perceived stigma related to PrEP use was an important barrier to PrEP initiation. Third, many struggled with overcoming perceived side effects or logistical challenges of taking daily PrEP, particularly when they themselves were not ill.ConclusionsLeveraging the facilitators and overcoming barriers to PrEP uptake may enhance the successful rollout of PrEP among HIV serodiscordant couples in Kenya and other areas in sub‐Saharan Africa, thereby reducing sexual transmission of HIV. Further research focused on how best to provide counselling on combination HIV prevention tools in the context of PrEP use is a crucial next step to delivering PrEP.

AbstractIntroductionPrivate pharmacies are an understudied setting for differentiated delivery of HIV services that may address barriers to clinic‐delivered services, such as stigma and long wait times. To understand the potential for pharmacy‐delivered HIV services in sub‐Saharan Africa, we conducted a scoping review of the published and grey literature.MethodsUsing a modified Cochrane approach, we searched electronic databases through March 2022 and HIV conference abstracts in the past 5 years for studies that: (1) focused on the delivery of HIV testing, antiretroviral therapy (ART) and/or pre‐exposure prophylaxis (PrEP) at private pharmacies in sub‐Saharan Africa; (2) reported on effectiveness outcomes (e.g. HIV incidence) or implementation outcomes, specifically feasibility and/or acceptability; and (3) were published in English. Two authors identified studies and extracted data on study setting, population, design, outcomes and findings by HIV service type.Results and discussionOur search identified 1646 studies. After screening and review, we included 28 studies: seven on HIV testing, nine on ART delivery and 12 on PrEP delivery. Most studies (n= 16) were conducted in East Africa, primarily in Kenya. Only two studies evaluated effectiveness outcomes; the majority (n= 26) reported on feasibility and/or acceptability outcomes. The limited effectiveness data (n= 2 randomized trials) suggest that pharmacy‐delivered HIV services can increase demand and result in comparable clinical outcomes (e.g. viral load suppression) to standard‐of‐care clinic‐based models. Studies assessing implementation outcomes found actual and hypothetical models of pharmacy‐delivered HIV services to be largely feasible (e.g. high initiation and continuation) and acceptable (e.g. preferable to facility‐based models and high willingness to pay/provide) among stakeholders, providers and clients. Potential barriers to implementation included a lack of pharmacy provider training on HIV service delivery, costs to clients and providers, and perceived low quality of care.ConclusionsThe current evidence suggests that pharmacy‐delivered HIV services may be feasible to implement and acceptable to clients and providers in parts of sub‐Saharan Africa. However, limited evidence outside East Africa exists, as does limited evidence on the effectiveness of and costs associated with pharmacy‐delivered HIV services. More research of this nature is needed to inform the scale‐up of this new differentiated service delivery model throughout the region.

AbstractIntroductionThe World Health Organization, while recommending pre‐exposure prophylaxis (PrEP) for HIV‐negative pregnant and postpartum women in HIV high‐burden settings, advocates for continued safety evaluation of PrEP in this population.MethodsThe PrEP Implementation in Young Women and Adolescents (PrIYA) program delivered PrEP to pregnant and postpartum women integrated within routine maternal and child health clinics (MCH) at 16 sites in Western Kenya. PrEP exposure and perinatal outcome data were collected among women obtaining postnatal services during programme evaluation. PrEP use was self‐reported and confirmed with clinical records. Perinatal outcomes including gestational age at birth, birthweight, congenital malformations and infant growth outcomes were abstracted from clinical records for mother‐infant pairs attending the six week visit. Associations between infant outcomes and maternal prenatal PrEP use were assessed using univariate and multivariate logistic and linear regression.ResultsThe PrIYA evaluation identified 1530 postpartum mother‐infant pairs with data on prenatal PrEP exposure: 206 with prenatal PrEP use, 1324 without. Median maternal age was 24 years in both groups. PrEP users (any reported PrEP use) were significantly more likely to report HIV risk factors such as: intimate partner violence, sexually transmitted infections and having a partner with positive or unknown HIV status. Most mothers initiated PrEP during the second trimester (n = 116, 57%) and used PrEP for more than one month (n = 110, 58%). The mean birthweight was 3.3 kg and gestational age at birth was 38.5 weeks in both groups. There were no major differences between PrEP exposed and unexposed infants in rates of preterm birth and low birthweight. There were no congenital malformations identified in the PrEP‐exposed group and five reported in the PrEP unexposed group. At six weeks postpartum, infants in both groups had similar growth. No differences in infant outcomes were found by duration PrEP exposure, trimester of PrEP initiation, a subset analysis of women 15 to 24 years old or in multivariate analyses. This analysis demonstrates that monitoring of infant outcomes is feasible within large‐scale programmatic implementation of PrEP among pregnant and postpartum populations.ConclusionsPregnancy outcomes and early infant growth did not differ by PrEP exposure.

AbstractIntroductionHIV testing is a required part of delivery of pre‐exposure prophylaxis (PrEP) for HIV prevention. However, repeat testing can be challenging in busy, under‐staffed clinical settings, which could negatively impact PrEP uptake and continuation. We prospectively evaluated optional facility‐based HIV self‐testing (HIVST) among young women using PrEP in an implementation programme.MethodsBetween February and November 2019, we collected data from young women receiving PrEP at two family planning facilities in Kisumu, Kenya. At each PrEP follow‐up visit, women were given the option to choose between provider‐initiated testing and HIVST. We assessed factors associated with HIVST uptake and compared satisfaction with HIV testing and clinic experience between acceptors and decliners of HIVST.ResultsA total of 172 women were offered HIVST at 202 PrEP follow‐up visits. The median age was 21 years, 27% had multiple partners and 15% reported previously using HIVST. HIVST was accepted at 34.7% (70/202) of visits. Age (adjusted relative risk (aRR) 1.09 per year, 95% CI (confidence interval) 1.01 to 1.18), never being married (aRR 1.81, 95% CI 1.11 to 2.95) and having more PrEP follow‐up visits (aRR 1.13 per visit, 95% CI 1.04 to 1.23) were associated with HIVST uptake. Compared to HIVST decliners, HIVST acceptors were more likely to be very happy with their overall testing experience (73% vs. 47% of visits, p = 0.003) and were more likely to say they would use HIVST in the future (96% vs. 76%, p < 0.001). Women who accepted HIVST had shorter visits than those choosing standard provider‐initiated HIV testing (median [IQR]: 33 [32, 38] vs. 54 [41.5, 81] minutes, p = 0.003).ConclusionsIn this pilot evaluation in Kenya, about one‐third of women using PrEP opted for HIVST over provider‐initiated testing, and those choosing HIVST spent less time in the clinic and were generally satisfied with their experience. HIVST in PrEP delivery is feasible and has the potential to simplify PrEP delivery and give clients testing autonomy. Additional studies are needed to explore optimal HIV retesting strategies in PrEP delivery, including the use of HIVST in PrEP at a larger scale and in different settings.

AbstractIntroductionAfrican adolescent girls and young women (AGYW) have high rates of HIV acquisition and are a priority population for HIV pre‐exposure prophylaxis (PrEP). PrEP implementation has been limited by AGYW's low perceived HIV risk and provider demands. A decision support tool (DST) with information about PrEP could improve clients' risk perception, knowledge about PrEP, informed decision‐making and motivation to use PrEP based on their risk, facilitating PrEP delivery in primary healthcare (PHC) clinics.MethodsWe designed MyPrEP, a client‐facing DST about PrEP and HIV prevention, with youth‐friendly information and images. The impact of the MyPrEP tool was assessed among HIV‐negative women aged 18–25 years presenting to a PHC clinic in Johannesburg, South Africa from March 2019 to 2020. AGYW were randomized by day to the DST or a general health website as the control condition. A clinician blinded to DST versus control allocation provided standard of care counselling about PrEP, offered PrEP, administered a questionnaire and conducted sexually transmitted infection testing. The primary outcome was PrEP initiation and the secondary outcome was PrEP persistence at 1 month, determined by pharmacy dispensation records.ResultsOf 386 AGYW screened, 353 were randomized (DSTn= 172, controln= 181) with a median age of 21 years (interquartile range [IQR] 20, 23) and 56% (199/353) attending the clinic for HIV testing, 46% (164/353) using contraception, 15% (53/353) using condoms consistently and 37% (108/353) with a curable sexually transmitted infection. PrEP was initiated by 97% in the DST group and 94% in the control group (OR 1.79; 95% confidence interval, CI = 0.79–1.53), of whom two‐thirds planned to continue PrEP until they decided if they liked PrEP. At 1 month, PrEP persistence was 19% in the DST and 10% in the control group (OR 1.97, 95% CI 1.08–3.69). Ninety‐nine percent randomized to the DST reported satisfaction with MyPrEP.ConclusionsAmong AGYW attending a South African PHC clinic, PrEP uptake was >90% with two‐fold higher PrEP persistence at 1 month in those randomized to use the MyPrEP DST. Given the need for strategies to support PrEP implementation and improve low PrEP persistence among African AGYW, a PrEP DST warrants further evaluation.

AbstractIntroductionAdolescent girls and young women (AGYW) in Africa have high HIV incidence despite scale‐up of HIV testing and HIV treatment. Placebo‐controlled trials of tenofovir‐based pre‐exposure prophylaxi (PrEP) in diverse populations demonstrated that PrEP works with close to 100% effectiveness if taken with high, but not perfect, adherence. Divergent efficacy estimates among African AGYW led to demonstration and implementation projects to better understand motivations for HIV prevention, uptake, adherence and persistence to PrEP. To inform PrEP programmes, the design and initial findings from PrEP demonstration projects for AGYW are reviewed.DiscussionEarly lessons from PrEP implementation projects among young African women include: (1) awareness and demand creation with positive messaging about the benefits of PrEP are critical to motivate AGYW to consider this novel prevention technology and to foster awareness among peers, partners, parents and guardians to support AGYW's effective PrEP use; (2) PrEP initiation is high in projects that are integrating PrEP into youth‐friendly clinics, family planning clinics and mobile clinics; (3) young African women at risk are initiating PrEP, based on behavioural characteristics, history of intimate partner violence, depression and 30% prevalence of chlamydia and/or gonorrhoea; (4) provision of youth‐friendly PrEP delivery programmes that integrate reproductive health services, including contraception and the diagnosis and treatment of sexually transmitted infections, increase health impact; (5) messages that emphasize the necessity for high adherence while at potential risk of HIV exposure and support strategies that addresses AGYW's adherence challenges are essential; and, (6) a substantial proportion of AGYW do not persist with PrEP, and strategies are needed to help AGYW assess their ongoing need, motivation and challenges with persisting with PrEP.ConclusionsPrEP is feasible to implement in integrated reproductive health service delivery models to reach African AGYW. While PrEP demonstration projects indicate that women with behavioural risks and high rates of sexually transmitted diseases are initiating PrEP; effective strategies to support AGYW's adherence and persistence with PrEP are needed. Lessons learned from oral PrEP delivery, a novel first generation HIV prevention product, are relevant to longer‐acting and less adherence‐dependent strategies which are currently in clinical trials.

AbstractIntroductionPre‐exposure prophylaxis (PrEP) to prevent HIV infection is being rolled out in Africa. The uptake of PrEP to date has varied across populations and locations. We seek to understand the drivers of demand for PrEP through analysis of qualitative data collected in conjunction with a PrEP demonstration project involving East African HIV serodiscordant couples. Our goal was to inform demand creation by understanding what PrEP means – beyond HIV prevention – for the lives of users.MethodsThe Partners Demonstration Project evaluated an integrated strategy of PrEP and antiretroviral therapy (ART) delivery in which time‐limited PrEP served as a "bridge" to long‐term ART. Uninfected partners in HIV serodiscordant couples were offered PrEP at baseline and encouraged to discontinue once infected partners had taken ART for six months. We conducted 274 open‐ended interviews with 93 couples at two Ugandan research sites. Interviews took place one month after enrolment and at later points in the follow‐up period. Topics included are as follows: (1) discovery of serodiscordance; (2) decisions to accept/decline PrEP and/or ART; (3) PrEP and ART initiation; (4) experiences of using PrEP and ART; (5) PrEP discontinuation; (6) impact of PrEP and ART on the partnered relationship. Interviews were audio‐recorded and transcribed. We used an inductive, content analytic approach to characterize meanings of PrEP stemming from its effectiveness for HIV prevention. Relevant content was represented as descriptive categories.ResultsDiscovery of HIV serodiscordance resulted in fear of HIV transmission for couples, which led to loss of sexual intimacy in committed relationships, and to abandonment of plans for children. As a result, partners became alienated from each other. PrEP countered the threat to the relationship by reducing fear and reinstating hopes of having children together. Condom use worked against the re‐establishment of intimacy and closeness. By increasing couples' sense of protection against HIV infection and raising the prospect of a return to "live sex" (sex without condoms), PrEP was perceived by couples as solving the problem of serodiscordance and preserving committed relationships.ConclusionsThe most effective demand creation strategies for PrEP may be those that address the everyday life priorities of potential users in addition to HIV prevention.Clinical Trial NumberNCT02775929