Targeted solutions to increase dolutegravir coverage, viral load testing coverage, and viral suppression among children living with HIV in Togo: An analysis of routine facility data.

BACKGROUND: According to UNAIDS, Togo halved AIDS-related deaths among children ages 0-14 from 2010 to 2020. However, available data show low dolutegravir (DTG)-containing antiretroviral therapy (ART) coverage and low viral load suppression (VLS) among children living with HIV (CLHIV). We analyzed routine facility data before and after implementation of root-cause-based solutions for improving DTG coverage, viral load (VL) testing coverage, and VLS among CLHIV. DESCRIPTION: We analyzed routine data for CLHIV ≤14 years from October 2019 through September 2022. We assessed proportion of CLHIV on ART receiving DTG, VL testing coverage (CLHIV on ART with documented VL test result), and VLS (CLHIV with documented VL test result of <1,000 copies among those with test result). From October 2019 to September 2020, 52% were on a DTG-containing regimen, 48% had documented VL test results, and 64% had VLS. Site-level teams conducted a root-cause analysis and designed corresponding solutions implemented beginning October 2020: line listing and contacting eligible CLHIV to start/transition to DTG-containing regimen and collect VL samples; ART adherence support; monthly DTG stock monitoring; tracking pending VL test results through laboratory focal persons; documenting VL test results; and informing caregivers within one week if CLHIV not virally suppressed. Granular data were used to prioritize technical assistance to sites with lowest DTG coverage, VL testing coverage, and VLS. RESULTS: From baseline (October 2019-September 2020) to endline (October 2021-September 2022), increases were observed for DTG coverage (52% to 71%), VL testing coverage (48% to 90%), and VLS (64% to 82%). Age-disaggregated data showed positive trends. CONCLUSIONS: Root-cause-based solutions and granular data use increased DTG coverage, resulting in increased VL testing and VLS among CLHIV. These interventions should be scaled and become the national standard of care.

Increasing multimonth dispensing of antiretrovirals and assessing the effect on viral load suppression among children and adolescents receiving HIV services in Nigeria.

INTRODUCTION: Multimonth dispensing (MMD) enables less frequent clinic visits and improved outcomes for people living with HIV, but few children and adolescents living with HIV (CALHIV) are on MMD. At the end of the October-December 2019 quarter, only 23% of CALHIV receiving antiretroviral therapy (ART) through SIDHAS project sites in Akwa Ibom and Cross River states, Nigeria, were receiving MMD. In March 2020, during COVID-19, the government expanded MMD eligibility to include children and recommended rapid implementation to minimize clinic visits. SIDHAS provided technical assistance to 36 "high-volume" facilities-≥5 CALHIV on treatment-in Akwa Ibom and Cross River to increase MMD and viral load suppression (VLS) among CALHIV, toward PEPFAR's 80% benchmark for people currently on ART. We present change in MMD, viral load (VL) testing coverage, VLS, optimized regimen coverage, and community-based ART group enrollment among CALHIV from the October-December 2019 quarter (baseline) to January-March 2021 (endline) based on retrospective analysis of routinely collected program data. MATERIALS AND METHODS: We compared MMD coverage (primary objective), and optimized regimen coverage, community-based ART group enrollment, VL testing coverage, and VLS (secondary objectives), among CALHIV 18 years and younger pre-/post-intervention (baseline/endline) at the 36 facilities. We excluded children younger than two years, who are not recommended for or routinely offered MMD. The extracted data included age, sex, ART regimen, months of ART dispensed at last refill, most recent VL test results, and community ART group enrollment. Data on MMD-three or more months of ARVs dispensed at one time-were disaggregated into three to five months (3-5-MMD) vs. six or more months (6-MMD). VLS was defined as ≤1,000 copies. We documented MMD coverage by site, optimized regimen, and VL testing and suppression. Using descriptive statistics, we summarized the characteristics of CALHIV on MMD and non-MMD, number of CALHIV on optimized regimens, and proportion enrolled in differentiated service delivery models and community-based ART refill groups. For the intervention, SIDHAS technical assistance was data driven: weekly data analysis/review, site-prioritization scoring, provider mentoring, line listing eligible CALHIV, pediatric regimen calculator, child-optimized regimen transitioning, and community ART models. RESULTS: The proportion of CALHIV ages 2-18 receiving MMD increased from 23% (620/2,647; baseline) to 88% (3,992/4,541; endline), while the proportion of sites reporting suboptimal MMD coverage among CALHIV (<80%) decreased (100% to 28%). In March 2021, 49% of CALHIV were receiving 3-5-MMD and 39% 6-MMD. In October-December 2019, 17%-28% of CALHIV were receiving MMD; by January-March 2021, 99% of those 15-18 years, 94% 10-14 years, 79% 5-9 years, and 71% 2-4 years were on MMD. VL testing coverage remained high (90%), while VLS increased (64% to 92%). The proportion on pediatric-optimized regimens increased (58% to 79%). CONCLUSIONS: MMD was feasible among CALHIV without compromising VLS. Expanded eligibility criteria, line listing eligible children, monitoring pediatric antiretroviral stock, and data use contributed to positive results. Future efforts should address low 6-MMD uptake related to stock limitations and synchronize antiretroviral refill pickup with VL sample collection.

Strategies to improve adherence and continuation of shorter-term hormonal methods of contraception.

BACKGROUND: Worldwide, hormonal contraceptives are among the most popular reversible contraceptives. Despite high perfect-use effectiveness rates, typical-use effectiveness rates for shorter-term methods such as oral and injectable contraceptives are much lower. In large part, this disparity reflects difficulties in ongoing adherence to the contraceptive regimen and low continuation rates. Correct use of contraceptives to ensure effectiveness is vital to reducing unintended pregnancy. OBJECTIVES: To determine the effectiveness of strategies aiming to improve adherence to, and continuation of, shorter-term hormonal methods of contraception compared with usual family planning care. SEARCH METHODS: We searched to July 2018 in the following databases (without language restrictions): The Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 7), PubMed via MEDLINE, POPLINE, Web of Science, ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing strategies aimed to facilitate adherence and continuation of shorter-term hormonal methods of contraception (such as oral contraceptives (OCs), injectable depot medroxyprogesterone acetate (DMPA or Depo-Provera), intravaginal ring, or transdermal patch) with usual family planning care in reproductive age women seeking to avoid pregnancy. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. Primary outcomes were continuation or discontinuation of contraceptive method, rates of discontinuation due to adverse events (menstrual disturbances and all other adverse events), and adherence to method use as indicated by missed pills and on-time/late injections. Pregnancy was a secondary outcome. MAIN RESULTS: We included 10 RCTs involving 6242 women. Six trials provided direct in-person counseling using either multiple counseling contacts or multiple components during one visit. Four trials provided intensive reminders of appointments or next dosing, of which two provided additional educational health information as well as reminders. All trials stated 'usual care' as the comparison.The certainty of the evidence ranged from very low to moderate. Main limitations were risk of bias (associated with poor reporting of methodological detail, lack of blinding, and incomplete outcome data), inconsistency, indirectness, and imprecision.Continuation of hormonal contraceptive methodsIt is uncertain whether intensive counseling improves continuation of hormonal contraceptive methods compared with usual care (OR 1.28, 95% CI 1.07 to 1.54; 2624 participants; 6 studies; I2 = 79%; very low certainty evidence). The evidence suggested: if the chance of continuation with usual care is 39%, the chance of continuation with intensive counseling would be between 41% and 50%. The overall pooled OR suggested continuation of improvement, however, when stratified by contraceptive method type, the positive results were restricted to DMPA.It is uncertain whether reminders (+/- educational information) improve continuation of hormonal contraceptive methods compared with usual care (OR 1.33, 95% CI 1.03 to 1.73; 933 participants; 2 studies; I2 = 69%; very low certainty evidence).The evidence suggested: if the chance of continuation with usual care is 52%, the chance of continuation with reminders would be between 52% and 65%.Discontinuation due to adverse eventsThe evidence suggested that counseling may be associated with a decreased rate of discontinuation due to adverse events compared with usual care, with a lower rate of discontinuation due to menstrual disturbances (OR 0.20, 95% CI 0.11 to 0.37; 350 participants; 1 study; low certainty evidence), but may make little or no difference to all other adverse events (OR 0.73, 95% CI 0.36 to 1.47; 350 participants; 1 study; low certainty evidence). The evidence suggested: if the chance of discontinuation with usual care due to menstrual disturbances is 32%, the chance of discontinuation with intensive counseling would be between 5% and 15%; and that if the chance of discontinuation with usual care due to other adverse events is 55%, the chance of discontinuation with intensive counseling would be between 30% and 64%.Discontinuation was not reported among trials that investigated the use of reminders (+/- educational information).Adherence Adherence was not reported among trials that investigated the use of intensive counseling.Among trials that investigated reminders (+/- educational information), there was no conclusive evidence of a difference in adherence as indicated by missed pills (MD 0.80, 95% CI -1.22 to 2.82; 73 participants; 1 study; moderate certainty evidence) or by on-time injections (OR 0.84, 95% CI 0.54 to 1.29; 350 participants; 2 studies; I2 = 0%; low certainty evidence). The evidence suggested: if the chance of adherence to method use as indicated by on-time injections with usual care is 50%, the chance of adherence with method use as indicated by on-time injections with reminders would be between 35% and 56%.PregnancyThere was no conclusive evidence of a difference in rates of pregnancy between intensive counseling and usual care (OR 1.24, 95% CI 0.98 to 1.57; 1985 participants; 3 studies; I2 = 0%, very low certainty evidence). The evidence suggested: if the chance of pregnancy with usual care is 18%, the chance of pregnancy with counseling would be between 18% and 25%.Pregnancy was not reported among trials that investigated the use of reminders (+/- educational information). AUTHORS' CONCLUSIONS: Despite the importance of this topic, studies have not been published since the last review in 2013 (nine studies) with only one study added in 2019 that neither changed the results nor improved the certainty of evidence.Overall, the certainty of evidence for strategies to improve adherence and continuation of contraceptives is low. Intensive counseling and reminders (with or without educational information) may be associated with improved continuation of shorter-term hormonal contraceptive methods when compared with usual family planning care. However, this should be interpreted with caution due to the low certainty of the evidence. Included trials used a variety of shorter-term hormonal contraceptive methods which may account for the high heterogeneity. It is possible that the effectiveness of strategies for improving adherence and continuation are contingent on the contraceptive method targeted. There was limited reporting of objectively measurable outcomes (e.g. electronic monitoring device) among included studies. Future trials would benefit from standardized definitions and measurements of adherence, and consistent terminology for describing interventions and comparisons. Further research requires larger studies, follow-up of at least one year, and improved reporting of trial methodology.

Assays for estimating HIV incidence: updated global market assessment and estimated economic value.

INTRODUCTION: Accurate incidence estimates are needed to characterize the HIV epidemic and guide prevention efforts. HIV Incidence assays are cost-effective laboratory assays that provide incidence estimates from cross-sectional surveys. We conducted a global market assessment of HIV incidence assays under three market scenarios and estimated the economic value of improved incidence assays. METHODS: We interviewed 27 stakeholders, and reviewed journal articles, working group proceedings, and manufacturers' sales figures. We determined HIV incidence assay use in 2014, and estimated use in 2015 to 2017 and in 5 to 10-years under three market scenarios, as well as the cost of conducting national and key population surveys using an HIV incidence assay with improved performance. RESULTS: Global 2014 HIV incidence assay use was 308,900 tests, highest in Asia and mostly for case- and population-based surveillance. Estimated 2015 to 2017 use was 94,475 annually, with declines due to China and the United States discontinuing incidence assay use for domestic surveillance. Annual projected 5 to 10 year use under scenario 1 - no change in technology - was 94,475. For scenario 2 - a moderately improved incidence assay - projected annual use was 286,031. Projected annual use for scenario 3 - game-changing technologies with an HIV incidence assay part of (a) standard confirmatory testing, and (b) standard rapid testing, were 500,000 and 180 million, respectively. As HIV incidence assay precision increases, decreased sample sizes required for incidence estimation resulted in $5 to 23 million annual reductions in survey costs and easily offset the approximately $3 million required to develop a new assay. CONCLUSIONS: Improved HIV incidence assays could substantially reduce HIV incidence estimation costs. Continued development of HIV incidence assays with improved performance is required to realize these cost benefits.

Attitudes and perceptions towards novel objective measures of ARV-based vaginal ring use: Results from a global stakeholder survey.

Results of recent microbicide and pre-exposure prophylaxis clinical trials have shown adherence to be a significant challenge with new HIV prevention technologies. As the vaginal ring containing dapivirine moves into two open label follow-on studies (HOPE/MTN-025 and DREAM) and other antiretroviral-based and multi-purpose prevention technology ring products advance through the development pipeline, there is a need for more accurate and reliable measures of adherence to microbicide ring products. We previously conducted a comprehensive landscape analysis to identify new technologies that could be applied to adherence measurement of vaginal rings containing antiretrovirals. To explore attitudes and perceptions towards the approaches that we identified, we conducted a survey of stakeholders with experience and expertise in microbicide and HIV prevention clinical trials. From May to July 2015 an electronic survey was distributed via email to 894 stakeholders; a total of 206 eligible individuals responded to at least one question and were included in the data analysis. Survey respondents were presented with various objective measures and asked about their perceived acceptability to trial participants, feasibility of implementation by study staff, usefulness for measuring adherence and ethical concerns. Methods that require no additional input from the participant and require no modifications to the existing ring product (i.e., measurement of residual drug or excipient, or a vaginal analyte that enters the ring) were viewed as being more acceptable to trial participants and more feasible to implement in the field. Respondents saw value in using objective measures to provide real-time feedback on adherence. However, approaches that involve unannounced home visits for sample collection or spot checks of ring use, which could provide significant value to adherence feedback efforts, were met with skepticism. Additional research on the acceptability of these methods to potential trial participants and trial staff is recommended.

Human Resource Challenges to Integrating HIV Pre-Exposure Prophylaxis (PrEP) into the Public Health System in Kenya: A Qualitative Study.

Extensive planning will be necessary to integrate HIV pre-exposure prophylaxis (PrEP) into public health systems. In Bondo and Kisumu, Kenya, we conducted interviews with 16 district and provincial public health stakeholders and held consultations with 18 provincial and 23 national public health stakeholders on topics related to PrEP rollout. We coded interview transcripts and created memos summarizing responses. We documented consultation discussions through note taking. Human resource challenges identified included increased workload and insufficient personnel, the need for task shifting/sharing, training needs, infrastructural requirements, discrimination and stigma by staff towards at-risk clients, and providers' personal priorities about offering PrEP. These challenges paralleled current challenges related to integration of antiretroviral therapy (ART) and could be partially addressed prior to PrEP rollout. The recommendations for training staff are likewise grounded in lessons from ART and have practical application for program planners developing training curricula for PrEP delivery.

The importance of choice in the rollout of ARV-based prevention to user groups in Kenya and South Africa: a qualitative study.

INTRODUCTION: Stakeholders continue to discuss the appropriateness of antiretroviral-based pre-exposure prophylaxis (PrEP) for HIV prevention among sub-Saharan African and other women. In particular, women need formulations they can adhere to given that effectiveness has been found to correlate with adherence. Evidence from family planning shows that contraceptive use, continuation and adherence may be increased by expanding choices. To explore the potential role of choice in women's use of HIV prevention methods, we conducted a secondary analysis of research with female sex workers (FSWs) and men and women in serodiscordant couples (SDCs) in Kenya, and adolescent and young women in South Africa. Our objective here is to present their interest in and preferences for PrEP formulations - pills, gel and injectable. METHODS: In this qualitative study, in Kenya we conducted three focus groups with FSWs, and three with SDCs. In South Africa, we conducted two focus groups with adolescent girls, and two with young women. All focus groups were audio-recorded, transcribed and translated into English as needed. We structurally and thematically coded transcripts using a codebook and QSR NVivo 9.0; generated code reports; and conducted inductive thematic analysis to identify major trends and themes. RESULTS: All groups expressed strong interest in PrEP products. In Kenya, FSWs said the products might help them earn more money, because they would feel safer accepting more clients or having sex without condoms for a higher price. SDCs said the products might replace condoms and reanimate couples' sex lives. Most sex workers and SDCs preferred an injectable because it would last longer, required little intervention and was private. In South Africa, adolescent girls believed it would be possible to obtain the products more privately than condoms. Young women were excited about PrEP but concerned about interactions with alcohol and drug use, which often precede sex. Adolescents did not prefer a particular formulation but noted benefits and limitations of each; young women's preferences also varied. CONCLUSIONS: The circumstances and preferences of sub-Saharan African women are likely to vary within and across groups and to change over time, highlighting the importance of choice in HIV prevention methods.

Barriers and facilitators to pre-exposure prophylaxis (PrEP) eligibility screening and ongoing HIV testing among target populations in Bondo and Rarieda, Kenya: results of a consultation with community stakeholders.

BACKGROUND: As pre-exposure prophylaxis (PrEP) moves closer to availability in developing countries, practical considerations for implementation become important. We conducted a consultation with district-level community stakeholders experienced in HIV-prevention interventions with at-risk populations in Bondo and Rarieda, Kenya to generate locally grounded approaches to the future rollout of oral PrEP to four populations: fishermen, widows, female sex workers, and serodiscordant couples. METHODS: The 20 consultation participants represented the Ministry of Health, faith- and community-based organizations, health facilities, community groups, and nongovernmental organizations. Participants divided into breakout groups and followed a structured discussion guide asking them to identify barriers to implementing HIV-prevention interventions (including PrEP) with each population. Questions also solicited solutions for addressing these barriers, as well as other facilitators for PrEP implementation. In particular, questions focused on how to encourage people to screen for PrEP eligibility by having HIV and other blood tests and how to encourage compliance with ongoing HIV testing. RESULTS: The barriers and facilitators/solutions discussants provided were frequently population-specific, but there were also broad-level similarities across populations. Service delivery barriers to HIV-prevention interventions concerned the need for staff trained to address the needs of particular populations. Service delivery facilitators to provision of ongoing HIV testing consisted of offering testing options besides facility-based testing. Stigma was the main community-level barrier for all groups, whereas barriers at the level of target populations included mobility; lifestyle and life circumstances, especially cultural norms among fishermen and widows; and fears, lack of awareness, and misinformation. Proposed facilitators and strategies for addressing community- and population-level barriers included topic-specific education within the populations and community, involvement of partners and family members, mass HIV testing, and peer educators. Barriers to PrEP uptake included non-adherence to pill taking and missing clinic visits. For drug adherence, facilitators were counselling and involving family members. Discussants suggested that client reminders, e.g., home visits, were needed to encourage clients to keep their clinic appointments. CONCLUSIONS: Strategies for encouraging eligibility screening and ongoing HIV testing will have local and population-specific aspects. Our results nonetheless apply to similar populations throughout sub-Saharan Africa and reach beyond oral PrEP to other ARV-based PrEP formulations.

Lost in translation: assessing effectiveness of focus group questioning techniques to develop improved translation of terminology used in HIV prevention clinical trials.

INTRODUCTION: Achieving participant comprehension has proven to be one of the most difficult, practical, and ethical challenges of HIV prevention clinical trials. It becomes even more challenging when local languages do not have equivalent scientific and technical vocabularies, rendering communication of scientific concepts in translated documents extremely difficult. Even when bilingual lexicons are developed, there is no guarantee that participants understand the terminology as translated. METHODS: We conducted twelve focus groups with women of reproductive age in Mwanza, Tanzania to explore the effectiveness of four questioning techniques for: (1) assessing participants' familiarity with existing technical terms and concepts, (2) generating a list of acceptable technical and non-technical terms, (3) testing our definitions of technical terms, and (4) verifying participants' preferences for terms. Focus groups were transcribed, translated, and qualitatively analyzed. RESULTS AND DISCUSSION: A translation process that uses all four questioning techniques in a step-wise approach is an effective way to establish a baseline understanding of participants' familiarity with research terms, to develop and test translatable definitions, and to identify participants' preferred terminology for international HIV clinical research. This may help to ensure that important concepts are not "lost in translation." The results emphasize the importance of using a variety of techniques depending on the level of participant familiarity with research concepts, the existence of colloquial or technical terms in the target language, and the inherent complexity of the terms.

Introducing female condoms to female sex workers in Central America.

CONTEXT: Female condoms have a potential role in reducing HIV infection among female sex workers in Central America. Research on how to introduce female condoms to this population is warranted. METHODS: Two rounds of focus groups with sex workers (115 in round one and 81 in round two) were conducted in El Salvador and Nicaragua in 2007-2008. In addition, we conducted structured interviews with 95 sex workers and direct observations of six health educators. RESULTS: Women reported that the design of the female condom made insertion and removal difficult to learn. About one-third of participants reported inserting it for the first time alone. Most women reported practicing 2-10 times before feeling skilled enough to use it with partners. Positive perceptions included lubrication, size, comfort and strength. Negative perceptions included the large package, initial physical discomfort and the possibility that the device would scare clients away. The participants preferred to learn to use female condoms from an instructional brochure plus instructor-led training in their workplace. They cited lack of exposure to female condoms among men and women as a barrier to female condom use and recommended education for both men and women; they also recommended distribution of female condoms at places where male condoms are available. CONCLUSIONS: If provisions are made for instructing women on female condom use in places where women will not feel stigmatized, and if supplies are easily and consistently available, uptake of the female condom among female sex workers in Central America seems likely. Health educators' use of promotional tools such as checklists and standardized messages is strongly recommended.

Central American sex workers' introduction of the female condom to different types of sexual partners.

Formative research was conducted in El Salvador and Nicaragua to inform promotion of female condoms to sex workers. Two rounds of focus groups with sex workers were conducted, with female condom training and supplies provided. Structured interviews with sex workers and direct observations of health educators were conducted. One third of sex acts were protected with female condoms in the previous 7 days. Women recommended nonpaying partners as "first try" partners but most frequently reported trying female condoms with clients. With clients, women preferred female condoms over male condoms but expressed no preference with nonpaying partners. Lack of exposure to female condoms among men and women was cited as a key barrier to female condom use. Strategies for persuading all partner types to try the female condom are suggested, and we provided promotional messages, based on results, to assist sex workers in introducing female condoms to different partners.

The exploitation of "Exploitation" in the tenofovir prep trial in Cameroon: Lessons learned from media coverage of an HIV prevention trial.

media coverage influences how clinical trials are perceived internationally and in communities where trials occur, affecting recruitment, retention, and political support for research. We conducted a discourse analysis of news coverage from 2004-2005 of a trial in Cameroon on oral PrEP for HIV prevention, to identify messages, communication techniques, and sources of messages that were amplified via media. We identified two parallel discourses: one on ethical concerns about the Cameroon trial, and a second, more general "science exploitation" discourse concerned with the potential for trials with vulnerable participant populations to be conducted unethically, benefiting only wealthy populations. Researchers should overtly address exploitation as an integral, ongoing component of research, particularly where historical or cultural conditions set the stage for controversy to emerge.

Partnering for Care in HIV Prevention Trials.

QUALITATIVE CASE STUDIES WERE conducted at seven international sites conducting HIV prevention research in Africa, Asia, and the Americas to identify strategies for ensuring that health needs of research participants identified in the course of research are adequately addressed. Key factors were identified that contribute to the balance between direct care and healthcare referrals at a research site, as well as the overall quality of the healthcare made available to research participants. The case studies exemplify the concept of "moral negotiation" in research (Weijer & LeBlanc, 2006), that is, a process where researchers and sponsors negotiate with increasingly empowered local communities and host countries to achieve meaningful and substantive benefits from biomedical research for all stakeholders.