Preferences for Long-Acting PrEP Products Among Women and Girls: A Quantitative Survey and Discrete Choice Experiment in Eswatini, Kenya, and South Africa.

While oral pre-exposure prophylaxis (PrEP) can substantially reduce HIV risk, there are important barriers to uptake and adherence. We explored preferences for long-acting injectable and implantable PrEP among women and girls in Eswatini, Kenya, and South Africa. We conducted an online quantitative survey and discrete choice experiment (DCE) among adolescent girls (15-17), young women (18-29), and adult women (30-49). Participants completed a survey about their demographics and behavior and a DCE with 5 attributes (format, insertion location, number of insertions, dual-protection, and palpability). We recruited 1236 respondents (Eswatini = 420; Kenya = 350; South Africa = 493) in May 2022. Most participants were sexually active (72%), nearly 29% of whom reported recently engaging in transactional sex. 46% had heard of oral PrEP, but of those, only 16% reported having ever used it. Product format and dual-protection were significant predictors of product choice. Relative to a 2-month injection, participants had 1.76 times the odds (95% CI 1.08-2.04) of choosing a 6-month injectable, and 1.70 the odds (95% CI 1.06-1.92) of choosing a 12-month removable implant. Compared to a single-indication product, respondents had 2.46 times the odds (95% CI 1.04-2.68) of preferring a product also protecting against pregnancy, and 2.81 the odds (95% CI 1.04-3.05) of choosing a product that also protected against STIs. Adolescent girls and women in these countries showed strong preferences for longer-acting PrEP product formats, as well as those offering dual-protection. Introduction of long-acting options could improve PrEP uptake and reduce HIV burdens in east and southern African settings.

Use of a hybrid digital training approach for hormonal IUD providers in Nigeria: results from a mixed method study.

BACKGROUND: In Nigeria, in-service trainings for new family planning (FP) methods have typically been conducted using a combination of classroom-based learning, skills labs, and supervised practicums. This mixed-methods study evaluated the feasibility, acceptability, provider competency, and costs associated with a hybrid digital and in-person training model for the hormonal intrauterine device (IUD). METHODS: The study was conducted in Enugu, Kano, and Oyo states, Nigeria, and enrolled FP providers previously trained on non-hormonal IUDs. Participants completed a digital didactic training, an in-person model-based practicum with an Objective Structured Clinical Examination (OSCE), followed by supervised provision of service to clients. Provider knowledge gains and clinical competency were assessed and described descriptively. Data on the feasibility, acceptability, and scalability of the approach were gathered from participating providers, clinical supervisors, and key stakeholders. Training costs were captured using an activity-based approach and used to calculate a cost per provider trained. All analyses were descriptive. RESULTS: Sixty-two providers took the hybrid digital training, of whom 60 (91%) were included in the study (n = 36 from public sector, n = 15 from private sector, and n = 9 both public/private). The average knowledge score increased from 62 to 86% pre- and post-training. Clinical competency was overall very high (mean: 94%), and all providers achieved certification. Providers liked that the digital training could be done at the time/place of their choosing (84%), was self-paced (79%), and reduced risk of COVID-19 exposure (75%). Clinical supervisors and Ministry of Health stakeholders also had positive impressions of the training and its scalability. The hybrid training package cost $316 per provider trained. CONCLUSIONS: We found that a hybrid digital training approach to hormonal IUD service provision in Nigeria was acceptable and feasible. Providers demonstrated increases in knowledge following the training and achieved high levels of clinical competency. Both providers and clinical supervisors felt that the digital training content was of high quality and an acceptable (sometimes preferable) alternative to classroom-based, in-person training. This study provided insights into a hybrid digital training model for a long-acting contraceptive, relevant to scale-up in Nigeria and similar settings.

End-user research in support of long-acting systemic antiretroviral delivery systems: insights from qualitative research with providers and target users in South Africa.

BACKGROUND: While oral pre-exposure prophylaxis (PrEP) has been shown to reduce the risk of HIV, challenges such as adhering to a daily-dosing regimen and persistence have emerged as barriers for at-risks populations in South Africa. This qualitative research sought to investigate perceptions of and preferences for a long-acting, biodegradable implantable PrEP product designed to address these barriers. METHODS: To identify and understand motivators, barriers, and preferences for the PrEP implant, we conducted qualitative in-depth interviews (IDIs) among health care providers (HCPs) and target end-users (young women, adolescent girls, and female sex workers) in urban and rural/peri-urban regions of Gauteng Province, South Africa. The IDIs focused on defining values, beliefs, habits, lifestyles, influencers, and information channels for potential PrEP implant end-users. RESULTS: We conducted 36 IDIs across health care providers and target end-user respondent segments. Respondents had generally positive reactions to the PrEP implant. Most end-users felt that some undesirable aspects of the implant (e.g., side effects, pain during insertion, potential scarring, and inability to remove implant) would be offset by having a highly effective, and long-lasting HIV prevention product. Although some HCPs believed the implantable PrEP would lead to increases in promiscuity and risky sexual behavior, most HCPs saw value in the PrEP implant's long duration of protection, its biodegradability, and the likelihood of higher adherence relative to oral PrEP. CONCLUSIONS: This study is a first step toward further research needed to demonstrate the demand for a biodegradable, long-acting implantable PrEP and suggests such a product would be accepted by end-users and HCPs in South Africa. This study indicates the need to develop more convenient, discreet, long-acting, and highly effective biomedical HIV prevention options for at-risk populations.

HIV Pre-exposure Prophylaxis Implant Stated Preferences and Priorities: Results of a Discrete Choice Experiment Among Women and Adolescent Girls in Gauteng Province, South Africa.

For adolescent girls (AG) and young women (YW), adherence barriers may limit the effectiveness of daily oral HIV pre-exposure prophylaxis (PrEP). Due to its low-burden and long-lasting product attributes, PrEP implants could remove some of the critical adherence barriers of oral PrEP products for individuals at risk of HIV. To explore stated preferences for a long-acting PrEP implant, we conducted a quantitative survey and discrete choice experiment with AG (ages 15-17), YW (18-34), and female sex workers (FSW; ≥ 18) in Gauteng Province, South Africa. We completed 600 quantitative surveys across the three subgroups of women. Respondents stated preference for an implant that provided longer HIV protection (24 months versus 6 months) and required a single insertion. They stated that they preferred a biodegradable implant that could be removed within 1 month of insertion. Respondents had no preference for a particular insertion location. Overall, 78% of respondents said they would be likely (33%) or very likely (45%) to use a PrEP implant were one available, with the majority (82%) stating preference for a product that would provide dual protection against HIV and unintended pregnancies. To reduce their risk of HIV, AG, YW, and FSW in our survey reported a strong willingness to use long-acting, highly-effective, dissolvable PrEP implants.

RESUMEN: Las niñas adolescentes (NA) y mujeres jóvenes (MJ), pueden enfrentar barreras de adherencia que limitan la eficacia de la profilaxis oral previa a la exposición al VIH (PrEP). Ya que el implante de PrEP es un producto que requiere de poca intervención de la usuaria y es de larga duración, podría eliminar algunas de las barreras de adherencia más importantes en el uso de los productos orales de PrEP para aquellas personas en riesgo de infección de VIH. Para explorar las preferencias declaradas en cuanto al implante de PrEP de acción prolongada, llevamos a cabo una encuesta cuantitativa y un experimento de elección discreta (DCE) con NA (de 15 a 17 años), MJ (de 18 a 34 años) y mujeres trabajadoras del sexo (MTS; ≥ 18 años) en la provincia de Gauteng, Sudáfrica. Administramos 600 encuestas cuantitativas en los tres subgrupos de mujeres. Los resultados indican la preferencia por un implante que proporciona una protección contra el VIH más prolongada (24 meses a comparación con 6 meses) y que requiere de una única inserción. Las participantes afirmaron que prefieren un implante biodegradable que puede retirarse un mes después de su inserción. Las participantes no tenían preferencia por un sitio específico de inserción. En general, el 78% de las participantes indicaron que probablemente (33%) o muy probablemente (45%) utilizarían un implante de PrEP si estuviera disponible, y la mayoría (82%) manifestó su preferencia por un producto que proporcionaba una doble protección contra el VIH y el embarazo no deseado. Para reducir el riesgo de contraer el VIH, las NA, MJ y MTS participantes se mostraron muy dispuestas a utilizar implantes de PrEP de larga duración, altamente eficaces y disolubles.

Implementation experiences and insights from the scale-up of an HIV assisted partner notification intervention in Central Asia.

INTRODUCTION: WHO recommends assisted partner notification (APN) for people living with HIV (PLHIV). These services have not been widely scaled in Central Asia. We describe the results from an APN intervention implemented within a programme focused on PLHIV and people who inject drugs in Kazakhstan, the Kyrgyz Republic and Tajikistan. METHODS: Routine data from index cases and their partners were analysed from equal-length periods before and after APN launch. Prior to APN index cases could recruit partners using passive referral, and under APN, had their choice of passive referral or APN (provider, contract or dual-referral). We compared the demographic characteristics of index cases and their sexual/injecting partners from the pre-APN and APN periods, described the number/proportion of HIV cases found (positivity rate) and evaluated predictors of HIV infection among partners using logistic regression. RESULTS: Under APN 2676 PLHIV served as index cases and recruited 3735 partners for testing, compared to 4418 index cases and 2240 partners during the pre-APN period. A total of 322 (8.6%) partners were rapid test positive during APN versus 161 (7.2%, p = 0.048) before APN. Women represented 38% of APN index cases (vs. 42% pre-APN), 52% of partners tested (vs. 50% pre-APN) and 56% of all PLHIV identified (vs. 63% pre-APN). Compared to the pre-APN period, the number of partners tested per index case recruited increased (0.5 to 1.4, p < 0.001) and the number of index cases needed to find one HIV-positive partner decreased significantly (27.4 to 8.3, p < 0.001) under APN. CONCLUSIONS: APN was feasibly integrated within a people who inject drugs and PLHIV-focused HIV programme, and was acceptable to high-risk populations in Central Asia. Under APN, large numbers of sexual and injecting partners of PLHIV - including women and non-marital partners - were tested while maintaining high positivity rates. Relative to the pre-APN period, APN approximately tripled the number of partners recruited per index case and reduced the number of index cases needed to find a positive partner by >3 times.

Yield of household contact tracing for tuberculosis in rural South Africa.

BACKGROUND: Efficient and effective strategies for identifying cases of active tuberculosis (TB) in rural sub-Saharan Africa are lacking. Household contact tracing offers a potential approach to diagnose more TB cases, and to do so earlier in the disease course. METHODS: Adults newly diagnosed with active TB were recruited from public clinics in Vhembe District, South Africa. Study staff visited index case households and collected sputum specimens for TB testing via smear microscopy and culture. We calculated the yield and the number of households needed to screen (NHNS) to find one additional case. Predictors of new TB among household contacts were evaluated using multilevel logistic regression. RESULTS: We recruited 130 index cases and 282 household contacts. We identified 11 previously undiagnosed cases of bacteriologically-confirmed TB, giving a prevalence of 3.9% (95% CI: 2.0-6.9%) among contacts, a yield of 8.5 per 100 (95% CI: 4.2-15.1) index cases traced, and NHNS of 12 (95% CI: 7-24). The majority of new TB cases (10/11, 90.9%) were smear negative, culture positive. The presence of TB symptoms was not associated with an increased odds of active TB (aOR: 0.3, 95% CI: 0.1-1.4). CONCLUSIONS: Household contacts of recently diagnosed TB patients in rural South Africa have high prevalence of TB and can be feasibly detected through contact tracing, but more sensitive tests than sputum smear are required. Symptom screening among household contacts had low sensitivity and specificity for active TB in this study.

Social network methods for HIV case-finding among people who inject drugs in Tajikistan.

INTRODUCTION: HIV testing programmes have struggled to reach the most marginalized populations at risk for HIV. Social network methods such as respondent-driven sampling (RDS) and peer-based active case-finding (ACF) may be effective in overcoming barriers to reaching these populations. We compared the client characteristics, proportion testing HIV positive (yield), and number of new cases found through two RDS strategies and an ACF approach to HIV case-finding among people who inject drugs (PWID) in Tajikistan. METHODS: Routine programme data from adult PWID recruited to testing under the HIV Flagship Project in Tajikistan were analysed to compare client demographic and clinical characteristics across the three approaches. We also compared the number of previously untested clients, the number of new HIV cases found, and the yield across the case-finding strategies, and evaluated predictors of new HIV diagnosis using fixed-effects logistic regression. RESULTS: From 24 October 2016 to 30 June 2017, Flagship tested 10,300 PWID for HIV, including 2143 under RDS with unrestricted waves (RDS1, yield: 1.5%), 3517 under restricted RDS (RDS2, yield: 2.6%), and 4640 under ACF (yield: 1.5%). Clients recruited under ACF were similar in age (35.8 vs. 36.8) and gender (91% vs. 90% male) to those recruited through RDS, though ACF clients were more likely to report being a first-time tester (85.1% vs. 68.3%, p < 0.001). After controlling for age, sex, previous testing history and accounting for clustering at the site level, we found that clients tested under both RDS1 (aOR: 1.74, 95% CI: 1.04 to 2.90) and RDS2 (aOR: 1.54, 95% CI: 1.11 to 2.15) had higher odds of testing newly positive for HIV relative to clients recruited through ACF. We did not find significant differences in the odds of new HIV infection between those recruited from RDS1 versus RDS2 (aOR: 1.12, 95% CI: 0.67 to 1.86). CONCLUSIONS: RDS-based interventions resulted in higher yields and overall case-finding, especially when recruitment was restricted. However, ACF identified a higher proportion of first-time testers. To find at least 90% of PWID living with HIV in Tajikistan, it may be necessary to implement multiple case-finding approaches concurrently to maximize testing coverage.

Perinatal Antiretroviral Exposure and Prevented Mother-to-child HIV Infections in the Era of Antiretroviral Prophylaxis in the United States, 1994-2010.

OBJECTIVES: Using published, nationally-representative estimates, we calculated the total number of perinatally HIV-exposed and HIV-infected infants born during 1978-2010, the number of perinatal HIV cases prevented by interventions designed for the prevention of mother-to-child transmission (PMTCT), and the number of infants exposed to antiretroviral (ARV) drugs during the prenatal and intrapartum periods. DESIGN: We calculated the number of infants exposed to ARV drugs since 1994, and the number of cases of mother-to-child HIV transmission prevented from 1994 to 2010 using published data. We generated confidence limits for our estimates by performing a simulation study. METHODS: Data were obtained from published, nationally-representative estimates from the Centers for Disease Control and Prevention. Model parameters included the annual numbers of HIV-infected pregnant women, the annual numbers of perinatally infected infants, the annual proportions of infants exposed to ARV drugs during the prenatal and intrapartum period and the estimated MTCT rate in the absence of preventive interventions. For the simulation study, model parameters were assigned distributions and we performed 1,000,000 repetitions. RESULTS: Between 1978 and 2010, an estimated 186,157 [95% confidence interval (CI): 185,312-187,003] HIV-exposed infants and approximately 21,003 (95% CI: 20,179-21,288) HIV-infected infants were born in the United States. Between 1994 and 2010, an estimated 124,342 (95% CI: 123,651-125,034) HIV-exposed infants were born in the US, and approximately 6083 (95% CI: 5931-6236) infants were perinatally infected with HIV. During this same period, about 100,207 (95% CI: 99,374-101,028) infants were prenatally exposed to ARV drugs. As a result of PMTCT interventions, an estimated 21,956 (95% CI: 20,191-23,759) MTCT HIV cases have been prevented in the United States since 1994. CONCLUSION: Although continued vigilance is needed to eliminate mother-to-child HIV transmission, PMTCT interventions have prevented nearly 22,000 cases of perinatal HIV transmission in the United States since 1994.

Integrated Source Case Investigation for Tuberculosis (TB) and HIV in the Caregivers and Household Contacts of Hospitalised Young Children Diagnosed with TB in South Africa: An Observational Study.

BACKGROUND: Contact tracing, to identify source cases with untreated tuberculosis (TB), is rarely performed in high disease burden settings when the index case is a young child with TB. As TB is strongly associated with HIV infection in these settings, we used source case investigation to determine the prevalence of undiagnosed TB and HIV in the caregivers and household contacts of hospitalised young children diagnosed with TB in South Africa. METHODS: Caregivers and household contacts of 576 young children (age ≤7 years) with TB diagnosed between May 2010 and August 2012 were screened for TB and HIV. The primary outcome was the detection of laboratory-confirmed, newly-diagnosed TB disease and/or HIV-infection in close contacts. RESULTS: Of 576 caregivers, 301 (52·3%) self-reported HIV-positivity. Newly-diagnosed HIV infection was detected in 63 (22·9%) of the remaining 275 caregivers who self-reported an unknown or negative HIV status. Screening identified 133 (23·1%) caregivers eligible for immediate anti-retroviral therapy (ART). Newly-diagnosed TB disease was detected in 23 (4·0%) caregivers. In non-caregiver household contacts (n = 1341), the prevalence of newly-diagnosed HIV infection and TB disease was 10·0% and 3·2% respectively. On average, screening contacts of every nine children with TB resulted in the identification of one case of newly-diagnosed TB disease, three cases of newly diagnosed HIV-infection, and three HIV-infected persons eligible for ART. CONCLUSION: In high burden countries, source case investigation yields high rates of previously undiagnosed HIV and TB infection in the close contacts of hospitalised young children diagnosed with TB. Furthermore, integrated screening identifies many individuals who are eligible for immediate ART. Similar studies, with costing analyses, should be undertaken in other high burden settings-integrated source case investigation for TB and HIV should be routinely undertaken if our findings are confirmed.

Costs and Consequences of Using Interferon-γ Release Assays for the Diagnosis of Active Tuberculosis in India.

BACKGROUND: There is growing concern that interferon-γ release assays (IGRAs) are being used off-label for the diagnosis of active tuberculosis (TB) disease in many high-burden settings, including India, where the background prevalence of latent TB infection is high. We analyzed the costs and consequences of using IGRAs for the diagnosis of active TB in India from the perspective of the Indian TB control sector. METHODS AND FINDINGS: We constructed a decision analytic model to estimate the incremental cost and effectiveness of IGRAs for the diagnosis of active TB in India. We compared a reference scenario of clinical examination and non-microbiological tests against scenarios in which clinical diagnosis was augmented by the addition of either sputum smear microscopy, IGRA, or Xpert MTB/RIF. We examined costs (in 2013 US dollars) and consequences from the perspective of the Indian healthcare sector. Relative to sputum smear microscopy, use of IGRA for active TB resulted in 23,700 (95% uncertainty range, UR: 3,800 - 38,300) additional true-positive diagnoses, but at the expense of 315,700 (95% UR: 118,300 - 388,400) additional false-positive diagnoses and an incremental cost of US$49.3 million (95% UR: $34.9 - $58.0 million) (2.9 billion Indian Rupees). Relative to Xpert MTB/RIF (including the cost of treatment for drug resistant TB), use of IGRA led to 400 additional TB cases treated (95% UR: [-8,000] - 16,200), 370,600 (95% UR: 252,200 - 441,700) more false-positive diagnoses, 70,400 (95% UR: [-7,900] - 247,200) fewer disability-adjusted life years averted, and US$14.6 million (95%UR: [-$7.2] - $28.7 million) (854 million Indian Rupees) in additional costs. CONCLUSION: Using IGRAs for diagnosis of active TB in a setting like India results in tremendous overtreatment of people without TB, and substantial incremental cost with little gain in health. These results support the policies by WHO and Standards for TB Care in India, which discourage the use of IGRAs for the diagnosis of active TB in India and similar settings.

Impact of community-based lymphedema management on perceived disability among patients with lymphatic filariasis in Orissa State, India.

BACKGROUND: Lymphatic filariasis (LF) infects approximately 120 million people worldwide. As many as 40 million have symptoms of LF disease, including lymphedema, elephantiasis, and hydrocele. India constitutes approximately 45% of the world's burden of LF. The Indian NGO Church's Auxiliary for Social Action (CASA) has been conducting a community-based lymphedema management program in Orissa State since 2007 that aims to reduce the morbidity associated with lymphedema and elephantiasis. The objective of this analysis is to evaluate the effects of this program on lymphedema patients' perceived disability. METHODOLOGY/PRINCIPAL FINDINGS: For this prospective cohort study, 370 patients ≥14 years of age, who reported lymphedema lasting more than three months in one or both legs, were recruited from villages in the Bolagarh sub-district, Khurda District, Orissa, India. The World Health Organization Disability Assessment Schedule II was administered to participants at baseline (July, 2009), and then at regular intervals through 24 months (July, 2011), to assess patients' perceived disability. Disability scores decreased significantly (p<0.0001) from baseline to 24 months. Multivariable analysis using mixed effects modeling found that employment and time in the program were significantly associated with lower disability scores after two years of program involvement. Older age, female gender, the presence of other chronic health conditions, moderate (Stage 3) or advanced (Stage 4-7) lymphedema, reporting an adenolymphangitis (ADL) episode during the previous 30 days, and the presence of inter-digital lesions were associated with higher disability scores. Patients with moderate or advanced lymphedema experienced greater improvements in perceived disability over time. Patients participating in the program for at least 12 months also reported losing 2.5 fewer work days per month (p<0.001) due to their lymphedema, compared to baseline. SIGNIFICANCE: These results indicate that community-based lymphedema management programs can reduce disability and prevent days of work lost. These effects were sustained over a 24 month period.

A review of evidence for transmission of HIV from children to breastfeeding women and implications for prevention.

BACKGROUND: Child-to-breastfeeding woman transmission (CBWT) of HIV occurs when an HIV-infected infant transmits the virus to an HIV-uninfected woman through breastfeeding. Transmission likely occurs as a result of breastfeeding contact during a period of epithelial disruption, such as maternal skin fissures and/or infant stomatitis. Despite extensive epidemiologic and phylogenetic evidence, however, CBWT of HIV continues to be overlooked. OBJECTIVE: This article summarizes the available evidence for CBWT from nosocomial outbreaks, during which nosocomially HIV-infected infants transmitted the virus to their mothers through breastfeeding. This article also explores the CBWT risk associated with HIV-infected orphans and their female caretakers, and the lack of guidance regarding CBWT prevention in infant feeding recommendations. METHODS: We searched online databases including PubMed and ScienceDirect for English language articles published from January 1975 to January 2011 using the search terms "HIV," "perinatal," "child-to-mother" and "breastfeeding." The citations from all selected articles were reviewed for additional studies. RESULTS: We identified 5 studies documenting cases of CBWT. Two studies contained data on the number of HIV-infected women, as well as the proportion breastfeeding. Rates of CBWT ranged from 40% to 60% among women reporting breastfeeding after their infants were infected. CONCLUSIONS: Poor infection control practices, especially in areas of high HIV prevalence, have resulted in pediatric HIV infections and put breastfeeding women at risk for CBWT. Current infant feeding guidelines and HIV prevention messages do not address CBWT, and fail to provide strategies to help women reduce their risk of acquiring HIV during breastfeeding.