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Youth-led strategies remain untested in clinic-based programs to improve viral suppression (VS) and reduce stigma among HIV-positive adolescents and young adults (AYA) in sub-Saharan Africa. In response, Project YES! placed paid HIV-positive youth peer mentors (YPM) in four HIV clinics in Ndola, Zambia including a Children's Hospital (pediatric setting), an adult Hospital and two primary care facilities (adult settings). A randomized controlled trial was conducted from December 2017 to February 2019. Consecutively recruited 15 to 24-year-olds were randomly assigned to an intervention arm with monthly YPM one-on-one and group sessions and optional caregiver support groups, or a usual care comparison arm. Survey data and blood samples were collected at baseline and at the six-month midline. Generalized estimating equation models evaluated the effect of study arm over time on VS, antiretroviral treatment (ART) adherence gap, and internalized stigma. Out of 276 randomized youth, 273 were included in the analysis (Intervention n = 137, Comparison n = 136). VS significantly improved in both arms (I:63.5% to 73.0%; C:63.7% to 71.3.0%) [OR:1.49, 95% CI:1.08, 2.07]. In a stratified analysis intervention (I:37.5% to 70.5%) versus the comparison (C:60.3% to 59.4%) participants from the pediatric clinic experienced a relative increase in the odds of VS by a factor of 4.7 [interaction term OR:4.66, 95% CI:1.84, 11.78]. There was no evidence of a study arm difference in VS among AYA in adult clinics, or in ART adherence gaps across clinics. Internalized stigma significantly reduced by a factor of 0.39 [interaction term OR:0.39, 95% CI:0.21,0.73] in the intervention (50.4% to 25.4%) relative to the comparison arm (45.2% to 39.7%). Project YES! engaged AYA, improving VS in the pediatric clinic and internalized stigma in the pediatric and adult clinics. Further research is needed to understand the intersection of VS and internalized stigma among AYA attending adult HIV clinics. ClinicalTrials.gov NCT04115813.

Background Different tools exist for assessing risk of bias of intervention studies for systematic reviews. We present a tool for assessing risk of bias across both randomized and non-randomized study designs. The tool was developed by the Evidence Project, which conducts systematic reviews and meta-analyses of behavioral interventions for HIV in low- and middle-income countries. Methods We present the eight items of the tool and describe considerations for each and for the tool as a whole. We then evaluate reliability of the tool by presenting inter-rater reliability for 125 selected studies from seven published reviews, calculating a kappa for each individual item and a weighted kappa for the total count of items. Results The tool includes eight items, each of which is rated as being present (yes) or not present (no) and, for some items, not applicable or not reported. The items include (1) cohort, (2) control or comparison group, (3) pre-post intervention data, (4) random assignment of participants to the intervention, (5) random selection of participants for assessment, (6) follow-up rate of 80% or more, (7) comparison groups equivalent on sociodemographics, and (8) comparison groups equivalent at baseline on outcome measures. Together, items (1)–(3) summarize the study design, while the remaining items consider other common elements of study rigor. Inter-rater reliability was moderate to substantial for all items, ranging from 0.41 to 0.80 (median κ  = 0.66). Agreement between raters on the total count of items endorsed was also substantial ( κ w  = 0.66). Conclusions Strengths of the tool include its applicability to a range of study designs, from randomized trials to various types of observational and quasi-experimental studies. It is relatively easy to use and interpret and can be applied to a range of review topics without adaptation, facilitating comparability across reviews. Limitations include the lack of potentially relevant items measured in other tools and potential threats to validity of some items. To date, the tool has been applied in over 30 reviews. We believe it is a practical option for assessing risk of bias in systematic reviews of interventions that include a range of study designs.

The Project YES! clinic-based peer mentoring program was a randomized controlled trial (RCT) conducted among 276 youth from four HIV clinics to test the impact of the program on promoting HIV self-management and reducing internalized stigma among youth living with HIV (ages 15–24 years) in Ndola, Zambia. We conducted a qualitative sub-study involving in-depth interviews with 40 intervention youth participants (21 female, 19 male) to explore their experiences with Project YES! which included: an orientation meeting led by a healthcare provider, monthly individual and group counseling sessions over six months, and three optional caregiver group sessions. Using baseline RCT data, we used maximum variation sampling to purposively select youth by sex, age, change in virologic results between baseline and midline, and study clinic. A four-person team conducted thematic coding. Youth described their increased motivation to take their HIV care seriously due to Project YES!, citing examples of improvements in ART adherence and for some, virologic results. Many cited changes in behavior in the context of greater feelings of self-worth and acceptance of their HIV status, resulting in less shame and fear associated with living with HIV. Youth also attributed Project YES! with reducing their sense of isolation and described Project YES! youth peer mentors and peers as their community and “family.” Findings highlight that self-worth and personal connections play a critical role in improving youths’ HIV outcomes. Peer-led programs can help foster these gains through a combination of individual and group counseling sessions. Greater attention to the context in which youth manage their HIV, beyond medication intake, is needed to reach global HIV targets.

Adolescents and young adults (AYAs) living with HIV face unique challenges and have poorer health outcomes than adults with HIV. Project YES! was a youth-led initiative to promote HIV self-management and reduce stigma among AYAs in four Ndola, Zambia clinics. Clinic health care providers (HCPs) were involved in multiple intervention aspects, including serving as expert resources during AYA and caregiver group meetings, facilitating resistance test-based AYA antiretroviral drug changes, meeting with participants referred through a safety protocol, and guiding a subset of participants' physical transition from pediatric to adult clinic settings. This study aimed to understand HCP insights on facilitators and barriers to implementing Project YES! and scaling up a clinic-based, youth-focused program. A trained interviewer conducted ten in-depth interviews with participating HCPs from November-December 2018 and analyzed data, identifying key themes. These themes were examined in terms of two implementation science outcomes-acceptability and feasibility-to inform scalability. HCPs found peer mentoring valuable for AYAs with HIV and the bimonthly caregiver meetings beneficial to AYA caregivers. HCPs voiced a desire for more involvement in specific processes related to patient clinical care, such as drug changes. HCPs' experiences with the study safety protocol, including referrals for youth experiences of violence, shifted their views of AYAs and informed their understanding of key issues youth face. Considering this, many HCPs requested more resources to support AYAs' varied needs. HCPs noted limited time and clinic space as implementation barriers but felt the program was valuable overall. HCPs concluded youth peer mentoring was highly acceptable and feasible, supporting scale-up of youth-led interventions addressing the multi-faceted needs of AYAs living with HIV. Continued provider involvement in resistance test-based antiretroviral drug changes, considered in the context of health system and clinic policy, would enhance long-term success of the program at scale.

HIV drug resistance (HIVDR) poses a threat to the HIV epidemic control in Zambia especially in sub-populations such as the 15-24 years where there is poor virological suppression. Understanding the prevalence and patterns of HIVDR in this population (15-24 years) will contribute to defining effective antiretroviral therapy (ART) regimens, improving clinical decision making, and supporting behavioral change interventions needed to achieve HIV epidemic control. A cross-sectional analysis of study enrollment data from the Project YES! Youth Engaging for Success randomized controlled trial was conducted. Participants were 15 to 24 years old, who knew their HIV status, and had been on ART for at least 6 months. All participants completed a survey and underwent viral load (VL) testing. Participants with viral failure (VL ≥1,000 copies/mL) underwent HIVDR testing which included analysis of mutations in the protease and reverse transcriptase genes. A total of 99 out of 273 analyzed participants receiving ART had VL failure, of whom 77 had successful HIVDR amplification and analysis. Out of the 77, 75% (58) had at least one drug resistant mutation, among which 83% (48/58) required a drug change. Among the 58 with HIVDR mutations, the prevalence of at least one HIVDR mutation to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 81%, 65.5% and 1.7%. The mutation M184V which confers resistance to NRTI drugs of lamivudine (3TC) and emtricitabine (FTC) was the most common (81%) among NRTI associated mutations followed by K65R (34.5%) which is associated with both tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF) resistance. Thymidine analogue mutations (TAMs) which confer resistance primarily to zidovudine (AZT), stavudine (d4T) and other NRTIs were observed at 32.8%. Common TAMs were K70RTQNE (32.8%), K219QE (22.4%), D67N (17.2%) and T215IT (15.5%). The most common NNRTI associated mutation was the K103N (65.5%) which confers resistance to both efavirenz (EFV) and nevirapine (NVP). There was a relatively high occurrence of other NNRTI mutations V106A (36.2%), as well as Y188C (36.2%) and Y181C (36.2%) which confer resistance to etravirine. There is a high prevalence of HIVDR including TAMs despite majority of these patients (90.48%) being on AZT or d4T sparing first line ART among the youth. Emergence of these mutations including the NNRTI associated mutations (Y181C and Y188C) may compromise future second- and third-line regimens in the absence of routine HIVDR testing. HIVDR monitoring at start of ART or at first-line failure can better inform clinical decision making and ART programing.

Little is known about youth-led approaches to addressing HIV-related outcomes among adolescents and young adults (AYA) living with HIV. In response, Project YES! hired and trained youth living with HIV as peer mentors (YPMs) in four HIV clinics in Ndola, Zambia to hold meetings with 276 15-24-year-olds living with HIV. Within this randomized controlled trial, a qualitative sub-study was conducted to explore YPMs' implementing experiences. In-depth interviews were conducted with the eight YPMs (50% female) ages 21-26 years. YPMs were asked about their experiences working with clients, their feedback on program components, and what the experience meant to them personally and professionally. Interviews were audio-recorded, transcribed verbatim, and thematic analysis was performed. YPMs connected with AYA clients by discussing shared struggles, modeling positive health behaviors, and establishing judgement-free environments. YPMs experienced powerful personal transformations in HIV-related health behaviors, conceptions of self, and plans for the future. Many expressed now seeing themselves as community leaders-\"ambassadors\", \"game changers\"-and \"not just alone in this world.\" They described newfound commitments to reaching personal and professional goals. YPMs were adamant that Project YES! should expand so other HIV-positive AYA might benefit. Well-trained and compensated YPMs who are integrated into HIV clinics can support AYA in unique and important ways due to their shared experiences. The transformational experience of becoming YPMs empowers youth to see themselves as role models and leaders. Future programs should engage youth living with HIV as partners in efforts to end the HIV epidemic.

Little is known about violence against HIV-positive adolescents and young adults (AYA) in sub-Saharan Africa. This analysis examines experiences of violence victimization, and the perpetrators of this violence, among AYA living with HIV, aged 15-24 years, in Zambia. We analyzed baseline data from 272 AYA (60.1% female, 71.0% perinatally infected) enrolled in Project YES! (Youth Engaging for Success), a randomized controlled trial conducted in four HIV clinics in Ndola, Zambia. Violence measures were adapted from the ICAST-C and the WHO Multi-Country Study on Women's Health and Domestic Violence. Youth could report up to 12 perpetrator types for past-year experiences of violence. We estimated lifetime and past-year prevalence of physical violence, psychological abuse, and forced sex, disaggregated by sex and age group. Estimates were weighted using sex and age data from the 2013-14 Zambian Demographic and Health Survey to be representative of HIV-positive AYA in Zambia. Estimated lifetime prevalence of any violence victimization was 78.2%. Past-year prevalence was 72.0% among males and 74.5% among females. Almost half of AYA (46.1%) had ever experienced polyvictimization (2+ types of violence). Psychological abuse was most common (70.4% lifetime, 65.3% past-year), followed by physical violence (50.8% lifetime, 44.7% past-year) and forced sex (10.4% lifetime, 4.7% past-year). Among past-year victims, males experienced more violence than females from a friend/peer (74.3% vs. 45.1%, p<0.001); females experienced more violence than males from a romantic partner (33.3% vs. 5.0%, p<0.001), parent/caregiver (32.4% vs. 17.6%, p = 0.02), and stranger (19.7% vs. 5.2%, p<0.001). The widespread and overlapping prevalence of multiple types of violence highlights the critical need for prevention and response efforts that are tailored to youths' sex and the perpetrator type. Future research should explore violence victimization and HIV outcomes, and the measurement of psychological abuse and sexual violence, among HIV-positive AYA in the region.

Infants born to HIV-infected mothers are more likely to be low birthweight (LBW) than other infants, a condition that is stigmatized in many settings worldwide, including sub-Saharan Africa. Few studies have characterized the social-cultural context and response to LBW stigma among mothers in sub-Saharan Africa or explored the views of women living with HIV (WLHIV) on the causes of LBW. We purposively sampled thirty postpartum WLHIV, who had given birth to either LBW or normal birthweight infants, from two tertiary hospitals in Accra, Ghana. Using semi-structured interviews, we explored women's understanding of the etiology of LBW, and their experiences of caring for a LBW infant. Interviews were analyzed using interpretive phenomenology. Mothers assessed their babies' smallness based on the baby's size, not hospital-recorded birthweight. Several participants explained that severe depression and a loss of appetite, linked to stigma following an HIV diagnosis during pregnancy, contributed to infants being born LBW. Women with small babies also experienced stigma due to the newborns' \"undesirable\" physical features and other people's unfamiliarity with their size. Consequently, mothers experienced blame, reluctance showing the baby to others, and social gossip. As a result of this stigma, women reported self-isolation and depressive symptoms. These experiences were layered on the burden of healthcare and infant feeding costs for LBW infants. LBW stigma appeared to attenuate with increased infant weight gain. A few of the women also did not breastfeed because they thought their baby's small size indicated pediatric HIV infection. Among WLHIV in urban areas in Ghana, mother and LBW infants may experience LBW-related stigma. A multi-component intervention that includes reducing LBW incidence, treating antenatal depression, providing psychosocial support after a LBW birth, and increasing LBW infants' weight gain are critically needed.

The effectiveness of HIV voluntary counseling and testing (VCT) in reducing HIV risk behaviors in developing countries was assessed using meta-analytic methods. A standardized protocol was used for searching, acquiring, and extracting study data and meta-analyzing the results. Seven studies met the inclusion criteria. VCT recipients were significantly less likely to engage in unprotected sex when compared to behaviors before receiving VCT, or as compared to participants who had not received VCT [OR 1.69; 95%CI 1.25–2.31]. VCT had no significant effect on the number of sex partners [OR 1.22; 95%CI 0.89–1.67]. While these findings provide only moderate evidence in support of VCT as an effective prevention strategy, neither do they negate the need to expand access to HIV testing and counseling services. Such expansion, however, must be accompanied by rigorous evaluation in order to test, refine and maximize the preventive benefits of learning one’s HIV infection status through HIV testing and counseling.

IntroductionSelf-collected samples (SCS) for sexually transmitted infection (STI) testing have been shown to be feasible and acceptable in high-resource settings. However, few studies have assessed the acceptability of SCS for STI testing in a general population in low-resource settings. This study explored the acceptability of SCS among adults in south-central Uganda.MethodsNested within the Rakai Community Cohort Study, we conducted semistructured interviews with 36 adults who SCS for STI testing. We analysed the data using an adapted version of the Framework Method.ResultsOverall, SCS was acceptable to both male and female participants, regardless of whether they reported recent STI symptoms. Perceived advantages of SCS over provider-collection included increased privacy and confidentiality, gentleness and efficiency. Disadvantages included the lack of provider involvement, fear of self-harm and the perception that SCS was unhygienic. Most participants preferred provider-collected samples to SCS. Nevertheless, almost all said they would recommend SCS and would do it again in the future.ConclusionSCS are acceptable among adults in this low-resource setting and could be offered as an additional option to expand STI diagnostic services.