Characterizing long-acting injectable antiretroviral therapy eligibility and initiation at a safety net academic medical center in the southeastern United States.

Background: Long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) extends dosing intervals from daily to every 8 weeks. Equitable implementation requires anticipating and addressing barriers to use. We described LAI-CAB/RPV eligibility and initiation among persons with HIV (PWH) receiving care at a Southeastern US academic medical center. Methods: We included PWH ≥18 years, in care 01/01/2020-12/31/2021, and participating in the UNC CFAR HIV Clinical Cohort. We characterized LAI-CAB/RPV eligibility, compared those with and without recent detectable viral load (VL), and described clinical outcomes on LAI-CAB/RPV. Results: Among 1672 PWH, 425 (25.4%) had LAI-CAB/RPV drug-resistance. Among 1238 LAI-eligible PWH, 8.9% had detectable VL. Median age was 53 (interquartile range 40, 61), 54.6% were non-Hispanic Black, and 73.6% male. Over one-third lived >50 miles from clinic, one-fifth were uninsured, and 7.4% reported hazardous alcohol use. Gaps in care (prior 12-month) were more common among PWH with detectable VL versus suppressed (23.1% vs 13.9%, p = 0.03). 6/47 initiated LAI-CAB/RPV had detectable VL prior to injection; >95% sustained suppression and those with detectable VL had a rapid decline in viremia. Conclusions: Three-quarters of PWH were eligible for LAI-CAB/RPV, but equitable implementation may require addressing challenges such as distance to care, inconsistent care engagement, and other comorbid conditions, particularly for PWH with viremia.

Updated Risk Score Algorithms for Acute HIV Infection Detection at a Sexually Transmitted Infections Clinic in Lilongwe, Malawi.

BACKGROUND: Detection of acute (pre-seroconversion) HIV infection (AHI), the phase of highest transmission risk, requires resource-intensive RNA- or antigen-based detection methods that can be infeasible for routine use. Risk score algorithms can improve the efficiency of AHI detection by identifying persons at highest risk of AHI for prioritized RNA/antigen testing, but prior algorithms have not considered geospatial information, potential differences by sex, or current antibody testing paradigms. METHODS: We used elastic net models to develop sex-stratified risk score algorithms in a case-control study of persons (136 with AHI, 250 without HIV) attending a sexually transmitted infections (STI) clinic in Lilongwe, Malawi from 2015 to 2019. We designed algorithms for varying clinical contexts according to three levels of data availability: 1) routine demographic and clinical information, 2) behavioral and occupational data obtainable through patient interview, and 3) geospatial variables requiring external datasets or field data collection. We calculated sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) to assess model performance and developed a web application to support implementation. RESULTS: The highest-performing AHI risk score algorithm for men (AUC=0.74) contained five variables (condom use, body aches, fever, rash, genital sores/ulcers) from the first two levels of data availability. The highest-performing algorithm for women (AUC=0.81) contained fifteen variables from all three levels of data availability. A risk score cut-point of 0.26 had an AHI detection sensitivity of 93% and specificity of 27% for males, and a cut-point of 0.15 had 97% sensitivity and 44% specificity for females. Additional models are available in the web application. CONCLUSION: Risk score algorithms can facilitate efficient AHI detection in STI clinic settings, creating opportunities for HIV transmission prevention interventions during this critical period of elevated transmission risk.

Low HIV Testing and PrEP Uptake of Adolescent and Young Men who have Sex with Men in Vietnam.

Little is known about HIV testing, pre-exposure prophylaxis (PrEP) awareness and uptake among adolescent and young men who have sex with men (AYMSM) in Vietnam. We conducted an online survey among AYMSM in Vietnam to determine the prevalence of HIV testing, PrEP awareness, uptake and their correlates. From December 2022-March 2023, 120 HIV-negative AYMSM from 15 to 19 years old in Hanoi and Ho Chi Minh city, Vietnam were recruited through peer referral to complete an online survey, which included questions on demographics, sexual behaviors, HIV risk perception and knowledge, HIV and sexually transmitted infections (STI) testing, PrEP awareness and uptake. Separate multivariable models were used to determine the correlates of HIV testing, PrEP awareness and uptake. Only 58% of participants had ever been tested for HIV. The majority of participants had heard of PrEP before (82%), but only 36% had ever used PrEP. HIV knowledge (aPR (adjusted prevalence ratio) = 1.59; 95%CI:1.06-2.39), a history of STI testing (aPR = 1.32; 95%CI:1.06-1.64), having had anal sex with another man (aPR = 4.49; 95%CI:1.40-14.38) and lower HIV risk perception (aPR = 0.62; 95%CI:0.47-0.83) were associated with HIV testing. HIV knowledge (aPR = 1.38; 95%CI:1.06-1.78) and a history of STI testing (aPR = 1.16; 95%CI:1.03-1.32) were also associated with PrEP awareness. Higher HIV risk perception was negatively associated with PrEP use (aPR = 0.59; 95%CI:0.35-0.99). Our findings underscored the urgent need for further research to explore the causes of the gaps in HIV testing and PrEP use as well as to design innovative interventions tailored to the needs of AYMSM to support HIV testing and PrEP use.

Evaluating the impact of HIV pre-exposure prophylaxis on pregnancy, infant, and maternal health outcomes in Malawi: PrIMO study protocol.

BACKGROUND: Incident HIV during the perinatal period significantly impedes elimination of Mother-to-Child HIV Transmission (eMTCT) efforts. Pre-Exposure Prophylaxis (PrEP) effectively reduces HIV acquisition, and new agents like injectable Cabotegravir (CAB-LA) offer potential advantages for pregnant and breastfeeding women. The Pregnancy, Infant, and Maternal health Outcomes (PrIMO) study will compare rates of composite adverse pregnancy outcomes, and infant adverse events, growth and neurodevelopment between mother-infant dyads receiving CAB-LA and those receiving oral PrEP in Malawi. METHODS: PrIMO is an observational cohort study involving: (1) the development of a PrEP Pregnancy Registry for longitudinal surveillance of pregnant women on PrEP in Malawi; and (2) the enrolment of a prospective safety cohort of 621 pregnant women initiating oral PrEP or CAB-LA and their subsequent infants. The registry will include all women continuing or initiating PrEP during pregnancy across targeted sites in Lilongwe and Blantyre districts. The safety cohort will enrol a subset of those women and their infants from Bwaila District Hospital in Lilongwe, Malawi. We hypothesize that CAB-LA's safety will be comparable to daily oral PrEP regarding adverse pregnancy outcomes, maternal/infant adverse events, and infant development. Participants in the cohort will choose either oral PrEP or CAB-LA and will be followed until 52 weeks post-delivery. Safety data will be collected from all mother-infant pairs and qualitative interviews will be conducted with a subset of purposively selected women (n = 50) to assess the acceptability of each PrEP modality. DISCUSSION: The PrIMO study will provide critical data on the safety of CAB-LA in pregnant and breastfeeding women and their infants. Results will guide clinical recommendations as the Malawi Ministry of Health prepares for the rollout of CAB-LA to this population. Evaluation of Registry implementation will inform its expansion to a nationwide safety monitoring system for PrEP use during pregnancy, with implications for similar systems in the region. TRIAL REGISTRATION NUMBER: NCT06158126. The study was prospectively registered (5 December 2023) in ClinicalTrials.gov.

A Brief Alcohol Intervention (BAI) to reduce alcohol use and improve PrEP outcomes among men who have sex with men in Vietnam: study protocol for a randomized controlled trial.

BACKGROUND: In Vietnam and other global settings, men who have sex with men (MSM) have become the population at greatest risk of HIV infection. Although HIV pre-exposure prophylaxis (PrEP) has been implemented as a prevention strategy, PrEP outcomes may be affected by low persistence and adherence among MSM with unhealthy alcohol use. MSM have a high prevalence of unhealthy alcohol use in Vietnam, which may affect PrEP outcomes. METHODS: Design: We will conduct a two-arm hybrid type 1 effectiveness-implementation randomized controlled trial of a brief alcohol intervention (BAI) compared to the standard of care (SOC) at the Sexual Health Promotion (SHP) clinic Hanoi, Vietnam. PARTICIPANTS: Sexually active MSM (n=564) who are newly initiating PrEP or re-initiating PrEP and have unhealthy alcohol use will be recruited and randomized 1:1 to the SOC or BAI arm. A subgroup of participants (n=20) in each arm will be selected for longitudinal qualitative interviews; an additional subset (n=48) in the BAI arm will complete brief quantitative and qualitative interviews after completion of the BAI to assess the acceptability of the intervention. Additional implementation outcomes will be assessed through interviews with clinic staff and stakeholders (n=35). INTERVENTION: Study participants in both arms will receive standard care for PrEP clients. In the BAI arm, each participant will receive two face-to-face intervention sessions and two brief booster phone sessions, based on cognitive behavioral therapy and delivered in motivational interviewing informed style, to address their unhealthy alcohol use. OUTCOMES: Effectiveness (PrEP and alcohol use) and cost-effectiveness outcomes will be compared between the two arms. Intervention implementation outcomes (acceptability, feasibility, adoption) will be assessed among MSM participants, clinic staff, and stakeholders. DISCUSSION: This proposed trial will assess an alcohol intervention for MSM with unhealthy alcohol use who initiate or re-initiate PrEP, while simultaneously preparing for subsequent implementation. The study will measure the effectiveness of the BAI for increasing PrEP persistence through reducing unhealthy alcohol use in a setting where excessive alcohol consumption is a normative behavior. If effective, implementation-focused results will inform future scale-up of the BAI in similar settings. TRIAL REGISTRATION: NCT06094634 on clinicaltrials.gov. Registered 16 October 2023.

"I Feel Like I Don't Even Have HIV Anymore"-Facilitators, Barriers, and Experience regarding Use of Long-Acting Injectable Antiretroviral Therapy Among Persons with HIV in North Carolina.

As access to long-acting injectable antiretroviral therapy (LAI ART) expands, understanding patient perceptions and experiences around LAI should inform equitable scale-up and effective implementation strategies. This study used qualitative research design relying on semi-structured interviews conducted among persons with HIV (PWH) who were either virally suppressed on oral treatment (n = 11) or had received at least one dose of injectables (n = 7). Approximately half of participants identified as male (10/18) and most identified as African American (17/18). Among participants on oral ART, many described the prospect of injectable treatment as likely convenient and discreet, relieving the stress of remembering to take daily pill. Nearly all had heard of LAI ART prior to the interview, often from television or internet commercials. Most were excited about less frequent dosing, though expressed concern about the logistics involved in coming to clinic every two months. Many expressed uncertainties regarding the relative effectiveness of LAI ART compared with oral therapy and were wary of potential pain related to injections. In contrast, all persons on LAI ART described injection-site soreness as manageable. In addition to acknowledging the convenience of every-two-month injections, some persons receiving LAI ART expressed relief by lifting the emotional stress of taking a daily-pill that reminded them of their HIV positive status. Emerging clinical trial data supports the individual and public health benefits of LAI ART, regardless of prior viral-suppression; our work adds to a growing body of literature demonstrating the potential psychological benefits associated with this novel treatment modality for PWH regardless of recent viral-suppression.

Examining the feasibility of assisted index case testing for HIV case-finding: a qualitative analysis of barriers and facilitators to implementation in Malawi.

BACKGROUND: Assisted index case testing (ICT), in which health care workers take an active role in referring at-risk contacts of people living with HIV for HIV testing services, has been widely recognized as an evidence-based intervention with high potential to increase status awareness in people living with HIV. While the available evidence from eastern and southern Africa suggests that assisted ICT can be an effective, efficient, cost-effective, acceptable, and low-risk strategy to implement in the region, it reveals that feasibility barriers to implementation exist. This study aims to inform the design of implementation strategies to mitigate these feasibility barriers by examining "assisting" health care workers' experiences of how barriers manifest throughout the assisted ICT process, as well as their perceptions of potential opportunities to facilitate feasibility. METHODS: In-depth interviews were conducted with 26 lay health care workers delivering assisted ICT in Malawian health facilities. Interviews explored health care workers' experiences counseling index clients and tracing these clients' contacts, aiming to inform development of a blended learning implementation package. Transcripts were inductively analyzed using Dedoose coding software to identify and describe key factors influencing feasibility of assisted ICT. Analysis included multiple rounds of coding and iteration with the data collection team. RESULTS: Participants reported a variety of barriers to feasibility of assisted index case testing implementation, including sensitivities around discussing ICT with clients, privacy concerns, limited time for assisted index case testing amid high workloads, poor quality contact information, and logistical obstacles to tracing. Participants also reported several health care worker characteristics that facilitate feasibility (knowledge, interpersonal skills, non-stigmatizing attitudes and behaviors, and a sense of purpose), as well as identified process improvements with the potential to mitigate barriers. CONCLUSIONS: Maximizing assisted ICT's potential to increase status awareness in people living with HIV requires equipping health care workers with effective training and support to address and overcome the many feasibility barriers that they face in implementation. Findings demonstrate the need for, as well as inform the development of, implementation strategies to mitigate barriers and promote facilitators to feasibility of assisted ICT. TRIAL REGISTRATION: NCT05343390. Date of registration: April 25, 2022.

Leveling Up PrEP: Implementation Strategies at System and Structural Levels to Expand PrEP Use in the United States.

PURPOSE OF REVIEW: Despite highly effective biomedical HIV pre-exposure prophylaxis (PrEP) options, suboptimal PrEP uptake impedes progress towards ending the epidemic in the United States of America (USA). Implementation science bridges what we know works in controlled clinical trial settings to the context and environment in which efficacious tools are intended to be deployed. In this review, we focus on strategies that target PrEP use barriers at the system or structural level, exploring the implications and opportunities in the context of the fragmented USA healthcare system. RECENT FINDINGS: Task shifting could increase PrEP prescribers, but effectiveness evidence is scarce in the USA, and generally focused in urban settings. Integration of PrEP within existing healthcare infrastructure concentrates related resources, but demonstration projects rarely present the resource implications of redirecting staff. Changing the site of service via expanded telehealth could improve access to more rural populations, though internet connectivity, technology access, and challenges associated with determining biomedical eligibility remain logistical barriers for some of the highest burden communities in the USA. Finally, a tailored care navigation and coordination approach has emerged as a highly effective component of PrEP service provision, attempting to directly modify the system-level determinants of PrEP use experienced by the individual. We highlight recent advances and evidence surrounding task shifting, integration, service delivery, and tailoring. With the exception of tailored care navigation, evidence is mixed, and the downstream impact and sustainability of task shifting and care integration require further attention. To maximize PrEP outcomes, research will need to continue to examine the interplay between individuals, clinics, and the healthcare system and associated policies within which they operate.

Dramatic Shift in the Etiology of Genital Ulcer Disease Among Patients Visiting a Sexually Transmitted Infections Clinic in Lilongwe, Malawi.

BACKGROUND: Genital ulcer diseases (GUDs) are a common syndrome associated with sexually transmitted infections. Genital ulcer diseases increase the risk of HIV transmission, necessitating appropriate diagnosis and treatment. We provide an updated GUD etiology assessment in Malawi to guide diagnostic development and treatment algorithms. METHODS: We enrolled patients 18 years or older presenting with GUD at a sexually transmitted infection clinic in Lilongwe, Malawi, between May and October 2021. We purposively sampled by HIV status. Swabs of ulcers were tested for Treponema pallidum, herpes simplex virus (HSV)-1 and HSV-2, Haemophilus ducreyi, and Chlamydia trachomatis using polymerase chain reaction. Blood was collected for syphilis and HSV-2 serologies and acute HIV testing. Participants were treated per Malawi guidelines. Ulcer resolution (size reduced by >50%) was evaluated 14 days later. RESULTS: Fifty participants enrolled (30 without HIV, 2 with acute HIV infection, 18 with HIV seropositivity; 32 men, 18 women). Forty-six (92%) had an etiology identified. Syphilis was more common among those without HIV (22 of 30 [73%]) than participants with HIV (PWH; 8 of 20 [40%]; P = 0.04). Herpes simplex virus was more common among PWH (11 of 20 [55%]) than participants without (2 of 30 [7%]; P = 0.0002). One-fifth (9 of 50 [18%]) had H. ducreyi. Among those who returned for follow-up (n = 45), 9 (20%) had unresolved ulcers; persistent GUD was slightly more common in PWH (6 of 19 [32%]) than participants without (3 of 26 [12%]; P = 0.14). CONCLUSIONS: We observed a dramatic increase in syphilis ulcer proportion in a population whose GUDs were previously HSV predominant. Observed differences in etiology and resolution by HIV status could play an important role in the ongoing transmission and treatment evaluation of GUD.

Examining the feasibility of assisted index case testing for HIV case-finding: a qualitative analysis of barriers and facilitators to implementation in Malawi.

Background: Assisted index case testing, in which health care workers take an active role in referring at-risk contacts of people living with HIV for HIV testing services, has been widely recognized as an evidence-based intervention with high potential to increase PLHIV status awareness. Promising evidence for the approach has led to several attempts to scale assisted index case testing throughout eastern and southern Africa in recent years. However, despite effective implementation being at the heart of any assisted index case testing strategy, there is limited implementation science research from the perspective of the HCWs who are doing the "assisting". This study examines the feasibility of assisted index case testing from the perspective of health care workers implementing the approach in Malawi. Methods: In-depth interviews were conducted with 26 lay health care workers delivering assisted index case testing in Malawian health facilities. Interviews explored health care workers' experiences counselling index clients and tracing these clients' contacts, aiming to inform development of a blended learning implementation package. Transcripts were inductively analyzed using Dedoose coding software to identify and describe key factors influencing feasibility of assisted index case testing. Analysis included multiple rounds of coding and iteration with the data collection team. Results: Participants reported a variety of barriers to feasibility of assisted index case testing implementation, including privacy concerns, limited time for assisted index case testing amid high workloads, poor quality contact information, logistical obstacles to tracing, and challenges of discussing sexual behavior with clients. Participants also reported several health care worker characteristics that facilitate feasibility: robust understanding of assisted index case testing's rationale and knowledge of procedures, strong interpersonal skills, positive attitudes towards clients, and sense of purpose in their work. Conclusions: Findings demonstrate that maximizing assisted index case testing's potential to increase HIV status awareness requires adequately equipping health care workers with appropriate knowledge, skills, and support to address and overcome the many feasibility challenges that they face in implementation. Trial Registration Number: NCT05343390 Date of registration: April 25, 2022.

Characterizing Network-Based HIV Testing Interventions to Guide HIV Testing and Contact Tracing at STI Clinics in Lilongwe, Malawi.

BACKGROUND: Understanding heterogeneity across patients in effectiveness of network-based HIV testing interventions may optimize testing and contact tracing strategies, expediting linkage to therapy or prevention for contacts of persons with HIV (PWH). SETTING: We analyzed data from a randomized controlled trial of a combination intervention comprising acute HIV testing, contract partner notification (cPN), and social contact referral conducted among PWH at 2 STI clinics in Lilongwe, Malawi, between 2015 and 2019. METHODS: We used binomial regression to estimate the effect of the combination intervention vs. passive PN (pPN) on having any (1) contact, (2) newly HIV-diagnosed contact, and (3) HIV-negative contact present to the clinic, overall and by referring participant characteristics. We repeated analyses comparing cPN alone with pPN. RESULTS: The combination intervention effect on having any presenting contact was greater among referring women than men [prevalence difference (PD): 0.17 vs. 0.10] and among previously vs. newly HIV-diagnosed referring persons (PD: 0.20 vs. 0.11). Differences by sex and HIV diagnosis status were similar in cPN vs. pPN analyses. There were no notable differences in the intervention effect on newly HIV-diagnosed referrals by referring participant characteristics. Intervention impact on having HIV-negative presenting contacts was greater among younger vs. older referring persons and among those with >1 vs. ≤1 recent sex partner. Effect differences by age were similar for cPN vs. pPN. CONCLUSION: Our intervention package may be particularly efficacious in eliciting referrals from women and previously diagnosed persons. When the combination intervention is infeasible, cPN alone may be beneficial for these populations.

Depression, Alcohol Use, and Sexual Behaviors by HIV Infection Stage and Diagnosis Timing Among STI Clinic Patients in Lilongwe, Malawi.

Understanding depression, alcohol use, and sexual behaviors according to HIV infection stage and diagnosis timing is important for HIV prevention efforts. We enrolled persons with recent infection and diagnosis (i.e., acute HIV infection (AHI) (n = 92) persons newly diagnosed seropositive (n = 360)) and persons previously diagnosed with HIV (n = 190) into a randomized controlled trial in Lilongwe, Malawi (N = 641) and estimated the prevalence of probable depression (Patient Health Questionnaire-9 ≥ 5), hazardous alcohol use (Alcohol Use Disorder Identification Test-C: men ≥ 4; women ≥ 3), and sexual behaviors (transactional sex, condomless sex). Compared with previously diagnosed participants, participants newly seropositive and those with AHI reported a higher proportion of probable depression (7%, 27%, 38%; AHI/Previous: Table Probability: 0.02, p < 0.01; AHI/New: Table Probability: <0.01, p < 0.01), hazardous alcohol use (8%, 18%, 29%; AHI/Previous and AHI/New: Table Probability: <0.01, p < 0.01), and transactional sex (5%, 14%, 20%; AHI/Previous: Table Probability: <0.01, p < 0.01; AHI/New: Table Probability: 0.06, p = 0.24), respectively. HIV prevention services addressing mental health and alcohol misuse may be particularly beneficial for persons with recent HIV infection and or diagnosis.

Acceptability and feasibility of long-acting injectable antiretroviral therapy for HIV-infected persons who inject drugs in Vietnam: A qualitative study.

Background: In Vietnam, HIV prevalence among people who inject drugs (PWID) is several times higher than in the general population (15% versus 0.3%). PWID also experience higher rates of HIV-related mortality, driven by poor antiretroviral therapy (ART) adherence. Long-acting injectable ART (LAI) is a compelling opportunity to improve treatment outcomes, but acceptability and feasibility among HIV-infected PWID remains unexplored. Methods: We conducted key informant in-depth interviews in Hanoi, Vietnam (February-November 2021). Participants were purposively sampled and included policymakers, ART clinic staff, and HIV-infected PWID. We applied the Consolidated Framework for Implementation Research to guide study design and analysis, using thematic coding to develop and iteratively refine a codebook and characterize barriers and facilitators to LAI implementation. Findings: We interviewed 38 key stakeholders: 19 PWID, 14 ART clinic staff, and five policymakers. Participants were enthusiastic about LAI convenience, highlighting less frequent and more discreet dosing. However, contrasting providers, several policymakers suggested LAI was not needed given perceived exceptional oral ART outcomes and rare viral failure among PWID. Policymakers also criticized strategies prioritizing PWID for LAI, emphasizing equity, whereas providers identified PWID as an ideal population for LAI given adherence challenges. LAI complexity, including storage and administration logistics, were deemed surmountable with training and resources. Finally, providers and policymakers acknowledged that adding LAI to drug formularies was key, but an onerous process. Interpretation: Although anticipated to be resource-intensive, LAI was a welcome addition for interviewed stakeholders and likely an acceptable alternative to oral ART among PWID living with HIV in Vietnam. Despite enthusiasm among PWID and providers that LAI could improve viral outcomes, some policymakers-whose buy-in is critical to LAI implementation-opposed strategies that preferentially distributed LAI to PWID, highlighting values of equity and revealing differences in perceived HIV outcomes among PWID. Results provide a vital foundation for developing LAI implementation strategies. Funding: Supported by National Institutes of Health.

Integrating Enhanced HIV Pre-exposure Prophylaxis Into a Sexually Transmitted Infection Clinic in Lilongwe: Protocol for a Prospective Cohort Study.

BACKGROUND: Pre-exposure prophylaxis (PrEP) reduces HIV acquisition risk by >90% and is a critical lever to reduce HIV incidence. Identifying individuals most likely to benefit from PrEP and retaining them on PrEP throughout HIV risk is critical to realize PrEP's prevention potential. Individuals with sexually transmitted infections (STIs) are an obvious priority PrEP population, but there are no data from sub-Saharan Africa (SSA) confirming the effectiveness of integrating PrEP into STI clinics. Assisted partner notification may further enhance STI clinic-based PrEP programming by recruiting PrEP users from the pool of named sexual partners of individuals presenting with an incident STI. However, the acceptability, feasibility, and effectiveness of these integrated and enhanced strategies are unknown. OBJECTIVE: This study aims to describe the implementation outcomes of acceptability, feasibility, and effectiveness (regarding PrEP uptake and persistence) of integrating an enhanced PrEP implementation strategy into an STI clinic in Malawi. METHODS: The enhanced PrEP STI study is a prospective cohort study enrolling patients who are eligible for PrEP (aged ≥15 years) who are seeking STI services at a Lilongwe-based STI clinic. Data collection relies on a combination of in-depth interviews, patient and clinic staff surveys, and clinic record review. All enrolled PrEP users will be screened for acute HIV infection and receive quarterly testing for Neisseria gonorrhea, Chlamydia trachomatis, and syphilis. Participants will be asked to name recent sexual partners for assisted notification; returning partners will be screened for PrEP eligibility and, if interested, enrolled into the cohort of PrEP initiators. We will also enroll patients who are eligible for PrEP but choose not to initiate it, from the STI clinic. Patient participants will be followed for 6 months; we will assess self-reported PrEP use, PrEP refills, sexual behaviors, perceived HIV risk, and incident STIs. Clinic staff participants will be interviewed at baseline and at approximately 6 months and will complete surveys examining the perceived acceptability and feasibility of the integrated and enhanced PrEP strategy. RESULTS: Enrollment began in March 2022 and is projected to continue until February 2023, with patient participant follow-up through August 2023. The results of this study are expected to be reported in 2024. CONCLUSIONS: This study will generate important evidence regarding the potential integration of PrEP services into STI clinics in SSA and preliminary data regarding the effectiveness of an enhanced intervention that includes assisted partner notification as a strategy to identify potential PrEP users. Furthermore, this trial will provide some of the first insights into STI incidence among PrEP users recruited from an STI clinic in SSA-critical data to inform the use of etiologic STI testing where syndromic management is the current standard. These findings will help to design future PrEP implementation strategies in SSA. TRIAL REGISTRATION: ClinicalTrials.gov NCT05307991; https://clinicaltrials.gov/ct2/show/NCT05307991. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37395.

Discontinuation, suboptimal adherence, and reinitiation of oral HIV pre-exposure prophylaxis: a global systematic review and meta-analysis.

BACKGROUND: Poor adherence to oral HIV pre-exposure prophylaxis (PrEP) diminishes its clinical and public health benefits. This study synthesises evidence regarding discontinuation, adherence, and reinitiation of PrEP among geographically diverse PrEP users. METHODS: We did a systematic review and meta-analysis evaluating studies published in MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to Dec 18, 2020. We included longitudinal studies that presented data for PrEP discontinuation, defined as investigator-reported loss to follow-up or participant self-reported PrEP stoppage. Data were extracted from published reports and assessed for risk of bias. We used a random-effects meta-analysis to pool estimates of discontinuation and I2 and τ2 to evaluate heterogeneity. This study is registered with PROSPERO, CRD42020155675. FINDINGS: We identified 4129 records, of which 59 articles were included (n=43 917 participants). 41·0% (95% CI 18·8-63·5) of participants discontinued PrEP within 6 months, with the highest rates in observational studies. The discontinuation rate in sub-Saharan Africa (47·5%, 95% CI: 29·4-66·4%) was higher than in other regions (p<0·001). Discontinuation rates were lower in studies with adherence interventions than in those without (24·7% vs 36·7%, p=0·015). Gay or bisexual men who have sex with men and transgender women offered daily or non-daily dosing options had lower discontinuation rates than those offered daily dosing alone (21·6% vs 31·5%; p<0·001). The pooled suboptimal adherence within 6 months was 37·7% (95% CI 8·4-66·9). Among people who discontinued PrEP, 47·3% (95% CI 31·5-63·2) reinitiated PrEP within 1 year of PrEP initiation. The included studies had poor quality in terms of study design, with a moderate risk of bias. INTERPRETATION: Strategies to encourage reinitiating PrEP for new or persistent risk should be a focus of future PrEP implementation strategies. FUNDING: National Institutes of Health and Nature Science Foundation of China.

Development of a Blended Learning Approach to Delivering HIV-Assisted Contact Tracing in Malawi: Applied Theory and Formative Research.

BACKGROUND: Despite progress toward the Joint United Nations Programme on HIV/AIDS "95-95-95" targets (95% of HIV-positive persons tested, 95% of tested persons on treatment, and 95% of treated persons virally suppressed), a gap remains in achieving the first 95% target. Assisted contact tracing (ACT), in which health workers support HIV-positive index clients to recruit their contacts (sexual partners and children) for HIV testing, efficiently identifies HIV-positive persons in need of treatment. Although many countries, including Malawi, began implementing ACT, testing outcomes in routine settings have been worse than those in trial settings. OBJECTIVE: The aim of this paper is to use formative research and frameworks to develop and digitize an implementation package to bridge the gap between ACT research and practice. METHODS: Semistructured qualitative research was conducted in 2019 in Malawi with key informants. Barriers and facilitators to intervention delivery were identified using the Consolidated Framework for Implementation Research. Approaches to digitization were examined using human-centered design principles. RESULTS: Limited clinic coordination and health worker capacity to address the complexities of ACT were identified as barriers. Ongoing individual training consisting of learning, observing, practicing, and receiving feedback, as well as group problem-solving were identified as facilitators. Important features of digitization included (1) culturally relevant visual content, (2) capability of offline use, and (3) simple designs and basic editing to keep costs low. CONCLUSIONS: Formative research and frameworks played a key role in designing and digitizing an implementation package for ACT delivery in a low-income setting such as Malawi.

Brief Report: Blood and Genital Fluid Viral Load Trajectories Among Treated and Untreated Persons With Acute HIV Infection in Malawi.

BACKGROUND: Persons with acute HIV infection (AHI) are highly infectious and responsible for a disproportionate share of incident infections. Immediate antiretroviral therapy (ART) rapidly reduces blood viral loads (VLs), but genital VLs after ART initiation during AHI are less well described. SETTING: Lilongwe, Malawi, 2012-2014. METHODS: HIV-seronegative and HIV-serodiscordant persons aged ≥18 years were screened for AHI (RNA positive) and randomized to standard of care, behavioral intervention, or behavioral intervention plus short-term ART (raltegravir/emtricitabine/tenofovir) (1:2:2). Persons who were ART eligible under Malawi guidelines could receive first-line therapy. Blood and genital VLs were assessed at weeks 1, 4, 8, and 12. Fisher's Exact test was used to compare viral suppression by ART status. RESULTS: Overall, 46 persons with AHI were enrolled; of whom, 17 started ART within 12 weeks. Median blood VL at AHI diagnosis was 836,115 copies/mL. At week 12, 7% (1/14) of those who initiated ART had a blood VL of ≥400 copies/mL, compared with 100% (23/23; P < 0.0001) of those who did not initiate ART (median VL: 61,605 copies/mL). Median genital VL at week 1 was 772 copies/mL, with 13 of 22 (59%) having VL of ≥400 copies/mL. At week 12, 0 of 10 (0%) of those who initiated ART had genital VL of ≥400 copies/mL, compared with 7 of 15 (47%) of those who did not initiate ART (P = 0.02). CONCLUSION: Although highly correlated, VLs in blood and genital fluids occupy discrete biological compartments with distinct virologic dynamics. Our results corroborate the dramatic reduction in both compartments after ART initiation. Increasing AHI screening and rapidly initiating treatment is key to interrupting transmission.

A randomized controlled trial evaluating combination detection of HIV in Malawian sexually transmitted infections clinics.

INTRODUCTION: HIV diagnosis is the necessary first step towards HIV care initiation, yet many persons living with HIV (PLWH) remain undiagnosed. Employing multiple HIV testing strategies in tandem could increase HIV detection and promote linkage to care. We aimed to assess an intervention to improve HIV detection within socio-sexual networks of PLWH in two sexually transmitted infections (STI) clinics in Lilongwe, Malawi. METHODS: We conducted a randomized controlled trial to evaluate an intervention combining acute HIV infection (AHI) screening, contract partner notification and social contact referral versus the Malawian standard of care: serial rapid serological HIV tests and passive partner referral. Enrolment occurred between 2015 and 2019. HIV-seropositive persons (two positive rapid tests) were randomized to the trial arms and HIV-seronegative (one negative rapid test) and -serodiscordant (one positive test followed by a negative confirmatory test) persons were screened for AHI with HIV RNA testing. Those found to have AHI were offered enrolment into the intervention arm. Our primary outcome of interest was the number of new HIV diagnoses made per index participant within participants' sexual and social networks. We also calculated total persons, sexual partners and PLWH (including those previously diagnosed) referred per index participant. RESULTS: A total of 1230 HIV-seropositive persons were randomized to the control arm, and 561 to the intervention arm. Another 12,713 HIV-seronegative or -serodiscordant persons underwent AHI screening, resulting in 136 AHI cases, of whom 94 enrolled into the intervention arm. The intervention increased the number of new HIV diagnoses made per index participant versus the control (ratio: 1.9; 95% confidence interval (CI): 1.2 to 3.1). The intervention also increased the numbers of persons (ratio: 2.5; 95% CI: 2.0 to 3.2), sexual partners (ratio: 1.7; 95% CI: 1.4 to 2.0) and PLWH (ratio: 2.3; 95% CI: 1.7 to 3.2) referred per index participant. CONCLUSIONS: Combining three distinct HIV testing and referral strategies increased the detection of previously undiagnosed HIV infections within the socio-sexual networks of PLWH seeking STI care. Combination HIV detection strategies that leverage AHI screening and socio-sexual contact networks offer a novel and efficacious approach to increasing HIV status awareness.

Initiation, discontinuation, and restarting HIV pre-exposure prophylaxis: ongoing implementation strategies.

When used appropriately, pre-exposure prophylaxis (PrEP) substantially reduces the risk of HIV acquisition. Early implementation outcomes often suggest poor PrEP adherence and persistence; however, this intervention is time-limited and the need for PrEP fluctuates as risk behaviours change. In this Viewpoint we examine the current guidelines and early programmatic outcomes after starting, stopping, and restarting PrEP, and we review the implications of PrEP in relation to HIV testing algorithms. Guidelines suggest to discontinue PrEP when a person is no longer at risk for HIV, but effectively implementing this strategy requires support tools to make the decision of stopping and restarting PrEP that considers the complex relationship between risk perceptions and risk behaviours. Safely discontinuing PrEP also requires greater understanding of the daily dosing duration that is needed to protect the person after their last HIV exposure. Additionally, clear strategies are needed to re-engage a person as their HIV exposure risk changes over time.