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.

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.

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.

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.

Human Immunodeficiency Virus (HIV)-1 Transmission Among Persons With Acute HIV-1 Infection in Malawi: Demographic, Behavioral, and Phylogenetic Relationships.

BACKGROUND: Understanding sexual networks involving acute human immunodeficiency virus (HIV)-1 infections (AHI) may lead to prevention opportunities to mitigate high rates of onward transmission. We evaluated HIV-1 phylogenetic and behavioral characteristics among persons with AHI and their referred partners. METHODS: Between 2012 and 2014, 46 persons with AHI in Malawi participated in a combined behavioral and biomedical intervention. Participants referred sexual partners by passive referral. Demographics and sexual behaviors were collected through interviews and HIV-1 genetic relationships were assessed with phylogenetics. RESULTS: Among 45 AHI participants with HIV-1 sequences, none was phylogenetically-linked with another AHI index. There were 19 (42%) AHI participants who referred a single partner that returned for testing. Most partners (n = 17) were HIV-infected, with 15 (88%) presenting with an established infection. There were 14 index-partner pairs that had sequences available; 13 (93%) pairs were phylogenetically-linked dyads. The AHI index was female in 7/13 (54%) dyads. Age-disparate relationships among dyads were common (≥5-year age difference in 67% of dyads), including 3/6 dyads involving a male index and a younger woman. Index participants with a referred partner were more likely to report no casual partners and to be living with their current partner than participants not in dyads. CONCLUSIONS: Passive-partner referral successfully identified partners with genetically-similar HIV infections-the likely source of infection-but only 40% of index cases referred partners who presented for HIV-1 testing. Future work evaluating assisted partner notification may help reach susceptible partners or more people with untreated HIV-1 infections connected to acute transmission. CLINICAL TRIALS REGISTRATION: NCT01450189.

Syphilis-Associated Acute Renal Failure and Hepatitis in the Setting of Human Immunodeficiency Virus Coinfection.

Two individuals with human immunodeficiency virus presented in acute renal failure with nephrotic range proteinuria and were diagnosed with secondary syphilis. One of them also had elevated transaminases. Kidney biopsies revealed membranous nephropathy, a rare complication of secondary syphilis, in both cases. Normal hepatic and renal function were restored after treatment with penicillin.

High rates of transmitted NNRTI resistance among persons with acute HIV infection in Malawi: implications for first-line dolutegravir scale-up.

High rates of non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance was a key consideration in the WHO policies transitioning first-line regimens to include integrase inhibitors (dolutegravir [DTG]). However, recent data suggests a relationship between DTG and neural tube defects among women exposed during conception, giving providers and policymakers pause regarding the planned regimen changes. We examined HIV drug resistance among a cohort of 46 acutely infected persons in Malawi. Our data demonstrates high levels of transmitted resistance, 11% using standard resistance surveillance mutations and 20% when additional NNRTI polymorphisms that may affect treatment response are included. High resistance rates in this treatment-naïve patient population reinforces the critical nature of DTG-based options in the context of public-health driven treatment programs.

Sustained Sexual Behavior Change After Acute HIV Diagnosis in Malawi.

BACKGROUND: Identification of acute HIV infection (AHI) allows for important opportunities for HIV prevention through behavior change and biomedical intervention. Here, we evaluate changes in sexual risk behaviors among persons with AHI enrolled in a combined behavioral and biomedical intervention designed to reduce onward transmission of HIV. METHODS: Participants were randomized to standard HIV counseling, a multisession behavioral intervention, or a multisession behavioral intervention plus antiretrovirals. Sexual behaviors were assessed periodically over 1 year. RESULTS: Four weeks after diagnosis, the predicted probability of reporting multiple sexual partners decreased from 24% to 9%, and the probability of reporting unprotected sex decreased from 71% to 27%. These declines in sexual risk behaviors were sustained over follow-up irrespective of study arm. CONCLUSIONS: Diagnosis of AHI alone may be sufficient to achieve immediate and sustained behavior change during this highly infectious period.

Laparoscopic hysterectomy with morcellation vs abdominal hysterectomy for presumed fibroids: an updated decision analysis following the 2014 Food and Drug Administration safety communications.

Previous decision analyses demonstrate the safety of minimally invasive hysterectomy for presumed benign fibroids, accounting for the risk of occult leiomyosarcoma and the differential mortality risk associated with laparotomy. Studies published since the 2014 Food and Drug Administration safety communications offer updated leiomyosarcoma incidence estimates. Incorporating these studies suggests that mortality rates are low following hysterectomy for presumed benign fibroids overall, and a minimally invasive approach remains a safe option. Risk associated with morcellation, however, increases in women age >50 years due to increased leiomyosarcoma rates, an important finding for patient-centered discussions of treatment options for fibroids.

Recruiting the social contacts of patients with STI for HIV screening in Lilongwe, Malawi: process evaluation and assessment of acceptability.

OBJECTIVES: To explore acceptability of recruiting social contacts for HIV and sexually transmitted infection (STI) screening in Lilongwe, Malawi. METHODS: In this observational study, three groups of 'seed' patients were enrolled: 45 HIV-infected patients with STI, 45 HIV-uninfected patients with STI and 45 community controls, who were also tested for HIV as part of the study. Each seed was given five coupons and asked to recruit up to five social contacts to the STI clinic. Seeds were told the programme for contacts would include HIV testing, STI screening and general health promotion. Seeds were asked to return after 1 month to report on the contact recruitment process. Seeds received $2 for each successfully recruited contact. RESULTS: Eighty-nine seeds (66%) returned for 1-month follow-up with no difference between the three seed groups (p=0.9). Returning seeds reported distributing most of their coupons (mean=4.1) and discussing each feature of the programme with most contacts-HIV testing (90%), STI screening (87%) and health promotion (91%). Seeds reported discussing their own HIV status with most contacts (52%), with a lower proportion of HIV-infected seeds discussing their HIV status (22%) than HIV-uninfected seeds (81%) or community seeds (64%) (p<0.001). Contact recruitment did not vary with socioeconomic status. CONCLUSIONS: Most seeds distributed all coupons and reported describing all aspects of the programme to most contacts. Patients with STI are able to act as health promoters within their social networks and may be a critical link to increasing STI and HIV status awareness among high-risk groups.

Predicting resistance as indicator for need to switch from first-line antiretroviral therapy among patients with elevated viral loads: development of a risk score algorithm.

BACKGROUND: In resource-limited settings, where resistance testing is unavailable, confirmatory testing for patients with high viral loads (VL) delays antiretroviral therapy (ART) switches for persons with resistance. We developed a risk score algorithm to predict need for ART change by identifying resistance among persons with persistently elevated VL. METHODS: We analyzed data from a Phase IV open-label trial. Using logistic regression, we identified demographic and clinical characteristics predictive of need for ART change among participants with VLs ≥1000 copies/ml, and assigned model-derived scores to predictors. We designed three models, including only variables accessible in resource-limited settings. RESULTS: Among 290 participants with at least one VL ≥1000 copies/ml, 51 % (148/290) resuppressed and did not have resistance testing; among those who did not resuppress and had resistance testing, 47 % (67/142) did not have resistance and 53 % (75/142) had resistance (ART change needed for 25.9 % (75/290)). Need for ART change was directly associated with higher baseline VL and higher VL at time of elevated measure, and inversely associated with treatment duration. Other predictors included body mass index and adherence. Area under receiver operating characteristic curves ranged from 0.794 to 0.817. At a risk score ≥9, sensitivity was 14.7-28.0 % and specificity was 96.7-98.6 %. CONCLUSIONS: Our model performed reasonably well and may be a tool to quickly transition persons in need of ART change to more effective regimens when resistance testing is unavailable. Use of this algorithm may result in public health benefits and health system savings through reduced transmissions of resistant virus and costs on laboratory investigations.

Cost-Effectiveness of Laparoscopic Hysterectomy With Morcellation Compared With Abdominal Hysterectomy for Presumed Myomas.

STUDY OBJECTIVE: Hysterectomy for presumed leiomyomata is 1 of the most common surgical procedures performed in nonpregnant women in the United States. Laparoscopic hysterectomy (LH) with morcellation is an appealing alternative to abdominal hysterectomy (AH) but may result in dissemination of malignant cells and worse outcomes in the setting of an occult leiomyosarcoma (LMS). We sought to evaluate the cost-effectiveness of LH versus AH. DESIGN: Decision-analytic model of 100 000 women in the United States assessing the incremental cost-effectiveness ratio (ICER) in dollars per quality-adjusted life-year (QALY) gained (Canadian Task Force classification III). SETTING: U.S. hospitals. PATIENTS: Adult premenopausal women undergoing LH or AH for presumed benign leiomyomata. INTERVENTIONS: We developed a decision-analytic model from a provider perspective across 5 years, comparing the cost-effectiveness of LH to AH in terms of dollar (2014 US dollars) per QALY gained. The model included average total direct medical costs and utilities associated with the procedures, complications, and clinical outcomes. Baseline estimates and ranges for cost and probability data were drawn from the existing literature. MEASUREMENTS AND MAIN RESULTS: Estimated overall deaths were lower in LH versus AH (98 vs 103). Death due to LMS was more common in LH versus AH (86 vs 71). Base-case assumptions estimated that average per person costs were lower in LH versus AH, with a savings of $2193 ($24 181 vs $26 374). Over 5 years, women in the LH group experienced 4.99 QALY versus women in the AH group with 4.91 QALY (incremental gain of .085 QALYs). LH dominated AH in base-case estimates: LH was both less expensive and yielded greater QALY gains. The ICER was sensitive to operative costs for LH and AH. Varying operative costs of AH yielded an ICER of $87 651/QALY gained (minimum) to AH being dominated (maximum). Probabilistic sensitivity analyses, in which all input parameters and costs were varied simultaneously, demonstrated a relatively robust model. The AH approach was dominated 68.9% of the time; 17.4% of simulations fell above the willingness-to-pay threshold of $50 000/QALY gained. CONCLUSION: When considering total direct hospital costs, complications, and morbidity, LH was less costly and yielded more QALYs gained versus AH. Driven by the rarity of occult LMS and the reduced incidence of intra- and postoperative complications, LH with morcellation may be a more cost-effective and less invasive alternative to AH and should remain an option for women needing hysterectomy for leiomyomata.

Laparoscopic hysterectomy with morcellation vs abdominal hysterectomy for presumed fibroid tumors in premenopausal women: a decision analysis.

OBJECTIVE: The purpose of this study was to model outcomes in laparoscopic hysterectomy with morcellation compared with abdominal hysterectomy for the presumed fibroid uterus and to examine short- and long-term complications and death. STUDY DESIGN: A decision tree was constructed to compare outcomes for a hypothetical cohort of 100,000 premenopausal women who underwent hysterectomy for presumed fibroid tumors over a 5-year time horizon. Parameter and quality-of-life utility estimates were determined from published literature for postoperative complications, leiomyosarcoma incidence, death related to leiomyosarcoma, and procedure-related death. RESULTS: The decision-tree analysis predicted fewer overall deaths with laparoscopic hysterectomy compared with abdominal hysterectomy (98 vs 103 per 100,000). Although there were more deaths from leiomyosarcoma after laparoscopic hysterectomy (86 vs 71 per 100,000), there were more hysterectomy-related deaths with abdominal hysterectomy (32 vs 12 per 100,000). The laparoscopic group had lower rates of transfusion (2400 vs 4700 per 100,000), wound infection (1500 vs 6300 per 100,000), venous thromboembolism (690 vs 840 per 100,000) and incisional hernia (710 vs 8800 per 100,000), but a higher rate of vaginal cuff dehiscence (640 vs 290 per 100,000). Laparoscopic hysterectomy resulted in more quality-adjusted life years (499,171 vs 490,711 over 5 years). CONCLUSION: The risk of leiomyosarcoma morcellation is balanced by procedure-related complications that are associated with laparotomy, including death. This analysis provides patients and surgeons with estimates of risk and benefit on which patient-centered decisions can be made.

"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.

Detection of acute HIV infection: a field evaluation of the determine® HIV-1/2 Ag/Ab combo test.

BACKGROUND: Most human immunodeficiency virus (HIV) point-of-care tests detect antibodies (Ab) but not p24 antigen (Ag) or RNA. In the absence of antibodies, p24 antigen and RNA typically indicate acute HIV infection. We conducted a field evaluation of the Determine® HIV-1/2 Ag/Ab Combo rapid test (Combo RT). METHODS: The antigen portion of the Combo RT (for acute HIV infection) was compared with a Roche Monitor HIV RNA polymerase chain reaction assay. The antibody portion of Combo RT (for established HIV infection) was compared with rapid test algorithms. Participants were enrolled at a sexually transmitted infection clinic and HIV testing and counseling center in Lilongwe, Malawi. Rapid testing was conducted with parallel testing in the clinic and serial testing in the center. The Combo RT was performed in clinic participants with negative or discordant antibody results and in all center participants. RESULTS: Of the participants 838 were HIV negative, 163 had established HIV infection, and 8 had acute HIV infection. For detecting acute HIV infection, the antigen portion had a sensitivity of 0.000 and a specificity of 0.983. For detecting established HIV infection, the antibody portion had a sensitivity of 0.994 and a specificity of 0.992. CONCLUSIONS: Combo RT displayed excellent performance for detecting established HIV infection and poor performance for detecting acute HIV infection. In this setting, Combo RT is no more useful than current algorithms.

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.

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.

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.

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.

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.