Prioritizing persons deprived of liberty in global guidelines for tuberculosis preventive treatment.

In this Policy Forum piece, Aditya Narayan and colleagues discuss the challenges and opportunities for tuberculosis preventive treatment in carceral settings.

Clinic presentation delay and tuberculosis treatment outcomes in the Lake Victoria region of East Africa: A multi-site prospective cohort study.

In the Lake Victoria region of East Africa, little is known about delays between tuberculosis (TB) symptom onset and presentation at a clinic. Associations between clinic presentation delay and TB treatment outcomes are also poorly understood. In 2019, we abstracted data from routine TB treatment records for all adults (n = 776) initiating TB treatment in a 6-month period across 12 health facilities near Lake Victoria. We interviewed 301 cohort members and assessed whether they experienced a clinic presentation delay longer than 6 weeks. We investigated potential clinical and demographic correlates of clinic presentation delay and examined the association between clinic presentation delay and an unfavorable TB treatment outcome (death, loss to follow-up, or treatment failure). Clinic presentation delay was common, occurring among an estimated 54.7% (95% CI: 48.9%, 61.2%) of cohort members, though no specific correlates were identified. Clinic presentation delay was slightly associated with unfavorable TB treatment outcomes. The 180-day risk of an unfavorable outcome was 14.2% (95% CI: 8.0%, 20.4%) among those with clinic presentation delay, compared to 12.7% (95% CI: 5.1%, 20.3%) among those presenting earlier. Multi-level community-based interventions may be necessary to reduce clinic presentation delays in communities near Lake Victoria.

Geographic mobility and treatment outcomes among people in care for tuberculosis in the Lake Victoria region of East Africa: A multi-site prospective cohort study.

Geographic mobility may disrupt continuity of care and contribute to poor clinical outcomes among people receiving treatment for tuberculosis (TB). This may occur especially where health services are not well coordinated across international borders, particularly in lower and middle income country settings. In this work, we describe mobility and the relationship between mobility and unfavorable TB treatment outcomes (i.e., death, loss to follow-up, or treatment failure) among a cohort of adults who initiated TB treatment at one of 12 health facilities near Lake Victoria. We abstracted data from health facility records for all 776 adults initiating TB treatment during a 6-month period at the selected facilities in Kenya, Tanzania, and Uganda. We interviewed 301 cohort members to assess overnight travel outside one's residential district/sub-county. In our analyses, we estimated the proportion of cohort members traveling in 2 and 6 months following initiation of TB treatment, explored correlates of mobility, and examined the association between mobility and an unfavorable TB treatment outcome. We estimated that 40.7% (95% CI: 33.3%, 49.6%) of people on treatment for TB traveled overnight at least once in the 6 months following treatment initiation. Mobility was more common among people who worked in the fishing industry and among those with extra-pulmonary TB. Mobility was not strongly associated with other characteristics examined, however, suggesting that efforts to improve TB care for mobile populations should be broad ranging. We found that in this cohort, people who were mobile were not at increased risk of an unfavorable TB treatment outcome. Findings from this study can help inform development and implementation of mobility-competent health services for people with TB in East Africa.

Estimating potential silent transfer using baseline viral load measures among people presenting as new to HIV care in Lusaka, Zambia: a cross-sectional study.

OBJECTIVES: To estimate potential silent transfer using baseline viral load measures among individuals presenting as new to HIV care in routine HIV clinical settings in Lusaka, Zambia. DESIGN: Cross-sectional study. SETTING: Two large, urban government-operated health facilities supported by the Centre for Infectious Disease Research in Zambia. PARTICIPANTS: A total of 248 participants with an incident positive HIV rapid test. OUTCOME MEASURES: The primary outcome measure was HIV viral suppression at baseline (i.e., potential silent transfer), defined as having a viral load ≤1000 RNA copies(c)/mL at the time of initiating HIV care. We also examined viral suppression at ≤60 c/mL. METHODS: We surveyed and measured baseline HIV viral load as part of the national recent infection testing algorithm among people living with HIV (PLWH) presenting as new to care. Using mixed effects Poisson regression, we identified characteristics among PLWH associated with potential silent transfer. RESULTS: Among the 248 PLWH included, 63% were women with median age of 30, and 66 (27% (66/248)) had viral suppression at ≤1000 c/mL and 53 (21% (53/248)) at ≤60 c/mL thresholds, respectively. Participants aged 40+ years had a significantly higher adjusted prevalence of potential silent transfer (adjusted prevalence ratio (aPR): 2.10; 95% CI: 2.08, 2.13) compared with participants aged 18-24 years. Participants reporting no formal education had a significantly higher adjusted prevalence of potential silent transfer (aPR: 1.63; 95% CI: 1.52, 1.75) compared with those completing primary education. Among 57 potential silent transfers who completed a survey, 44 (77%) indicated having tested positive previously at ≥1 of 38 clinics in Zambia. CONCLUSIONS: The high proportion of PLWH with potential silent transfer points to clinic shopping and/or co-enrolment at multiple care sites simultaneously, suggesting an opportunity to improve care continuity at the time of HIV care entry.

Experiences of Justice-Involved People Transitioning to HIV Care in the Community After Prison Release in Lusaka, Zambia: A Qualitative Study.

INTRODUCTION: In sub-Saharan Africa (SSA), incarcerated people experience a higher HIV burden than the general population. While access to HIV care and treatment for incarcerated people living with HIV (PLHIV) in SSA has improved in some cases, little is known about their transition to and post-release experience with care in the community. To address this gap, we conducted a qualitative study to describe factors that may influence post-release HIV care continuity in Zambia. METHODS: In March-December 2018, we recruited study participants from a larger prospective cohort study following incarcerated and newly released PLHIV at 5 correctional facilities in 2 provinces in Zambia. We interviewed 50 participants immediately before release; 27 (54%) participated in a second interview approximately 6 months post-release. Demographic and psychosocial data were collected through a structured survey. RESULTS: The pre-release setting was strongly influenced by the highly structured prison environment and assumptions about life post-release. Participants reported accessible HIV services, a destigmatizing environment, and strong informal social supports built through comradery among people facing the same trying detention conditions. Contrary to their pre-release expectations, during the immediate post-release period, participants struggled to negotiate the health system while dealing with unexpected stressors. Long-term engagement in HIV care was possible for participants with strong family support and a high level of self-efficacy. CONCLUSION: Our study highlights that recently released PLHIV in Zambia face acute challenges in meeting their basic subsistence needs, as well as social isolation, which can derail linkage to and retention in community HIV care. Releasees are unprepared to face these challenges due to a lack of community support services. To improve HIV care continuity in this population, new transitional care models are needed that develop client self-efficacy, facilitate health system navigation, and pragmatically address structural and psychosocial barriers like poverty, gender inequality, and substance use.

Scaling up evidence-based approaches to tuberculosis screening in prisons.

People deprived of liberty have among the highest rates of tuberculosis globally. The incidence of tuberculosis is ten times greater than the incidence of tuberculosis in the general population. In 2021, WHO updated its guidance to strongly recommend systematic screening for tuberculosis in prisons and penitentiary systems. Which case-finding strategies should be adopted, and how to effectively implement these strategies in these settings, will be crucial questions facing ministries of health and justice. In this Viewpoint, we review the evidence base for tuberculosis screening and diagnostic strategies in prisons, highlighting promising approaches and knowledge gaps. Drawing upon past experiences of implementing active case-finding and care programmes in settings with a high tuberculosis burden, we discuss challenges and opportunities for improving the tuberculosis diagnosis and treatment cascade in these settings. We argue that improved transparency in reporting of tuberculosis notifications and outcomes in prisons and renewed focus and resourcing from WHO and other stakeholders will be crucial for building the commitment and investments needed from countries to address the continued crisis of tuberculosis in prisons.

Initial implementation of HIV pre-exposure prophylaxis for people who are incarcerated in Zambia: a cross-sectional observational study.

BACKGROUND: There are over 23 000 incarcerated people in Zambia, a population which has higher HIV prevalence than the general population yet has no access to HIV prevention. To evaluate the feasibility of HIV pre-exposure prophylaxis (PrEP) implementation in Zambian criminal justice facilities, we offered PrEP services to incarcerated people and aimed to describe early implementation outcomes. METHODS: In this cross-sectional observational study, we implemented a PrEP programme between Oct 1, 2020, and March 31, 2021, supporting 16 criminal justice facilities in four Zambian provinces. Before implementation, we held stakeholder engagement meetings with Zambia Correctional Service officials to discuss PrEP benefits, and trained Zambia Correctional Service health-care workers in PrEP management using the national PrEP training package. People who were incarcerated and screened positive for substantial HIV risk by use of a standardised HIV risk assessment tool were offered voluntary HIV testing and counselling. Those who tested positive were linked to antiretroviral therapy, and those who tested negative and met national HIV prevention eligibility criteria were offered PrEP. We assessed PrEP uptake and used descriptive statistics to characterise programme beneficiaries and the cascade of PrEP services. FINDINGS: During the study period, we reached 12 367 people older than 15 years with HIV risk assessment and counselling, including 11 794 (95·4%) men and 573 (4·6%) women. Of these, 2610 people received HIV testing, with 357 (13·7%) testing HIV positive; positivity was significantly higher in women (20·6%) than men (13·2%, p=0·011). 1276 people were identified as HIV negative and PrEP eligible. Of these, 1190 (93·3%) initiated PrEP. The age group with the highest proportion reached and initiated on PrEP was those aged 25-29 years, representing 19·2% (2377 of 12 367) of all people reached and 24·1% (287 of 1190) of those who initiated PrEP. INTERPRETATION: Delivery of PrEP to people who are incarcerated is feasible with adequate resourcing and support to the criminal justice health system, and can result in high uptake among eligible individuals. Further assessment is needed of PrEP persistence and adherence, and the perceptions of people who are incarcerated regarding their HIV risk and preferences for combination HIV prevention services. FUNDING: US President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention.

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.

Evaluation of a COVID-19 convalescent plasma program at a U.S. academic medical center.

Amidst the therapeutic void at the onset of the COVID-19 pandemic, a critical mass of scientific and clinical interest coalesced around COVID-19 convalescent plasma (CCP). To date, the CCP literature has focused largely on safety and efficacy outcomes, but little on implementation outcomes or experience. Expert opinion suggests that if CCP has a role in COVID-19 treatment, it is early in the disease course, and it must deliver a sufficiently high titer of neutralizing antibodies (nAb). Missing in the literature are comprehensive evaluations of how local CCP programs were implemented as part of pandemic preparedness and response, including considerations of the core components and personnel required to meet demand with adequately qualified CCP in a timely and sustained manner. To address this gap, we conducted an evaluation of a local CCP program at a large U.S. academic medical center, the University of North Carolina Medical Center (UNCMC), and patterned our evaluation around the dimensions of the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to systematically describe key implementation-relevant metrics. We aligned our evaluation with program goals of reaching the target population with severe or critical COVID-19, integrating into the structure of the hospital-wide pandemic response, adapting to shifting landscapes, and sustaining the program over time during a compassionate use expanded access program (EAP) era and a randomized controlled trial (RCT) era. During the EAP era, the UNCMC CCP program was associated with faster CCP infusion after admission compared with contemporaneous affiliate hospitals without a local program: median 29.6 hours (interquartile range, IQR: 21.2-48.1) for the UNCMC CCP program versus 47.6 hours (IQR 32.6-71.6) for affiliate hospitals; (P<0.0001). Sixty-eight of 87 CCP recipients in the EAP (78.2%) received CCP containing the FDA recommended minimum nAb titer of ≥1:160. CCP delivery to hospitalized patients operated with equal efficiency regardless of receiving treatment via a RCT or a compassionate-use mechanism. It was found that in a highly resourced academic medical center, rapid implementation of a local CCP collection, treatment, and clinical trial program could be achieved through re-deployment of highly trained laboratory and clinical personnel. These data provide important pragmatic considerations critical for health systems considering the use of CCP as part of an integrated pandemic response.

"Testing Can Be Done Anywhere": A Qualitative Assessment of Targeted Community-Based Point-of-Care Early Infant Diagnosis of HIV in Lusaka, Zambia.

INTRODUCTION: Delayed HIV diagnosis in HIV-exposed infants (HEIs) results in missed opportunities for early antiretroviral therapy (ART), causing significant morbidity and mortality. Early infant diagnosis (EID) depends on the availability of accessible and reliable testing services. We explored the acceptability, appropriateness, and feasibility of deploying a targeted community-based point-of-care (POC) EID testing model (i.e., "community POC model") to reach high-risk mother-infant pairs (MIPs) in Lusaka, Zambia. METHODS: We conducted in-depth interviews with a purposive sample of health care workers, study staff, and caregivers in high-risk MIPs at 6 health facilities included in a larger implementation research study evaluating the community POC model. We defined "high-risk MIPs" as mothers who did not receive antenatal testing or an attended delivery or infants who missed EID testing milestones. Interviews were audio-recorded, translated, and transcribed verbatim in English. Content and thematic analysis were done using NVivo 10 software. RESULTS: Health care workers (n=20) and study staff (n=12) who implemented the community POC model noted that the portability and on-screen prompts of the POC platform made it mobile and easy to use, but maintenance and supply chain management were key to field operations. Respondents also felt that the community POC model reached more infants who had never had EID testing, allowing them to find infants with HIV infection and immediately initiate them on ART. Caregivers (n=22) found the community POC model acceptable, provided that privacy could be ensured because the service was convenient and delivered close to home. CONCLUSION: We demonstrate the acceptability, appropriateness, and feasibility of implementing the community POC model in Zambia, while identifying potential challenges related to client privacy and platform field operations. The community POC model may represent a promising strategy to further facilitate active HIV case finding and linkage to ART for children with undiagnosed HIV infection in the community.

Costs of implementing universal test and treat in three correctional facilities in South Africa and Zambia.

INTRODUCTION: Universal test and treat (UTT) is a population-based strategy that aims to ensure widespread HIV testing and rapid antiretroviral therapy (ART) for all who have tested positive regardless of CD4 count to decrease HIV incidence and improve health outcomes. Little is known about the specific resources required to implement UTT in correctional facilities for incarcerated people. The primary aim of this study was to describe the resources used to implement UTT and to provide detailed costing to inform UTT scale-up in similar settings. METHODS: The costing study was a cross-sectional descriptive study conducted in three correctional complexes, Johannesburg Correctional Facility in Johannesburg (>4000 inmates) South Africa, and Brandvlei (~3000 inmates), South Africa and Lusaka Central (~1400 inmates), Zambia. Costing was determined through a survey conducted between September and December 2017 that identified materials and labour used for three separate components of UTT: HIV testing services (HTS), ART initiation, and ART maintenance. Our study participants were staff working in the correctional facilities involved in any activity related to UTT implementation. Unit costs were reported as cost per client served while total costs were reported for all clients seen over a 12-month period. RESULTS: The cost of HIV testing services (HTS) per client was $ 92.12 at Brandvlei, $ 73.82 at Johannesburg, and $ 65.15 at Lusaka. The largest cost driver for HIV testing at Brandvlei were staff costs at 55.6% of the total cost, while at Johannesburg (56.5%) and Lusaka (86.6%) supplies were the largest contributor. The cost per client initiated on ART was $917 for Brandvlei, $421.8 for Johannesburg, and $252.1 for Lusaka. The activity cost drivers were adherence counselling at Brandvlei (59%), and at Johannesburg and Lusaka it was the actual ART initiation at 75.6% and 75.8%, respectively. The annual unit cost for ART maintenance was $2,640.6 for Brandvlei, $710 for Johannesburg, and $385.5 for Lusaka. The activity cost drivers for all three facilities were side effect monitoring, and initiation of isoniazid preventive treatment (IPT), cotrimoxazole, and fluconazole, with this comprising 44.7% of the total cost at Brandvlei, 88.9% at Johannesburg, and 50.5% at Lusaka. CONCLUSION: Given the needs of this population, the opportunity to reach inmates at high risk for HIV, and overall national and global 95-95-95 goals, the UTT policies for incarcerated individuals are of vital importance. Our findings provide comparator costing data and highlight key drivers of UTT cost by facility.

A Two-stage Approach for Rapid Assessment of the Proportion Achieving Viral Suppression Using Routine Clinical Data.

BACKGROUND: Improving viral suppression among people with HIV reduces morbidity, mortality, and transmission. Accordingly, monitoring the proportion of patients with a suppressed viral load is important to optimizing HIV care and treatment programs. But viral load data are often incomplete in clinical records. We illustrate a two-stage approach to estimate the proportion of treated people with HIV who have a suppressed viral load in the Dominican Republic. METHODS: Routinely collected data on viral load and patient characteristics were recorded in a national database, but 74% of patients on treatment at the time of the study did not have a recent viral load measurement. We recruited a subset of these patients for a rapid assessment that obtained additional viral load measurements. We combined results from the rapid assessment and main database using a two-stage weighting approach and compared results to estimates obtained using standard approaches to account for missing data. RESULTS: Of patients with recent routinely collected viral load data, 60% had a suppressed viral load. Results were similar after applying standard approaches to account for missing data. Using the two-stage approach, we estimated that 77% (95% confidence interval [CI] = 74, 80) of those on treatment had a suppressed viral load. CONCLUSIONS: When assessing the proportion of people on treatment with a suppressed viral load using routinely collected data, applying standard approaches to handle missing data may be inadequate. In these settings, augmenting routinely collected data with data collected through sampling-based approaches could allow more accurate and efficient monitoring of HIV treatment program effectiveness.

Mitigating the effects of COVID-19 on HIV treatment and care in Lusaka, Zambia: a before-after cohort study using mixed effects regression.

INTRODUCTION: The Zambian Ministry of Health (MoH) issued COVID-19 mitigation guidance for HIV care immediately after the first COVID-19 case was confirmed in Zambia on 18 March 2020. The Centre for Infectious Disease Research in Zambia implemented MoH guidance by: 1) extending antiretroviral therapy (ART) refill duration to 6 multi-month dispensation (6MMD) and 2) task-shifting communication and mobilisation of those in HIV care to collect their next ART refill early. We assessed the impact of COVID-19 mitigation guidance on HIV care 3 months before and after guidance implementation. METHODS: We reviewed all ART pharmacy visit data in the national HIV medical record for PLHIV in care having ≥1 visit between 1 January-30 June 2020 at 59 HIV care facilities in Lusaka Province, Zambia. We undertook a before-after evaluation using mixed-effects Poisson regression to examine predictors and marginal probability of early clinic return (pharmacy visit >7 days before next appointment), proportion of late visit (>7 days late for next appointment) and probability of receiving a 6MMD ART refill. RESULTS: A total of 101 371 individuals (64% female, median age 39) with 130 486 pharmacy visits were included in the analysis. We observed a significant increase in the adjusted prevalence ratio (4.63; 95% CI 4.45 to 4.82) of early return before compared with after guidance implementation. Receipt of 6MMD increased from a weekly mean of 47.9% (95% CI 46.6% to 49.2%) before to 73.4% (95% CI 72.0% to 74.9%) after guidance implementation. The proportion of late visits (8-89 days late) was significantly higher before (18.8%, 95% CI17.2%to20.2%) compared with after (15.1%, 95% CI13.8%to16.4%) guidance implementation . CONCLUSIONS: Timely issuance and implementation of COVID-19 mitigation guidance involving task-shifted patient communication and mobilisation alongside 6MMD significantly increased early return to ART clinic, potentially reducing interruptions in HIV care during a global public health emergency.

Preferences for transitional HIV care among people living with HIV recently released from prison in Zambia: a discrete choice experiment.

INTRODUCTION: No studies from sub-Saharan Africa have attempted to assess HIV service delivery preferences among incarcerated people living with HIV as they transition from prisons to the community ("releasees"). We conducted a discrete choice experiment (DCE) to characterize releasee preferences for transitional HIV care services in Zambia to inform the development of a differentiated service delivery model to promote HIV care continuity for releasees. METHODS: Between January and October 2019, we enrolled a consecutive sample of 101 releasees from a larger cohort prospectively following 296 releasees from five prisons in Zambia. We administered a DCE eliciting preferences for 12 systematically designed choice scenarios, each presenting three hypothetical transitional care options. Options combined six attributes: (1) clinic type for post-release HIV care; (2) client focus of healthcare workers; (3) transitional care model type; (4) characteristics of transitional care provider; (5) type of transitional care support; and (6) HIV status disclosure support. We analysed DCE choice data using a mixed logit model, with coefficients describing participants' average ("mean") preferences for each option compared to the standard of care and their distributions describing preference variation across participants. RESULTS: Most DCE participants were male (n = 84, 83.2%) and had completed primary school (n = 54, 53.5%), with 29 (28.7%) unemployed at follow-up. Participants had spent an average of 8.2 months in the community prior to the DCE, with 18 (17.8%) reporting an intervening episode of re-incarceration. While we observed significant preference variation across participants (p < 0.001 for most characteristics), releasees were generally averse to clinics run by community-based organizations versus government antiretroviral therapy clinics providing post-release HIV care (mean preference = -0.78, p < 0.001). On average, releasees most preferred livelihood support (mean preference = 1.19, p < 0.001) and HIV care support (mean preference = 1.00, p < 0.001) delivered by support groups involving people living with HIV (mean preference = 1.24, p < 0.001). CONCLUSIONS: We identified preferred characteristics of transitional HIV care that can form the basis for differentiated service delivery models for prison releasees. Such models should offer client-centred care in trusted clinics, provide individualized HIV care support delivered by support groups and/or peer navigators, and strengthen linkages to programs providing livelihood support.

Effects of implementing universal and rapid HIV treatment on initiation of antiretroviral therapy and retention in care in Zambia: a natural experiment using regression discontinuity.

BACKGROUND: Universal testing and treatment (UTT) for all people living with HIV has only been assessed under experimental conditions in cluster-randomised trials. The public health effectiveness of UTT policies on the HIV care cascade under real-world conditions is not known. We assessed the real-world effectiveness of universal HIV treatment policies that were implemented in Zambia on Jan 1, 2017. METHODS: We used data from Zambia's routine electronic health record system to analyse antiretroviral therapy (ART)-naive adults who newly enrolled in HIV care up to 1 year before and after the implementation of universal treatment (ie, Jan 1, 2016, to Jan 1, 2018) at 117 clinics supported by the Centre for Infectious Disease Research in Zambia. We used a regression discontinuity design to estimate the effects of implementing UTT on same-day ART initiation, ART initiation within 1 month, and retention on ART at 12 months (defined as clinic attendance 9-15 months after enrolment and at least 6 months on ART), under the assumption that patients presenting immediately before and after UTT implementation were balanced on both measured and unmeasured characteristics. We did an instrumental variable analysis to estimate the effect of same-day ART initiation under routine conditions on 12-month retention on ART. FINDINGS: 65 673 newly enrolled patients with HIV (40 858 [62·2%] female, median age 32 years [IQR 26-39], median CD4 count 287 cells per µL [IQR 147-466]) were eligible for inclusion in the analyses; 31 145 enrolled before implementation of UTT, and 34 528 enrolled after UTT. Implementation of universal treatment increased same-day ART initiation from 41·7% to 74·8% (risk difference [RD] 33·1%, 95% CI 30·5-35·7), ART initiation by 1 month from 69·6% to 87·0% (RD 17·4%, 15·5-19·3), and 12-month retention on ART from 56·2% to 63·3% (RD 7·1%, 4·3-9·9). ART initiation rates became more uniform across patient subgroups after implementation of universal treatment, but heterogeneity in 12-month retention on ART between subgroups was unchanged. Instrumental variable analyses indicated that same-day ART initiation in routine settings led to a 15·8% increase (95% CI 12·1-19·5) in 12-month retention on ART. INTERPRETATION: UTT policies implemented in Zambia increased the rapidity and uptake of ART, as well as retention on ART at 12 months, although overall retention on ART remained suboptimal. UTT policies reduced disparities in treatment initiation, but not 12-month retention on ART. Natural experiments reveal both the anticipated and unanticipated effects of real-world implementation and indicate the need for new strategies leveraging the short-term effects of UTT to cultivate long-term treatment success. FUNDING: National Institutes of Health.

Community-facility linkage models and maternal and infant health outcomes in Malawi's PMTCT/ART program: A cohort study.

BACKGROUND: In sub-Saharan Africa, 3 community-facility linkage (CFL) models-Expert Clients, Community Health Workers (CHWs), and Mentor Mothers-have been widely implemented to support pregnant and breastfeeding women (PBFW) living with HIV and their infants to access and sustain care for prevention of mother-to-child transmission of HIV (PMTCT), yet their comparative impact under real-world conditions is poorly understood. METHODS AND FINDINGS: We sought to estimate the effects of CFL models on a primary outcome of maternal loss to follow-up (LTFU), and secondary outcomes of maternal longitudinal viral suppression and infant "poor outcome" (encompassing documented HIV-positive test result, LTFU, or death), in Malawi's PMTCT/ART program. We sampled 30 of 42 high-volume health facilities ("sites") in 5 Malawi districts for study inclusion. At each site, we reviewed medical records for all newly HIV-diagnosed PBFW entering the PMTCT program between July 1, 2016 and June 30, 2017, and, for pregnancies resulting in live births, their HIV-exposed infants, yielding 2,589 potentially eligible mother-infant pairs. Of these, 2,049 (79.1%) had an available HIV treatment record and formed the study cohort. A randomly selected subset of 817 (40.0%) cohort members underwent a field survey, consisting of a questionnaire and HIV biomarker assessment. Survey responses and biomarker results were used to impute CFL model exposure, maternal viral load, and early infant diagnosis (EID) outcomes for those missing these measures to enrich data in the larger cohort. We applied sampling weights in all statistical analyses to account for the differing proportions of facilities sampled by district. Of the 2,049 mother-infant pairs analyzed, 62.2% enrolled in PMTCT at a primary health center, at which time 43.7% of PBFW were ≤24 years old, and 778 (38.0%) received the Expert Client model, 640 (31.2%) the CHW model, 345 (16.8%) the Mentor Mother model, 192 (9.4%) ≥2 models, and 94 (4.6%) no model. Maternal LTFU varied by model, with LTFU being more likely among Mentor Mother model recipients (adjusted hazard ratio [aHR]: 1.45; 95% confidence interval [CI]: 1.14, 1.84; p = 0.003) than Expert Client recipients. Over 2 years from HIV diagnosis, PBFW supported by CHWs spent 14.3% (95% CI: 2.6%, 26.1%; p = 0.02) more days in an optimal state of antiretroviral therapy (ART) retention with viral suppression than women supported by Expert Clients. Infants receiving the Mentor Mother model (aHR: 1.24, 95% CI: 1.01, 1.52; p = 0.04) and ≥2 models (aHR: 1.44, 95% CI: 1.20, 1.74; p < 0.001) were more likely to undergo EID testing by age 6 months than infants supported by Expert Clients. Infants receiving the CHW and Mentor Mother models were 1.15 (95% CI: 0.80, 1.67; p = 0.44) and 0.84 (95% CI: 0.50, 1.42; p = 0.51) times as likely, respectively, to experience a poor outcome by 1 year than those supported by Expert Clients, but not significantly so. Study limitations include possible residual confounding, which may lead to inaccurate conclusions about the impacts of CFL models, uncertain generalizability of findings to other settings, and missing infant medical record data that limited the precision of infant outcome measurement. CONCLUSIONS: In this descriptive study, we observed widespread reach of CFL models in Malawi, with favorable maternal outcomes in the CHW model and greater infant EID testing uptake in the Mentor Mother model. Our findings point to important differences in maternal and infant HIV outcomes by CFL model along the PMTCT continuum and suggest future opportunities to identify key features of CFL models driving these outcome differences.

Differences in Access to HIV Services and Risky Sexual Behaviors Among Malawian Women at Social Venues Who Do and Do Not Engage in Sex Work.

In the high HIV-burden country of Malawi, female sex workers (FSW) are one of the populations most profoundly affected by HIV. The Malawi Priorities for Local AIDS Control Efforts (PLACE) surveyed 1,004 self-identified FSW, 213 other FSW (OFSW), and 130 other high risk women (OHRW) at social venues. Analyses compared the three groups using survey-weighted log binomial regression models. Each group had a distinct pattern of usage and access to services: OFSW and FSW had greater access to condoms, while using a condom ever was greatest among FSW. Nearly all women knew where to get tested for HIV but very few used FSW drop-in centers. HIV prevalence was high in all three groups (35% FSW, 20% OFSW, 20% OHRW). Given these results, HIV services should be targeted to all women at social venues in Malawi, regardless of sex worker status to improve health outcomes and limit onward transmission of HIV.

Timing of HIV testing among pregnant and breastfeeding women and risk of mother-to-child HIV transmission in Malawi: a sampling-based cohort study.

INTRODUCTION: Pregnant women living with HIV can achieve viral suppression and prevent HIV mother-to-child transmission (MTCT) with timely HIV testing and early ART initiation and maintenance. Although it is recommended that pregnant women undergo HIV testing early in antenatal care in Malawi, many women test positive during breastfeeding because they did not have their HIV status ascertained during pregnancy, or they tested negative during pregnancy but seroconverted postpartum. We sought to estimate the association between the timing of last positive HIV test (during pregnancy vs. breastfeeding) and outcomes of maternal viral suppression and MTCT in Malawi's PMTCT programme. METHODS: We conducted a two-stage cohort study among mother-infant pairs in 30 randomly selected high-volume health facilities across five nationally representative districts of Malawi between 1 July 2016 and 30 June 2017. Log-binomial regression was used to estimate prevalence ratios (PR) and risk ratios (RR) for associations between timing of last positive HIV test (i.e. breastfeeding vs. pregnancy) and maternal viral suppression and MTCT, controlling for confounding using inverse probability weighting. RESULTS: Of 822 mother-infant pairs who had available information on the timing of the last positive HIV test, 102 mothers (12.4%) had their last positive test during breastfeeding. Women who lived one to two hours (PR = 2.15; 95% CI: 1.29 to 3.58) or >2 hours (PR = 2.36; 95% CI: 1.37 to 4.10) travel time to the nearest health facility were more likely to have had their last positive HIV test during breastfeeding compared to women living <1 hour travel time to the nearest health facility. The risk of unsuppressed VL did not differ between women who had their last positive HIV test during breastfeeding versus pregnancy (adjusted RR [aRR] = 0.87; 95% CI: 0.48 to 1.57). MTCT risk was higher among women who had their last positive HIV test during breastfeeding compared to women who had it during pregnancy (aRR = 6.57; 95% CI: 3.37 to 12.81). CONCLUSIONS: MTCT in Malawi occurred disproportionately among women with a last positive HIV test during breastfeeding. Testing delayed until the postpartum period may lead to higher MTCT. To optimize maternal and child health outcomes, PMTCT programmes should focus on early ART initiation and providing targeted testing, prevention, treatment and support to breastfeeding women.

Phase 1 Human Immunodeficiency Virus (HIV) Vaccine Trial to Evaluate the Safety and Immunogenicity of HIV Subtype C DNA and MF59-Adjuvanted Subtype C Envelope Protein.

BACKGROUND: The Pox-Protein Public-Private Partnership is performing a suite of trials to evaluate the bivalent subtype C envelope protein (TV1.C and 1086.C glycoprotein 120) vaccine in the context of different adjuvants and priming agents for human immunodeficiency virus (HIV) type 1 (HIV-1) prevention. METHODS: In the HIV Vaccine Trials Network 111 trial, we compared the safety and immunogenicity of DNA prime followed by DNA/protein boost with DNA/protein coadministration injected intramuscularly via either needle/syringe or a needle-free injection device (Biojector). One hundred thirty-two healthy, HIV-1-uninfected adults were enrolled from Zambia, South Africa, and Tanzania and were randomized to 1 of 6 arms: DNA prime, protein boost by needle/syringe; DNA and protein coadministration by needle/syringe; placebo by needle/syringe; DNA prime, protein boost with DNA given by Biojector; DNA and protein coadministration with DNA given by Biojector; and placebo by Biojector. RESULTS: All vaccinations were safe and well tolerated. DNA and protein coadministration was associated with increased HIV-1 V1/V2 antibody response rate, a known correlate of decreased HIV-1 infection risk. DNA administration by Biojector elicited significantly higher CD4+ T-cell response rates to HIV envelope protein than administration by needle/syringe in the prime/boost regimen (85.7% vs 55.6%; P = .02), but not in the coadministration regimen (43.3% vs 48.3%; P = .61). CONCLUSIONS: Both the prime/boost and coadministration regimens are safe and may be promising for advancement into efficacy trials depending on whether cellular or humoral responses are desired. CLINICAL TRIALS REGISTRATION: South African National Clinical Trials Registry (application 3947; Department of Health [DoH] no. DOH-27-0715-4917) and ClinicalTrials.gov (NCT02997969).