Programme science in action: lessons from an observational study of HIV prevention programming for key populations in Lusaka, Zambia.

INTRODUCTION: Optimizing uptake of pre-exposure prophylaxis (PrEP) for individuals at risk of HIV acquisition has been challenging despite clear scientific evidence and normative guidelines, particularly for key populations (KPs) such as men who have sex with men (MSM), female sex workers (FSWs), transgender (TG) people and persons who inject drugs (PWID). Applying an iterative Programme Science cycle, building on the effective programme coverage framework, we describe the approach used by the Centre for Infectious Disease Research in Zambia (CIDRZ) to scale up PrEP delivery and address inequities in PrEP access for KP in Lusaka, Zambia. METHODS: In 2019, CIDRZ partnered with 10 local KP civil society organizations (CSOs) and the Ministry of Health (MOH) to offer HIV services within KP-designated community safe spaces. KP CSO partners led KP mobilization, managed safe spaces and delivered peer support; MOH organized clinicians and clinical commodities; and CIDRZ provided technical oversight. In December 2021, we introduced a community-based intervention focused on PrEP delivery in venues where KP socialize. We collected routine programme data from September 2019 to June 2023 using programme-specific tools and the national electronic health record. We estimated the before-after effects of our intervention on PrEP uptake, continuation and equity for KP using descriptive statistics and interrupted time series regression, and used mixed-effects regression to estimate marginal probabilities of PrEP continuity. RESULTS: Most (25,658) of the 38,307 (67.0%) Key Population Investment Fund beneficiaries were reached with HIV prevention services at community-based venues. In total, 23,527 (61.4%) received HIV testing services, with 15,508 (65.9%) testing HIV negative and found PrEP eligible, and 15,241 (98.3%) initiating PrEP. Across all programme quarters and KP types, PrEP uptake was >90%. After introducing venue-based PrEP delivery, PrEP uptake (98.7% after vs. 96.5% before, p < 0.001) and the number of initiations (p = 0.014) increased significantly. The proportion of KP with ≥1 PrEP continuation visit within 6 months of initiation was unchanged post-intervention (46.7%, 95% confidence interval [CI]: 45.7%, 47.6%) versus pre-intervention (47.2%, 95% CI: 45.4%, 49.1%). CONCLUSIONS: Applying Programme Science principles, we demonstrate how decentralizing HIV prevention services to KP venues and safe spaces in partnership with KP CSOs enabled successful community-based PrEP delivery beyond the reach of traditional facility-based services.

The Social Construction of Aging Among a Clinic-Based Population and Their Healthcare Workers in Zambia.

Objectives: We sought to understand the social construction of aging in a clinic-based population, with and without HIV, to address gaps in care for older individuals living with HIV in Zambia. Methods: Our exploratory qualitative study included 36 in-depth interviews with clinic clients and four focus group discussions with 36 professional and lay healthcare workers providing services to the clients. We identified themes based on social construction theory. Results: At the individual level, aging was multidimensional, perceived both as an achievement in the HIV era and as a period of cognitive, physical, and economic decline. In social interactions, older individuals were often stereotyped and treated as helpless, poor, and "witches." Those living with HIV faced the additional stigma of being labeled as promiscuous. Some of the participants living without HIV refused to take daily medication for non-communicable diseases to avoid being mistaken for taking antiretroviral therapy for HIV. Older individuals wanted quality healthcare and family support to address the intersectional stigma of aging, poverty, and chronic illness. Conclusion: Multifaceted interventions are required to combat age-related prejudice, intersectional stigma, and discriminatory practices, particularly for people living with HIV.

Trends in SARS-CoV-2 seroprevalence among pregnant women attending first antenatal care visits in Zambia: A repeated cross-sectional survey, 2021-2022.

SARS-CoV-2 serosurveys help estimate the extent of transmission and guide the allocation of COVID-19 vaccines. We measured SARS-CoV-2 seroprevalence among women attending ANC clinics to assess exposure trends over time in Zambia. We conducted repeated cross-sectional SARS-CoV-2 seroprevalence surveys among pregnant women aged 15-49 years attending their first ANC visits in four districts of Zambia (two urban and two rural) during September 2021-September 2022. Serologic testing was done using a multiplex bead assay which detects IgG antibodies to the nucleocapsid protein and the spike protein receptor-binding domain (RBD). We calculated monthly SARS-CoV-2 seroprevalence by district. We also categorized seropositive results as infection alone, infection and vaccination, or vaccination alone based on anti-RBD and anti-nucleocapsid test results and self-reported COVID-19 vaccination status (vaccinated was having received ≥1 dose). Among 8,304 participants, 5,296 (63.8%) were cumulatively seropositive for SARS-CoV-2 antibodies from September 2021 through September 2022. SARS-CoV-2 seroprevalence primarily increased from September 2021 to September 2022 in three districts (Lusaka: 61.8-100.0%, Chongwe: 39.6-94.7%, Chipata: 56.5-95.0%), but in Chadiza, seroprevalence increased from 27.8% in September 2021 to 77.2% in April 2022 before gradually dropping to 56.6% in July 2022. Among 5,906 participants with a valid COVID-19 vaccination status, infection alone accounted for antibody responses in 77.7% (4,590) of participants. Most women attending ANC had evidence of prior SARS-CoV-2 infection and most SARS-CoV-2 seropositivity was infection-induced. Capturing COVID-19 vaccination status and using a multiplex bead assay with anti-nucleocapsid and anti-RBD targets facilitated distinguishing infection-induced versus vaccine-induced antibody responses during a period of increasing COVID-19 vaccine coverage in Zambia. Declining seroprevalence in Chadiza may indicate waning antibodies and a need for booster vaccines. ANC clinics have a potential role in ongoing SARS-CoV-2 serosurveillance and can continue to provide insights into SARS-CoV-2 antibody dynamics to inform near real-time public health responses.

Acceptability and tolerability of long-acting injectable cabotegravir or rilpivirine in the first cohort of virologically suppressed adolescents living with HIV (IMPAACT 2017/MOCHA): a secondary analysis of a phase 1/2, multicentre, open-label, non-comparative dose-finding study.

BACKGROUND: Long-acting injectable cabotegravir and rilpivirine have demonstrated safety, acceptability, and efficacy in adults living with HIV-1. The IMPAACT 2017 study (MOCHA study) was the first to use these injectable formulations in adolescents (aged 12-17 years) living with HIV-1. Herein, we report acceptability and tolerability outcomes in cohort 1 of the study. METHODS: In this a secondary analysis of a phase 1/2, multicentre, open-label, non-comparative dose-finding study, with continuation of pre-study oral combination antiretroviral treatment (ART), 55 adolescents living with HIV-1 were enrolled to receive sequential doses of either long-acting cabotegravir or rilpivirine and 52 received at least two injections. Participants had a body weight greater than 35 kg and BMI less than 31·5 kg/m2 and had been on stable ART for at least 90 consecutive days with an HIV-1 viral load of less than 50 copies per mL at a participating IMPAACT study site. Participants had to be willing to continue their pre-study ART during cohort 1. The primary objectives of the study were to confirm doses for oral and injectable cabotegravir and for injectable rilpivirine in adolescents living with HIV. This analysis of participant-reported outcomes included a face scale assessment of pain at each injection and a Pediatric Quality of Life Inventory (PedsQL) at baseline and week 16 for participants in the USA, South Africa, Botswana, and Thailand. A subset of 11 adolescents and 11 parents or caregivers in the USA underwent in-depth interviews after receipt of one or two injections. This trial is registered at ClinicalTrials.gov, NCT03497676. FINDINGS: Between March 19, 2019, and Nov 25, 2021, 55 participants were enrolled into cohort 1. Using the six-point face scale, 43 (83%) of participants at week 4 and 38 (73%) at week 8 reported that the injection caused "no hurt" or "hurts little bit", while only a single (2%) participant for each week rated the pain as one of the two highest pain levels. Quality of life was not diminished by the addition of one injectable antiretroviral. In-depth interviews revealed that parents and caregivers in the USA frequently had more hesitancy than adolescents about use of long-acting formulations, but parental acceptance was higher after their children received injections. INTERPRETATION: High acceptability and tolerability of long-acting cabotegravir or rilpivirine injections suggests that these are likely to be favoured treatment options for some adolescents living with HIV. FUNDING: National Institutes of Health and ViiV Healthcare.

Safety and pharmacokinetics of oral and long-acting injectable cabotegravir or long-acting injectable rilpivirine in virologically suppressed adolescents with HIV (IMPAACT 2017/MOCHA): a phase 1/2, multicentre, open-label, non-comparative, dose-finding study.

BACKGROUND: Combined intramuscular long-acting cabotegravir and long-acting rilpivirine constitute the first long-acting combination antiretroviral therapy (ART) regimen approved for adults with HIV. The goal of the IMPAACT 2017 study (MOCHA [More Options for Children and Adolescents]) was to assess the safety and pharmacokinetics of these drugs in adolescents. METHODS: In this phase 1/2, multicentre, open-label, non-comparative, dose-finding study, virologically suppressed adolescents (aged 12-17 years; weight ≥35 kg; BMI ≤31·5 kg/m2) with HIV-1 on daily oral ART were enrolled at 15 centres in four countries (Botswana, South Africa, Thailand, and the USA). After 4-6 weeks of oral cabotegravir (cohort 1C) or rilpivirine (cohort 1R), participants received intramuscular long-acting cabotegravir or long-acting rilpivirine every 4 weeks or 8 weeks per the adult dosing regimens, while continuing pre-study ART. The primary outcomes were assessments of safety measures, including all adverse events, until week 4 for oral cabotegravir and until week 16 for long-acting cabotegravir and long-acting rilpivirine, and pharmacokinetic measures, including the area under the plasma concentration versus time curve during the dosing interval (AUC0-tau) and drug concentrations, at week 2 for oral dosing of cabotegravir and at week 16 for intramuscular dosing of cabotegravir and rilpivirine. Enrolment into cohort 1C or cohort 1R was based on the participant's pre-study ART, meaning that masking was not done. For pharmacokinetic analyses, blood samples were drawn at weeks 2-4 after oral dosing and weeks 4-16 after intramuscular dosing. Safety outcome measures were summarised using frequencies, percentages, and exact 95% CIs; pharmacokinetic parameters were summarised using descriptive statistics. This trial is registered at ClinicalTrials.gov, NCT03497676, and is closed to enrolment. FINDINGS: Between March 19, 2019, and Nov 25, 2021, 55 participants were enrolled: 30 in cohort 1C and 25 in cohort 1R. At week 16, 28 (97%, 95% CI 82-100) of the 29 dose-evaluable participants in cohort 1C and 21 (91%; 72-99) of the 23 dose-evaluable participants in cohort 1R had reported at least one adverse event, with the most common being injection-site pain (nine [31%] in cohort 1C; nine [39%] in cohort 1R; none were severe). One (4%, 95% CI 0-22) participant in cohort 1R had an adverse event of grade 3 or higher, leading to treatment discontinuation, which was defined as acute rilpivirine-related allergic reaction (self-limiting generalised urticaria) after the first oral dose. No deaths or life-threatening events occurred. In cohort 1C, the week 2 median cabotegravir AUC0-tau was 148·5 (range 37·2-433·1) µg·h/mL. The week 16 median concentrations for the every-4-weeks and every-8-weeks dosing was 3·11 µg/mL (range 1·22-6·19) and 1·15 µg/mL (<0·025-5·29) for cabotegravir and 52·9 ng/mL (31·9-148·0) and 39·1 ng/mL (27·2-81·3) for rilpivirine, respectively. These concentrations were similar to those in adults. INTERPRETATION: Study data support using long-acting cabotegravir or long-acting rilpivirine, given every 4 weeks or 8 weeks, per the adult dosing regimens, in virologically suppressed adolescents aged 12 years and older and weighing at least 35 kg. FUNDING: The National Institutes of Health and ViiV Healthcare.

The Tuberculosis Sentinel Research Network (TB-SRN) of the International epidemiology Databases to Evaluate AIDS (IeDEA): protocol for a prospective cohort study in Africa, Southeast Asia and Latin America.

INTRODUCTION: Tuberculosis (TB) is a leading infectious cause of death globally. It is the most common opportunistic infection in people living with HIV, and the most common cause of their morbidity and mortality. Following TB treatment, surviving individuals may be at risk for post-TB lung disease. The TB Sentinel Research Network (TB-SRN) provides a platform for coordinated observational TB research within the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. METHODS AND ANALYSIS: This prospective, observational cohort study will assess treatment and post-treatment outcomes of pulmonary TB (microbiologically confirmed or clinically diagnosed) among 2600 people aged ≥15 years, with and without HIV coinfection, consecutively enrolled at 16 sites in 11 countries, across 6 of IeDEA's global regions. Data regarding clinical and sociodemographic factors, mental health, health-related quality of life, pulmonary function, and laboratory and radiographic findings will be collected using standardised questionnaires and data collection tools, beginning from the initiation of TB treatment and through 12 months after the end of treatment. Data will be aggregated for proposed analyses. ETHICS AND DISSEMINATION: Ethics approval was obtained at all implementing study sites, including the Vanderbilt University Medical Center Human Research Protections Programme. Participants will provide informed consent; for minors, this includes both adolescent assent and the consent of their parent or primary caregiver. Protections for vulnerable groups are included, in alignment with local standards and considerations at sites. Procedures for requesting use and analysis of TB-SRN data are publicly available. Findings from TB-SRN analyses will be shared with national TB programmes to inform TB programming and policy, and disseminated at regional and global conferences and other venues.

Drivers of uptake of HIV testing services, a snapshot of barriers and facilitators among adolescent boys and young men in Lusaka: a qualitative study.

BACKGROUND: Striking gender and rural-urban disparities highlight the need to redesign HIV services to improve HIV testing and linkage by adolescent boys and young men (ABYM) in sub-Saharan African cities. PURPOSE: We sought to understand drivers of HIV testing among ABYM living in urban Lusaka in order to design a targeted intervention that may increase their entry into the HIV prevention and treatment cascade. METHODS: In May and June 2019, two male moderators conducted three focus group discussions lasting 1.25 hours with seven to nine ABYM per group and six in-depth interviews with healthcare providers (HCPs) working with adolescents. ABYM were conveniently selected from first aid training, sports and youth-friendly sites in three settlement areas. We purposefully selected HCP from community, facility and district levels. Thematic analyses using inductive reasoning were applied. RESULTS: The 24 ABYM were 18-24 years old (median 21 years), single, from 11 different neighbourhoods and 79% had 9-12 years of education. Facilitators of HIV testing uptake included the importance ABYM placed on good health and planning their future in order to fulfil their masculine identity and societal roles. Barriers included peer norms, life-long treatment along with anticipated changes to sexual life and alcohol use, fear of results and judgement and disappointment among HCP. HCPs agreed that masculine roles ('many things to do') and arduous clinical processes deterred ABYM from accessing testing services. They suggested that ABYM were prone to depression which both caused and resulted from behavioural issues such as alcohol use and risk-taking, which prevented uptake of HIV testing services. Both parties agreed that ABYM needed services specifically designed for them and that offered convenient, private, swift and non-judgemental services. CONCLUSIONS: ABYM disillusioned by standard counselling procedures, systemic barriers and stigma, avoid HIV test and treat services. Innovative ways and youth-specific spaces are needed to increase access to non-judgemental services that facilitate entry into the HIV prevention and treatment cascade in this population.

Patterns of person-centred communications in public HIV clinics: a latent class analysis using the Roter interaction analysis system.

INTRODUCTION: Poor client-provider communication is a critical barrier to long-term retention in care among people living with HIV. However, standardized assessments of this key metric are limited in Africa. We used the Roter Interaction Analysis System (RIAS) to quantitatively characterize patterns of person-centred communication (PCC) behaviours in Zambia. METHODS: We enrolled pairs of people living with HIV making routine HIV follow-up visit and their providers at 24 Ministry of Health-facilities supported by the Centre for Infectious Disease Research in Zambia in Lusaka province between August 2019 and November 2021. Client-provider encounters were audio-recorded and coded using RIAS by trained research staff. We performed latent class analysis to identify interactions with distinctive patterns of provider PCC behaviours (i.e. rapport building, person-centred counselling, PCC micropractices [e.g. brief empathy statements], assessing barriers to care, shared decision-making and leveraging discretionary power) and compared their distribution across client, provider, interaction and facility characteristics. RESULTS: We enrolled 478 people living with HIV and 139 providers (14% nurses, 73.6% clinical officers, 12.3% were medical officers). We identified four distinct profiles: (1) "Medically Oriented Interaction, Minimal PCC Behaviours" (47.6% of interactions) was characterized by medical discussion, minimal psychosocial/non-medical talk and low use of PCC behaviours; (2) "Balanced Medical/Non-medical Interaction, Low PCC Behaviours" (21.0%) was characterized by medical and non-medical discussion but limited use of other PCC behaviours; (3) "Medically Oriented Interaction, Good PCC Behaviours" (23.9%) was characterized by medically oriented discussion, more information-giving and increased use of PCC behaviours; and (4) "Highly person-centred Interaction" (7.5%) was characterized by both balanced medical/non-medical focus and the highest use of PCC behaviours. Nurse interactions were more likely to be characterized by more PCC behaviours (i.e. Class 3 or 4) (44.8%), followed by medical officers (33.9%) and clinical officers (27.3%) (p = 0.031). Longer interactions were also more likely to integrate more PCC behaviours (p < 0.001). CONCLUSIONS: PCC behaviours are relatively uncommon in HIV care in Zambia, and often limited to brief rapport-building statements and PCC micropractices. Strengthening PCC, such as shared decision-making and leveraging discretionary power to better accommodate client needs and preferences, may be an important strategy for improving the quality in HIV treatment programmes.

Comparison of patient exit interviews with unannounced standardised patients for assessing HIV service delivery in Zambia: a study nested within a cluster randomised trial.

OBJECTIVES: To compare unannounced standardised patient approach (eg, mystery clients) with typical exit interviews for assessing patient experiences in HIV care (eg, unfriendly providers, long waiting times). We hypothesise standardised patients would report more negative experiences than typical exit interviews affected by social desirability bias. SETTING: Cross-sectional surveys in 16 government-operated HIV primary care clinics in Lusaka, Zambia providing antiretroviral therapy (ART). PARTICIPANTS: 3526 participants aged ≥18 years receiving ART participated in the exit surveys between August 2019 and November 2021. INTERVENTION: Systematic sample (every nth file) of patients in clinic waiting area willing to be trained received pre-visit training and post-visit interviews. Providers were unaware of trained patients. OUTCOME MEASURES: We compared patient experience among patients who received brief training prior to their care visit (explaining each patient experience construct in the exit survey, being anonymous, without manipulating behaviour) with those who did not undergo training on the survey prior to their visit. RESULTS: Among 3526 participants who participated in exit surveys, 2415 were untrained (56% female, median age 40 (IQR: 32-47)) and 1111 were trained (50% female, median age 37 (IQR: 31-45)). Compared with untrained, trained patients were more likely to report a negative care experience overall (adjusted prevalence ratio (aPR) for aggregate sum score: 1.64 (95% CI: 1.39 to 1.94)), with a greater proportion reporting feeling unwelcome by providers (aPR: 1.71 (95% CI: 1.20 to 2.44)) and witnessing providers behaving rude (aPR: 2.28 (95% CI: 1.63 to 3.19)). CONCLUSION: Trained patients were more likely to identify suboptimal care. They may have understood the items solicited better or felt empowered to be more critical. We trained existing patients, unlike studies that use 'standardised patients' drawn from outside the patient population. This low-cost strategy could improve patient-centred service delivery elsewhere. TRIAL REGISTRATION NUMBER: Assessment was nested within a parent study; www.pactr.org registered the parent study (PACTR202101847907585).

Correction: Evaluation of kidney function among people living with HIV initiating antiretroviral therapy in Zambia.

[This corrects the article DOI: 10.1371/journal.pgph.0000124.].

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.

Cross-sectional study to assess depression among healthcare workers in Lusaka, Zambia during the COVID-19 pandemic.

OBJECTIVES: We sought to assess depression among healthcare workers (HCWs) in the context of COVID-19 in Lusaka Province, Zambia. DESIGN: This cross-sectional study is nested within a larger study, the Person-Centred Public Health for HIV Treatment in Zambia (PCPH), a cluster-randomised trial to assess HIV care and outcomes. SETTING: The research was conducted in 24 government-run health facilities from 11 August to 15 October 2020 during the first wave of the COVID-19 pandemic in Lusaka, Zambia. PARTICIPANTS: We used convenience sampling to recruit HCW participants who were previously enrolled in the PCPH study, had more than 6 months' experience working at the facility and were voluntarily willing to participate. PRIMARY OUTCOME MEASURES: We implemented the well-validated 9-question Patient Health Questionnaire (PHQ-9) to assess HCW depression. We used mixed-effects, adjusted Poisson regression to estimate the marginal probability of HCWs experiencing depression that may warrant intervention (PHQ-9 score ≥5) by healthcare facility. RESULTS: We collected PHQ-9 survey responses from 713 professional and lay HCWs. Overall, 334 (46.8%, 95% CI 43.1%, 50.6%) HCWs recorded a PHQ-9 score ≥5, indicating the need for further assessment and potential intervention for depression. We identified significant heterogeneity across facilities and observed a greater proportion of HCWs with symptoms of depression in facilities providing COVID-19 testing and treatment services. CONCLUSIONS: Depression may be a concern for a large proportion of HCWs in Zambia. Further work to understand the magnitude and aetiologies of depression among HCWs in the public sector is needed to design effective prevention and treatment interventions to meet the needs for mental health support and to minimise poor health outcomes.

Global HIV prevention, care and treatment services for children: a cross-sectional survey from the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium.

OBJECTIVES: To assess access children with HIV have to comprehensive HIV care services, to longitudinally evaluate the implementation and scale-up of services, and to use site services and clinical cohort data to explore whether access to these services influences retention in care. METHODS: A cross-sectional standardised survey was completed in 2014-2015 by sites providing paediatric HIV care across regions of the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium. We developed a comprehensiveness score based on the WHO's nine categories of essential services to categorise sites as 'low' (0-5), 'medium', (6-7) or 'high' (8-9). When available, comprehensiveness scores were compared with scores from a 2009 survey. We used patient-level data with site services to investigate the relationship between the comprehensiveness of services and retention. RESULTS: Survey data from 174 IeDEA sites in 32 countries were analysed. Of the WHO essential services, sites were most likely to offer antiretroviral therapy (ART) provision and counselling (n=173; 99%), co-trimoxazole prophylaxis (168; 97%), prevention of perinatal transmission services (167; 96%), outreach for patient engagement and follow-up (166; 95%), CD4 cell count testing (126; 88%), tuberculosis screening (151; 87%) and select immunisation services (126; 72%). Sites were less likely to offer nutrition/food support (97; 56%), viral load testing (99; 69%) and HIV counselling and testing (69; 40%). 10% of sites rated 'low', 59% 'medium' and 31% 'high' in the comprehensiveness score. The mean comprehensiveness of services score increased significantly from 5.6 in 2009 to 7.3 in 2014 (p<0.001; n=30). Patient-level analysis of lost to follow-up after ART initiation estimated the hazard was highest in sites rated 'low' and lowest in sites rated 'high'. CONCLUSION: This global assessment suggests the potential care impact of scaling-up and sustaining comprehensive paediatric HIV services. Meeting recommendations for comprehensive HIV services should remain a global priority.

Integrating isoniazid preventive therapy into the fast-track HIV treatment model in urban Zambia: A proof-of -concept pilot project.

Most people living with HIV (PLHIV) established on treatment in Zambia receive multi-month prescribing and dispensing (MMSD) antiretroviral therapy (ART) and are enrolled in less-intensive differentiated service delivery (DSD) models such as Fast Track (FT), where clients collect ART every 3-6 months and make clinical visits every 6 months. In 2019, Zambia introduced Isoniazid Preventive Therapy (IPT) with scheduled visits at 2 weeks and 1, 3, and 6 months. Asynchronous IPT and HIV appointment schedules were inconvenient and not client centered. In response, we piloted integrated MMSD/IPT in FT HIV treatment model. We implemented and evaluated a proof-of-concept project at one purposively selected high-volume facility in Lusaka, Zambia between July 2019 and May 2020. We sensitized stakeholders, adapted training materials, standard operating procedures, and screened adults in FT for TB as per national guidelines. Participants received structured TB/IPT education, 6-month supply of isoniazid and ART, aligned 6th month IPT/MMSD clinic appointment, and phone appointments at 2 weeks and months 1-5 following IPT initiation. We used descriptive statistics to characterize IPT completion rates, phone appointment keeping, side effect frequency and Fisher's exact test to determine variation by participant characteristics. Key lessons learned were synthesized from monthly meeting notes. 1,167 clients were screened with 818 (70.1%) enrolled, two thirds (66%) were female and median age 42 years. 738 (90.2%) completed 6-month IPT course and 66 (8.1%) reported IPT-related side effects. 539 clients (65.9%) attended all 7 telephone appointments. There were insignificant differences of outcomes by age or sex. Lessons learnt included promoting project ownership, client empowerment, securing supply chain, adapting existing processes, and cultivating collaborative structured learning. Integrating multi-month dispensing and telephone follow up of IPT into the FT HIV treatment model is a promising approach to scaling-up TB preventive treatment among PLHIV, although limited by barriers to consistent phone access.

Trajectories of re-engagement: factors and mechanisms enabling patient return to HIV care in Zambia.

INTRODUCTION: While disengagement from HIV care threatens the health of persons living with HIV (PLWH) and incidence-reduction targets, re-engagement is a critical step towards positive outcomes. Studies that establish a deeper understanding of successful return to clinical care among previously disengaged PLWH and the factors supporting re-engagement are essential to facilitate long-term care continuity. METHODS: We conducted narrative, patient-centred, in-depth interviews between January and June 2019 with 20 PLWH in Lusaka, Zambia, who had disengaged and then re-engaged in HIV care, identified through electronic medical records (EMRs). We applied narrative analysis techniques, and deductive and inductive thematic analysis to identify engagement patterns and enablers of return. RESULTS: We inductively identified five trajectories of care engagement, suggesting patterns in patient characteristics, experienced barriers and return facilitators that may aid intervention targeting including: (1) intermittent engagement;(2) mostly engaged; (3) delayed linkage after testing; (4) needs time to initiate antiretroviral therapy (ART); and (5) re-engagement with ART initiation. Patient-identified periods of disengagement from care did not always align with care gaps indicated in the EMR. Key, interactive re-engagement facilitators experienced by participants, with varied importance across trajectories, included a desire for physical wellness and social support manifested through verbal encouragement, facility outreach or personal facility connections and family instrumental support. The mechanisms through which facilitators led to return were: (1) the promising of living out one's life priorities; (2) feeling valued; (3) fostering interpersonal accountability; (4) re-entry navigation support; (5) facilitated care and treatment access; and (6) management of significant barriers, such as depression. CONCLUSIONS: While preliminary, the identified trajectories may guide interventions to support re-engagement, such as offering flexible ART access to patients with intermittent engagement patterns instead of stable patients only. Further, for re-engagement interventions to achieve impact, they must activate mechanisms underlying re-engagement behaviours. For example, facility outreach that reminds a patient to return to care but does not affirm a patient's value or navigate re-entry is unlikely to be effective. The demonstrated importance of positive health facility connections reinforces a growing call for patient-centred care. Additionally, interventions should consider the important role communities play in fostering treatment motivation and overcoming practical barriers.

Nongovernmental organizations supporting the HIV service delivery response in Africa - an engine for innovation.

PURPOSE OF REVIEW: Nongovernmental organizations (NGOs) are pivotal to the HIV response, supporting access to HIV services since the start of the epidemic. Against the backdrop of the impact of NGOs, is the recognition of the unique role that local NGOs bring to the HIV response, drawing from their deep understanding of the context and knowledge of local health problems. RECENT FINDINGS: The Centre for Infectious Disease Research in Zambia (CIDRZ) is one such NGO. Through various implementation science research and programs, CIDRZ has supported the Zambian government's HIV response. As Zambia moves closer to epidemic control, understanding reasons for patient disengagement from care and patient preferences for HIV care demonstrated by CIDRZ have contributed to global and national HIV treatment and care guidelines. SUMMARY: This paper offers a case study for how NGOs like CIDRZ can serve as health system-wide catalyst to identify, integrate, and scale up evidence-based practices for HIV prevention, care, and treatment. It draws from the public health literature, CIDRZ extensive program and research experience and implementation science theory, to illustrate key strategies that can be deployed by local NGOs to spark innovation, quality improvement, and support governments to achieve and sustain HIV epidemic control.

Immediate and early engagement of same-day antiretroviral therapy initiation among newly diagnosed people living with HIV in urban Zambia: a retrospective cohort study

Introduction: as Zambia moves towards attaining human immunodeficiency virus (HIV) epidemic control, it is clear significant efforts are required to facilitate achievement of UNAIDS treatment targets by 2030. To accelerate progress towards global target of 95% of people living with HIV (PLHIV) knowing their status, country is promoting community-based HIV testing and same-day antiretroviral therapy (ART) initiation. However, there are uncertainties of how this strategy affects immediate and early engagement in program settings. To address this research gap, we analysed a programme data of PLHIV newly diagnosed and initiated on ART in community and health facility settings. Study objectives were to estimate the proportion of immediate engagement, to estimate early engagement among newly diagnosed PLHIV and, to examine factors independently associated with immediate and early engagement in care among newly diagnosed PLHIV offered same-day ART initiation. Methods: we included all newly diagnosed PLHIV aged 18 years or older and provided same-day ART initiation between October 2018 and January 2019 in Lusaka District. Immediate engagement was estimated as proportion of newly diagnosed PLHIV who visited the health facility at least once within 14 days after same-day ART initiation, whereas early engagement as proportion of newly diagnosed PLHIV active 6 months after same-day ART initiation. Pearson's chi-squared test was used to assess association of outcomes with key background characteristics. Results: of 12,777 newly diagnosed PLHIV who initiated same day ART 7,943 (62%) were tested and initiated in the community. Overall, 6,257 (49%) engaged within 14 days (median 15, IQR: 13-37). Older individuals (36-49 years) were more likely to be engaged at 14 days (aRR 1.29; 95%CI 1.06 - 1.18; p<0.001) and retained at 6 months (aRR1.27;95%CI 1.21-1.34P<0.001) whilst risk of attrition at 6 months was highest in younger ages (18-24 years) (aRR 0.79;95 %CI 0.76-0.82; p<0.001). Conclusion: to adequately address the HIV epidemic targeted engagement approaches are required particularly in the younger ages.

Metabolic syndrome among treatment-naïve people living with and without HIV in Zambia and Zimbabwe: a cross-sectional analysis.

INTRODUCTION: Chronic viral replication has been linked to an increased risk of cardiovascular and metabolic diseases in people living with HIV (PLWH), but few studies have evaluated this association in Southern Africa. We explored the determinants of metabolic syndrome (MetS) among treatment-naïve adults living with and without HIV in Southern Africa. METHODS: Treatment-naïve PLWH and people living without HIV (PLWOH) ≥30 years were consecutively enrolled from primary care clinics in Zambia and Zimbabwe. PLWOH were seronegative partners or persons presenting for HIV testing. We defined MetS as the presence of central obesity plus any two of the following: raised blood pressure, impaired fasting glucose, reduced high-density lipoprotein cholesterol and raised triglycerides, as defined by the International Diabetes Federation. We used logistic regression to determine factors associated with MetS. RESULTS: Between August 2019 and March 2022, we screened 1285 adults and enrolled 420 (47%) PLWH and 481 (53%) PLWOH. The median age was similar between PLWH and PLWOH (40 vs. 38 years, p < 0.24). In PLWH, the median CD4+ count was 228 cells/mm3 (IQR 108-412) and the viral load was 24,114 copies/ml (IQR 277-214,271). Central obesity was present in 365/523 (70%) females and 57/378 males (15%). MetS was diagnosed in 172/901 (19%, 95% confidence interval [CI] 17-22%), and prevalence was higher among females than males (27% vs. 9%). In multivariable analyses, HIV status was not associated with MetS (adjusted odds ratio [aOR] 1.05, 95% CI 0.74-1.51). Risk factors for MetS included age older than 50 years (aOR 2.31, 95% CI 1.49-3.59), female sex (aOR 3.47, 95% CI 2.15-5.60), highest income (aOR 2.19, 95% CI 1.39-3.44) and less than World Health Organization recommended weekly physical activity (aOR 3.35, 95% CI 1.41-7.96). CONCLUSIONS: We report a high prevalence of MetS and central obesity among females in urban Zambia and Zimbabwe. Lifestyle factors and older age appear to be the strongest predictors of MetS in our population, with no evident difference in MetS prevalence between treatment-naïve PLWH and PLWOH.

HIV care experiences and health priorities during the first wave of COVID-19: clients' perspectives - a qualitative study in Lusaka, Zambia.

BACKGROUND: The novel COVID-19 pandemic threatened to disrupt access to human immunodeficiency (HIV) treatment for persons living with HIV (PLHIV), two-thirds of whom live in sub-Saharan Africa. To inform a health system response supportive of continuity of care, we sought to understand clients' HIV care experiences and health priorities during the first wave of COVID-19 outbreak in Lusaka, Zambia. METHODS: Leveraging a study cohort of those who completed periodic SMS surveys on HIV care, we purposefully sampled 25 PLHIV after first confirmed COVID-19 case was reported in Zambia on 18th March 2020. We phone-interviewed participants, iteratively refining interview guide to capture emergent themes on COVID-19 awareness, health facility interactions, and social circumstances, which we analyzed using matrix analysis. RESULTS: All participants were aware of COVID-19, and HIV care experiences and health priorities of clients were affected by associated changes at health system, household, and individual level. The health system instituted early clinic visits to provide 6-months of antiretroviral therapy (ART) for stable patients and 3-months for unstable patients to reduce clinic visits and wait times. Most patients welcomed this long-desired extended appointment spacing. Some reported feeling respected and engaged when health care workers telephoned requesting their early clinic visit. However, others felt discouraged by an absence of physical distancing during their clinic visit due to 'severe acute respiratory syndrome coronavirus 2' (SARS-CoV-2) infection concerns. Several expressed a lack of clarity regarding next viral load monitoring date and means for receiving results. Patients suggested regular patient-facility communication by telephone and SMS. Patients emphasized that COVID-19 restrictions led to loss of employment and household income, exacerbating poverty and difficulties in taking ART. At individual level, most participants felt motivated to stay healthy during COVID-19 by ART adherence and regular laboratory monitoring. CONCLUSIONS: Clients' HIV care and health priorities during the first wave of COVID-19 in Lusaka province were varied with a combination of positive and negative experiences that occurred especially at health system and individual levels, while at household level, the experiences were all negative. More research is needed to understand how patients practice resiliency in the widespread context of socio-economic instability. Governments and patients must work together to find local, health systems solutions to support ART adherence and monitoring. Additionally, the health system should consider how to build on changes for long-term HIV management and service delivery.

Temporal changes in paediatric and adolescent HIV outcomes across the care continuum in Zambia: an interrupted time-series analysis.

BACKGROUND: Paediatric and adolescent HIV treatment programmes in sub-Saharan Africa have rapidly expanded and evolved over the past decade. Real-world evidence of how the implementation of new policies over time has affected treatment outcomes is inadequate, but is crucial for guiding the implementation of the next phases of the HIV treatment response for children. We examined how treatment outcomes in Zambia's national paediatric and adolescent HIV treatment programmes have changed over time as new policies were implemented. METHODS: We used data from Zambia's routine electronic health record to analyse children and adolescents living with HIV who were antiretroviral therapy (ART) naive between the ages of 0 and 19 years who were newly enrolled in care between Jan 1, 2011, and March 31, 2019, at 102 health facilities in Lusaka and Western provinces supported by the Centre for Infectious Disease Research in Zambia. Sociodemographic factors, clinical data, facility-level data, and visit history were obtained from the national electronic health record and laboratory systems used in routine HIV care in Zambia. We aimed to characterise the changes in the distribution of the age and sex of new enrolees over time. We used an interrupted time-series design to examine the rates of ART initiation, retention in care, time to ART initiation, and first-line ART regimens among new enrolees across different age strata as they changed over time with the adoption of new ART guidelines in 2014 and 2017. FINDINGS: Between Jan 1, 2011, and March 31, 2019, 26 214 children and adolescents living with HIV who were ART naïve were newly enrolled at one of 102 ART facilities in two provinces in Zambia. Rates of new enrolees increased by 25-35% among children younger than 15 years over time, but by 92·3% between 2011 and 2017 among adolescents, with the largest absolute increase among adolescent girls. Rates of ART initiation increased steadily and in parallel across all age groups from before the implementation of the 2014 guidelines to after the implementation of the 2017 guidelines (<2 years, 42·4% for 2014 and 81·6% for 2017; 2 to <5 years, 39·3% for 2014 and 82·8% for 2017; 5 to <15 years, 49·2% for 2014 and 86·6% for 2017; 15 to 19 years, 52·4% for 2014 and 86·2% for 2017); median time to ART initiation went from 2-3 months to same-day initiation during this same time period. Rates of retention on ART 6 months after linkage saw much smaller improvements over time (<2 years, 35·4% for 2014 and 52·0% for 2017; 2 to <5 years, 40·2% for 2014 and 54·4% for 2017; 5 to <15 years, 46·7% for 2014 and 63·4% for 2017; 15 to 19 years, 40·1% for 2014 and 52·7% for 2017). INTERPRETATION: Improvements in ART initiation occurred largely in parallel across age groups over time, despite universal treatment being implemented at different timepoints for different ages. Although the rates of ART initiation reach high levels, retention on ART was low. This analysis provides a comprehensive examination of how paediatric and adolescent outcomes have evolved over the past decade in Zambia and identifies where more targeted efforts will be needed over the next decade. FUNDING: National Institutes of Health.