Looking back to see forward: multidirectional learning between the US Ryan White HIV/AIDS Program and the US President's Emergency Plan for AIDS Relief.

To end the HIV epidemic as a public health threat, there is urgent need to increase the frequency, depth and intentionality of bidirectional and mutually beneficial collaboration and coordination between the USA and global HIV/AIDS response. The US Health Resources and Services Administration (HRSA) is uniquely positioned to showcase bidirectional learning between high-income and low-income and middle-income countries (LMICs) in the fight against HIV. For 30 years, HRSA has successfully administered the Ryan White HIV/AIDS Program (RWHAP), the largest federal programme designed specifically for people with HIV in the USA. Further, HRSA has developed and delivered innovative, cost-effective, impactful HIV programmes in over 30 countries as an implementing agency for the US President's Emergency Plan for AIDS Relief (PEPFAR). When PEPFAR was authorised in 2003, HRSA rapidly developed systems and infrastructures to deliver life-saving treatment, initiated workforce development programmes to mitigate health worker shortages, and laid the path for transitioning PEPFAR activities from US-based organisations to sustainable, country-led entities. As global programmes matured, lessons learnt within LMICs gradually began strengthening health services in the USA. To fully optimise synergies between RWHAP and PEPFAR, there is a critical need to build on successful initiatives, harness innovation and technology, and inculcate the spirt of multidirectional learning into global health. HRSA is promoting bidirectional learning between domestic and international HIV programming through documenting, sharing and implementing strategies, lessons learnt, best practices and effective models of care to accelerate achievement of HIV epidemic control and support country-led, sustained responses to public health threats.

A prospective cohort study identifies two types of HIV+ Kaposi Sarcoma lesions: proliferative and inflammatory.

Kaposi sarcoma (KS) is the most common cancer in people living with HIV (PLWH) in many countries where KS-associated herpesvirus is endemic. Treatment has changed little in 20 years, but the disease presentation has. This prospective cohort study enrolled 122 human immunodeficiency virus (HIV) positive KS patients between 2017 and 2019 in Malawi. Participants were treated with bleomycin, vincristine and combination antiretroviral therapy, the local standard of care. One-year overall survival was 61%, and progression-free survival was 58%. The 48-week complete response rate was 35%. RNAseq (n = 78) differentiated two types of KS lesions, those with marked endothelial characteristics and those enriched in inflammatory transcripts. This suggests that different KS lesions are in different disease states consistent with the known heterogeneous clinical response to treatment. In contrast to earlier cohorts, the plasma HIV viral load of KS patients in our study was highly variable. A total of 25% of participants had no detectable HIV; all had detectable KSHV viral load. Our study affirms that many KS cases today develop in PLWH with well-controlled HIV infection and that different KS lesions have differing molecular compositions. Further studies are needed to develop predictive biomarkers for this disease.

Characterising persons diagnosed with HIV as either recent or long-term using a cross-sectional analysis of recent infection surveillance data collected in Malawi from September 2019 to March 2020.

OBJECTIVES: In Malawi, a recent infection testing algorithm (RITA) is used to characterise infections of persons newly diagnosed with HIV as recent or long term. This paper shares results from recent HIV infection surveillance and describes distribution and predictors. SETTING: Data from 155 health facilities in 11 districts in Malawi were pooled from September 2019 to March 2020. PARTICIPANTS: Eligible participants were ≥13 years, and newly diagnosed with HIV. Clients had RITA recent infections if the rapid test for recent infection (RTRI) test result was recent and viral load (VL) ≥1000 copies/mL; if VL was <1000 copies/mL the RTRI result was reclassified as long-term. Results were stratified by age, sex, pregnancy/breastfeeding status and district. RESULTS: 13 838 persons consented to RTRI testing and 12 703 had valid RTRI test results and VL results after excluding clients not newly HIV-positive, RTRI negative or missing data (n=1135). A total of 12 365 of the 12 703 were included in the analysis after excluding those whose RTRI results were reclassified as long term (n=338/784 or 43.1%). The remainder, 446/12 703 or 3.5%, met the definition of RITA recent infection. The highest percentage of recent infections was among breastfeeding women (crude OR (COR) 3.2; 95% CI 2.0 to 5.0), young people aged 15-24 years (COR 1.6; 95% CI 1.3 to 1.9) and persons who reported a negative HIV test within the past 12 months (COR 3.3; 95% CI 2.6 to 4.2). Factors associated with recent infection in multivariable analysis included being a non-pregnant female (adjusted OR (AOR) 1.4; 95% CI 1.2 to 1.8), a breastfeeding female (AOR 2.2; 95% CI 1.4 to 3.5), aged 15-24 years (AOR 1.6; 95% CI 1.3 to 1.9) and residents of Machinga (AOR 2.0; 95% CI 1.2 to 3.5) and Mzimba (AOR 2.4; 95% CI 1.3 to 4.5) districts. CONCLUSIONS: Malawi's recent HIV infection surveillance system demonstrated high uptake and identified sub-populations of new HIV diagnoses with a higher percentage of recent infections.

Acceptability and feasibility of HIV recent infection surveillance by healthcare workers using a rapid test for recent infection at HIV testing sites - Malawi, 2019.

BACKGROUND: The Malawi Ministry of Health implemented a new surveillance activity in April 2019 to detect recent HIV infections using a rapid test for recent infection (RTRI) to identify areas of ongoing transmission and guide response activities. SETTING: At 23 health facilities in Blantyre District, healthcare workers (HCWs) were trained to conduct recent infection testing. In September 2019, we conducted a cross-sectional survey at these sites to explore the acceptability and feasibility of integrating this activity into routine HIV testing services (HTS). METHODS: Research assistants interviewed HCWs using a semi-structured survey. Descriptive statistics were used to summarize quantitative responses and thematic analysis was used to group open-ended text. RESULTS: We interviewed 119 HCWs. Eighty-two percent of participants reported the RTRI was easy-to-use. HCWs perceived high client acceptability; 100% reported clients as 'somewhat' or 'very accepting'. Challenges included 68% of HCWs estimating they spend ≥20 min beyond routine HTS per client for this activity and 51% performing at least two additional finger pricks to complete the testing algorithm. HCWs differed in their perceptions of whether results should be returned to clients. CONCLUSION: This study assessed HCW experiences using point-of-care RTRIs for HIV recent infection surveillance. Overall, HCWs perceived RTRIs to be acceptable, easy-to-use, and valuable. Though only clients with new HIV diagnoses are tested for recent infection, additional time may be substantial at high-volume health service delivery points. Providing response plans or aggregated recent infection results to HCWs and/or clients may support motivation and sustainability of this novel surveillance activity.

Geospatial Transmission Hotspots of Recent HIV Infection - Malawi, October 2019-March 2020.

Persons infected with HIV are more likely to transmit the virus during the early stages (acute and recent) of infection, when viral load is elevated and opportunities to implement risk reduction are limited because persons are typically unaware of their status (1,2). Identifying recent HIV infections (acquired within the preceding 12 months)* is critical to understanding the factors and geographic areas associated with transmission to strengthen program intervention, including treatment and prevention (2). During June 2019, a novel recent infection surveillance initiative was integrated into routine HIV testing services in Malawi, a landlocked country in southeastern Africa with one of the world's highest prevalences of HIV infection.† The objectives of this initiative were to collect data on new HIV diagnoses, characterize the epidemic, and guide public health response (2). New HIV diagnoses were classified as recent infections based on a testing algorithm that included results from the rapid test for recent infection (RTRI)§ and HIV viral load testing (3,4). Among 9,168 persons aged ≥15 years with a new HIV diagnosis who received testing across 103 facilities during October 2019-March 2020, a total of 304 (3.3%) were classified as having a recent infection. Higher proportions of recent infections were detected among females, persons aged <30 years, and clients at maternal and child health and youth clinics. Using a software application that analyzes clustering in spatially referenced data, transmission hotspots were identified with rates of recent infection that were significantly higher than expected. These near real-time HIV surveillance data highlighted locations across Malawi, allowing HIV program stakeholders to assess program gaps and improve access to HIV testing, prevention, and treatment services. Hotspot investigation information could be used to tailor HIV testing, prevention, and treatment to ultimately interrupt transmission.

Adherence to Antiretroviral Treatment Among People Who Started Treatment on the Same-Day of HIV Diagnosis in Ethiopia: A Multicenter Observational Study.

INTRODUCTION: Since the launch of universal "test and treat" approach in 2016, there has been a significant increase in persons initiated on antiretroviral therapy (ART) on the same-day of human immunodeficiency virus (HIV) diagnosis in low-income settings. However, there are limited studies that investigated the effect of rapid treatment initiation on adherence. In this study, we compared adherence to ART in people who started ART on the same-day of HIV diagnosis and those started more than 7 days after HIV diagnosis. METHODS: We conducted a retrospective cohort analysis using routinely collected data from multiple ART clinics. Participants were at least 15 years old, were newly diagnosed and started on ART between October 2016 and July 2018 in the Amhara region of Ethiopia. We used doubly-robust multivariable logistic regression model to estimate the adjusted effects on adherence. RESULTS: A total of 415 individuals who started ART on the same-day of HIV diagnosis and 527 individuals who started 7 days after their HIV diagnosis were included in the analysis. The proportion of participants who reported optimal adherence was significantly lower in the same-day group at 6- and 12-months (absolute risk difference of 6.5%; 95% CI: 1.1%, 11.9% and 6.8%; 95% CI: 1.2%, 12.5%, respectively) compared to the >7 days group. After adjusting for baseline and non-baseline covariates, the same-day group was less likely to have optimal adherence both at 6- and 12-months (adjusted RR=0.90; 95% CI: 0.86, 0.94 and RR=0.89; 95% CI: 0.83, 0.95, respectively) compared to the >7 days group. CONCLUSION: We observed lower optimal adherence among individuals who started ART on the same-day of HIV diagnosis compared to those who started ART >7 days after their HIV diagnosis. Our findings highlight the importance of identifying adherence barriers, providing support, and ensuring treatment readiness before initiating individuals on same-day ART.

Virologic outcomes of people living with human immunodeficiency virus who started antiretroviral treatment on the same-day of diagnosis in Ethiopia: A multicenter observational study.

INTRODUCTION: There have been tremendous achievements in scaling-up antiretroviral therapy (ART) for treatment of human immunodeficiency virus (HIV), following universal "test and treat" policy implementation in low- and middle-income countries. However, its effects on virologic outcomes is not yet well investigated. We compared low viral load status in people living with HIV between those who were initiated on ART on the same-day and after 7 days of being diagnosed with HIV infection. METHODS: We conducted a retrospective cohort study of persons age ≥15 years-old who were newly diagnosed and started on ART between October 2016 and July 2018 at 11 public health facilities in northwest Ethiopia. Exposure was initiation of ART on the same-day of HIV diagnosis. The outcome was low viral load at 12-months following ART initiation. We used double-robust estimator using inverse-probability-weighted regression adjustment to compare the groups. RESULTS: A total of 398 people who started ART on the same-day of HIV diagnosis and 479 people who started 7 days after the initial diagnosis were included in this study. By 12-months following ART initiation, 73.4% (292) in the same-day group vs 83.7% (401) in the >7 days group achieved low viral load (absolute difference = 10.3% (95% CI: 4.9%, 15.8%)). After adjusting for baseline and follow-up covariates, there was statistically significant difference in low viral load status (adjusted difference = 8.3% (95% CI: 3.5%, 13.0%)) between the same-day group and the >7 days group. CONCLUSIONS: Achievement of low viral load by 12-months post-initiation of ART was not optimal among participants who started ART on the same-day of HIV diagnosis. Efforts should be made to reinforce treatment adherence while initiating same-day ART.

Educational Content and Acceptability of Training Using Mobile Instant Messaging in Large HIV Clinics in Malawi.

Background: In resource-limited settings, many HIV-infected patients with advanced HIV-related disease need specialized care not represented in guidelines. Training opportunities for healthcare providers on advanced HIV care are limited. The aim of this study was to evaluate the educational content and acceptability of mobile instant messaging (MIM) as a training and telemedicine tool for HIV care providers in Malawi. Methods: At the Lighthouse Clinic, Malawi, a MIM group using WhatsApp® was created for clinical officers and moderated by an infectious disease consultant. Questions encountered in the clinics as well as educational cases were posted; identifying data was not to be posted. MIM conversation was analyzed and in-depth interviews with users on its perceptions were performed. Results: MIM was utilized by 25 clinical officers and five physicians with an average of 2.3 threads/week over the observation period of 15 months. Discussed topics related to tuberculosis (25 threads), adverse drug reaction (22 threads), antiretroviral treatment (21 threads), cryptococcal meningitis (12 threads), and drug dosing/logistics. In 20% of the threads at least one image file was shared (mainly pictures of skin conditions and chest X-rays). In-depth interviews showed that clinical officers appreciated MIM group as a telemedicine consulting and training tool. Conclusion: MIM was a successful and well-accepted telemedicine tool for support and training of clinical officers providing HIV care in a resource-limited setting. MIM may be integrated in training strategies to expand the knowledge of HIV care providers.

Near Point-of-Care HIV Viral Load: Targeted Testing at Large Facilities.

INTRODUCTION: Point-of-care (POC) technologies in resource-limited settings can circumvent challenges of centralized laboratory testing, improving clinical management. However, higher device costs and uncertain indications for use have inhibited scaling up POC modalities. To address this gap, we investigated the feasibility and cost of targeted near-POC viral load (VL) testing in 2 large HIV clinics in Lilongwe, Malawi. METHODS: VL testing using GeneXpert was targeted for patients suspected of treatment failure or returning to care after a previously elevated VL (>1000 copies/mL). Descriptive analysis of retrospective clinical and cost data is presented. RESULTS: Two thousand eight hundred thirteen near-POC VL tests were conducted. One thousand five hundred eleven (54%) tests were for patients for whom results and reason for the test were documented: 57% (794/1389) of tests were to confirm a previously high VL, and 33% (462/1389) were due to clinical indications. Sixty-one percent (926/1511) of patients had a high VL, of whom 78% (719/926) had a recorded clinical action: 77% (557/719) switched to second line antiretroviral therapy, and 15% (194/719) were referred for intensive adherence counseling. Eighty-two percent (567/687) of patients received a clinical action on the same day as testing. The "all-in" cost was $33.71 for a valid POC VL test, compared with an international benchmark for a centralized VL test of $28.62. CONCLUSION: Targeted, near-POC VL testing was feasible and consistently enabled prompt clinical action. The difference between the "all-in" cost of near-POC VL and centralized testing of $5.09 could be further reduced in an optimized national program by combining targeted near-POC testing and centralized testing.

Effectiveness of same-day antiretroviral therapy initiation in retention outcomes among people living with human immunodeficiency virus in Ethiopia: empirical evidence.

BACKGROUND: In August 2016, Ethiopia endorsed a universal "test and treat" strategy for people living with human immunodeficiency virus (PLHIV) based on World Health Organization recommendation. However, there is limited evidence on the routine application of the same-day "test and treat" recommendation in low-income settings. This study assessed the effect of same-day treatment initiation on individual-level retention at 6- and 12-months follow-up. METHODS: A multicenter facility-based retrospective cohort study was conducted to compare retention-in-care between PLHIV who started antiretroviral therapy (ART) on the same-day and those started ART > 7 days following HIV diagnoses. Participants were at least 15 years-old and were newly diagnosed and started on ART between October 2016 and July 2018 in 11 health facilities in the Amhara region of Ethiopia. Multivariable logistic regression controlling for potential confounders and Kaplan-Meier survival analysis were used to assess differences in outcomes between the groups. RESULTS: In total, 433 PLHIV started ART on the same-day of diagnosis and 555 PLHIV who started ART > 7 days after HIV diagnosis were included in the study. At 6-months, 82.0% (355) in the same-day group vs 89.4% (496) in the > 7 days group were retained-in-care (absolute risk difference (RD) = 7.4%; 95% confidence interval (CI): 2.9-11.8%). At 12-months, 75.8% (328) in the same-day group vs 82.0% (455) in the > 7 days group were retained-in-care (absolute RD = 6.2%; 95% CI: 1.1, 11.4%). The major drop in retention was in the first 30 days following ART initiation among same-day group. After adjusting for baseline and non-baseline covariates, the same-day group was less likely to be retained-in-care at 6- and 12-months (adjusted risk ratio (RR) = 0.89; 95% CI: 0.87, 0.90 and adjusted RR = 0.86; 95% CI: 0.83, 0.89, respectively). CONCLUSIONS: Reduced retention-in-care can threaten the benefit of the same-day "test and treat" policy. The policy needs to be implemented cautiously with greater emphasis on assessment and preparation of PLHIV for ART to ensure treatment readiness before starting them on same-day ART and close monitoring of patients during early follow-up periods.

Patient and nurse perspectives of a nurse-led community-based model of HIV care delivery in Malawi: a qualitative study.

BACKGROUND: Differentiated models of care (DMOC) are used to make antiretroviral therapy (ART) accessible to people living with HIV (PLHIV). In Malawi, Lighthouse Trust has piloted various DMOCs aimed at providing quality care while reducing personal and logistical barriers when accessing clinic-based healthcare. One of the approaches was community-based provision of ART by nurses to stable patients. METHODS: To explore how the nurse-led community ART programme (NCAP) is perceived, we interviewed eighteen purposively selected patients receiving ART through NCAP and the four nurses providing the community-based health care. Information obtained from them was complemented with observations by the study team. Interviews were recorded and transcribed. Data was analysed using manual coding and thematic analysis. RESULTS: Through the NCAP, patients were able to save money on transportation and the time it took them to travel to a health facility. Caseloads and waiting times were also reduced, which made patients more comfortable and gave nurses the time to conduct thorough consultations. Closer relationships were built between patients and care providers, creating a space for more open conversations (although this required care providers to set clear boundaries and stick to schedule). Patients' nutritional needs and concerns related to stigma remain a concern, while operational issues affect the quality of the services provided in the community. Considerations for community-led healthcare programmes include the provision of transportation for care providers; the physical structure of community sites (in regard to private spaces); the timely consolidation of data collected in the field to a central database; and the need for care providers to cover multiple facility-based staff roles. CONCLUSIONS: The patients interviewed in this study preferred the NCAP approach to the facility-based model of care because it saved them money on transport, reduced waiting-times, and allowed for a more thorough consultation, while continuing to provide quality HIV care. However, when considering a community-level DMOC approach, certain factors - including staff transportation and workload - must be taken into consideration and purposefully planned.

Contraceptive use and pregnancy rates among women receiving antiretroviral therapy in Malawi: a retrospective cohort study.

BACKGROUND: In 2011, family planning (FP) services were integrated at Martin Preuss Centre (MPC), in urban Lilongwe, Malawi. To date, no previous study evaluated pregnancy rates among HIV-positive women after the integration of FP services into HIV care at the facility. In this study, we investigated whether integration of FP services into HIV clinical care led to increased use of contraceptives and decreased pregnancy rates. METHODS: This was a retrospective cohort analysis of HIV-positive women from 15 to 49 years of age who accessed antiretroviral therapy (ART) services at MPC. Ascertainment of FP needs, contraceptive methods and pregnancy status were done at ART initiation, and at each ART follow-up visit. Women were offered a wide range of contraceptive methods. Outcomes of interest were contraceptive use and rate of pregnancy. Incident pregnancy was ascertained through patient self-reports during clinic consultation. Trends of contraceptive use and pregnancy rates were analyzed using chi-square (χ2). RESULTS: A total of 10,472 women were included in the analysis and contributed 15,700 person-years of observation. Contraceptive use among all women receiving ART increased from 28% in 2012 to 62% in 2016 (p < 0.001). A total of 501 pregnancies occurred, including 13 multiple pregnancies, resulting in an overall pregnancy rates of 3.2 per 100 person-years. Rates of pregnancy decreased from 6.8 per 100 person-years in 2012 to 1.3 per 100 person-years in 2016 (p < 0.001). CONCLUSION: Integration of FP services into HIV care resulted in increased contraceptive use and, subsequently, decreased pregnancy rates in women receiving ART. HIV programs should consider offering FP services to women who are receiving ART.

Loss to follow-up before and after initiation of antiretroviral therapy in HIV facilities in Lilongwe, Malawi.

INTRODUCTION: Although several studies have explored factors associated with loss to follow-up (LTFU) from HIV care, there remains a gap in understanding how these factors vary by setting, volume of patient and patients' demographic and clinical characteristics. We determined rates and factors associated with LTFU in HIV care Lilongwe, Malawi. METHODS: We conducted a retrospective cohort study of HIV-infected individuals aged 15 years or older at the time of registration for HIV care in 12 ART facilities, between April 2012 and March 2013. HIV-positive individuals who had not started ART (pre-ART patients) were clinically assessed to determine ART eligibility at registration and during clinic follow-up visits. ART-eligible patients were initiated on triple antiretroviral combination. Study data were abstracted from patients' cards, facility ART registers or electronic medical record system from the date of registration for HIV care to a maximum follow-up period of 24 months. Descriptive statistics were undertaken to summarize characteristics of the study patients. Separate univariable and multivariable poisson regression models were used to explore factors associated with LTFU in pre-ART and ART care. RESULTS: A total of 10,812 HIV-infected individuals registered for HIV care. Of these patients, 1,907 (18%) and 8,905 (82%) enrolled in pre-ART and ART care, respectively. Of the 1,907 pre-ART patients, 490 (26%) subsequently initiated ART and were included in both the pre-ART and ART analyses. The LTFU rates among patients in pre-ART and ART care were 48 and 26 per 100 person-years, respectively. Of the 9,105 ART patients with reasons for starting ART, 2,451 (27%) were initiated on ART because of pregnancy or breastfeeding (Option B+) status. Multivariable analysis showed that being ≥35 years and female were associated with decreased risk of LTFU in the pre-ART and ART phases of HIV care. However, being in WHO clinical stage 3 (adjusted risk ratio (aRR) 1.35, 95% confidence interval (CI): 1.20-1.51) and stage 4 (aRR 1.87, 95% CI: 1.62-2.18), body mass index ≤ 18.4 (aRR 1.24, 95% CI: 1.11-1.39) at ART initiation, poor adherence to clinic appointments (aRR 4.55, 95% CI: 4.16-4.97) and receiving HIV care in rural facilities (aRR 2.32, 95% CI: 1.94-2.87) were associated with increased risk of LTFU among ART patients. Being re-initiated on ART once (aRR 0.20, 95% CI: 0.17-0.22), more than once (aRR 0.06, 95% CI: 0.05-0.07), and being enrolled at a low-volume facility (aRR 0.25, 95% CI: 0.20-0.30) were associated with decreased risk of LTFU from ART care. CONCLUSION: A sizeable proportion of ART LTFU occurred among women enrolled during pregnancy or breast-feeding. Non- compliance to clinic and receiving ART in a rural facility or high-volume facility were associated with increased risk of LTFU from ART care. Developing effective interventions that target high-risk subgroups and contexts may help reduce LTFU from HIV care.

A cross-sectional study to evaluate second line virological failure and elevated bilirubin as a surrogate for adherence to atazanavir/ritonavir in two urban HIV clinics in Lilongwe, Malawi.

BACKGROUND: Malawi's national antiretroviral therapy program provides atazanavir/ritonavir-based second line regimens which cause concentration-dependent rise in indirect bilirubin. We sought to determine if elevated bilirubin, as a surrogate of atazanavir/ritonavir adherence, can aid in the evaluation of second line virological failure in Malawi. METHODS: We conducted a cross-sectional study of HIV-infected patients ≥15 years who were on boosted protease inhibitor-based second line antiretroviral therapy for at least 6 months in two urban HIV clinics in Lilongwe, Malawi. Antiretroviral therapy history and adherence data were extracted from the electronic medical records and blood was drawn for viral load, complete blood count, total bilirubin, and CD4 cell count at a clinic visit. Factors associated with virological failure were assessed using multivariate logistic regression model. RESULTS: Out of 376 patients on second line antiretroviral therapy evaluated, 372 (98.9%) were on atazanavir/ritonavir-based therapy and 142 (37.8%) were male. Mean age was 40.9 years (SD ± 10.1), mean duration on second line antiretroviral therapy was 41.9 months (SD ± 27.6) and 256 patients (68.1%) had elevated bilirubin >1.3 mg/dL. Overall, 35 (9.3%) patients had viral load >1000 copies/ml (virological failure). Among the virologically failing vs. non-failing patients, bilirubin was elevated in 34.3% vs. 72.0% respectively (p < 0.001), although adherence by pill count was similar (62.9% vs. 60.7%, p = 0.804). The odds of virological failure were higher for adults aged 25-40 years (adjusted odds ratio (aOR) 2.5, p = 0.048), those with CD4 cell count <100 (aOR 17.5, p < 0.001), and those with normal bilirubin levels (aOR 5.4, p < 0.001); but were lower for the overweight/obese patients (aOR 0.3, p = 0.026). Poor pill count adherence (aOR 0.7, p = 0.4) and male gender (aOR 1.2, p = 0.698) were not associated with second line virological failure. CONCLUSIONS: Among patients receiving atazanavir/ritonavir-based second line antiretroviral therapy, bilirubin levels better predicted virological failure than pill count adherence. Therefore, strategic use of bilirubin and viral load testing to target adherence counseling and support may be cost-effective in monitoring second line antiretroviral therapy adherence and virological failure. Drug resistance testing targeted for patients with virological failure despite elevated bilirubin levels would facilitate timely switch to third line antiretroviral regimens whenever available.

Characteristics and outcomes of older HIV-infected patients receiving antiretroviral therapy in Malawi: A retrospective observation cohort study.

OBJECTIVE: To estimate patients enrolling on antiretroviral therapy (ART) over time; describe trends in baseline characteristics; and compare immunological response, loss to follow-up (LTFU), and mortality by three age groups (25-39, 40-49 and ≥50 years). DESIGN: A retrospective observation cohort study. METHODS: This study used routine ART data from two public clinics in Lilongwe, Malawi. All HIV-infected individuals, except pregnant or breastfeeding women, aged ≥ 25 years at ART initiation between 2006 and 2015 were included. Poisson regression models estimated risk of mortality, stratified by age groups. RESULTS: Of 37,378 ART patients, 3,406 were ≥ 50 years old. Patients aged ≥ 50 years initiated ART with more advanced WHO clinical stage and lower CD4 cell count than their younger counterparts. Older patients had a significantly slower immunological response to ART in the first 18 months on ART compared to patients aged 25-39 years (p = 0.04). Overall mortality rates were 2.3 (95% confidence Interval (CI) 2.2-2.4), 2.9 (95% CI 2.7-3.2) and 4.6 (95% CI 4.2-5.1) per 100 person-years in patients aged 25-39 years, 40-49 years and 50 years and older, respectively. Overall LTFU rates were 6.3 (95% CI 6.1-6.5), 4.5 (95% CI 4.2-4.7), and 5.6 (95% CI 5.1-6.1) per 100 person years among increasing age cohorts. The proportion of patients aged ≥ 50 years and newly enrolling into ART care remained stable at 9% while the proportion of active ART patients aged ≥50 years increased from 10% in 2006 to 15% in 2015. CONCLUSION: Older people had slower immunological response and higher mortality. Malawi appears to be undergoing a demographic shift in people living with HIV. Increased consideration of long-term ART-related problems, drug-drug interactions and age-related non-communicable diseases is warranted.

Baseline characteristics of study sites and women enrolled in a three-arm cluster randomized controlled trial: PMTCT uptake and retention (pure) Malawi.

BACKGROUND: Malawi introduced an ambitious public health program known as "Option B+" which provides all HIV-infected pregnant and breastfeeding women with lifelong combination antiretroviral therapy, regardless of WHO clinical stage or CD4 cell count. The PMTCT Uptake and REtention (PURE) study aimed at evaluating the effect of peer-support on care-seeking and retention in care. METHODS/DESIGN: PURE Malawi was a three-arm cluster randomized controlled trial that compared facility-based and community-based models of peer support to standard of care under Option B+ strategy. Each arm was expected to enroll a minimum of 360 women with a total minimum sample size of 1080 participants. 21 sites (clusters) were selected for inclusion in the study. This paper describes the site selection, recruitment, enrollment process and baseline characteristics of study sites and women enrolled in the trial. RESULTS: Study implementation was managed by 3 partner organizations; each responsible for 7 study sites. The trial was conducted in the South East, South West, and Central West zones of Malawi, the zones where the implementing partners operate. Study sites included 2 district hospitals, 2 mission hospitals, 2 rural hospitals, 13 health centers and 1 private clinic. Enrollment occurred from November 2013 to November 2014, over a median period of 31 weeks (range 17-51) by site. A total of 1269 HIV-infected pregnant (1094) and breastfeeding (175) women, who were eligible to initiate ART under Option B+, were enrolled. Each site reached or surpassed the minimum sample size. Comparing the number of women enrolled versus antenatal cohort reports, sites recruited a median of 90% (IQR 75-100) of eligible reported women. In the majority of sites the ratio of pregnant and lactating women enrolled in the study was similar to the ratio of reported pregnant and lactating women starting ART in the same sites. The median age of all women was 27 (IQR 22-31) years. All women have ≥20 months of possible follow-up time; 96% ≥ 2 years (24-32 months). CONCLUSION: The PURE Malawi study showed that 3 implementing partner organizations could successfully recruit a complex cohort of pregnant and lactating women across 3 geographical zones in Malawi within a reasonable timeline. TRIAL REGISTRATION: This study is registered at clinicaltrials.gov - ID Number NCT02005835 . Registered 4 December, 2013.

Exploring factors associated with ART adherence and retention in care under Option B+ strategy in Malawi: A qualitative study.

Although several studies have documented challenges related to inadequate adherence to antiretroviral therapy (ART) and high loss to follow-up (LTFU) among Option B+ women, there is limited understanding of why these challenges occur and how to address them. This qualitative study examines women's experiences with ART adherence and retention in care. Between July and October 2015, in-depth interviews were conducted with 39 pregnant and lactating women who initiated ART at Bwaila Hospital in Lilongwe, Malawi. Study participants included 14 in care and 25 out of care women, according to facility records. Data were analyzed using an inductive, open-coding approach to thematic analysis. Ten of the respondents (7 out of care, 3 in-care) had stopped and re-started treatment before the interview date. One of the most important factors influencing adherence and retention was the strength of women's support systems. In contrast to women in-care, most out-of-care women lacked emotional and financial support from male partners, received minimal counseling from providers at initiation, lacked designated guardians to assist with medication refills or clinic appointments, and were highly mobile. Mobility led to difficulties in accessing treatment in new settings. The most common reasons women re-started treatment following interruptions were due to providers' counseling and encouragement and the mother's desire to be healthy. Improved counseling at initiation, active follow-up counseling, women's economic empowerment interventions, promotion of peer counseling schemes and meaningful engagement of male partners can help in addressing the identified barriers and promoting sustained retention of Option B+ women.

Impact of Facility- and Community-Based Peer Support Models on Maternal Uptake and Retention in Malawi's Option B+ HIV Prevention of Mother-to-Child Transmission Program: A 3-Arm Cluster Randomized Controlled Trial (PURE Malawi).

BACKGROUND: Many sub-Saharan African countries have adopted Option B+, a prevention of mother-to-child transmission approach providing HIV-infected pregnant and lactating women with immediate lifelong antiretroviral therapy. High maternal attrition has been observed in Option B+. Peer-based support may improve retention. METHODS: A 3-arm stratified cluster randomized controlled trial was conducted in Malawi to assess whether facility- and community-based peer support would improve Option B+ uptake and retention compared with standard of care (SOC). In SOC, no enhancements were made (control). In facility-based and community-based models, peers provided patient education, support groups, and patient tracing. Uptake was defined as attending a second scheduled follow-up visit. Retention was defined as being alive and in-care at 2 years without defaulting. Attrition was defined as death, default, or stopping antiretroviral therapy. Generalized estimating equations were used to estimate risk differences (RDs) in uptake. Cox proportional hazards regression with shared frailties was used to estimate hazard of attrition. RESULTS: Twenty-one facilities were randomized and enrolled 1269 women: 447, 428, and 394 in facilities that implemented SOC, facility-based, and community-based peer support models, respectively. Mean age was 27 years. Uptake was higher in facility-based (86%; RD: 6%, confidence interval [CI]: -3% to 15%) and community-based (90%; RD: 9%, CI: 1% to 18%) models compared with SOC (81%). At 24 months, retention was higher in facility-based (80%; RD: 13%, CI: 1% to 26%) and community-based (83%; RD: 16%, CI: 3% to 30%) models compared with SOC (66%). CONCLUSIONS: Facility- and community-based peer support interventions can benefit maternal uptake and retention in Option B+.

Viral Suppression and HIV Drug Resistance at 6 Months Among Women in Malawi's Option B+ Program: Results From the PURE Malawi Study.

BACKGROUND: In 2011, Malawi launched Option B+, a program of universal antiretroviral therapy (ART) treatment for pregnant and lactating women to optimize maternal health and prevent pediatric HIV infection. For optimal outcomes, women need to achieve HIVRNA suppression. We report 6-month HIVRNA suppression and HIV drug resistance in the PURE study. METHODS: PURE study was a cluster-randomized controlled trial evaluating 3 strategies for promoting uptake and retention; arm 1: Standard of Care, arm 2: Facility Peer Support, and arm 3: Community Peer support. Pregnant and breastfeeding mothers were enrolled and followed according to Malawi ART guidelines. Dried blood spots for HIVRNA testing were collected at 6 months. Samples with ART failure (HIVRNA ≥1000 copies/ml) had resistance testing. We calculated odds ratios for ART failure using generalized estimating equations with a logit link and binomial distribution. RESULTS: We enrolled 1269 women across 21 sites in Southern and Central Malawi. Most enrolled while pregnant (86%) and were WHO stage 1 (95%). At 6 months, 950/1269 (75%) were retained; 833/950 (88%) had HIVRNA testing conducted, and 699/833 (84%) were suppressed. Among those with HIVRNA ≥1000 copies/ml with successful amplification (N = 55, 41% of all viral loads > 1000 copies/ml), confirmed HIV resistance was found in 35% (19/55), primarily to the nonnucleoside reverse transcriptase inhibitor class of drugs. ART failure was associated with treatment default but not study arm, age, WHO stage, or breastfeeding status. CONCLUSIONS: Virologic suppression at 6 months was <90% target, but the observed confirmed resistance rates suggest that adherence support should be the primary approach for early failure in option B+.