A sub-group evaluation of the multi-month dispensing strategy for differentiated HIV care: is personalization of care guidelines warranted in Haiti?

BACKGROUND: Differentiated care strategies are rapidly becoming the norm for HIV care delivery globally. Building upon an interest in tailoring antiretroviral therapy (ART) delivery for client-centered needs, the Ministry of Health and Population in Haiti formally endorsed multiple-month dispenses (MMD) in the 2016 national ART guidelines This study explores heterogeneity in retention in care with MMD for specific Haitian populations living with HIV and evaluates if a targeted algorithm for optimal ART prescription intervals is warranted in Haiti. METHODS: This study included ART-naïve individuals who started ART on or after January 1st, 2017 in Haiti. To identify subgroups in which to explore heterogeneity of retention, we implemented a double-lasso regression method to determine which individual characteristics would define the subgroups. Characteristics evaluated for potential subgroup definition included: sex, age category, WHO clinical stage, and body mass index category. We employed instrumental variable models to estimate the causal effect of increasing ART dispensing length on ART retention, by client subgroup. The outcome of interest was retention in care after one year in treatment. We then estimated the marginal effect of a 30-day increase to ART dispensing length to retention in care for each of these subgroups. RESULTS: There was evidence for heterogeneity in the effect of extending ART dispensing intervals on retention by WHO clinical stage. We observed significant improvements to retention in care at one year with a 30-day increase in ART dispense length for all subgroups defined by WHO clinical stages 1-4. The effects ranged from a 14.7% increase (95% CI: 12.4-17.0) to the likelihood of retention for people with HIV in WHO stage 1 to a 21.6% increase (95% CI: 18.7-24.5) to the likelihood of retention for those in WHO stage 3. CONCLUSIONS: All the subgroups defined by WHO clinical stage experienced a benefit of extending ART intervals to retention in care at one year. Though the effect did differ slightly by WHO stage, the effects went in the same direction and were of similar magnitude. Therefore, a standardized recommendation for MMD among those living with HIV and new on ART is appropriate for Haiti treatment guidelines.

Timely initiation of HIV antiretroviral therapy in Haiti 2004-2018: a retrospective cohort study.

OBJECTIVE: To describe trends in timing of ART initiation for newly diagnosed people living with HIV before and after Haiti adopted its Test and Start policy for universal HIV antiretroviral therapy (ART) in July 2016, and to explore predictors of timely ART initiation for both newly and previously diagnosed people living with HIV following Test and Start adoption. METHODS: This retrospective cohort study explored timing of ART initiation among 147 900 patients diagnosed with HIV at 94 ART clinics in 2004-2018 using secondary electronic medical record data. The study used survival analysis methods to assess time trends and risk factors for ART initiation. RESULTS: Timely uptake of ART expanded with Test and Start, such that same-day ART initiation rates increased from 3.7% to 45.0%. However, only 11.0% of previously diagnosed patients initiated ART after Test and Start. In adjusted analyses among newly diagnosed people living with HIV, factors negatively associated with timely ART initiation included being a pediatric patient aged 0-14 years (HR = 0.23, p < 0.001), being male (HR = 0.92, p = 0.03), being 50+ years (HR = 0.87, p = 0.03), being underweight (HR = 0.79, p < 0.001), and having WHO stage 3 (HR = 0.73, p < 0.001) or stage 4 disease (HR = 0.49, p < 0.001). Variation in timely ART initiation by geographic department and health facility was observed. CONCLUSIONS: Haiti has made substantial progress in scaling up Test and Start, but further work is needed to enroll previously diagnosed patients and to ensure rapid ART in key patient subgroups. Further research is needed on facility and geographic factors and on strategies for improving timely ART initiation among vulnerable subgroups.

Timely initiation of HIV antiretroviral therapy in Haiti 2004–2018: a retrospective cohort study

[ABSTRACT]. Objective. To describe trends in timing of ART initiation for newly diagnosed people living with HIV before and after Haiti adopted its Test and Start policy for universal HIV antiretroviral therapy (ART) in July 2016, and to explore predictors of timely ART initiation for both newly and previously diagnosed people living with HIV following Test and Start adoption. Methods. This retrospective cohort study explored timing of ART initiation among 147 900 patients diagnosed with HIV at 94 ART clinics in 2004–2018 using secondary electronic medical record data. The study used survival analysis methods to assess time trends and risk factors for ART initiation. Results. Timely uptake of ART expanded with Test and Start, such that same-day ART initiation rates increased from 3.7% to 45.0%. However, only 11.0% of previously diagnosed patients initiated ART after Test and Start. In adjusted analyses among newly diagnosed people living with HIV, factors negatively associated with timely ART initiation included being a pediatric patient aged 0–14 years (HR = 0.23, p < 0.001), being male (HR = 0.92, p = 0.03), being 50+ years (HR = 0.87, p = 0.03), being underweight (HR = 0.79, p < 0.001), and having WHO stage 3 (HR = 0.73, p < 0.001) or stage 4 disease (HR = 0.49, p < 0.001). Variation in timely ART initiation by geographic department and health facility was observed. Conclusions. Haiti has made substantial progress in scaling up Test and Start, but further work is needed to enroll previously diagnosed patients and to ensure rapid ART in key patient subgroups. Further research is needed on facility and geographic factors and on strategies for improving timely ART initiation among vulnerable subgroups.

[RESUMO]. Objetivo. Descrever as tendências para o momento do início da terapia antirretroviral (TAR) em pessoas recém diagnosticadas vivendo com HIV antes de e após o Haiti adotar a política Testar e Tratar com a TAR universal para HIV, em julho de 2016, e analisar os preditores do início precoce da TAR em pessoas recém ou previamente diagnosticadas que vivem com HIV após a adoção da política Testar e Tratar. Métodos. Este estudo de coorte retrospectivo analisou o momento do início da TAR de 147 900 pacientes diagnosticados com HIV em 94 ambulatórios de TAR entre 2004 e 2018, usando dados de registros médicos eletrônicos secundários. O estudo usou métodos de análise de sobrevivência para avaliar as tendências temporais e os fatores de risco para o início da TAR. Resultados. A adoção precoce da TAR foi ampliada com a política Testar e Tratar de tal maneira que as taxas do início da TAR no mesmo dia do diagnóstico aumentaram de 3,7% para 45%. Porém, somente 11% dos pacientes previamente diagnosticados iniciaram a TAR após a política Testar e Tratar. Nas análises ajustadas entre as pessoas recém diagnosticadas vivendo com HIV, os fatores negativamente associados ao início precoce da TAR incluíram: ser paciente pediátrico de 0 a 14 anos de idade (HR = 0,23, p < 0,001), ser do sexo masculino (HR = 0,92, p = 0,03), ter 50 anos de idade ou mais (HR = 0,87, p = 0,03), ter peso inferior ao normal (HR = 0,79, p < 0.001) e estar na fase 3 da OMS (HR = 0,73, p < 0,001) ou fase 4 da doença (HR = 0,49, p < 0,001). Foi observada variação no início precoce da TAR por região geográfica e instituição de saúde. Conclusões. O Haiti obteve avanços substanciais na ampliação da política Testar e Tratar, mas é necessário mais trabalho para inscrever pacientes previamente diagnosticados e para assegurar a TAR rápida em subgrupos-chave de pacientes. Mais pesquisas são necessárias sobre fatores geográficos e de instituições de saúde e sobre estratégias para a melhoria do início precoce da TAR entre subgrupos vulneráveis.

[RESUMEN]. Objetivo. Describir las tendencias en cuanto al momento de iniciar el tratamiento antirretroviral (TAR) de personas con infección por el VIH recién diagnosticadas antes y después de julio del 2016, cuando Haití adoptó la política de prueba e inicio del tratamiento con el TAR universal contra el VIH, y explorar los factores predictivos del inicio oportuno del TAR en personas con infección por el VIH recién diagnosticada y diagnosticada con anterioridad después de la adopción de esta política. Métodos. En este estudio de cohortes retrospectivo se exploró el momento en que se inició el TAR en 147 900 pacientes con diagnóstico de infección por el VIH en 94 consultorios que administran TAR del 2004 al 2018 mediante datos secundarios de expedientes médicos electrónicos. El estudio empleó métodos de análisis de supervivencia para evaluar las tendencias temporales y los factores de riesgo del inicio del TAR. Resultados. La observancia oportuna del TAR se amplió con la política de prueba e inicio del tratamiento, de tal manera que el inicio del TAR en el mismo día aumentó de 3,7 % a 45,0 %. Sin embargo, solo 11,0 % de los pacientes anteriormente diagnosticados iniciaron el TAR tras la adopción de la política. En los análisis ajustados con personas con infección por el VIH recién diagnosticadas, los factores asociados negativamente con el inicio oportuno del TAR comprendían ser un paciente pediátrico entre 0 y 14 años de edad (HR = 0,23, p < 0,001), ser varón (HR = 0,92, p = 0,03), tener más de 50 años (HR = 0,87, p = 0,03), tener un peso bajo (HR = 0,79,p < 0.001) y estar en el estadio 3 (de HR = 0,73, p < 0,001) o en estadio 4 (HR = 0,49, p < 0,001) de la enfermedad según la OMS. Se consideró la variación en el inicio oportuno del TAR según departamento geográfico y establecimiento de salud. Conclusiones. Haití ha logrado avances considerables en la ampliación a mayor escala de la política de prueba e inicio del tratamiento, pero es necesario seguir trabajando para registrar a los pacientes diagnosticados con anterioridad y para asegurar el inicio rápido del TAR en los subgrupos de pacientes clave. Es preciso llevar a cabo investigaciones adicionales sobre los factores geográficos y los relacionados con los establecimientos y sobre las estrategias para mejorar el inicio oportuno del TAR en los subgrupos vulnerables.

Estimating the effect of increasing dispensing intervals on retention in care for people with HIV in Haiti.

BACKGROUND: Multi-month dispensing (MMD) for antiretroviral therapy (ART) is a promising care strategy to improve HIV treatment adherence. The effectiveness of MMD in routine settings has not yet been evaluated within a causal inference framework. We analyzed data from a robust clinical data system to evaluate MMD in Haiti. METHODS: We assessed 1-year retention in care among 21,880 ART-naïve HIV-positive persons who started ART on or after January 1, 2017, up until November 1, 2018. We used an instrumental variable analysis to estimate the causal impact of MMD. This approach was used to address potential selection into specific dispensing intervals because MMD is not randomly applied to individuals. FINDINGS: We found that extending ART dispensing intervals increased the probability of retention at 12 months after ART initiation, with up to a 24·2%-point increase (95%CI: 21·9, 26·5) in the likelihood of retention with extending dispenses by 30 days for those receiving one-month dispenses. We observed statistically significant gains to retention with MMD with up to an approximately 4-month supply of ART; +5·1%-points (95%CI: 2·4,7·8). Increasing dispensing lengths for those already receiving ≥5-month supply of ART had a potentially negative effect on retention. INTERPRETATION: MMD for ART is an effective service delivery strategy that improves care retention for new ART recipients. There is a potentially negative effect of increasing prescription lengths for those new ART recipients already receiving longer ART supplies, though more research is needed to characterize this effect given medication supplies of this length are not common for newer ART recipients.

Risk factors for delayed viral suppression on first-line antiretroviral therapy among persons living with HIV in Haiti, 2013-2017.

Studies of viral suppression on first-line antiretroviral therapy (ART) in persons living with human immunodeficiency virus (PLHIV) in Haiti are limited, particularly among PLHIV outside of the Ouest department, where the capital Port-au-Prince is located. This study described the prevalence and risk factors for delayed viral suppression among PLHIV in all geographic departments of Haiti between 2013 and 2017. Individuals who received viral load testing 3 to 12 months after ART initiation were included. Data on demographics and clinical care were obtained from the Haitian Active Longitudinal Tracking of HIV database. Multivariable logistic regression was performed to predict delayed viral suppression, defined as a viral load ≥1000 HIV-1 RNA copies/mL after at least 3 months on ART. Viral load test results were available for 3,368 PLHIV newly-initiated on ART. Prevalence of delayed viral suppression was 40%, which is slightly higher than previous estimates in Haiti. In the multivariable analysis, delayed viral suppression was significantly associated with younger age, receiving of care in the Ouest department, treatment with lamivudine (3TC), zidovudine (AZT), and nevirapine (NVP) combined ART regimen, and CD4 counts below 200 cells/mm3. In conclusion, this study was the first to describe and compare differences in delayed viral suppression among PLHIV by geographic department in Haiti. We identified populations to whom public health interventions, such as more frequent viral load testing, drug resistance testing, and ART adherence counseling should be targeted.

Closing the gap in implementation of HIV clinical guidelines in a low resource setting using electronic medical records.

BACKGROUND: Universal health coverage promises equity in access to and quality of health services. However, there is variability in the quality of the care (QoC) delivered at health facilities in low and middle-income countries (LMICs). Detecting gaps in implementation of clinical guidelines is key to prioritizing the efforts to improve quality of care. The aim of this study was to present statistical methods that maximize the use of existing electronic medical records (EMR) to monitor compliance with evidence-based care guidelines in LMICs. METHODS: We used iSanté, Haiti's largest EMR to assess adherence to treatment guidelines and retention on treatment of HIV patients across Haitian HIV care facilities. We selected three processes of care - (1) implementation of a 'test and start' approach to antiretroviral therapy (ART), (2) implementation of HIV viral load testing, and (3) uptake of multi-month scripting for ART, and three continuity of care indicators - (4) timely ART pick-up, (5) 6-month ART retention of pregnant women and (6) 6-month ART retention of non-pregnant adults. We estimated these six indicators using a model-based approach to account for their volatility and measurement error. We added a case-mix adjustment for continuity of care indicators to account for the effect of factors other than medical care (biological, socio-economic). We combined the six indicators in a composite measure of appropriate care based on adherence to treatment guidelines. RESULTS: We analyzed data from 65,472 patients seen in 89 health facilities between June 2016 and March 2018. Adoption of treatment guidelines differed greatly between facilities; several facilities displayed 100% compliance failure, suggesting implementation issues. Risk-adjusted continuity of care indicators showed less variability, although several facilities had patient retention rates that deviated significantly from the national average. Based on the composite measure, we identified two facilities with consistently poor performance and two star performers. CONCLUSIONS: Our work demonstrates the potential of EMRs to detect gaps in appropriate care processes, and thereby to guide quality improvement efforts. Closing quality gaps will be pivotal in achieving equitable access to quality care in LMICs.

An EMR-Based Alert with Brief Provider-Led ART Adherence Counseling: Promising Results of the InfoPlus Adherence Pilot Study Among Haitian Adults with HIV Initiating ART.

To promote HIV antiretroviral therapy (ART) outcomes in Haiti, we developed a culturally relevant intervention (InfoPlus Adherence) that combines an electronic medical record alert identifying patients at elevated risk of treatment failure and provider-delivered brief problem-solving counseling. We conducted a quasi-experimental mixed-methods study among 146 patients at two large ART clinics in Haiti with 728 historical controls. We conducted quantitative assessments of patients at baseline and intervention completion (6 months) as well as focus groups with health workers and exit interviews with patients. The primary quantitative outcome measures were HIV viral suppression according to medical record and ART adherence in terms of ≥ 90% for "proportion of days covered" (PDC) according to pharmacy dispensing data. Results indicated that the proportion of intervention patients with suppressed VL during the study/historical periods was 80.0%/86.0% and 76.8%/87.4% for controls. In a difference-in-differences (DID) analytic model, the adjusted relative risk for viral suppression with the intervention was 1.15 (95% CI 0.92-1.45, p = 0.21), representing favorable but non-significant association between the intervention and the trajectory of VL outcomes. PDC ≥ 90% during the study/historical periods was 30.9%/11.0% among intervention participants and 16.9%/19.4% among controls. In the adjusted DID model, the relative risk for of PDC ≥ 90% with the intervention was 4.00 (95% CI 1.91-8.38, p < 0.001), representing a highly favorable association between the intervention and the trajectory of PDC outcomes. Qualitative data affirmed acceptability of the intervention, although providers reported some challenges consistently implementing it. Future research is needed to demonstrate efficacy and explore optimal implementation strategies.

Expanded access to viral load testing and use of second line regimens in Haiti: time trends from 2010-2017.

BACKGROUND: Haiti initiated the scale-up of HIV viral load (VL) testing in 2015-2016, with plans to achieve 100% coverage for all patients on antiretroviral therapy (ART) for treatment of HIV/AIDS. In the absence of HIV drug susceptibility testing, VL testing is a key tool for monitoring response to ART and optimizing treatment results. This study describes trends in expanded use of VL testing, VL results, and use of second-line ART regimens, and explores the association between VL testing and second-line regimen switching in Haiti from 2010 to 2017. METHODS: We conducted a retrospective cohort study with 66,042 patients drawn from 88 of Haiti's 160 national ART clinics. Longitudinal data from the iSanté electronic data system was used to analyze the trends of interest. We described patients' VL testing status in five categories based on up to two most recent VL test results: no test; suppressed; unsuppressed followed by no test; re-suppressed; and confirmed failure. Among those with confirmed failure, we described ART adherence level. Finally, we used Cox proportional hazards regression to estimate the risk of second-line regimen switching by VL testing status, after adjusting for other individual characteristics. RESULTS: The number of patients who had tests done increased annually from 11 in 2010 to 18,828 in the first 9 months of 2017, while the number of second-line regimen switches rose from 21 to 279 during this same period. Compared with patients with no VL test, the hazard ratio (HR) for switching to a second-line regimen was 22.2 for patients with confirmed VL failure (95% confidence interval [CI] for HR: 18.8-26.3; p < 0.005) after adjustment for individual characteristics. Among patients with confirmed VL failure, 44.7% had strong adherence, and fewer than 20% of patients switched to a second-line regimen within 365 days of VL failure. CONCLUSIONS: Haiti has significantly expanded access to VL testing since 2016. In order to promote optimal patient health outcomes, it is essential for Haiti to continue broadening access to confirmatory VL testing, to expand evidence-based initiatives to promote strong ART adherence, and to embrace timely switching for patients with confirmed ART failure despite strong ART adherence.

Toward Universal HIV Treatment in Haiti: Time Trends in ART Retention After Expanded ART Eligibility in a National Cohort From 2011 to 2017.

BACKGROUND: The World Health Organization (WHO) recommends universal antiretroviral therapy (ART) for persons living with HIV (PLWH), but evidence about effects of expanded ART access on ART retention in low-resource settings is limited. SETTING: Haiti's Ministry of Health endorsed universal ART for pregnant women in March 2013 (Option B+) and for all PLWH in July 2016. This study included 51,579 ART patients from 2011 to 2017 at 94 hospitals and clinics in Haiti. METHODS: This observational, retrospective cohort study described time trends in 6-month ART retention using secondary data, and compared results during 3 periods using an interrupted time series model: pre-Option B+ (period 1: 1/11-2/13), Option B+ (period 2: 3/13-6/16), and Test and Start (T&S, period 3: 7/16-9/17). RESULTS: From the pre-Option B+ to the T&S period, the monthly count of new ART patients increased from 366/month to 877/month, and the proportion with same-day ART increased from 6.3% to 42.1% (P < 0.001). The proportion retained on ART after 6 months declined from 78.4% to 75.0% (P < 0.001). In the interrupted time series model, ART retention improved by a rate of 1.4% per quarter during the T&S period after adjusting for patient characteristics (adjusted incidence rate ratio = 1.014; 95% confidence interval: 1.002 to 1.026, P < 0.001). However, patients with same-day ART were 14% less likely to be retained compared to those starting ART >30 days after HIV diagnosis (adjusted incidence rate ratio = 0.86; 95% confidence interval: 0.84-0.89, P < 0.001). CONCLUSIONS: Achieving targets for HIV epidemic control will require increasing ART retention and reducing the disparity in retention for those with same-day ART.

Retention Throughout the HIV Care and Treatment Cascade: From Diagnosis to Antiretroviral Treatment of Adults and Children Living with HIV-Haiti, 1985-2015.

Monitoring retention of people living with HIV (PLHIV) in the HIV care and treatment cascade is essential to guide program strategy and evaluate progress toward globally-endorsed 90-90-90 targets (i.e., 90% of PLHIV diagnosed, 81% on sustained antiretroviral therapy (ART), and 73% virally suppressed). We describe national retention from diagnosis throughout the cascade for patients receiving HIV services in Haiti during 1985-2015, with a focus on those receiving HIV services during 2008-2015. Among the 266,256 newly diagnosed PLHIV during 1985-2015, 49% were linked-to-care, 30% started ART, and 18% were retained on ART by the time of database closure. Similarly, among the 192,187 newly diagnosed HIV-positive patients during 2008-2015, 50% were linked to care, 31% started ART, and 19% were retained on ART by the time of database closure. Most patients (90-92%) at all cascade steps were adults (≥ 15 years old), among whom the majority (60-61%) were female. During 2008-2015, outcomes varied significantly across 42 administrative districts (arrondissements) of residence; cumulative linkage-to-care ranged from 23% to 69%, cumulative ART initiation among care enrollees ranged from 2% to 80%, and cumulative ART retention among ART enrollees ranged from 30% to 88%. Compared with adults, children had lower cumulative incidence of ART initiation among care enrollees (64% versus 47%) and lower cumulative retention among ART enrollees (64% versus 50%). Cumulative linkage-to-care was low and should be prioritized for improvement. Variations in outcomes by arrondissement and between adults and children require further investigation and programmatic response.

Trends in Prevalence of Advanced HIV Disease at Antiretroviral Therapy Enrollment - 10 Countries, 2004-2015.

Monitoring prevalence of advanced human immunodeficiency virus (HIV) disease (i.e., CD4+ T-cell count <200 cells/µL) among persons starting antiretroviral therapy (ART) is important to understand ART program outcomes, inform HIV prevention strategy, and forecast need for adjunctive therapies.*,†,§ To assess trends in prevalence of advanced disease at ART initiation in 10 high-burden countries during 2004-2015, records of 694,138 ART enrollees aged ≥15 years from 797 ART facilities were analyzed. Availability of national electronic medical record systems allowed up-to-date evaluation of trends in Haiti (2004-2015), Mozambique (2004-2014), and Namibia (2004-2012), where prevalence of advanced disease at ART initiation declined from 75% to 34% (p<0.001), 73% to 37% (p<0.001), and 80% to 41% (p<0.001), respectively. Significant declines in prevalence of advanced disease during 2004-2011 were observed in Nigeria, Swaziland, Uganda, Vietnam, and Zimbabwe. The encouraging declines in prevalence of advanced disease at ART enrollment are likely due to scale-up of testing and treatment services and ART-eligibility guidelines encouraging earlier ART initiation. However, in 2015, approximately a third of new ART patients still initiated ART with advanced HIV disease. To reduce prevalence of advanced disease at ART initiation, adoption of World Health Organization (WHO)-recommended "treat-all" guidelines and strategies to facilitate earlier HIV testing and treatment are needed to reduce HIV-related mortality and HIV incidence.

Lower Levels of Antiretroviral Therapy Enrollment Among Men with HIV Compared with Women - 12 Countries, 2002-2013.

Equitable access to antiretroviral therapy (ART) for men and women with human immunodeficiency virus (HIV) infection is a principle endorsed by most countries and funding bodies, including the U.S. President's Emergency Plan for AIDS (acquired immunodeficiency syndrome) Relief (PEPFAR) (1). To evaluate gender equity in ART access among adults (defined for this report as persons aged ≥15 years), 765,087 adult ART patient medical records from 12 countries in five geographic regions* were analyzed to estimate the ratio of women to men among new ART enrollees for each calendar year during 2002-2013. This annual ratio was compared with estimates from the Joint United Nations Programme on HIV/AIDS (UNAIDS)(†) of the ratio of HIV-infected adult women to men in the general population. In all 10 African countries and Haiti, the most recent estimates of the ratio of adult women to men among new ART enrollees significantly exceeded the UNAIDS estimates for the female-to-male ratio among HIV-infected adults by 23%-83%. In six African countries and Haiti, the ratio of women to men among new adult ART enrollees increased more sharply over time than the estimated UNAIDS female-to-male ratio among adults with HIV in the general population. Increased ART coverage among men is needed to decrease their morbidity and mortality and to reduce HIV incidence among their sexual partners. Reaching more men with HIV testing and linkage-to-care services and adoption of test-and-treat ART eligibility guidelines (i.e., regular testing of adults, and offering treatment to all infected persons with ART, regardless of CD4 cell test results) could reduce gender inequity in ART coverage.