In September 2015 the World Health Organization (WHO) recommended universal antiretroviral therapy (ART) for all persons living with HIV (PLWH), regardless of level of HIV disease progression.¹ This recommendation was based on studies showing improved levels of viral suppression and reduced morbidity and mortality with ART, even for patients with high CD4 counts, ²–⁴ as well as modeling studies demonstrating that universal ART could reduce onward HIV transmission. Subsequent clinical trials on same-day and rapid ART⁵–⁷ contributed to additional WHO recommendations in July 2016 that patients without evidence of opportunistic infections (OIs) should initiate ART within 7 days, or on the same day of HIV diagnosis with demonstrated ART readiness, and that symptomatic patients should initiate ART within 2–8 weeks in conjunction with clinical management of co-occurring opportunistic infections.⁸

Evaluating universal ART implemented at scale in resource-limited settings is important in order to identify policy successes and outstanding gaps.^9,10 Several countries have contributed evidence on ART retention and other health outcomes following adoption of universal ART among pregnant women (Option B+)^11–16 and evidence timely uptake of treatment under universal ART for all PLWH,^17–19 but there is less evidence on health outcomes following national-scale adoption of universal ART policies.²⁰

Haiti has a national HIV prevalence rate of 2.0% among adults,²¹ representing the largest absolute burden of HIV in the Caribbean region. The Haiti Ministère de la Santé Publique et de la Population (MSPP, or Ministry of Health) endorsed universal treatment for pregnant and postpartum women in March 2013 (Option B+) and extended universal ART (known in Haiti as “Test and Start”, or T&S) to all PLWH in July 2016. Our study’s objectives were to 1) describe trends in timing of ART initiation, patient characteristics, and ART retention in Haiti; and 2) explore the association between rapid ART initiation and ART retention as national guidelines for ART eligibility changed.

We restricted the dataset to patients first diagnosed with HIV starting in January 2004, when the iSanté EMR began. We excluded PLWH first diagnosed at a site outside of the iSanté network of 94 sites, since we could not definitively determine their pre-ART interval; this exclusion represented approximately 3% of all unique patients in the dataset. Finally, we restricted the dataset to ART patients with at least 183 days of follow up time within our dataset.

We used descriptive statistics to characterize the cohort and ART retention levels across time periods. We compared pre-ART interval, other patient covariates, and ART retention across time using the Chi-2 test of equality of proportions, Wilcoxan rank sum test, and Students t-test. We graphed the time trend in proportion of patients with ART retention at 6 months by period and calendar month, by pre-ART interval group. We assessed for seasonality of the outcomes by visual inspection for a cyclical pattern in ART retention by calendar month.

Next, we used an uncontrolled interrupted time series (ITS) model to evaluate the association between pre-ART interval and ART retention outcomes and the three periods of policy change on ART eligibility. ITS is a useful quasi-experimental method for leveraging routine data sources to infer the effects of large-scale policy changes, when investigator-controlled, experimental methods are not feasible.^29–31 Our ITS model used the form: Yret=1= β0+ βm1−26+ βm27−66+ βm67−81+ ∑m=212βm+ βpre−ARTinterval+βcovars

The model grouped patient-level binary ART retention outcomes by calendar month over the 81 months of the study and estimated rates of change, or slopes during each of three periods (βm1−26 , βm27−66 , βm67−81). The model allowed for a change in slope at the start of each policy period but no immediate discontinuous level effects, since the official adoption of guidelines did not necessarily represent a moment of sudden practice change. The model included individual month fixed-effects (βm), to address seasonality of the outcome. The model adjusted for pre-ART interval (βpre−ARTinterval)with ART >30 days after diagnosis as the reference category) and other patient covariates (βcovars), to control for the changing profile of ART patients over time. Covariates were included in the final multivariable model based upon statistical significance at the p<0.05 level in separate ITS models which included the outcome, time components, and each single covariate. In a sensitivity analysis, we used an ITS model which included discontinuous level effects and which allowed for interaction of pre-ART interval and time, as well as discontinuous levels by period.

The ITS model used generalized estimating equations (GEE) with Poisson family and log link, in order to estimate a measure of relative risk rather than an odds ratio for the binary outcome. The model treated patient observations as correlated at the health facility level, and used an exchangeable correlation structure and robust variances to address correlation of data by health facility.^32,33 Last, we assessed the marginal predicted probability of ART retention at the start and end of each period, by pre-ART interval category, to obtain the post-estimation probability of the outcome among individuals with different pre-ART interval categories but like profiles in all other characteristics. We used Stata 15.1 (StataCorp, College Station, TX) for all analyses.

The study received scientific and ethical review and approval from the US Centers for Disease Control and Prevention and the Haiti National Committee on Bioethics, and was exempted from human subjects review by University of Washington.

Universal ART is a critical pillar of efforts to achieve the 95–95–95 targets for HIV epidemic control. Our study of a large cohort of ART patients from 94 clinics in Haiti demonstrated a 2.4 fold increase in monthly enrollment of new ART patients from the pre-Option B+ period before March 2013 to the T&S period after July 2016. The share of new ART patients with WHO Stage 1 or 2 nearly tripled over this time frame, reflecting the success of the policy changes in ensuring earlier treatment initiation for PLWH.

Six-month ART retention declined from 78.4% to 75.0% in Haiti over the three periods in our study, and fell short of targets for HIV epidemic control. This could reflect the challenges of extending treatment to hard-to-reach patients as well as to asymptomatic patients with less motivation to remain on treatment. The level of 71.6% among same-day ART patients also fell short of the 12-month retention level of 80% reported in an earlier randomized controlled clinical trial of same-day ART set in Port-au-Prince, Haiti.⁵ It can be challenging to translate results of clinical trials in real-world conditions. The results from Haiti echo the experience with scaled up universal treatment in Nigeria, where high loss to follow up (LTFU) of 34% at 12 months was reported following adoption of universal treatment.²⁰

On the other hand, after taking into account the changing sociodemographic and clinical profile of ART patients over the time frame of our study, we found evidence of a favorable time trend in ART retention after adoption of T&S, estimated at a 1.4% increase per quarter during period 3. This result could reflect normalization of universal treatment in the eyes of patients and providers, as well as improvements in program procedures like post-test counseling, linkage to care services, and other clinical practices.

A discouraging finding was the disparity in ART retention among same-day ART patients, estimated to be 14% less likely to be retained on ART at 6 months, compared to those starting ART >30 days after diagnosis. Indeed, one in five same-day ART patients failed to return to pick up ART following their initial dispense during the T&S period. In Haiti as in other low-resource settings, starting and being retained on treatment are modifiable outcomes shaped by individual, social, and health system factors.⁹ The process of diagnosis and ART initiation must help patients accept their diagnosis, understand the process of treatment, develop behavioral skills for ART adherence, and build social support for long-term ART retention. Strategies for enhancing patient-centeredness of care services at the time of HIV diagnosis and ART initiation, and for intensifying early support for patients newly initiating ART, especially same-day ART patients, are needed in Haiti. More evidence is needed from other resource-limited settings to identify similarities and differences in patterns of ART retention following scale-up of universal treatment.

A key strength of this study was our ability to link records for patients who were multiply registered or who transferred care between health facilities. The inability to establish valid values for date of initial HIV diagnosis and for ART retention based on unique records has bedeviled many observational studies using secondary data sources.³⁴ While some patients in our study may have silently transferred care to sites outside of the iSanté network, leading us to underestimate ART retention, we believe this minimally affected our estimates given the low rates of transfer of care between the 94 iSanté clinics.

There are several limitations to our study. First, we could not differentiate mortality from LTFU. Further understanding of the role of mortality versus LFTU is important in identifying interventions to improve overall ART retention and reduce the disparity in outcomes for same-day ART patients. Second, the changes in ART eligibility occurred in tandem with other changes in the national ART program. In the early days of Haiti’s ART program, donor funding was used to support a robust model of ancillary services for ART patients, including psychosocial support, food assistance, transportation subsidies, microenterprise development, and even school fees for children. As donor’s focus shifted to expanded ART access and HIV care cascade targets, the robust model of “social advantages” was pared back. However, our study was not able to separately estimate effects of changes in ART eligibility guidelines versus other types of ART program changes. Third, our study was not able to take into account certain patient-, provider- and facility-level factors which influence ART retention, such as socio-economic status, food security, travel distance to the clinic and access to transportation, knowledge and motivation about treatment, level of social support for treatment, clinic wait times, perceived technical competence or friendliness of health providers, or availability of ancillary services. Finally, measurement of covariates was imperfect, with high levels of missingness and potential misclassification of variables like ART adherence counseling (which may have been offered but not documented), introducing bias in our estimates in unknown directions. Additional research on these topics would be helpful.

Observational studies play an important role in setting global guidelines and in demonstrating the feasibility, acceptability, and effectiveness of strategies like T&S.¹⁰ This large-scale study demonstrated expanded access to ART and a narrowing of the disparity in ART retention between patients with same day ART compared to delayed ART. Further observational and pragmatic intervention studies are needed in order to refine guidelines for the process of rapid ART initiation and to optimize ART retention under universal treatment.