Same-day testing with initiation of antiretroviral therapy or tuberculosis treatment versus standard care for persons presenting with tuberculosis symptoms at HIV diagnosis: A randomized open-label trial from Haiti.

BACKGROUND: Same-day HIV testing and antiretroviral therapy (ART) initiation is being widely implemented. However, the optimal timing of ART among patients with tuberculosis (TB) symptoms is unknown. We hypothesized that same-day treatment (TB treatment for those diagnosed with TB; ART for those not diagnosed with TB) would be superior to standard care in this population. METHODS AND FINDINGS: We conducted an open-label trial among adults with TB symptoms at initial HIV diagnosis at GHESKIO in Haiti; participants were recruited and randomized on the same day. Participants were randomized in a 1:1 ratio to same-day treatment (same-day TB testing with same-day TB treatment if TB diagnosed; same-day ART if TB not diagnosed) versus standard care (initiating TB treatment within 7 days and delaying ART to day 7 if TB not diagnosed). In both groups, ART was initiated 2 weeks after TB treatment. The primary outcome was retention in care with 48-week HIV-1 RNA <200 copies/mL, with intention to treat (ITT) analysis. From November 6, 2017 to January 16, 2020, 500 participants were randomized (250/group); the final study visit occurred on March 1, 2021. Baseline TB was diagnosed in 40 (16.0%) in the standard and 48 (19.2%) in the same-day group; all initiated TB treatment. In the standard group, 245 (98.0%) initiated ART at median of 9 days; 6 (2.4%) died, 15 (6.0%) missed the 48-week visit, and 229 (91.6%) attended the 48-week visit. Among all who were randomized, 220 (88.0%) received 48-week HIV-1 RNA testing; 168 had <200 copies/mL (among randomized: 67.2%; among tested: 76.4%). In the same-day group, 249 (99.6%) initiated ART at median of 0 days; 9 (3.6%) died, 23 (9.2%) missed the 48-week visit, and 218 (87.2%) attended the 48-week visit. Among all who were randomized, 211 (84.4%) received 48-week HIV-1 RNA; 152 had <200 copies/mL (among randomized: 60.8%; among tested: 72.0%). There was no difference between groups in the primary outcome (60.8% versus 67.2%; risk difference: -0.06; 95% CI [-0.15, 0.02]; p = 0.14). Two new grade 3 or 4 events were reported per group; none were judged to be related to the intervention. The main limitation of this study is that it was conducted at a single urban clinic, and the generalizability to other settings is uncertain. CONCLUSIONS: In patients with TB symptoms at HIV diagnosis, we found that same-day treatment was not associated with superior retention and viral suppression. In this study, a short delay in ART initiation did not appear to compromise outcomes. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov NCT03154320.

Lessons learned from over a decade of data audits in international observational HIV cohorts in Latin America and East Africa.

Introduction: Routine patient care data are increasingly used for biomedical research, but such "secondary use" data have known limitations, including their quality. When leveraging routine care data for observational research, developing audit protocols that can maximize informational return and minimize costs is paramount. Methods: For more than a decade, the Latin America and East Africa regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium have been auditing the observational data drawn from participating human immunodeficiency virus clinics. Since our earliest audits, where external auditors used paper forms to record audit findings from paper medical records, we have streamlined our protocols to obtain more efficient and informative audits that keep up with advancing technology while reducing travel obligations and associated costs. Results: We present five key lessons learned from conducting data audits of secondary-use data from resource-limited settings for more than 10 years and share eight recommendations for other consortia looking to implement data quality initiatives. Conclusion: After completing multiple audit cycles in both the Latin America and East Africa regions of the IeDEA consortium, we have established a rich reference for data quality in our cohorts, as well as large, audited analytical datasets that can be used to answer important clinical questions with confidence. By sharing our audit processes and how they have been adapted over time, we hope that others can develop protocols informed by our lessons learned from more than a decade of experience in these large, diverse cohorts.

Prevalence of hypertension and cardiovascular risk factors among long-term AIDS survivors: A report from the field.

HIV infection is associated with increased risk and progression of cardiovascular disease (CVD), yet little is known about the prevalence of CVD risk factors among long-term AIDS survivors in resource-limited settings. Using routinely collected data, we conducted a retrospective study to describe the prevalence of CVD risk factors among a cohort of HIV-infected patients followed for over 10 years in Port-au Prince, Haiti. This cohort includes 910 adults who initiated antiretroviral therapy (ART) between 2003 and 2004 and remained in care between 2014 and 2016 when routine screening for CVD risk factors was implemented at a large clinic in Haiti. A total of 397 remained in care ≥10 years and received screening. At ART initiation, 59% were female, median age was 38 years (IQR 33-44), and median CD4 count was 117 cells/mm3 (IQR 34-201). Median follow-up time from ART initiation was 12.1 years (IQR 11.7-12.7). At screening, median CD4 count was 574 cells/mm3 (IQR 378-771), and 84% (282 of 336 screened) had HIV-1 RNA < 1000 copies/mL. Seventy-four percent of patients had at least 1 risk factor including 58% (224/385) with hypertension, 8% (24/297) diabetes, 43% (119/275) hypercholesterolemia, 8% (20/248) active smoking, and 10% (25/245) obesity. Factors associated with hypertension were age (adjusted OR 1.06, P < .001) and weight at screening (adjusted OR 1.02, P = .019). Long-term AIDS survivors have a high prevalence of CVD risk factors, primarily hypertension. Integration of cardiovascular screening and management into routine HIV care is needed to maximize health outcomes among aging HIV patients in resource-limited settings.

Predicting death and lost to follow-up among adults initiating antiretroviral therapy in resource-limited settings: Derivation and external validation of a risk score in Haiti.

BACKGROUND: Over 18 million adults have initiated life-saving antiretroviral therapy (ART) in resource-poor settings; however, mortality and lost-to-follow-up rates continue to be high among patients in their first year after treatment start. Clinical decision tools are needed to identify patients at high risk for poor outcomes in order to provide individualized risk assessment and intervention. This study aimed to develop and externally validate risk prediction tools that estimate the probability of dying or of being lost to follow-up (LTF) during the year after starting ART. METHODS: We used a derivation cohort of 7,031 adults age 15-70 years initiating ART from 2007 to 2013 at 6 clinics in Haiti; 242 (3.5%) had documented death and 1,521 (21.6%) were LTF at 1 year after starting ART. The following routinely collected data were used as predictors in two logistic regression models (one to predict death and another to predict LTF): age, gender, weight, CD4 count, WHO Stage, and diagnosis of tuberculosis (TB). The validation cohort consisted of 1,835 adults initiating ART at a different HIV clinic in Haiti during 2012. We assessed model discrimination by measuring the C-statistic, and measured model calibration by how closely the predicted probabilities approximated actual probabilities of the two outcomes. We derived a nomogram and a point-based risk score from the predictive models. FINDINGS: The model predicting death within the year after starting ART had a C-statistic of 0.75 (95% CI 0.74 to 0.81). There was no evidence for significant overfitting and the predictions were well calibrated. The strongest predictors of 1-year mortality were male gender, low weight, low CD4 count, advanced WHO stage, and the absence of TB. In the validation cohort, the C-statistic was 0.69 (95% CI 0.59 to 0.77). A point-based risk score for death had a C-statistic 0.73 (95% CI 0.69 to 0.76) and categorizes patients as low risk (<2% risk of death), average risk (3-4%), and high-risk (8-10%) and very high-risk (14-19%) with likelihood ratios to be used in settings where the baseline risk is different from our study population. The model predicting LTF did not discriminate well (C-statistic 0.59). CONCLUSIONS: A simple risk-score using routinely collected data can predict 1-year mortality after ART initiation for HIV-positive adults in Haiti. However, predicting lost to follow-up using routinely collected data was not as successful. The next step is to assess whether use of this risk score can identify patients who need tailored services to reduce mortality in resource-poor settings such as Haiti.

Retention in Care among Patients with Early HIV Disease in Haiti.

In September 2015, the World Health Organization updated their guidelines to recommend antiretroviral therapy (ART) for all people living with HIV. Countries are now in the process of implementing strategies to provide universal HIV treatment. We analyzed the rate of retention and time to ART eligibility (according to 2013 WHO guidelines) among 3,345 adult patients receiving positive HIV test results between February 1, 2003 and March 31, 2013 at the GHESKIO Clinic in Haiti, with WHO stage 1 or 2 disease and initial CD4 cell count >500 cells/mm3. Among the 3,345 patients, 2,423 (72%) were female, the median age was 33 years, 3,089 (92%) lived in Port-au-Prince, and 1,944 (58%) had attended no school or primary school only. The median initial CD4 cell count was 668 cells/mm3 (IQR: 572-834); over the subsequent 2 years, 1,485 patients (44%) were lost to follow-up and 7 (<1%) died pre-ART, 1,041 (31%) were retained in pre-ART care, and 819 (24%) initiated ART. In multivariate analysis, secondary education (aOR 1.27; 95% CI: 1.10-1.47), female gender (aOR: 1.28; 95% CI: 1.09-1.50), co-habitation (aOR: 1.31; 95% CI: 1.09-1.57), and residence in Port-au-Prince (aOR: 1.43; 95% CI: 1.09-1.88) were associated with retention in care. The median time from baseline CD4 count to ART eligibility was 1.7 years. Prior to the implementation of universal treatment, pre-ART attrition was high among patients who did not qualify for ART at presentation. Though implementing WHO recommendations for universal ART will require service expansion, it will likely result in improved retention for those at risk of being lost to follow-up.

Trends in CD4 Count Testing, Retention in Pre-ART Care, and ART Initiation Rates over the First Decade of Expansion of HIV Services in Haiti.

BACKGROUND: High attrition during the period from HIV testing to antiretroviral therapy (ART) initiation is widely reported. Though treatment guidelines have changed to broaden ART eligibility and services have been widely expanded over the past decade, data on the temporal trends in pre-ART outcomes are limited; such data would be useful to guide future policy decisions. METHODS: We evaluated temporal trends and predictors of retention for each step from HIV testing to ART initiation over the past decade at the GHESKIO clinic in Port-au-Prince Haiti. The 24,925 patients >17 years of age who received a positive HIV test at GHESKIO from March 1, 2003 to February 28, 2013 were included. Patients were followed until they remained in pre-ART care for one year or initiated ART. RESULTS: 24,925 patients (61% female, median age 35 years) were included, and 15,008 (60%) had blood drawn for CD4 count within 12 months of HIV testing; the trend increased over time from 36% in Year 1 to 78% in Year 10 (p<0.0001). Excluding transfers, the proportion of patients who were retained in pre-ART care or initiated ART within the first year after HIV testing was 84%, 82%, 64%, and 64%, for CD4 count strata ≤200, 201 to 350, 351 to 500, and >500 cells/mm3, respectively. The trend increased over time for each CD4 strata, and in Year 10, 94%, 95%, 79%, and 74% were retained in pre-ART care or initiated ART for each CD4 strata. Predictors of pre-ART attrition included male gender, low income, and low educational status. Older age and tuberculosis (TB) at HIV testing were associated with retention in care. CONCLUSIONS: The proportion of patients completing assessments for ART eligibility, remaining in pre-ART care, and initiating ART have increased over the last decade across all CD4 count strata, particularly among patients with CD4 count ≤350 cells/mm3. However, additional retention efforts are needed for patients with higher CD4 counts.

A Second Look at the Association between Gender and Mortality on Antiretroviral Therapy.

OBJECTIVE: We assessed the association between gender and mortality on antiretroviral therapy (ART) using identical models with and without sex-specific categories for weight and hemoglobin. DESIGN: Cohort study of adult patients on ART. SETTING: GHESKIO Clinic in Port-au-Prince, Haiti. PARTICIPANTS: 4,717 ART-naïve adult patients consecutively enrolled on ART at GHESKIO from 2003 to 2008. MAIN OUTCOME MEASURE: Mortality on ART; multivariable analyses were conducted with and without sex-specific categories for weight and hemoglobin. RESULTS: In Haiti, male gender was associated with mortality (OR 1.61; 95% CI: 1.30-2.00) in multivariable analyses with hemoglobin and weight included as control variables, but not when sex-specific interactions with hemoglobin and weight were used. CONCLUSIONS: If sex-specific categories are omitted, multivariable analyses indicate a higher risk of mortality for males vs. females of the same weight and hemoglobin. However, because males have higher normal values for weight and hemoglobin, the males in this comparison would generally have poorer health status than the females. This may explain why gender differences in mortality are sometimes observed after controlling for differences in baseline variables when gender-specific interactions with weight and hemoglobin are omitted.

Attrition from HIV testing to antiretroviral therapy initiation among patients newly diagnosed with HIV in Haiti.

OBJECTIVE: We report rates and risk factors for attrition in the first cohort of patients followed through all stages from HIV testing to antiretroviral therapy (ART) initiation. DESIGN: Cohort study of all patients diagnosed with HIV between January and June 2009. METHODS: We calculated the proportion of patients who completed CD4 cell counts and initiated ART or remained in pre-ART care during 2 years of follow-up and assessed predictors of attrition. RESULTS: Of 1427 patients newly diagnosed with HIV, 680 (48%) either initiated ART or were retained in pre-ART care for the subsequent 2 years. One thousand eighty-three patients (76%) received a CD4 cell count, and 973 (90%) returned for result; 297 (31%) had CD4 cell count <200 cells per microliter, and of these, 256 (86%) initiated ART. Among 429 patients with CD4 >350 cells per microliter, 215 (50%) started ART or were retained in pre-ART care. Active tuberculosis was associated with not only lower odds of attrition before CD4 cell count [odds ratio (OR): 0.08; 95% confidence interval (CI): 0.03 to 0.25] but also higher odds of attrition before ART initiation (OR: 2.46; 95% CI: 1.29 to 4.71). Lower annual income (≤US $125) was associated with higher odds of attrition before CD4 cell count (OR: 1.65; 95% CI: 1.25 to 2.19) and before ART initiation among those with CD4 cell count >350 cells per microliter (OR: 1.74; 95% CI: 1.20 to 2.52). After tracking patients through a national database, the retention rate increased to only 57%. CONCLUSIONS: Fewer than half of patients newly diagnosed with HIV initiate ART or remain in pre-ART care for 2 years in a clinic providing comprehensive services. Additional efforts to improve retention in pre-ART are critically needed.

Consideration of postpartum management in HIV-positive Haitian women: an analysis of CD4 decline, mortality, and follow-up after delivery.

BACKGROUND: A previous study at the GHESKIO HIV clinic confirmed that highly active antiretroviral therapy (HAART) prophylaxis reduced mother-to-child transmission (MTCT) and infant mortality in Haiti. This analysis looks at maternal outcomes in this cohort after delivery. METHODS: Records of 508 HIV-positive Haitian women who delivered between 1999 and 2005 were analyzed. We examined mortality, loss to follow-up, time to death or HAART initiation, and time of decline of CD4 count to 350 cells/µL. RESULTS: One hundred seventy women reached a CD4 ≤200 or developed clinical AIDS and were started on long-term HAART. The median CD4 count at HAART initiation was 178 (interquartile range, 106-227). CD4 decline was stratified by CD4 at delivery to project the mean months to a CD4 of 350. With an initial CD4 of 350-499 cells/µL, it was 19 months (95% confidence interval: 14 to 28) while with a CD4 >500 cells/µL, it was 71 months (95% confidence interval: 59 to 88). At study close, 257 women remained in follow-up, with loss to follow-up 3 times less in those on HAART (3.2/100 person-years) than those not on HAART (9.8/100 person-years). CONCLUSIONS: The threshold for starting treatment was often missed in HIV-infected women after delivery. Success of follow-up of women after delivery was favorably influenced by being on HAART. Women with high (>500) initial CD4 counts had a protracted time (5-7 years) before they reach a threshold CD4 count, in contrast to those with CD4 <500 cells/µL. Strategies for postpartum treatment of women should be informed by the speed with which they are likely to progress.