High rates of patient attrition from care between HIV testing and antiretroviral therapy (ART) initiation have been documented in sub-Saharan Africa, contributing to persistently low CD4 cell counts ...at treatment initiation. One reason for this is that starting ART in many countries is a lengthy and burdensome process, imposing long waits and multiple clinic visits on patients. We estimated the effect on uptake of ART and viral suppression of an accelerated initiation algorithm that allowed treatment-eligible patients to be dispensed their first supply of antiretroviral medications on the day of their first HIV-related clinic visit.
RapIT (Rapid Initiation of Treatment) was an unblinded randomized controlled trial of single-visit ART initiation in two public sector clinics in South Africa, a primary health clinic (PHC) and a hospital-based HIV clinic. Adult (≥18 y old), non-pregnant patients receiving a positive HIV test or first treatment-eligible CD4 count were randomized to standard or rapid initiation. Patients in the rapid-initiation arm of the study ("rapid arm") received a point-of-care (POC) CD4 count if needed; those who were ART-eligible received a POC tuberculosis (TB) test if symptomatic, POC blood tests, physical exam, education, counseling, and antiretroviral (ARV) dispensing. Patients in the standard-initiation arm of the study ("standard arm") followed standard clinic procedures (three to five additional clinic visits over 2-4 wk prior to ARV dispensing). Follow up was by record review only. The primary outcome was viral suppression, defined as initiated, retained in care, and suppressed (≤400 copies/ml) within 10 mo of study enrollment. Secondary outcomes included initiation of ART ≤90 d of study enrollment, retention in care, time to ART initiation, patient-level predictors of primary outcomes, prevalence of TB symptoms, and the feasibility and acceptability of the intervention. A survival analysis was conducted comparing attrition from care after ART initiation between the groups among those who initiated within 90 d. Three hundred and seventy-seven patients were enrolled in the study between May 8, 2013 and August 29, 2014 (median CD4 count 210 cells/mm3). In the rapid arm, 119/187 patients (64%) initiated treatment and were virally suppressed at 10 mo, compared to 96/190 (51%) in the standard arm (relative risk RR 1.26 1.05-1.50). In the rapid arm 182/187 (97%) initiated ART ≤90 d, compared to 136/190 (72%) in the standard arm (RR 1.36, 95% confidence interval CI, 1.24-1.49). Among 318 patients who did initiate ART within 90 d, the hazard of attrition within the first 10 mo did not differ between the treatment arms (hazard ratio HR 1.06; 95% CI 0.61-1.84). The study was limited by the small number of sites and small sample size, and the generalizability of the results to other settings and to non-research conditions is uncertain.
Offering single-visit ART initiation to adult patients in South Africa increased uptake of ART by 36% and viral suppression by 26%. This intervention should be considered for adoption in the public sector in Africa.
ClinicalTrials.gov NCT01710397, and South African National Clinical Trials Register DOH-27-0213-4177.
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Systematic reviews have described high rates of attrition in patients with HIV receiving antiretroviral therapy (ART). However, migration and clinical transfer may lead to an overestimation of ...attrition (death and loss to follow-up). Using a newly linked national laboratory database in South Africa, we assessed national retention in South Africa's national HIV program.
Patients receiving care in South Africa's national HIV program are monitored through regular CD4 count and viral load testing. South Africa's National Health Laboratory Service has maintained a database of all public-sector CD4 count and viral load results since 2004. We linked individual laboratory results to patients using probabilistic matching techniques, creating a national HIV cohort. Validation of our approach in comparison to a manually matched dataset showed 9.0% undermatching and 9.5% overmatching. We analyzed data on patients initiating ART in the public sector from April 1, 2004, to December 31, 2006, when ART initiation could be determined based on first viral load among those whose treatment followed guidelines. Attrition occurred on the date of a patient's last observed laboratory measure, allowing patients to exit and reenter care prior to that date. All patients had 6 potential years of follow-up, with an additional 2 years to have a final laboratory measurement to be retained at 6 years. Data were censored at December 31, 2012. We assessed (a) national retention including all laboratory tests regardless of testing facility and (b) initiating facility retention, where laboratory tests at other facilities were ignored. We followed 55,836 patients initiating ART between 2004 and 2006. At ART initiation, median age was 36 years (IQR: 30-43), median CD4 count was 150 cells/mm3 (IQR: 81-230), and 66.7% were female. Six-year initiating clinic retention was 29.1% (95% CI: 28.7%-29.5%). After allowing for transfers, national 6-year retention was 63.3% (95% CI: 62.9%-63.7%). Results differed little when tightening or relaxing matching procedures. We found strong differences in retention by province, ranging from 74.2% (95% CI: 73.2%-75.2%) in Western Cape to 52.2% (95% CI: 50.6%-53.7%) in Mpumalanga at 6 years. National attrition was higher among patients initiating at lower CD4 counts and higher viral loads, and among patients initiating ART at larger facilities. The study's main limitation is lack of perfect cohort matching, which may lead to over- or underestimation of retention. We also did not have data from KwaZulu-Natal province prior to 2010.
In this study, HIV care retention was substantially higher when viewed from a national perspective than from a facility perspective. Our results suggest that traditional clinical cohorts underestimate retention.
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One of the key risk factors for cardiovascular disease is hypertension. Hypertension, which leads to heart attacks and strokes, already affects one billion people worldwide, making it a global public ...health issue. Incidence and prevalence of the condition is on the rise in low- and middle-income countries, with the biggest increase in sub-Saharan Africa and South Africa at the forefront. We examined the prevalence, incidence, predictors, treatment, and control of hypertension among HIV-positive patients on ART in a large South African observational cohort.
We conducted a prospective study of ART naïve adults initiating ART at a public sector HIV clinic in South Africa between April 2004-2017. Patients with diagnosed hypertension at ART initiation were excluded from the incidence analysis. Log-binomial regression was used to estimate predictors of hypertension at ART initiation, while competing risks regression was used to evaluate the relationship between predictors of incident hypertension, accounting for death as a competing risk.
Among 77,696 eligible patients, 22.0% had prevalent hypertension at ART initiation. Of the remaining patients with no hypertension at ART initiation, 8,125 incident hypertension cases were diagnosed over the period of follow-up, corresponding to an incident rate of 5.4 per 100 person-years (95% confidence interval (CI): 5.3-5.6). We found patients ≥40 years of age and patients with a body mass index (BMI) ≥25kg/m2 were at increased risk of both prevalent and incident hypertension. Male patients and those with pre-hypertension at ART initiation had increased hazards of hypertension over the period of follow-up. When assessing the choice of antiretroviral drug in first-line ART, patients initiated on nevirapine were at 27% increased risk of developing hypertension compared to those initiated on efavirenz, while patients who initiated on either zidovudine or stavudine had a 40% increased risk of developing hypertension compared to patients initiated on tenofovir. Patientswith poorer health status at ART initiation (i.e. WHO III/IV stage, low CD4 count, low hemoglobin levels and low BMI) had a decrease risk of prevalent hypertension. We found an inverse relationship in patients with a CD4 count <50 cells/mm3 at ART initiation who had a 25% increased risk of incident hypertension compared to those with a CD4 count ≥350 cells/mm3.
Over 20% of patients in our cohort had hypertension at ART initiation, and 13% of those with normal blood pressure at ART initiation developed hypertension while on ART. Older patients, males, those on nevirapine, zidovudine or stavudine, and those who are overweight/obese should be targeted for frequent blood pressure monitoring and the identification of other cardiovascular risk factors to encourage lifestyle modifications. Additionally, these groups should be offered pharmaceutical therapy to help prevent myocardial infarction, heart failure, stroke, and kidney disease. Further research is needed to determine the level of access and adherence to pharmaceutical treatment for hypertension in this population. Additionally, an HIV-negative comparison population is needed to assess the association of the HIV virus itself with hypertension.
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ObjectivesAs countries have scaled up access to antiretroviral therapy (ART) for HIV, attrition rates of up to 30% annually have created a large pool of individuals who initiate treatment with prior ...ART experience. Little is known about the proportion of non-naïve reinitiators within the population presenting for treatment initiation.DesignSystematic review of published articles and abstracts reporting proportions of non-naïve adult patients initiating ART in sub-Saharan Africa.Data sourcesPubMed, Embase Elsevier, Web of Science Core Collection, International AIDS Society conferences, Conference on Retroviruses and Opportunistic Infections conferences.Eligibility criteriaClinical trials and observational studies; reporting on adults in sub-Saharan Africa who initiated lifelong ART; published in English between 1 January 2018 and 11 July 2023 and with data collected after January 2016. Initiator self-report, laboratory discernment of antiretroviral metabolites, and viral suppression at initiation or in the medical record were accepted as evidence of prior exposure.Data extraction and synthesisWe captured study and sample characteristics, proportions with previous ART exposure and the indicator of previous exposure reported. We report results of each eligible study, estimate the risk of bias and identify gaps in the literature.ResultsOf 2740 articles, 11 articles describing 12 cohorts contained sufficient information for the review. Proportions of initiators with evidence of prior ART use ranged from 5% (self-report only) to 53% (presence of ART metabolites in hair or blood sample). The vast majority of screened studies did not report naïve/non-naïve status. Metrics used to determine and report non-naïve proportions were inconsistent and difficult to interpret.ConclusionsThe proportion of patients initiating HIV treatment who are truly ART naïve is not well documented. It is likely that 20%–50% of ART patients who present for ART are reinitiators. Standard reporting metrics and diligence in reporting are needed, as is research to understand the reluctance of patients to report prior ART exposure.PROSPERO registration numberCRD42022324136.
Data on invasive cervical cancer (ICC) incidence in HIV‐positive women and the effect of cervical cancer screening in sub‐Saharan Africa are scarce. We estimated i) ICC incidence rates in women (≥18 ...years) who initiated antiretroviral therapy (ART) at the Themba Lethu Clinic (TLC) in Johannesburg, South Africa, between 2004 and 2011 and ii) the effect of a Pap‐based screening program. We included 10,640 women; median age at ART initiation: 35 years interquartile range (IQR) 30–42, median CD4 count at ART initiation: 113 cells/µL (IQR 46–184). During 27,257 person‐years (pys), 138 women were diagnosed with ICC; overall incidence rate: 506/100,000 pys 95% confidence interval (CI) 428–598. The ICC incidence rate was highest (615/100,000 pys) in women who initiated ART before cervical cancer screening became available in 04/2005 and was lowest (260/100,000 pys) in women who initiated ART from 01/2009 onward when the cervical cancer screening program and access to treatment of cervical lesions was expanded adjusted hazard ratio (aHR) 0.42, 95% CI 0.20–0.87. Advanced HIV/AIDS stage (4 versus 1, aHR 1.95, 95% CI 1.17–3.24) and middle age at ART initiation (36–45 versus 18–25 years, aHR 2.51, 95% CI 1.07–5.88) were risk factors for ICC. The ICC incidence rate substantially decreased with the implementation of a Pap‐based screening program and improved access to treatment of cervical lesions. However, the risk of developing ICC after ART initiation remained high. To inform and improve ICC prevention and care for HIV‐positive women in sub‐Saharan Africa, implementation and monitoring of cervical cancer screening programs are essential.
What's new?
Data on invasive cervical cancer (ICC) incidence in HIV‐positive women and the effect of cervical cancer screening in sub‐Saharan Africa are scarce. This South African cohort analysis found that ICC incidence substantially decreased after the implementation of a Pap‐based screening program and improved access to treatment of cervical lesions. However, ICC risk remained high in women who initiated ART at low CD4 cell counts. Patient‐level monitoring of screening programs is essential to improve ICC prevention.
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South Africa is home to more people living with HIV than any other country, including nearly one in three pregnant women attending antenatal care. Access to antiretroviral therapy (ART) has increased ...substantially since the start of the national ART program in 2004, with > 95% ART coverage during pregnancy and delivery, and vertical transmission of HIV greatly reduced. However, women who initiate ART during pregnancy are at heightened risk of dropping out of care, particularly after delivery, leading to the potential for viral transmission, morbidity and mortality. It is difficult to evaluate the success of policies of expanded access to ART care, and assess continuity of care, due to the lack of a national longitudinal HIV care database. Also, patient movement between unlinked facilities. For the first time on a national level, we propose to utilize routinely-collected laboratory data to develop and validate a cohort of pregnant women living with HIV in South Africa in a way that is uniquely robust to facility transfer.
Using laboratory test data matched to facility type, we will identify entry to antenatal care to build the cohort, then describe key treatment milestones, including 1) engagement in antenatal care, 2) initiation of ART, 3) HIV viremia, and 4) continuity of HIV care in the postpartum period. Second, we will measure the effect of system-wide factors impacting continuity of care among pregnant women. We will assess policies of expanded treatment access on continuity of care using regression-discontinuity analyses. We then will assess mobility and its effect on continuity of care during and after pregnancy. Third, we will identify individual-level risk factors for loss from HIV care in order to develop targeted interventions to improve engagement in HIV care.
This work will create the world's largest national cohort of pregnant women living with HIV. This novel cohort will be a powerful tool available to policymakers, clinicians and researchers for improving our understanding of engagement in care among pregnant women in South Africa and assessing the performance of the South African national ART program in caring for pregnant women living with HIV.
N/A (not a clinical trial).
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Introduction In its 2017 revision of the global guidelines for HIV care and treatment, the World Health Organization (WHO) called for rapid or same-day initiation of antiretroviral therapy (ART) for ...eligible patients testing positive for HIV 1, with the goal of reducing losses of treatment-eligible patients from care before they receive their first dose of antiretroviral (ARV) medications 2–4. The algorithm, previously reported in 15 and illustrated in Fig 1, consisted of four screening tools, each evaluating an area of eligibility required for same-day ART initiation: (1) symptom report, (2) medical history, (3) brief physical examination, and (4) patient readiness assessment. Patients were excluded if they were pregnant (pregnancy was an exclusion criterion because treatment guidelines for pregnant women differ from those for nonpregnant adults; most pregnant women are diagnosed with HIV and initiated on ART in antenatal clinics, not general adult HIV clinics); did not intend to return to this clinic for further HIV care in the coming year; refused to be traced by phone or in person for follow-up care if test results received after the enrollment visit indicated that further care was needed; were not physically, mentally, or emotionally able to participate in the study in the opinion of the investigators or study staff; were not willing or able to provide written informed consent to participate in the study; or had previously enrolled in the same study or the SLATE I study. After exclusion of pregnant women, all study participants completed an interviewer-administered questionnaire exploring patients’ demographic characteristics, HIV history, knowledge and treatment preferences, employment and primary activities, and visit costs.
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Abstract
HIV treatment programs face challenges in identifying patients at risk for loss-to-follow-up and uncontrolled viremia. We applied predictive machine learning algorithms to anonymised, ...patient-level HIV programmatic data from two districts in South Africa, 2016–2018. We developed patient risk scores for two outcomes: (1) visit attendance ≤ 28 days of the next scheduled clinic visit and (2) suppression of the next HIV viral load (VL). Demographic, clinical, behavioral and laboratory data were investigated in multiple models as predictor variables of attending the next scheduled visit and VL results at the next test. Three classification algorithms (logistical regression, random forest and AdaBoost) were evaluated for building predictive models. Data were randomly sampled on a 70/30 split into a training and test set. The training set included a balanced set of positive and negative examples from which the classification algorithm could learn. The predictor variable data from the unseen test set were given to the model, and each predicted outcome was scored against known outcomes. Finally, we estimated performance metrics for each model in terms of sensitivity, specificity, positive and negative predictive value and area under the curve (AUC). In total, 445,636 patients were included in the retention model and 363,977 in the VL model. The predictive metric (AUC) ranged from 0.69 for attendance at the next scheduled visit to 0.76 for VL suppression, suggesting that the model correctly classified whether a scheduled visit would be attended in 2 of 3 patients and whether the VL result at the next test would be suppressed in approximately 3 of 4 patients. Variables that were important predictors of both outcomes included prior late visits, number of prior VL tests, time since their last visit, number of visits on their current regimen, age, and treatment duration. For retention, the number of visits at the current facility and the details of the next appointment date were also predictors, while for VL suppression, other predictors included the range of the previous VL value. Machine learning can identify HIV patients at risk for disengagement and unsuppressed VL. Predictive modeling can improve the targeting of interventions through differentiated models of care before patients disengage from treatment programmes, increasing cost-effectiveness and improving patient outcomes.
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While momentum for increasing treatment thresholds is growing, if patients cannot be retained in HIV care from the time of testing positive through long-term adherence to antiretroviral therapy ...(ART), such strategies may fall short of expected gains. While estimates of retention on ART exist, few cohorts have data on retention from testing positive through long-term ART care.
We explored attrition (loss or death) at the Themba Lethu HIV clinic, Johannesburg, South Africa in 3 distinct cohorts enrolled at HIV testing, pre-ART initiation, and ART initiation.
Between March 2010 and August 2012 we enrolled 380 patients testing HIV+, 206 initiating pre-ART care, and 185 initiating ART. Of the 380 patients enrolled at testing HIV-positive, 38.7% (95%CI: 33.9-43.7%) returned for eligibility staging within ≤3 months of testing. Of the 206 enrolled at pre-ART care, 84.5% (95%CI: 79.0-88.9%) were ART eligible at their first CD4 count. Of those, 87.9% (95%CI: 82.4-92.2%) initiated ART within 6 months. Among patients not ART eligible at their first CD4 count, 50.0% (95%CI: 33.1-66.9%) repeated their CD4 count within one year of the first ineligible CD4. Among the 185 patients in the ART cohort, 22 transferred out and were excluded from further analysis. Of the remaining 163, 81.0% (95%CI: 74.4-86.5%) were retained in care through two years on treatment.
Our findings from a well-resourced clinic demonstrate continual loss from all stages of HIV care and strategies to reduce attrition from all stages of care are urgently needed.
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The World Health Organization recommends "same-day" initiation of antiretroviral therapy (ART) for HIV patients who are eligible and ready. Identifying efficient, safe, and feasible procedures for ...determining same-day eligibility and readiness is now a priority. The Simplified Algorithm for Treatment Eligibility (SLATE) study evaluated a clinical algorithm that allows healthcare workers to determine eligibility for same-day treatment and to initiate ART at the patient's first clinic visit.
SLATE was an individually randomized trial at three outpatient clinics in urban settlements in Johannesburg, South Africa and three hospital clinics in western Kenya. Adult, nonpregnant, HIV-positive, ambulatory patients presenting for any HIV care, including HIV testing, but not yet on ART were enrolled and randomized to the SLATE algorithm arm or standard care. The SLATE algorithm used four screening tools-a symptom self-report, medical history questionnaire, physical examination, and readiness assessment-to ascertain eligibility for same-day initiation or refer for further care. Follow-up was by record review, and analysis was conducted by country. We report primary outcomes of 1) ART initiation ≤28 days and 2) initiation ≤28 days and retention in care ≤8 months of enrollment. From March 7, 2017 to April 17, 2018, we enrolled 600 patients (median IQR age 34 29-40 and CD4 count 286 128-490; 63% female) in South Africa and 477 patients in Kenya (median IQR age 35 29-43 and CD4 count 283 117-541; 58% female). In the intervention arm, 78% of patients initiated ≤28 days in South Africa, compared to 68% in the standard arm (risk difference RD 95% confidence interval (CI) 10% 3%-17%); in Kenya, 94% of intervention-arm patients initiated ≤28 days compared to 89% in the standard arm (6% 0.5%-11%). By 8 months in South Africa, 161/298 (54%) intervention-arm patients had initiated and were retained, compared to 146/302 (48%) in the standard arm (6% (2% to 14%). By 8 months in Kenya, the corresponding retention outcomes were identical in both arms (137/240 57% of intervention-arm patients and 136/237 57% of standard-arm patients). Limitations of the trial included limited geographic representativeness, exclusion of patients too ill to participate, missing viral load data, greater study fidelity to the algorithm than might be achieved in standard care, and secular changes in standard care over the course of the study.
In South Africa, the SLATE algorithm increased uptake of ART within 28 days by 10% and showed a numerical increase (6%) in retention at 8 months. In Kenya, the algorithm increased uptake of ART within 28 days by 6% but found no difference in retention at 8 months. Eight-month retention was poor in both arms and both countries. These results suggest that a simple structured algorithm for same-day treatment initiation procedures is feasible and can increase and accelerate ART uptake but that early retention on treatment remains problematic.
Clinicaltrials.gov NCT02891135, registered September 1, 2016. First participant enrolled March 6, 2017 in South Africa and July 13, 2017 in Kenya.
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