Does Engagement in HIV Care Affect Screening, Diagnosis, and Control of Noncommunicable Diseases in Sub-Saharan Africa? A Systematic Review and Meta-analysis.

Low- and middle-income countries are facing a growing burden of noncommunicable diseases (NCDs). Providing HIV treatment may provide opportunities to increase access to NCD services in under-resourced environments. We conducted a systematic review and meta-analysis to evaluate whether use of antiretroviral therapy (ART) was associated with increased screening, diagnosis, treatment, and control of diabetes, hypertension, chronic kidney disease, or cardiovascular disease among people living with HIV in sub-Saharan Africa (SSA). A comprehensive search of electronic literature databases for studies published between 01 January 2011 and 31 December 2022 yielded 26 studies, describing 13,570 PLWH in SSA, 61% of whom were receiving ART. Random effects models were used to calculate summary odds ratios (ORs) of the risk of diagnosis by ART status and corresponding 95% confidence intervals (95% CIs), where appropriate. ART use was associated with a small but imprecise increase in the odds of diabetes diagnosis (OR 1.07; 95% CI 0.71, 1.60) and an increase in the odds of hypertension diagnosis (OR 2.10, 95% CI 1.42, 3.09). We found minimal data on the association between ART use and screening, treatment, or control of NCDs. Despite a potentially higher NCD risk among PLWH and regional efforts to integrate NCD and HIV care, evidence to support effective care integration models is lacking.

Gaps in the type 2 diabetes care cascade: a national perspective using South Africa's National Health Laboratory Service (NHLS) database.

BACKGROUND: Research out of South Africa estimates the total unmet need for care for those with type 2 diabetes mellitus (diabetes) at 80%. We evaluated the care cascade using South Africa's National Health Laboratory Service (NHLS) database and assessed if HIV infection impacts progression through its stages. METHODS: The cohort includes patients from government facilities with their first glycated hemoglobin A1c (HbA1c) or plasma glucose (fasting (FPG); random (RPG)) measured between January 2012 to March 2015 in the NHLS. Lab-diagnosed diabetes was defined as HbA1c ≥ 6.5%, FPG ≥ 7.0mmol/l, or RPG ≥ 11.1mmol/l. Cascade stages post diagnosis were retention-in-care and glycaemic control (defined as an HbA1c < 7.0% or FPG < 8.0mmol/l or RPG < 10.0mmol/l) over 24-months. We estimated gaps at each stage nationally and by people living with HIV (PLWH) and without (PLWOH). RESULTS: Of the 373,889 patients tested for diabetes, 43.2% had an HbA1c or blood glucose measure indicating a diabetes diagnosis. Amongst those with lab-diagnosed diabetes, 30.9% were retained-in-care (based on diabetes labs) and 8.7% reached glycaemic control by 24-months. Prevalence of lab-diagnosed diabetes in PLWH was 28.6% versus 47.3% in PLWOH. Among those with lab-diagnosed diabetes, 34.3% of PLWH were retained-in-care versus 30.3% PLWOH. Among people retained-in-care, 33.8% of PLWH reached glycaemic control over 24-months versus 28.6% of PLWOH. CONCLUSIONS: In our analysis of South Africa's NHLS database, we observed that 70% of patients diagnosed with diabetes did not maintain in consistent diabetes care, with fewer than 10% reaching glycemic control within 24 months. We noted a disparity in diabetes prevalence between PLWH and PLWOH, potentially linked to different screening methods. These differences underscore the intricacies in care but also emphasize how HIV care practices could guide better management of chronic diseases like diabetes. Our results underscore the imperative for specialized strategies to bolster diabetes care in South Africa.

Integration of point-of-care screening for type 2 diabetes mellitus and hypertension into the COVID-19 vaccine programme in Johannesburg, South Africa.

BACKGROUND: South Africa grapples with a substantial burden of non-communicable diseases (NCDs), particularly type 2 diabetes (diabetes) and hypertension. However, these conditions are often underdiagnosed and poorly managed, further exacerbated by the strained primary healthcare (PHC) system and the disruptive impact of the COVID-19 pandemic. Integrating NCD screening with large-scale healthcare initiatives, such as COVID-19 vaccination campaigns, offers a potential solution, especially in low- and middle-income countries (LMICs). We investigated the feasibility and effectiveness of this integration. METHODS: A prospective cohort study was conducted at four government health facilities in Johannesburg, South Africa. NCD screening was incorporated into the COVID-19 vaccination campaign. Participants underwent COVID-19 rapid tests, blood glucose checks, blood pressure assessments, and anthropometric measurements. Those with elevated blood glucose or blood pressure values received referrals for diagnostic confirmation at local PHC centers. RESULTS: Among 1,376 participants screened, the overall diabetes prevalence was 4.1%, combining previously diagnosed cases and newly identified elevated blood glucose levels. Similarly, the hypertension prevalence was 19.4%, comprising pre-existing diagnoses and newly detected elevated blood pressure cases. Notably, 46.1% of participants displayed waist circumferences indicative of metabolic syndrome, more prevalent among females. Impressively, 7.8% of all participants screened were potentially newly diagnosed with diabetes or hypertension. Approximately 50% of individuals with elevated blood glucose or blood pressure successfully linked to follow-up care within four weeks. CONCLUSION: Our study underscores the value of utilizing even brief healthcare interactions as opportunities for screening additional health conditions, thereby aiding the identification of previously undiagnosed cases. Integrating NCD screenings into routine healthcare visits holds promise, especially in resource-constrained settings. Nonetheless, concerted efforts to strengthen care linkage are crucial for holistic NCD management and control. These findings provide actionable insights for addressing the NCD challenge and improving healthcare delivery in LMICs.

The cost of adding rapid screening for diabetes, hypertension, and COVID-19 to COVID-19 vaccination queues in Johannesburg, South Africa.

Background: Non-communicable diseases (NCDs) are responsible for 51% of total mortality in South Africa, with a rising burden of hypertension (HTN) and diabetes mellitus (DM). Incorporating NCD and COVID-19 screening into mass activities such as COVID-19 vaccination programs could offer significant long-term benefits for early detection interventions. However, there is limited knowledge of the associated costs and resources required. We evaluated the cost of integrating NCD screening and COVID-19 antigen rapid diagnostic testing (Ag-RDT) into a COVID-19 vaccination program. Methods: We conducted a prospective cost analysis at three public sector primary healthcare clinics and one academic hospital in Johannesburg, South Africa, conducting vaccinations. Participants were assessed for eligibility and recruited during May-Dec 2022. Costs were estimated from the provider perspective using a bottom-up micro-costing approach and reported in 2022 USD. Results: Of the 1,376 enrolled participants, 240 opted in to undergo a COVID-19 Ag-RDT, and none tested positive for COVID-19. 138 (10.1%) had elevated blood pressure, with 96 (70%) having no prior HTN diagnosis. 22 (1.6%) were screen-positive for DM, with 12 (55%) having no prior diagnosis. The mean and median costs per person screened for NCDs were $2.53 (SD: 3.62) and $1.70 (IQR: $1.38-$2.49), respectively. The average provider cost per person found to have elevated blood glucose levels and blood pressure was $157.99 and $25.19, respectively. Finding a new case of DM and HTN was $289.65 and $36.21, respectively. For DM and DM + HTN screen-positive participants, diagnostic tests were the main cost driver, while staff costs were the main cost driver for - and HTN screen-positive and screen-negative participants. The mean and median cost per Ag-RDT was $6.13 (SD: 0.87) and $5.95 (IQR: $5.55-$6.25), with costs driven mainly by test kit costs. Conclusions: We show the cost of finding new cases of DM and HTN in a vaccine queue, which is an essential first step in understanding the feasibility and resource requirements for such initiatives. However, there is a need for comparative economic analyses that include linkage to care and retention data to fully understand this cost and determine whether opportunistic screening should be added to general mass health activities.

Health systems performance for hypertension control using a cascade of care approach in South Africa, 2011-2017.

Hypertension is a major contributor to global morbidity and mortality. In South Africa, the government has employed a whole systems approach to address the growing burden of non-communicable diseases. We used a novel incident care cascade approach to measure changes in the South African health system's ability to manage hypertension between 2011 and 2017. We used data from Waves 1-5 of the National Income Dynamics Study (NIDS) to estimate trends in the hypertension care cascade and unmet treatment need across four successive cohorts with incident hypertension. We used a negative binomial regression to identify factors that may predict higher rates of hypertension control, controlling for socio-demographic and healthcare factors. In 2011, 19.6% (95%CI 14.2, 26.2) of individuals with incident hypertension were diagnosed, 15.4% (95%CI 10.8, 21.4) were on treatment and 7.1% had controlled blood pressure. By 2017, the proportion of individuals with diagnosed incident hypertension had increased to 24.4% (95%CI 15.9, 35.4). Increases in treatment (23.3%, 95%CI 15.0, 34.3) and control (22.1%, 95%CI 14.1, 33.0) were also observed, translating to a decrease in unmet need for hypertension care from 92.9% in 2011 to 77.9% in 2017. Multivariable regression showed that participants with incident hypertension in 2017 were 3.01 (95%CI 1.77, 5.13) times more likely to have a controlled blood pressure compared to those in 2011. Our data show that while substantial improvements in the hypertension care cascade occurred between 2011 and 2017, a large burden of unmet need remains. The greatest losses in the incident hypertension care cascades came before diagnosis. Nevertheless, whole system programming will be needed to sufficiently address significant morbidity and mortality related to having an elevated blood pressure.

Integration of point-of-care screening for type 2 diabetes mellitus and hypertension with COVID-19 rapid antigen screening in Johannesburg, South Africa.

AIMS: We sought to evaluate the yield and linkage-to-care for diabetes and hypertension screening alongside a study assessing the use of rapid antigen tests for COVID-19 in taxi ranks in Johannesburg, South Africa. METHODS: Participants were recruited from Germiston taxi rank. We recorded results of blood glucose (BG), blood pressure (BP), waist circumference, smoking status, height, and weight. Participants who had elevated BG (fasting ≥7.0; random ≥11.1mmol/L) and/or BP (diastolic ≥90 and systolic ≥140mmHg) were referred to their clinic and phoned to confirm linkage. RESULTS: 1169 participants were enrolled and screened for elevated BG and elevated BP. Combining participants with a previous diagnosis of diabetes (n = 23, 2.0%; 95% CI:1.3-2.9%) and those that had an elevated BG measurement (n = 60, 5.2%; 95% CI:4.1-6.6%) at study enrollment, we estimated an overall indicative prevalence of diabetes of 7.1% (95% CI:5.7-8.7%). When combining those with known hypertension at study enrollment (n = 124, 10.6%; 95% CI:8.9-12.5%) and those with elevated BP (n = 202; 17.3%; 95% CI:15.2-19.5%), we get an overall prevalence of hypertension of 27.9% (95% CI:25.4-30.1%). Only 30.0% of those with elevated BG and 16.3% of those with elevated BP linked-to-care. CONCLUSION: By opportunistically leveraging existing COVID-19 screening in South Africa to screen for diabetes and hypertension, 22% of participants received a potential new diagnosis. We had poor linkage-to-care following screening. Future research should evaluate options for improving linkage-to-care, and evaluate the large-scale feasibility of this simple screening tool.

Uptake of same-day initiation of HIV treatment in Malawi, South Africa, and Zambia as reported in routinely collected data: the SPRINT retrospective cohort study.

Background: Since 2017 global guidelines have recommended "same-day initiation" (SDI) of antiretroviral treatment (ART) for patients considered ready for treatment on the day of HIV diagnosis. Many countries have incorporated a SDI option into national guidelines, but SDI uptake is not well documented. We estimated average time to ART initiation at 12 public healthcare facilities in Malawi, five in South Africa, and 12 in Zambia. Methods: We sequentially enrolled patients eligible to start ART between January 2018 and June 2019 and reviewed their medical records from the point of HIV diagnosis or first HIV-related interaction with the clinic to the earlier date of treatment initiation or 6 months. We estimated the proportion of patients initiating ART on the same day or within 7, 14, 30, or 180 days of baseline. Results: We enrolled 826 patients in Malawi, 534 in South Africa, and 1,984 in Zambia. Overall, 88% of patients in Malawi, 57% in South Africa, and 91% in Zambia were offered and accepted SDI. In Malawi, most who did not receive SDI had not initiated ART ≤6 months. In South Africa, an additional 13% initiated ≤1 week, but 21% had no record of initiation ≤6 months. Among those who did initiate within 6 months in Zambia, most started ≤1 week. There were no major differences by sex. WHO Stage III/IV and tuberculosis symptoms were associated with delays in ART initiation. Conclusions: As of 2020, SDI of ART was widespread, if not nearly universal, in Malawi and Zambia but considerably less common in South Africa. Limitations of the study include pre-COVID-19 data that do not reflect pandemic adaptations and potentially missing data for Zambia. South Africa may be able to increase overall ART coverage by reducing numbers of patients who do not initiate ≤6 months. Registration: Clinicaltrials.gov ( NCT04468399; NCT04170374; NCT04470011).

Change in body weight and risk of hypertension after switching from efavirenz to dolutegravir in adults living with HIV: evidence from routine care in Johannesburg, South Africa.

Background: The integrase strand transfer inhibitor (INSTI) dolutegravir is recommended in World Health Organization guidelines, but is associated with weight gain. We evaluated weight change in patients switching from efavirenz to dolutegravir in first-line antiretroviral therapy (ART) in Johannesburg, South Africa. Methods: We conducted a prospective cohort study of adults (≥16 years) of black African ancestry with HIV who initiated ART between January 2010-December 2020. Patients were propensity score-matched 1:1 (unexposed i.e. remaining on efavirenz: exposed i.e. switched from efavirenz to dolutegravir) on sex, age, months on ART, first ART regimen, haemoglobin, body mass index (BMI), blood pressure, viral load and CD4 count. We used linear regression to assess the effect of switching from efavirenz to dolutegravir on weight change and hypertension 12 months after exposure. Findings: We matched 794 patients switching to dolutegravir to 794 remaining on efavirenz. Exposed patients had a higher mean change in weight (1.78 kg; 95% confidence interval (CI):1.04,2.52 kg) from start of follow-up to 12 months vs. unexposed. We also found a 14.2 percentage point increase (95% CI: 10.6,17.7) in the risk of hypertension in those exposed to dolutegravir vs those that remained on efavirenz. Interpretation: In a real-world population, patients gained more weight and were at higher risk of hypertension after switching from efavirenz to dolutegravir than those remaining on efavirenz. Longer follow-up is needed, however, to determine if INSTI-associated weight gain is associated with changes in non-communicable disease risk over the long-term, or whether weight gain is sustained, as seen in clinical trials. Funding: This study has been made possible by the generous support of the American People and the President's Emergency Plan for AIDS Relief (PEPFAR) through the United States Agency for International Development (USAID), under the terms of cooperative agreement cooperative Agreement 72067419CA00004. In addition to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 1K01MH105320-01A1.

Does engagement in HIV care affect screening, diagnosis, and control of noncommunicable diseases in sub-Saharan Africa? A systematic review and meta-analysis.

Objective: Low- and middle-income countries are facing a growing burden of noncommunicable diseases (NCDs). Providing HIV treatment may also provide opportunities to increase access to NCD services in under-resourced environments. We sought to investigate whether reported use of antiretroviral therapy (ART) was associated with increased screening, diagnosis, treatment, and/or control of diabetes, hypertension, chronic kidney disease, or cardiovascular disease among people living with HIV (PLWH) in sub-Saharan Africa (SSA). Design: Systematic review and meta-analysis. Methods: We searched 10 electronic literature databases for studies published between 01 January 2011 and 31 December 2022 using a comprehensive search strategy. We sought studies reporting on screening, diagnosis, treatment, and/or control of NCDs of interest by ART use among non-pregnant adults with HIV ≥16 years of age in SSA. Random effects models were used to calculate summary odds ratios (ORs) of the risk of diagnosis by ART status and corresponding 95% confidence intervals (95% CIs), where appropriate. Results: Twenty-six studies, describing 13,570 PLWH in SSA, 61% of whom were receiving ART, were included. ART use was associated with a small but imprecise increase in the odds of diabetes diagnosis (OR: 1.07; 95% CI: 0.71, 1.60) and an increase in the odds of hypertension diagnosis (OR: 2.10, 95% CI: 1.42, 3.09). We found minimal data on the association between ART use and screening, treatment, or control of NCDs. Conclusion: Despite a potentially higher NCD risk among PLWH and regional efforts to integrate NCD and HIV care, evidence to support effective care integration models is lacking.

Evaluation of the impact of PEPFAR transition on retention in care in South Africa's Western Cape.

Background: Research on the impact of the PEPFAR transition in South Africa (SA) in 2012 found varying results in retention in care (RIC) of people living with HIV (PLWH). Objectives: We investigated the factors that impacted RIC during the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) transition in Western Cape, South Africa in 2012. Methods: We used aggregate data from 61 facilities supported by four non-governmental organizations from to 2007-2015. The main outcome was RIC at 12-months after antiretroviral therapy initiation for two time periods. We used quantile regression to estimate the effect of the PEPFAR pull-out and other predictors on RIC. The models were adjusted for various covariates. Results: Regression models (50th quantile) for 12-month RIC showed a 4.6% (95%CI: -8.4, -0.8%) decline in RIC post direct service. Facilities supported by Anova/Kheth'impilo fared worst post PEFPAR; a decline in RIC of (-5.8%; 95% CI: -9.7, -1.8%), while that'sit fared best (6.3% increase in RIC; 95% CI:2.5,10.1%). There was a decrease in RIC when comparing urban to rural areas (-5.8%; 95% CI: -10.1, -1.5%). City of Cape town combined with Western Cape Government Health facilities showed a substantial decrease (-9.1%; 95% CI: -12.3, -5.9%), while community health clinic (vs. primary health clinic) declined slightly (-4.4; 95% CI: -9.6, 0.9%) in RIC. We observed no RIC difference by facility size and a slight increase when two or more human resources transitioned from PEPFAR to the government. Conclusions: When PEPFAR funding decreased in 2012, there was a decrease in RIC. To ensure the continuity of HIV care when a major funder withdraws sufficient and stable transition resources, investment in organizations that understand the local context, joint planning, and coordination are required.

Cohort profile: the South African National Health Laboratory Service (NHLS) National HIV Cohort.

PURPOSE: South Africa's National Health Laboratory Service (NHLS) National HIV Cohort was established in 2015 to facilitate monitoring, evaluation and research on South Africa's National HIV Treatment Programme. In South Africa, 84.8% of people living with HIV know their HIV status; 70.7% who know their status are on ART; and 87.4% on ART are virologically suppressed. PARTICIPANTS: The NHLS National HIV Cohort includes the laboratory data of nearly all patients receiving HIV care in the public sector since April 2004. Patients are included in the cohort if they have received a CD4 count or HIV RNA viral load (VL) test. Using an anonymised unique patient identifier that we have developed and validated to linked test results, we observe patients prospectively through their laboratory results as they receive HIV care and treatment. Patients in HIV care are seen for laboratory monitoring every 6-12 months. Data collected include age, sex, facility location and test results for CD4 counts, VLs and laboratory tests used to screen for potential treatment complications. FINDINGS TO DATE: From April 2004 to April 2018, 63 million CD4 count and VL tests were conducted at 5483 facilities. 12.6 million unique patients had at least one CD4 count or VL, indicating they had accessed HIV care, and 7.1 million patients had a VL test indicating they had started antiretroviral therapy. The creation of NHLS National HIV Cohort has enabled longitudinal research on all lab-monitored patients in South Africa's national HIV programme, including analyses of (1) patient health at presentation; (2) care outcomes such as 'CD4 recovery', 'retention in care' and 'viral resuppression'; (3) patterns of transfer and re-entry into care; (4) facility-level variation in care outcomes; and (5) impacts of policies and guideline changes. FUTURE PLANS: Continuous updating of the cohort, integration with available clinical data, and expansion to include tuberculosis and other lab-monitored comorbidities.

Retention in care and viral suppression after same-day ART initiation: One-year outcomes of the SLATE I and II individually randomized clinical trials in South Africa.

INTRODUCTION: Same-day initiation (SDI) of antiretroviral therapy (ART) for HIV consistently increases ART uptake, but concerns remain about higher attrition from care after initiation. We analysed 12-month retention in the SLATE SDI trials. METHODS: SLATE I (Simplified Algorithms for Treatment Eligibility I, enrolment 06 March-28 July 2017) and SLATE II (enrolment 14 March-18 September 2018) were individually randomized trials at public outpatient clinics in Johannesburg that enrolled patients not yet on ART and administered the SLATE I or II algorithm. This included a symptom self-report, medical history, brief physical examination and readiness questionnaire to assess the eligibility for SDI. The studies compared the offer of SDI using the SLATE algorithms to standard of care initiation procedures. ART uptake and early retention were previously reported. Using routine clinic records, we conducted a pooled analysis of retention in care and HIV viral suppression 14 months after study enrolment, a time point equivalent to 12 months potential on ART, with an additional month allowed on either end to initiate ART and to return for the 12-month visit. RESULTS AND DISCUSSION: We enrolled 1193 study participants (standard arms, n = 599, 50%; intervention arms, n = 594, 50%) and analysed by originally assigned groups. By 14 months after enrolment, 50% of intervention arm patients and 46% of standard arm patients remained in care at the initiating site (crude risk difference 4% (95% confidence interval -1%-10%); crude relative risk 1.10 (0.97-1.23), with similar viral suppression between arms. Observed attrition from care at site by 14 months was high in both study arms, but we found no evidence that the offer of SDI led to greater overall attrition or lower rates of viral suppression 1 year after starting ART and may have generated small improvements. SDI may have shifted some attrition from before to after dispensing of the first dose of medication. CONCLUSIONS: An offer of SDI of ART, following a carefully designed protocol to identify patients who are eligible and ready to start treatment, is not inherently associated with an overall increase in patient attrition from care and leads to similar rates of viral suppression. TRIAL REGISTRATION: Clinicaltrials.gov NCT02891135, registered 01 September 2016. First participant enrolled 06 March 2017 in South Africa. Clinicaltrials.gov NCT03315013, registered 19 October 2017. First participant enrolled 14 March 2018.

An underappreciated misclassification mechanism: implications of nondifferential dependent misclassification of covariate and exposure.

Misclassification is a pervasive problem in assessing relations between exposures and outcomes. While some attention has been paid to the impact of dependence in measurement error between exposures and outcomes, there is little awareness of the potential impact of dependent error between exposures and covariates, despite the fact that this latter dependency may occur much more frequently, for example, when both are assessed by questionnaire. We explored the impact of nondifferential dependent exposure-confounder misclassification bias by simulating a dichotomous exposure (E), disease (D) and covariate (C) with varying degrees of non-differential dependent misclassification between C and E. We demonstrate that under plausible scenarios, an adjusted association can be a poorer estimate of the true association than the crude. Correlated errors in the measurement of covariate and exposure distort the covariate-exposure, covariate-outcome and exposure-outcome associations creating observed associations that can be greater than, less than, or in the opposite direction of the true associations. Under these circumstances adjusted associations may not be bounded by the crude association and true effect, as would be expected with nondifferential independent confounder misclassification. The degree and direction of distortion depends on the amount of dependent error, prevalence of covariate and exposure, and magnitude of true effect.

Patient Perspectives of Quality of the Same-Day Antiretroviral Therapy Initiation Process in Gauteng Province, South Africa: Qualitative Dominant Mixed-Methods Analysis of the SLATE II Trial.

BACKGROUND: HIV patients in South Africa continue to report operational barriers to starting antiretroviral therapy (ART). In the Simplified Algorithm for Treatment Eligibility (SLATE) II trial, same-day initiation (SDI) of ART increased the number of patients commencing ART and achieving HIV viral suppression by using a screening tool to distinguish between patients eligible for SDI and those requiring additional care before starting treatment. We conducted a mixed-methods evaluation to explore trial patients' perceptions and experiences of SDI. METHODS: SLATE II was implemented at three urban, public primary health care clinics in Gauteng Province, South Africa. We conducted a short quantitative survey and in-depth interviews among a purposive sample of 89 of the 593 trial participants in the intervention and standard arms, using a mixed inductive-deductive framework approach. RESULTS: Nearly all respondents (95%) were satisfied with their care, despite reporting clinic wait times of ≥ 3 h (72%). Intervention patients found the initiation process to be easy; standard patients found it complicated and were frustrated with being shuffled around the clinic. No intervention arm patients felt that SDI was "too fast" or indicated a preference for a more gradual process. Both groups highlighted the need for good counselling and non-judgmental, respectful staff. Standard patients suggested improving patient-provider relations, strengthening counselling, reducing wait times, and minimising referrals. CONCLUSIONS: While it is difficult to untangle the role of providers from that of the SLATE algorithm in influencing patient experiences, adoption of SLATE II implementation procedures could improve patient experience of treatment initiation. TRIAL REGISTRATION: Clinicaltrials.gov NCT03315013, registered October 19, 2017.

A clinical algorithm for same-day HIV treatment initiation in settings with high TB symptom prevalence in South Africa: The SLATE II individually randomized clinical trial.

BACKGROUND: Many countries encourage same-day initiation of antiretroviral therapy (ART), but evidence on eligibility for same-day initiation, how best to implement it, and its impact on outcomes remains scarce. Building on the Simplified Algorithm for Treatment Eligibility (SLATE) I trial, in which nearly half of participants were ineligible for same-day initiation mainly because of TB symptoms, the study evaluated the revised SLATE II algorithm, which allowed same-day initiation for patients with mild TB symptoms and other less serious reasons for delay. METHODS AND FINDINGS: SLATE II was a nonblinded, 1:1 individually randomized pragmatic trial at three primary healthcare clinics in Johannesburg, South Africa. It randomized adult patients presenting for an HIV test or any HIV care but not yet on ART. Intervention arm patients were assessed with a symptom screen, medical history, brief physical examination, and readiness questionnaire to distinguish between patients eligible for immediate ART dispensing and those requiring further care before initiation. Standard arm patients received usual care. Follow-up was by review of routine clinic records. Primary outcomes were (1) ART initiation in ≤7 days and (2) ART initiation in ≤28 days and retention in care at 8 months (composite outcome). From 14 March to 18 September 2018, 593 adult HIV+, nonpregnant patients were enrolled (median interquartile range [IQR] age 35 [29-43]; 63% (n = 373) female; median CD4 count 293 [133-487]). Half of study patients (n = 295) presented with TB symptoms, whereas only 13 (4%) standard arm and 7 (2%) intervention arm patients tested positive for TB disease. Among 140 intervention arm patients with TB symptoms, 72% were eligible for same-day initiation. Initiation was higher in the intervention (n = 296) versus standard arm (n = 297) by 7 days (91% versus 68%; risk difference [RD] 23% [95% confidence interval (CI) 17%-29%]) and 28 days (94% versus 82%; RD 12% [7%-17%]) after enrollment. In total, 87% of intervention and 38% of standard arm patients initiated on the same day. By 8 months after study enrollment, 74% (220/296) of intervention and 59% (175/297) of standard arm patients had both initiated ART in ≤28 days and been retained in care (RD 15% [7%-23%]). Among the 41% of participants with viral load results available, suppression was 90% in the standard arm and 92% in the intervention arm among patients initiated in ≤28 days. No ART-associated adverse events were reported after initiation; two intervention and four standard arm patients were reported to have died during passive follow-up. Limitations of the study included limited geographic generalizability, exclusion of patients too sick to consent, fluctuations in procedures in the standard arm over the course of the study, high fidelity to the trial protocol by study staff, and the possibility of overestimating loss to follow-up due to data constraints. CONCLUSIONS: More than 85% of patients presenting for HIV testing or care, including those newly diagnosed, were eligible and ready for same-day initiation under the SLATE II algorithm. The algorithm increased initiation within 7 days without appearing to compromise retention and viral suppression at 8 months, offering a practical and acceptable approach that can be widely and immediately utilized by existing providers. TRIAL REGISTRATION: Clinicaltrials.gov NCT03315013, registered 19 October 2017. First participant enrolled 14 March 2018.

Delays in repeat HIV viral load testing for those with elevated viral loads: a national perspective from South Africa.

INTRODUCTION: In South Africa, HIV patients with an elevated viral load (VL) should receive repeat VL testing after adherence counselling. We set out to use a national HIV Cohort to describe time to repeat viral load testing across South Africa and identify predictors of time to repeat testing. METHODS: We conducted a cohort study of prospectively collected laboratory data. HIV treatment guidelines have changed over time in South Africa, but call for repeat VL testing within six months if 400 to 1000 copies/mL and two to three months if >1000 copies/mL. We included patients with suppressed viral loads (indicating they are on ART) and a first elevated VL (>400 copies/mL) between April 2004 and December 2014. Follow-up began at first elevated VL and continued until repeat testing, loss to follow-up or December 2016. We calculated adjusted hazard ratios (aHR) using Cox proportional hazard models. RESULTS: Of 371,648 patients with a VL > 400, 83.9% (311,790) had a repeat VL, in a median (IQR) of 7.0 (4.1 to 12.2) months. Of those with a first viral load 400 to 1000 copies/mL, 56.4% had a repeat VL within guideline recommended six months (defined as up to nine months), whereas among those >1000 copies/mL only 47.7% had a repeat viral load within guideline recommended two to three months (defined as up to six months). We found a small increase in repeat testing associated with higher VL value (aHR 1.11; 95% CI: 1.10 to 1.12 comparing >1000 vs 400 to 1000 copies/mL) and very low CD4 counts at first elevated VL (aHR 1.16; 95% CI: 1.13 to 1.19 comparing CD4 < 50 vs <500 cells/mm3 ). We also found strong variation in time to repeat VL testing by province. CONCLUSIONS: Median time to repeat viral load testing for those with an elevated viral load was longer than guidelines recommend. Future work should identify whether delays are due to patient or provider factors.

Impact of Viral Load Monitoring on Retention and Viral Suppression: A Regression Discontinuity Analysis of South Africa's National Laboratory Cohort.

South African guidelines recommend repeat viral load testing within 6 months when human immunodeficiency virus (HIV) viral loads exceed 1,000 copies/mL. We assessed whether South African facilities follow viral load monitoring guidelines and whether guidelines improve HIV-related outcomes, using a regression discontinuity design in a national HIV cohort of 174,574 patients (2013-2015). We assessed whether patients with viral loads just above versus just below 1,000 copies/mL were more likely to receive repeat testing in 6 months, and we compared differences in clinic transfers, retention, and viral suppression. The majority (67%) of patients with viral loads of >1,000 copies/mL did not receive repeat testing within 6 months, and these patients were 8.0% (95% confidence interval (CI): 6.2, 9.7) more likely to receive repeat testing compared with ≤1,000 copies/mL. Eligibility for repeat testing (>1,000 copies/mL) was associated with greater 12-month retention (risk difference = 2.9%, 95% CI: 0.6, 5.2) and combined suppression and retention (risk difference = 5.8%, 95% CI: 3.0, 8.6). Patients with viral loads of >1,000 copies/mL who actually received repeat testing were 85.2% more likely to be both retained and virally suppressed at 12 months (95% CI: 35.9, 100.0). Viral load monitoring might improve patient outcomes, but most patients with elevated viral loads do not receive monitoring within recommended timelines.

Growth curve modelling to determine distinct BMI trajectory groups in HIV-positive adults on antiretroviral therapy in South Africa.

OBJECTIVE: Obesity is a major long-term concern in HIV-positive patients due to the pathogenic link between obesity and noncommunicable chronic diseases (NCDs). We aim to characterize changes in BMI over time on antiretroviral therapy (ART) and investigate the association between weight gain and survival in South Africa. DESIGN AND METHODS: A prospective cohort study among HIV-positive adults on first-line ART between April 2004 and 2015 in Johannesburg, South Africa. We used latent-class growth modelling (adjusted for age, sex and CD4 cell count) to identify groups of individuals with similar patterns of change in BMI over time. RESULTS: Eleven thousand, two hundred and sixty-three patients were included. The best fit model involved two linear and two quadratic trajectories. Thirty-five percent of patients were categorized into group one (mean BMI at ART initiation, 20.4 kg/m; mean BMI after 8 years of follow-up, 20.9 kg/m), 38% into group two (24.5-26.2 kg/m), 21% into group three (29.5-32.6 kg/m) and 6% into group four (36.5-40.0 kg/m). Over the 8 years of follow-up, 6% of our cohort went down in BMI standard category, while 45% went up. The largest increase occurred in the first 12 months on ART. In years 2 through 8, we saw a more gradual increase in BMI. CONCLUSION: The largest gain in BMI in HIV patients occurred in the first year on ART. During follow-up, over 50% of our population changed BMI categories putting them at an increased risk for NCDs. Consistent counselling on nutritional and lifestyle changes could help improve ART patients' long-term health outcomes.

Who is seeking antiretroviral treatment for HIV now? Characteristics of patients presenting in Kenya and South Africa in 2017-2018.

INTRODUCTION: Many African countries have had at least two years' experience with universal treatment eligibility for HIV. The literature contains few descriptions, though, of populations starting treatment since adoption of universal eligibility. Using baseline data from a clinical trial of same-day ART initiation, we describe the populations presenting for HIV testing or care at study clinics in Kenya and South Africa in 2017-18, during the era of same-day initiation. METHODS: The Simplified Algorithm for Treatment Eligibility (SLATE) trials in Kenya (SLATE I) and South Africa (SLATE II) were multicenter, non-blinded, individually randomized, pragmatic trials evaluating simple, standardized algorithms to determine eligibility for same-day initiation of ART without relying on laboratory results, point of care tests or multiple clinic visits. In Kenya, enrolment occurred during July 2017 to April 2018. In South Africa, enrolment occurred during March to September 2018. We describe demographic, socioeconomic and clinical characteristics of patients randomized to the same-day initiation arm for both studies. RESULTS AND DISCUSSION: A total of 240 and 296 participants were enrolled in Kenya and South Africa. The majority were female (59% and 64% respectively), with a median age of 35 years. In both countries, most subjects were newly diagnosed with HIV on the day of enrolment (62%, 55%), believed they already had adequate knowledge to begin ART (78%, 68%), and preferred to start ART immediately (same-day) (98% in both countries). About 40% of all patients had at least one symptom related to tuberculosis (cough, fever, night sweats, weight loss) and/or cryptococcal meningitis (continuous headache). More than a third of patients (37%, 36%) presented with advanced disease (CD4 <200 cells/mm3 ), a fifth presented with very advanced disease (CD4 < 100), and approximately 1 in 20 presented with very advanced disease and were asymptomatic. CONCLUSIONS: Despite >2 years of universal eligibility for ART in Kenya and South Africa, in 2017-2018 more than half of HIV-positive patients presenting at public sector clinics were not yet aware of their status, and more than a third presented for care with advanced HIV disease. These proportions remain similar to those observed before the introduction of universal eligibility.

Simplified clinical algorithm for identifying patients eligible for same-day HIV treatment initiation (SLATE): Results from an individually randomized trial in South Africa and Kenya.

BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: Clinicaltrials.gov NCT02891135, registered September 1, 2016. First participant enrolled March 6, 2017 in South Africa and July 13, 2017 in Kenya.