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1 | INTRODUCTION Since 2017, when the World Health Organization recommended 'same-day initiation' (SDI) of antiretroviral therapy (ART) for people living with HIV who are ready for treatment on the [...], 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 -196-10%); 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. Keywords: implementation science; randomized trial; retention; same-day ART; South Africa; viral suppression

1 | INTRODUCTION South Africa has experienced a dramatic increase in the number of patients initiating antiretroviral therapy (ART) since the start of the national HIV treatment programme in 2004. [...], Introduction: Policies for Universal Test & Treat (UTT) and same-day initiation (SDI) of antiretroviral therapy (ART) were instituted in South Africa in September 2016 and 2017 respectively. However, there is limited evidence on whether these changes have improved patient retention after HIV diagnosis. Methods: We enrolled three cohorts of newly diagnosed HIV-infected adults from two primary health clinics in Johannesburg from April to November 2015 (Pre-UTT, N = 144), May-September 2017 (UTT, N = 178) and October-December 2017 (SDI, N = 88). A baseline survey was administered immediately after HIV diagnosis after which follow-up using clinical records (paper charts, electronic health records and laboratory data) ensued for 12 months. The primary outcome was patient loss to follow-up (being >90 days late for the last scheduled appointment) at 12 months post-HIV diagnosis. We modelled attrition across HIV policy periods with Cox proportional hazard regression. Results: Overall, 410 of 580 screened HIV-positive patients were enrolled. Overall, attrition at 12 months was 30% lower in the UTT guideline period (38.2%) compared to pre-UTT (47.2%, aHR 0.7, 95% CI: 0.5 to 1.0). However, the total attrition was similar between the SDI (47.7%) and pre-UTT cohorts (aHR 1.0, 95% CI: 0.7 to 1.5). Older age at HIV diagnosis (aHR 0.5 for [greater than or equal to]40 vs. 25 to 29 years, 95% CI: 0.3 to 0.8) and being in a non-marital relationship (aHR 0.5 vs. being single, 95% CI: 0.3 to 0.8) protected against LTFU at 12 months, whereas LTFU rates increased with longer travel time to the diagnosing clinic (aHR 1.8 for [greater than or equal to]30 minutes vs. [less than or equal to]15 minutes, 95% CI: 1.1 to 3.1). In analyses adjusted for the time-varying ART initiation status, compared to the pre-ART period of care, the hazard of on-ART LTFU was 90% higher among participants diagnosed under the SDI policy compared to pre-UTT (aHR 1.9, 95% CI: 1.1 to 2.9). Conclusions: Overall, nearly two-fifths of HIV positive patients are likely to disengage from care by 12 months after HIV diagnosis under the new SDI policy. Furthermore, the increase in on-ART patient attrition after the introduction of the SDI policy is cause for concern. Further research is needed to determine the best way for rapidly initiating patients on ART and also reducing long-term attrition from care. Keywords: HIV; attrition from HIV care; ART adherence; Universal Test and Treat; same-day initiation of ART; HIV; ART access; attrition from HIV care; ART adherence; Universal Test and Treat; same-day initiation of ART

1 | INTRODUCTION After patients initiate antiretroviral therapy (ART) for treatment of HIV, laboratory monitoring of patient progress is critical to ensuring treatment success. For individual patients, this means reaching [...], 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 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. Keywords: viral load; viral suppression; monitoring; retention; laboratory testing; cohort; HIV

1 | INTRODUCTION The World Health Organization's (WHO) 2016 consolidated guidelines recommended that all adults living with HIV should initiate antiretroviral treatment (ART) regardless of WHO clinical stage or CD4 [...], Introduction: Many African countries have had at least two years&apos; experience with universal treatment eligibility for HIV. The iterature contains few descriptions, though, of populations starting treatment since adoption of universal eligibility. Using base-ine 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 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 universa eligibility. Keywords: HIV/AIDS; presenting for care; patient characteristics; randomized trial; SLATE I Kenya; SLATE II South Africa

1 | INTRODUCTION The 2015 World Health Organization (WHO) recommendation to offer treatment to all HIV-positive persons regardless of CD4 count [1] has compressed the HIV care cascade, removing several [...], Introduction: South Africa is moving into a new era of HIV treatment with "treat all" policies where people may be on treatment for most of their lives. We need to understand treatment outcomes and facilitators of long-term antiretroviral treatment (ART) adherence and retention-in-care in the South African context. In one of the first studies to investigate long-term treatment outcomes in South Africa, we aimed to describe ten-year patient outcomes at a large public-sector HIV clinic in Johannesburg and explore patient experiences of the treatment programme over this time in order to ascertain factors that may aid or hinder long-term adherence and retention. Methods: We conducted a cohort analysis (n = 6644) and in-depth interviews (n = 24) among HIV-positive adults initiating first-line ART between April 2004 and March 2007. Using clinical records, we ascertained twelve-month and ten-year all-cause mortality and loss to follow-up (LTF). Cox proportional hazards regression was used to identify baseline predictors of attrition (mortality and LTF (>3 months late for the last scheduled visit)) at twelve months and ten years. Twenty-four patients were purposively selected and interviewed to explore treatment programme experiences over ten years on ART. Results: Excluding transfers, 79.5% (95% confidence intervals (CI): 78.5 to 80.5) of the cohort were alive, in care at twelve months dropping to 35.1% (95% CI: 33.7 to 36.4) at ten years. Over 44% of deaths occurred within 12 months. Tenyear all-cause mortality increased, while LTF decreased slightly, with age. Year and age at ART initiation, sex, nationality, baseline CD4 count, anaemia, body mass index and initiating regimen were predictors of ten-year attrition. Among patients interviewed, the pretreatment clinic environment, feelings of gratitude and good fortune, support networks, and self-efficacy were facilitators of care; side effects, travel and worsening clinical conditions were barriers. Participants were generally optimistic about their futures and were committed to continued care. Conclusions: This study demonstrates the complexities of long-term chronic HIV treatment with declining all-cause mortality and increasing LTF over ten years. Barriers to long-term retention still present a significant challenge. As more people become eligible for ART in South Africa under "treatment for all," new healthcare delivery challenges will arise; interventions are needed to ensure long-term programme successes continue. Keywords: South Africa; HIV/AIDS; long-term ART treatment outcomes; loss to follow-up; attrition; adherence

Author(s): Jacob Bor 1,2,3,*, Anna Gage 4, Dorina Onoya 2, Mhairi Maskew 2, Yorghos Tripodis 5, Matthew P. Fox 1,2,3, Adrian Puren 6, Sergio Carmona 6, Koleka Mlisana 6, William [...], Background Despite widespread availability of HIV treatment, patient outcomes differ across facilities. We propose and evaluate an approach to measure quality of HIV care at health facilities in South Africa&apos;s national HIV program using routine laboratory data. Methods and findings Data were extracted from South Africa&apos;s National Health Laboratory Service (NHLS) Corporate Data Warehouse. All CD4 counts, viral loads (VLs), and other laboratory tests used in HIV monitoring were linked, creating a validated patient identifier. We constructed longitudinal HIV care cascades for all patients in the national HIV program, excluding data from the Western Cape and very small facilities. We then estimated for each facility in each year (2011 to 2015) the following cascade measures identified a priori as reflecting quality of HIV care: median CD4 count among new patients; retention 12 months after presentation; 12-month retention among patients established in care; viral suppression; CD4 recovery; monitoring after an elevated VL. We used factor analysis to identify an underlying measure of quality of care, and we assessed the persistence of this quality measure over time. We then assessed spatiotemporal variation and facility and population predictors in a multivariable regression context. We analyzed data on 3,265 facilities with a median (IQR) annual size of 441 (189 to 988) lab-monitored HIV patients. Retention 12 months after presentation increased from 42% to 47% during the study period, and viral suppression increased from 66% to 79%, although there was substantial variability across facilities. We identified an underlying measure of quality of HIV care that correlated with all cascade measures except median CD4 count at presentation. Averaging across the 5 years of data, this quality score attained a reliability of 0.84. Quality was higher for clinics (versus hospitals), in rural (versus urban) areas, and for larger facilities. Quality was lower in high-poverty areas but was not independently associated with percent Black. Quality increased by 0.49 (95% CI 0.46 to 0.53) standard deviations from 2011 to 2015, and there was evidence of geospatial autocorrelation (p < 0.001). The study&apos;s limitations include an inability to fully adjust for underlying patient risk, reliance on laboratory data which do not capture all relevant domains of quality, potential for errors in record linkage, and the omission of Western Cape. Conclusions We observed persistent differences in HIV care and treatment outcomes across South African facilities. Targeting low-performing facilities for additional support could reduce overall burden of disease.

Author(s): Sydney Rosen 1,2,*, Mhairi Maskew 2, Bruce A. Larson 1, Alana T. Brennan 1,2,3, Isaac Tsikhutsu 4,5, Matthew P. Fox 1,2,3, Lungisile Vezi 2, Margaret Bii 4,5, Willem D. [...], 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&apos;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 [less than or equal to]28 days and 2) initiation [less than or equal to]28 days and retention in care [less than or equal to]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 [less than or equal to]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 [less than or equal to]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.

Author(s): Matthew P. Fox 1,2,3,*, Jacob Bor 2, Alana T. Brennan 2,3, William B. MacLeod 2,3, Mhairi Maskew 3, Wendy S. Stevens 4,5, Sergio Carmona 4 Introduction In 2015, the [...], Background 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&apos;s national HIV program. Methods and findings Patients receiving care in South Africa&apos;s national HIV program are monitored through regular CD4 count and viral load testing. South Africa&apos;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&apos;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/mm.sup.3 (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&apos;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. Conclusions 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.

Background: As stavudine remains an important and widely prescribed drug in resource‐limited settings, the effect of a reduced dose of stavudine (from 40 mg to 30 mg) on outcomes of highly active antiretroviral therapy (HAART) remains an important public health question. Methods: We analyzed prospectively collected data from the Themba Lethu Clinic in Johannesburg, South Africa. We assessed the relationship between stavudine dose and six‐ and/or 12‐month outcomes of stavudine substitution, failure to suppress viral load to below 400 copies/ml, development of peripheral neuropathy, lipoatrophy and hyperlactatemia/lactic acidosis. Since individuals with a baseline weight of less than 60 kg were expected to have received the same dose of stavudine throughout the study period, analysis was restricted to individuals who weighed 60 kg or more at baseline. Data were analyzed using logistic regression. Results: Between 1 April 2004 and 30 September 2009, 3910 patients were initiated on antiretroviral therapy (ART) with a recorded stavudine dose and were included in the analysis. Of these, 2445 (62.5%) received a 40 mg stavudine dose while 1565 (37.5%) received 30 mg. In multivariate analysis, patients receiving a 40 mg dose were more likely to discontinue stavudine use (adjusted odds ratio, OR 1.71; 95% confidence limits, CI 1.13‐2.57) than those receiving 30 mg by 12 months on ART. Additionally, patients receiving 40 mg doses of stavudine were more likely to report peripheral neuropathy (OR 3.12; 95% CI 1.86‐5.25), lipoatrophy (OR 11.8; 95% CI 3.2‐43.8) and hyperlactatemia/lactic acidosis (OR 8.37; 95% CI 3.83‐18.29) in the same time period. Failure to suppress HIV viral load within 12 months of HAART initiation was somewhat more common among those given 40 mg doses (OR 1.62; 95% CI 0.88, 2.97) although this result lacked precision. Sensitivity analyses accounting for death and loss to follow up generally supported these estimates. Conclusions: Lower stavudine dosage is associated with fewer reports of several stavudine‐associated adverse events and also a lower risk of stavudine discontinuation within the first year on ART., Background Stavudine (d4T) is a nucleoside analogue that has been widely used as part of highly active antiretroviral therapy (HAART). Despite being highly effective [1,2], use of stavudine‐based regimens has [...]

Background: Adherence to care and treatment are essential for HIV‐infected individuals to benefit from antiretroviral therapy (ART). We sought to quantify the effects on treatment outcomes of missing visits soon after initiating ART. Methods: We analyzed data from HIV‐infected patients initiating ART at Themba Lethu Clinic, Johannesburg, South Africa, from April 2004 to August 2008. We used log‐binomial regression to evaluate the relative risk of missing visits during the first six months of ART on immunological response and virologic suppression. Cox models were used to evaluate the relationship between missed visits and mortality and loss to follow up over 12 months. Results: Of 4476 patients, 65% missed no visits, while 26% missed one visit, 7% missed two and 1.6% missed three or more visits during the first six months on treatment. Patients who missed three or more medical or antiretroviral (ARV) visits had a two‐fold increased risk of poor CD4 response by six months, while the risk of failing to achieve virologic suppression by six months increased two‐ to five‐fold among patients who missed two and three or more medical or ARV visits. Adjusted Cox models showed that patients who missed two (HR 2.1; 95% CI: 1.0‐4.3) and three or more (HR 4.7; 95% CI: 1.4‐16.2) medical visits had an increased risk of death, while those who missed two ARV (HR 3.8; 95% CI: 2.5‐5.8) or three or more medical (HR 3.0; 95% CI: 1.1‐8.1) visits had an increased risk of loss to follow up. Conclusions: Thirty‐five percent of patients missed one or more visits in the first six months on treatment, increasing their risk of poorer outcomes. These patients could be targeted for additional adherence counselling to help improve ART outcomes., Background Expansion of antiretroviral therapy (ART) treatment programmes in resource‐limited settings has helped to substantially improve patient outcomes on ART [1]; however, programmatic outcomes, such as death and loss to [...]