Costs and outcomes of routine HIV oral pre-exposure prophylaxis implementation across different service delivery models and key populations in South Africa.

Background: Oral pre-exposure prophylaxis (PrEP) is a highly efficacious biomedical HIV prevention tool, yet despite being recommended by the World Health Organization (WHO) since 2015, uptake and persistence remain limited in much of the world, including sub Saharan Africa (SSA). There is a dearth of evidence-based interventions to improve PrEP uptake and persistence in SSA, and the full costs of PrEP programs implemented in routine care settings remain largely unknown. This study aimed to evaluate the cost of delivery of daily oral PrEP, and associated outcomes, to different key and priority populations across different service delivery models (SDMs) in South Africa. Methods: We conducted bottom-up micro-costing of PrEP service delivery from the provider perspective within twelve urban SDMs providing routine PrEP services to various key and propriety populations in Gauteng and KwaZulu-Natal provinces in South Africa. The SDMs included in-facility and outreach models that focused on men who have sex with men (MSM), female sex workers (FSW) and adolescent girls and young women (AGYW). We identified all within- and above-facility activities supporting PrEP delivery, obtained input costs from program budgets, expenditure records and staff interviews, and determined individual resource usage between February 2019 and February 2020 through retrospective medical record review. Our primary outcome was PrEP coverage at six months (defined as having sufficient PrEP drug dispensed at the last visit to be covered at six months post PrEP-initiation). A subset (N=633) of all enrolled subjects had the potential for 12 months of follow-up and were included in a 12-month outcome analysis. We report the cost per client initiated on PrEP in 2021 United States Dollars (USD). Findings: We collected medical record data from 1,281 people who initiated PrEP at 12 SDMs between February and August 2019 and had at least six months of potential follow-up. The average number of visits was 2.3 for in-facility models and 1.5 for outreach models and 3,086 months of PrEP was dispensed. PrEP coverage at six months varied greatly across SDMs, from 41.8% at one MSM-focused fixed clinic to 0% in an MSM-focused outreach model. In general, in-facility programs had higher six-month coverage than outreach programs. Across all SDMs with PrEP clients with potential for 12 months of follow-up (n=633), PrEP coverage at 12 months was 13.6%, with variability between SDMs. The average six-month cost per client initiated on PrEP ranged from $29 to $590, with higher average costs generally observed for the in-facility programs ($152 in-facility versus $84 for outreach). The average monthly cost per PrEP client who had six-month PrEP coverage ranged from $18 to $160 dependent on SDM. Interpretation: This study is an important addition to the PrEP outcome and cost literature in the SSA region. Results show that costs and outcomes vary considerably across different SDMs and populations in real world PrEP programs and provide crucial information for further scale-up of the oral PrEP program in South Africa and the greater SSA region.

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).

One Pill, Once a Day: Simplified Treatment Regimens and Retention in HIV Care.

Simplified drug regimens may improve retention in care for persons with chronic diseases. In April 2013, South Africa adopted a once-daily single-pill human immunodeficiency virus (HIV) treatment regimen as the standard of care, replacing a multiple-pill regimen. Because the regimens had similar biological efficacy, the shift to single-pill therapy offered a real-world test of the impact of simplified drug-delivery mechanisms on patient behavior. Using a quasi-experimental regression discontinuity design, we assessed retention in care among patients starting HIV treatment just before and just after the guideline change. The study included 4,484 patients starting treatment at a large public sector clinic in Johannesburg, South Africa. The share of patients prescribed a single-pill regimen increased by over 40 percentage points between March and April 2013. Initiating treatment after the policy change was associated with 11.7-percentage-points' higher retention at 12 months (95% confidence interval: -2.2, 29.4). Findings were robust to different measures of retention, different bandwidths, and different statistical models. Patients starting treatment early in HIV infection-a key population in the test-and-treat era-experienced the greatest improvements in retention from single-pill regimens.

HIV Treatment Outcomes Among Patients Initiated on Antiretroviral Therapy Pre and Post-Universal Test and Treat Guidelines in South Africa.

INTRODUCTION: Officially rolled out on 01 September 2016, South Africa's Universal Test and Treat (UTT) policy calls for first-line antiretroviral treatment (ART) initiation among all known HIV-positive patients, irrespective of CD4 cell count. We evaluate treatment outcomes of patients initiated on first-line ART directly before and after the implementation of UTT. METHODS: We analysed prospectively collected clinical cohort data among ART-naïve adult patients within two HIV clinics in Johannesburg, South Africa. We compare two groups: 1) an unexposed pre-UTT group initiating treatment from 01 December 2014 to 31 May 2015; and 2) an exposed UTT group initiating treatment from 01 December 2016 to 31 May 2017. Primary treatment outcomes included lost to follow-up (LTFU) (>90 days late for the last scheduled visit with no subsequent clinical visit). Cox proportional hazards models were used to estimate the association between pre-UTT vs UTT initiation on LTFU by 12 months. RESULTS: We included 2410 patients. A total of 1267 (52.6%) patients initiated ART before UTT implementation and 1143 (47.4%) after the change in policy. LTFU (adjusted Hazard Ratio (aHR): 1.51; 95% Confidence Interval (CI): 1.16-1.98) between groups and specifically among those initiating with a CD4 cell count ≤500 cells/mm3 (aHR: 1.59; 95% CI: 1.21-2.10) was higher among patients initiating ART under UTT. CONCLUSION: LTFU under UTT proved higher than that of previous periods. Patients initiating first-line therapy under the treat-all policy may often start treatment in better health, subsequently not perceiving a direct benefit to treatment which may deter patients from consistent engagement in HIV treatment programmes.

Using a Self-Administered Electronic Adherence Questionnaire to Identify Poor Adherence Amongst Adolescents and Young Adults on First-Line Antiretroviral Therapy in Johannesburg, South Africa.

INTRODUCTION: The best method to measure adherence to antiretroviral therapy (ART) in resource-limited settings has not yet been established, particularly among adolescents and young adults (AYAs). The use of mobile technology may address the need for standardized tools in measuring adherence in this often marginalized population. METHODS: We conducted a cross-sectional validation study among AYAs (18-35 years) attending a South African HIV clinic between 07/2015-09/2017. We determine the diagnostic accuracy of two modes of delivering an adherence questionnaire (self-administered electronic vs interviewer-administered paper-adherence questionnaire) comprising two self-reported adherence tools (South African National Department of Health (NDoH) adherence questionnaire and the Simplified Medication Adherence Questionnaire (SMAQ)) to identify poor adherence compared to; 1) a detectable viral load (≥1000 copies/mL) and 2) a sub-optimal concentration of efavirenz (EFV) (EFV ≤1.00 µg/mL) measured by therapeutic drug monitoring (TDM). RESULTS: Of 278 included participants, 7.1% and 7.3% completing the electronic- and paper-questionnaires had a detectable viral load, while 14.7% and 16.5% had a sub-optimal concentration of EFV, respectively. According to viral load monitoring, the electronic-adherence questionnaire had a higher sensitivity (Se) in detecting poor adherence than the paper-based version across the NDoH adherence questionnaire (Se: 63.6% vs 33.3%) and SMAQ (Se: 90.9% vs 66.7%). In contrast, when using blood drug concentration (EFV ≤1.00 µg/mL), the paper-adherence questionnaire produced a higher sensitivity across both adherence tools; namely the NDoH adherence questionnaire (Se: 50.0% vs 38.1%) and SMAQ (Se: 75.0% vs 57.1%). CONCLUSION: When using more accurate real-time measures of poor adherence such as TDM in this young adult population, we observe a higher sensitivity of an interviewer-administered paper-adherence questionnaire than an identical set of self-administered adherence questions on an electronic tablet. An interviewer-administered questionnaire may elicit more accurate responses from participants through a sense of increased accountability when engaging with health care workers.

Cost outcome analysis of decentralized care for drug-resistant tuberculosis in Johannesburg, South Africa.

BACKGROUND: Drug resistant-tuberculosis is a growing burden on the South African health care budget. In response the National Department of Health implemented two important strategies in 2011; universal access to drug-sensitivity testing for rifampicin with Xpert MTB/RIF as the first-line diagnostic test for TB; and decentralization of treatment for RR/MDR-TB to improve access and reduce costs of treatment. OBJECTIVE: Estimate the costs by treatment outcome of decentralized care for rifampicin and multi-drug resistant tuberculosis under routine conditions. The study was set at an outpatient drug resistant-tuberculosis treatment facility at a public academic hospital in Johannesburg, South Africa. During the study period 18-24 month long course treatment was offered for rifampicin-resistant and multi-drug-resistant tuberculosis. METHODS: Data are from a prospective observational cohort study. Costs of treatment were estimated from the provider perspective using bottom-up micro-costing. Costs were estimated as patient-level resource use multiplied by the unit cost of the resource. Clinic visits, drugs, laboratory tests, and total days hospitalized were collected from patients' medical records. Staff time was estimated through a time and motion study. A successful treatment outcome was defined as cure or completion of the regimen. RESULTS: We enrolled 124 patients with 52% having a successful outcome. The average total cost/patient for all patients was $3,430 and $4,530 for successfully treated patients. The largest contributors to total cost across all outcomes were drugs (43%) and staff (28%). The average cost to achieve a successful outcome including all patients who started treatment ("production cost") in the cohort is $6,684. CONCLUSIONS: Decentralized, outpatient RR/MDR-TB care under South Africa's 2011 strategy costs 74% less per patient than the previous strategy of inpatient care. The treatment cost of RR/MDR-TB is primarily driven by drug and staff costs, which are in turn dependant on treatment length.

High rates of death and loss to follow-up by 12 months of rifampicin resistant TB treatment in South Africa.

INTRODUCTION: Treatment success rates of rifampicin resistant (RR)/multi-drug resistant (MDR) tuberculosis (TB) in South Africa range from 43-48%, falling short of the World Health Organization's target of ≥75%. We present rates and assess predictors of attrition by 12 months on treatment. METHODS: Prospective observational cohort analysis of adults (≥18 years) initiating RR/MDR-TB treatment from 01 March 2013 to 30 September 2016. Attrition was defined as a combination of death and loss to follow-up (LTFU; treatment interruption ≥2 months) by 12 months on treatment. Predictors of attrition were identified using Cox Proportional Hazards models to estimate crude (HR) and adjusted hazard ratios (aHR) with corresponding 95% confidence intervals. RESULTS: By 12 months on treatment, 75/240 (31.3%) patients had either died (37/240; 15.4%) or been LTFU (38/240; 15.8%). Patients with moderate/severe anaemia (aHR: 2.10; 95% CI 1.00-4.39), and those who were smear positive at baseline (aHR: 2.04; 95% CI 1.01-4.12) were significantly more likely to die or be lost from care. CONCLUSION: At this outpatient DR-TB treatment site, there was a high rate of attrition halfway through the standard treatment course at 12 months of 31%. High rates of attrition by 12 months on treatment may continue during the second-half of therapy.

Low prevalence of depressive symptoms among stable patients on antiretroviral therapy in Johannesburg, South Africa.

BACKGROUND: Depression is a leading cause of disability and may be associated with decreased adherence to ART. We sought to describe the prevalence of depressive symptoms and outcomes one year after screening among patients receiving ART at a large HIV Clinic in Johannesburg, South Africa. METHODS: Adult (≥18) patients who had been on first-line ART between 6-18 months who could communicate in English were eligible. Depressive symptoms were evaluated using the Patient Health Questionnaire (PHQ)-9 and a score ≥10 indicated depression. RESULTS: 97 patients enrolled. Patients had been on ART for a median (IQR) of 8 (7-10) months, 61% were female, the median (IQR) age at enrollment was 38 (33-42) years, and the median (IQR) CD4 count at ART initiation was 154.5 (65-263) cells/mm3. 7 (7%) patients were found to have symptoms of depression; 4 (4%) had symptoms of moderate depression (PHQ score of 10-14) and 3 (3%) had symptoms of moderate/severe depression (PHQ score of 15-19). Women (10%) were more likely to have symptoms of depression than men (3%; prevalence difference [PD]: 7.5%; 95% confidence interval [CI]:-1.7%-16.8%); as were patients under the age of 30 (14%) compared to those 30-39 (4%; PD: -10.2; 95% CI: -29.4-9.0%) or ≥40 (9%; PD: -5.5%; -26.1%-15.2%), those with lower CD4 counts at ART initiation (<200 cells/mm3 vs ≥200 cells/mm3: 8% vs 3%; PD: 4.8%; 95% CI: -4.5%-14.0%), and those with high viral loads (>1000 copies/mL vs. <400 copies/mL: 40% vs. 5%; PD: 34.6%; 95% CI: -8.6%-77.6%). No relationship between depressive symptoms and retention in HIV care one year after screening was observed. CONCLUSIONS: We found a lower prevalence of depressive symptoms compared to findings from other HIV-positive populations in South Africa but more than one-third of patients with an elevated viral load had evidence of depression. Further research on the relationship between depression, adherence, and viral failure is warranted as this may present an opportunity for early interventions to improve treatment outcomes and reduce the need for second-line treatment.

Adverse Drug Reactions Among Patients Initiating Second-Line Antiretroviral Therapy in South Africa.

INTRODUCTION: Understanding the occurrence of antiretroviral (ARV)-related adverse events (AEs) among patients receiving second-line antiretroviral therapy (ART) is important in preventing switches to more limited and expensive third-line regimens. OBJECTIVE: This study aimed to estimate the rates and examine predictors of AEs among adult HIV-1-infected patients receiving second-line ART in the Right to Care (RTC) clinical cohort in South Africa. METHODS: This was a cohort study of HIV-1-infected adult patients (≥ 18 years of age) initiating standard second-line ART in South Africa from 1 April 2004 to 10 January 2016. Our primary outcome was the development of an AE within 24 months of initiating second-line therapy. We used Kaplan-Meier survival analysis to determine AE incidence in the first 24 months of second-line ART. Predictors of AEs were modelled using a Cox proportional hazards model. RESULTS: A total of 7708 patients initiated second-line ART, with 44.5% developing at least one AE over the first 24 months of second-line treatment. The highest AE incidence was observed among patients receiving abacavir (ABC) + lamivudine (3TC) + ritonavir-boosted lopinavir/atazanavir (LPVr/ATVr) (52.7/100 person-years (PYs), 95% confidence interval (CI): 42.9-64.8), while patients initiated on a tenofovir (TDF) + emtricitabine (FTC)/3TC + LPVr regimen had the lowest rate of AEs (26.4/100 PYs, 95% CI: 24.9-28.3). Clinical predictors of AEs included experiencing AEs when receiving first-line ART (adjusted hazard ratio (aHR) 2.3, 95% CI: 1.9-2.8), lower CD4 cell count (0-199 vs. ≥ 350 cells/mm3; aHR 1.4, 95% CI: 1.4-1.8), and switching to second-line therapy from an ABC-base first-line regimen (ABC + 3TC + efavirenz/nevirapine [EFV/NVP] vs. TDF + 3TC/FTC + EFV/NVP; aHR 3.4, 95% CI: 1.1-11.1). CONCLUSIONS: The rates of AEs were lowest among patients receiving a TDF-based second-line regimen. Patients with poorer health at the time of switch were at higher risk of AEs when receiving second-line ART and may require closer monitoring to improve the durability of second-line therapy.

Predictors of switch to and early outcomes on third-line antiretroviral therapy at a large public-sector clinic in Johannesburg, South Africa.

BACKGROUND: While efficacy data exist, there are limited data on the outcomes of patients on third-line antiretroviral therapy (ART) in sub-Saharan Africa in actual practice. Being able to identify predictors of switch to third-line ART will be essential for planning for future need. We identify predictors of switch to third-line ART among patients with significant viraemia on a protease inhibitor (PI)-based second-line ART regimen. Additionally, we describe characteristics of all patients on third-line at a large public sector HIV clinic and present their early outcomes. METHODS: Retrospective analysis of adults (≥ 18 years) on a PI-based second-line ART regimen at Themba Lethu Clinic, Johannesburg, South Africa as of 01 August 2012, when third-line treatment became available in South Africa, with significant viraemia on second-line ART (defined as at least one viral load ≥ 1000 copies/mL on second-line ART after 01 August 2012) to identify predictors of switch to third-line (determined by genotype resistance testing). Third-line ART was defined as a regimen containing etravirine, raltegravir or ritonavir boosted darunavir, between August 2012 and January 2016. To assess predictors of switch to third-line ART we used Cox proportional hazards regression among those with significant viraemia on second-line ART after 01 August 2012. Then among all patients on third-line ART we describe viral load suppression, defined as a viral load < 400 copies/mL, after starting third-line ART. RESULTS: Among 719 patients in care and on second-line ART as of August 2012 (with at least one viral load ≥ 1000 copies/mL after 01 August 2012), 36 (5.0% over a median time of 54 months) switched to third-line. Time on second-line therapy (≥ 96 vs. < 96 weeks) (adjusted Hazard Ratio (aHR): 2.53 95% CI 1.03-6.22) and never reaching virologic suppression while on second-line ART (aHR: 3.37 95% CI 1.47-7.73) were identified as predictors of switch. In a separate cohort of patients on third-line ART, 78.3% (47/60) and 83.3% (35/42) of those in care and with a viral load suppressed their viral load at 6 and 12 months, respectively. CONCLUSIONS: Our results show that the need for third-line is low (5%), but that patients' who switch to third-line ART have good early treatment outcomes and are able to suppress their viral load. Adherence counselling and resistance testing should be prioritized for patients that are at risk of failure, in particular those who never suppress on second-line and those who have been on PI-based regimen for extended periods.

The right combination - treatment outcomes among HIV-positive patients initiating first-line fixed-dose antiretroviral therapy in a public sector HIV clinic in Johannesburg, South Africa.

BACKGROUND: Long-term antiretroviral therapy (ART) adherence is critical for achieving optimal HIV treatment outcomes. Fixed-dose combination (FDC) single-pill regimens, introduced in South Africa in April 2013, has simplified pill taking. We evaluated treatment outcomes among patients initiated on a FDC compared to a similar multi-pill ART regimen in Johannesburg, South Africa. METHODS: We conducted a retrospective cohort study of ART-naïve HIV-positive non-pregnant adult (≥18 years) patients without tuberculosis who initiated first-line ART on tenofovir and emtricitabine or lamivudine with efavirenz at Themba Lethu Clinic in Johannesburg, South Africa. We compared those initiated on a multi-pill ART regimen (3-5 pills/day; September 1, 2011-August 31, 2012) to those initiated on a FDC ART regimen (one pill/day; September 1, 2013-August 31, 2014). Treatment outcomes included attrition (combination of lost to follow-up and mortality), missed medical visits, and virologic suppression (viral load <400 copies/mL) by 12 months post-ART initiation. Cox proportional hazards models and Poisson regression were used to estimate the association between FDCs vs multiple pills and treatment outcomes. RESULTS: We included 3151 patients in our analysis; 2230 (70.8%) patients initiated multi-pill ART and 921 (29.2%) patients initiated on a FDC. By 12 months post-initiation, attrition (adjusted hazard ratio: 0.98; 95% CI: 0.77-1.24) was similar across regimen types (FDC vs multi-pill). Although not significant, patients on a FDC were marginally more likely to achieve viral suppression by 6 (adjusted relative rate [aRR]: 1.10; 95% CI: 0.99-1.23) and 12 months (aRR: 1.12; 95% CI: 0.92-1.36) on ART. Patients initiated on a FDC were significantly less likely to miss medical visits during the first 12 months of treatment (aRR: 0.66; 95% CI: 0.52-0.83). CONCLUSION: Our results suggest FDCs may have a role to play in supporting patient adherence and medical monitoring through improved medical visit attendance. This may potentially improve treatment outcomes later on in treatment.

Predicting the Need for Third-Line Antiretroviral Therapy by Identifying Patients at High Risk for Failing Second-Line Antiretroviral Therapy in South Africa.

Although third-line antiretroviral therapy (ART) is available in South Africa's public sector, its cost is substantially higher than first and second line. Identifying risk factors for failure on second-line treatment remains crucial to reduce the need for third-line drugs. We conducted a case-control study including 194 adult patients (≥18 years; 70 cases and 124 controls) who initiated second-line ART in Johannesburg, South Africa. Unconditional logistic regression was used to assess predictors of virologic failure (defined as 2 consecutive viral load measures ≥1000 copies/mL, ≥3 months after switching to second line). Variables included a social instability index, ART adherence, self-reported as well as diagnosed adverse drug reactions (ADRs), HIV disclosure, depression, and factors affecting access to HIV clinics. Overall 60.0% of cases and 54.0% of controls were female. Mean ages of cases and controls were 41.8 ± 9.6 and 43.3 ± 8.0, respectively. Virologic failure was predicted by ART adherence <90% [odds ratio (OR) 4.7; 95% confidence interval (95% CI): 2.1-10.5], younger age (<40 years of age; OR 0.6; 95% CI: 0.3-1.1), high social instability (OR 3.8; 95% CI: 1.30-11.5), self-reported ADR (OR 1.9; 95% CI: 1.0-3.5), disclosure to friends/colleagues rather than partner/relatives (OR 3.4; 95% CI: 1.3-9.1), and medium/high depression compared to low/no depression (OR 4.4; 95% CI: 1.5-13.4). Our results suggest complex socioeconomic factors contributing to risk of virologic failure, possibly by impacting ART adherence, among patients on second-line therapy in South Africa. Identifying patients with possible indicators of nonadherence could facilitate targeted interventions to reduce the risk of second-line treatment failure and mitigate the demand for third-line regimens.

Early Outcomes Of Decentralized Care for Rifampicin-Resistant Tuberculosis in Johannesburg, South Africa: An Observational Cohort Study.

OBJECTIVE: We describe baseline characteristics, time to treatment initiation and interim patient outcomes at a decentralized, outpatient treatment site for rifampicin-resistant TB (RR-TB). METHODS: Prospective observational cohort study of RR-TB patients from March 2013 until December 2014. Study subjects were followed until completion of the intensive phase of treatment (6 months), transfer out, or a final outcome (loss from treatment (LFT) or death). RESULTS: 214 patients with RR-TB were enrolled in the study. Xpert MTB/RIF was the diagnostic test of rifampicin resistance for 87% (n = 186), followed by direct PCR on AFB positive specimen in 14 (7%) and indirect PCR on cultured isolate in 5 (2%). Median time between sputum testing and treatment initiation was 10 days (IQR 6-21). Interim outcomes were available in 148 patients of whom 78% (n = 115) were still on treatment, 9% (n = 13) had died, and 14% (n = 20) were LFT. Amongst 131 patients with culture positive pulmonary TB, 85 (64.9%) were culture negative at 6 months, 12 were still sputum culture positive (9.2%) and 34 had no culture documented or contaminated culture (26%). Patients who initiated as outpatients within 1 week of sputum collection for diagnosis of RR-TB had a significantly lower incidence of LFT (IRR 0.30, 95% CI: 0.09-0.98). HIV co-infection occurred in 178 patients (83%) with a median CD4 count 88 cells/ml3 (IQR 27-218). CONCLUSIONS: Access to decentralized treatment coupled with the rapid diagnosis of RR-TB has resulted in short time to treatment initiation. Despite the lack of treatment delays, early treatment outcomes remain poor with high rates of death and loss from care.