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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: To report predictors of outcomes of second-line ART for HIV treatment in a resource-limited setting.Methods: All adult ART-naïve patients who initiated standard first-line treatment between April 2004 and February 2012 at four public-sector health facilities in Johannesburg, South Africa, experienced virologic failure and initiated standard second-line therapy were included. We assessed predictors of attrition (death and loss to follow-up [≥3 months late for a scheduled visit]) using Cox proportional hazards regression and predictors of virologic suppression (viral load <400 copies/ml ≥3 months after switch) using modified Poisson regression with robust error estimation at 1 year and ever after second-line ART initiation.Results: A total of 1236 patients switched to second-line treatment in a median (IQR) of 1.9 (0.9-4.6) months after first-line virologic failure. Approximately 13% and 45% of patients were no longer in care at 1 year and at the end of follow-up, respectively. Patients with low CD4 counts (<50 vs. ≥200, aHR: 1.85; 95% CI: 1.03-3.32) at second-line switch were at greater risk for attrition by the end of follow-up. About 75% of patients suppressed by 1 year, and 85% had ever suppressed by the end of follow-up.Conclusions: Patients with poor immune status at switch to second-line ART were at greater risk of attrition and were less likely to suppress. Additional adherence support after switch may improve outcomes. [ABSTRACT FROM AUTHOR]

Background: In 2010 South Africa revised its HIV treatment guidelines to allow the initiation and management of patients on antiretroviral therapy (ART) by nurses, rather than solely doctors, under a program called NIMART (Nurse Initiated and Managed Antiretroviral Therapy). We compared the outcomes and costs of NIMART between the two major public sector HIV treatment delivery models in use in South Africa today, primary health clinics and hospital-based HIV clinics. Methods and findings: The study was conducted at one hospital-based outpatient HIV clinic and one primary health clinic (PHC) in Gauteng Province. A retrospective cohort of adult patients initiated on ART at the PHC was propensity-score matched to patients initiated at the hospital outpatient clinic. Each patient was assigned a 12-month outcome of alive and in care or died/lost to follow up. Costs were estimated from the provider perspective for the 12 months after ART initiation. The proportion of patients alive and in care at 12 months did not differ between the PHC (76.5%) and the hospital-based site (74.2%). The average annual cost per patient alive and in care at 12 months after ART initiation was significantly lower at the PHC (US$238) than at the hospital outpatient clinic (US$428). Conclusions: Initiating and managing ART patients at PHCs under NIMART is producing equally good outcomes as hospital-based HIV clinic care at much lower cost. Evolution of hospital-based clinics into referral facilities that serve complicated patients, while investing most program expansion resources into PHCs, may be a preferred strategy for achieving treatment coverage targets. [ABSTRACT FROM AUTHOR]

Background: Despite the widely documented success of antiretroviral therapy (ART), stakeholders continue to face the challenges of poor HIV treatment outcomes. While many studies have investigated patient-level causes of poor treatment outcomes, data on the effect of health systems on ART outcomes are scarce. Objective: We compare treatment outcomes among patients receiving HIV care and treatment at a public and private HIV clinic in Johannesburg, South Africa. Patients and methods: This was a retrospective cohort analysis of ART naïve adults (≥18.0 years), initiating ART at a public or private clinic in Johannesburg between July 01, 2007 and December 31, 2012. Cox proportional-hazards regression was used to identify baseline predictors of mortality and loss to follow-up (>3 months late for the last scheduled visit). Generalized estimating equations were used to determine predictors of failure to suppress viral load (≥400 copies/mL) while the Wilcoxon rank-sum test was used to compare the median absolute change in CD4 count from baseline to 12 months post-ART initiation. Results: 12,865 patients initiated ART at the public clinic compared to 610 at the private clinic. The patients were similar in terms of sex and age at initiation. Compared to public clinic patients, private clinic patients initiated ART at higher median CD4 counts (159 vs 113 cells/mm3) and World Health Organization stage I/II (76.1% vs 58.5%). Adjusted hazard models showed that compared to public clinic patients, private clinic patients were less likely to die (adjusted hazard ratio [aHR] 0.50; 95% confidence interval [CI] 0.35-0.70) but were at increased risk of loss to follow-up (aHR 1.80; 95% CI 1.59-2.03). By 12 months post-ART initiation, private clinic patients were less likely to have a detectable viral load (adjusted relative risk 0.65; 95% CI 0.49-0.88) and recorded higher median CD4 change from baseline (184 cells/mm3 interquartile range 101-300 vs 158 cells/mm³ interquartile range 91-244), when compared to public clinic patients. Conclusion: We identified differences in treatment outcomes between the two HIV clinics. Findings suggest that the type of clinic at which ART patients initiate and receive treatment can have an impact on treatment outcomes. Further research is necessary to provide more conclusive results. [ABSTRACT FROM AUTHOR]

Background: Challenges to HIV care in resource limited settings (RLS) include malnutrition. Limited evidence supports the benefit of nutritional supplementation when starting antiretroviral therapy (ART) in RLS. Methods: Randomized controlled pilot study. HIV-positive ART-naive adults with self-reported weight loss were randomized to receive ART plus FutureLife porridge® nutritional supplement (NS) (388 kcal/day) or ART alone (Controls) for 6 months. Patients returned for monthly assessments and blood was drawn at enrolment and 6 months on ART. Differences in body composition, biochemical and laboratory parameters were estimated at 6 months on treatment. Results: Of the 36 randomized patients, 26 completed the 6 month follow-up (11 NS vs 15 Controls). At enrolment, groups were similar in terms of age, gender, body mass index (BMI) and bioelectrical impedance. NS patients had a lower median CD4 count (60 cells/mm³ [IQR 12-105 vs 107 cells/mm³ [IQR 63-165]; p = 0.149) and hemoglobin (10.3 g/dL [IQR 9.0-11.3] vs 13.1 g/dL [IQR 11.1-14.7]; p = 0.001). At 6 months, NS patients increased their median CD4 count by 151 cells/mm³ [IQR 120-174) vs 77 cells/mm³ [IQR 33-145] in the Controls. NS patients had higher mean percentage change in body weight (12.7% vs 4.9%; p = 0.047), BMI (7.8% vs 5.5%; p = 0.007), absolute CD4 count (83.0% vs 46.4%, p = 0.002) and hemoglobin (9.5% vs 1.0%; p = 0.026). Patients in the NS arm had a higher mean percentage fat-free mass (16.7% vs -3.5%, p = 0.036), total body water (13.0% vs -1.9%, p = 0.026), intracellular water (16.1% vs -4.1%, p = 0.010) and basal metabolic rate (5.3% vs -0.2%, p = 0.014) compared to Controls. Patients in the NS arm also showed an improvement in physical activity at 6 months post-ART initiation compared to Controls (p = 0.037). Conclusion: Preliminary results are encouraging and suggest that NS taken concurrently with ART can promote weight gain, improve immune response and improve physical activity in HIV-positive patients that present at ART initiation with weight loss. [ABSTRACT FROM AUTHOR]

Background: Little is known about the impact of pregnancy on response to highly active antiretroviral therapy (HAART) in sub-Saharan Africa. We examined the effect of incident pregnancy after HAART initiation on clinical response to HAART. Methods: We evaluated a prospective clinical cohort of adult women initiating HAART in Johannesburg, South Africa between 1 April 2004 and 31 March 2011, and followed up until an event, transfer, drop-out, or administrative end of follow-up on 30 September 2011. Women over age 45 and women who were pregnant at HAART initiation were excluded from the study. Main exposure was having experienced pregnancy after HAART initiation; main outcome was death and (separately) death or new AIDS event. We calculated adjusted hazard ratios (HRs) and 95% confidence limits (CL) using marginal structural Cox proportional hazards models. Results: The study included 7,534 women, and 20,813 person-years of follow-up; 918 women had at least one recognized pregnancy during follow-up. For death alone, the weighted (adjusted) HR was 0.84 (95% CL 0.44, 1.60). Sensitivity analyses confirmed main results, and results were similar for analysis of death or new AIDS event. Incident pregnancy was associated with a substantially reduced hazard of drop-out (HR = 0.62, 95% CL 0.51, 0.75). Conclusions: Recognized incident pregnancy after HAART initiation was not associated with increases in hazard of clinical events, but was associated with a decreased hazard of drop-out. High rates of pregnancy after initiation of HAART may point to a need to better integrate family planning services into clinical care for HIV-infected women. [ABSTRACT FROM AUTHOR]

Objective: To assess the outcomes of linkage to TB and HIV care and identify risk factors for poor referral outcomes. Design: Cohort study of TB patients diagnosed at an urban hospital. Methods: Linkage to care was determined by review of clinic files, national death register, and telephone contact, and classified as linked to care, delayed linkage to care (>7 days for TB treatment, >30 days for HIV care), or failed linkage to care. We performed log-binomial regression to identify patient and referral characteristics associated with poor referral outcomes. Results: Among 593 TB patients, 23% failed linkage to TB treatment and 30.3% of the 77.0% who linked to care arrived late. Among 486 (86.9%) HIV-infected TB patients, 38.3% failed linkage to HIV care, and 32% of the 61.7% who linked to care presented late. One in six HIV-infected patients failed linkage to both TB and HIV care. Only 20.2% of HIV-infected patients were referred to a single clinic for integrated care. A referral letter was present in 90.3%, but only 23.7% included HIV status and 18.8% CD4 cell count. Lack of education (RR 1.85) and low CD4 count (CD4≤50 vs. >250cells/mm³ ; RR 1.66) were associated with failed linkage to TB care. Risk factors for failed linkage to HIV care were antiretroviral-naïve status (RR 1.29), and absence of referral letter with HIV or CD4 cell count (RR1.23). Conclusions: Linkage to TB/HIV care should be strengthened by communication of HIV and CD4 results, ART initiation during hospitalization and TB/HIV integration at primary care. [ABSTRACT FROM AUTHOR]

In South Africa, abacavir (ABC) is currently recommended as part of first- and second-line antiretroviral therapy (ART) for HIV-positive paediatric patients. Concerns about overprescribing of the drug, particularly to adults, led to an analysis of ABC use in public sector ART programmes. We investigated current prescription of the drug to adults and children accessing ART in 4 public sector programmes across Gauteng Province, South Africa. ABC was almost exclusively prescribed to children initiating ART and adults requiring regimen changes due to drug toxicities. Patterns of ABC use among HIV-positive paediatric patients followed national ART treatment guidelines on the application of the drug. Although ABC is commonly used in the private sector for adults, the current national ART treatment guidelines for adults and adolescents should include ABC as an alternative to standard first- or second-line ART. [ABSTRACT FROM AUTHOR]

Peripheral neuropathy (PN) is associated with advanced HIV disease and may be a complication of antiretroviral therapy (ART) or anti-tuberculosis (TB) drugs, specifically isoniazid (INH). The effect of non-ART-drug-related PN on treatment outcomes is yet to be determined. We analysed prospectively collected cohort data for HIV-infected ART-naive adults initiating ART at the Themba Lethu Clinic, Johannesburg, South Africa from June 2004 to June 2009. Patients who presented with signs and symptoms of numbness or dysesthesia prior to initiation of ART were defined as having PN. Cox proportional hazard models were used to estimate the effect of PN alone (HIV-related PN) or PN with a history of INH use (TB-related PN) on mortality, lost to follow-up (LTFU), persistent and recurrent PN by 12 months of follow-up. Of the 9,399 patients initiating ART, 3.9 % had HIV-related PN while a further 1.8 % had TB-related PN. Patients with PN did not have a significantly higher risk of mortality compared to those without PN (hazard ratio (HR) 1.17 95 % CI 0.92-1.49). Patients with TB-related PN were less likely to be LTFU by 12 months (HR 0.65 95 % CI 0.44-0.97) compared to those without PN. Patients with HIV-related PN were at increased risk of persistent PN at 3 months post-ART initiation. Patients with HIV-related PN had a similar risk of recurrent PN compared to those with TB-related PN (HR 1.28 95 % CI 0.72-2.27). We demonstrate that patients with PN at initiation of ART present with advanced HIV disease. Completion of TB treatment may reduce the risk of persistent PN in patients with TB-related PN. Use of HIV drugs, even neurotoxic ones, may overall limit neuropathy. [ABSTRACT FROM AUTHOR]

Background: To assess the quality and completeness of treatment and outcome data in the electronic tuberculosis (TB) and antiretroviral treatment (ART) registers in drug-resistant (DR-) TB patients at three treatment facilities in South Africa.Methods: We did a retrospective cohort study using routinely-collected data from DR-TB registers of rifampicin resistant adults (≥18 years old), on ART, initiating DR-TB treatment between January 2012 and December 2013. We linked patient information from the DR-TB register to the ART register using patient identifiers and an algorithm based on string edit distance and date of birth. We describe data gaps and discrepancies found.Results: Overall, 2852 DR-TB patients met our inclusion criteria based on the DR-TB register data, and of these, 1685 (59%) could be matched to the ART registers. An additional 253 patients from the DR-TB registers were found in the ART registers, having initiated ART, despite the DR-TB register indicating that they were not on ART (or this data was missing). 11% of matched patients did not have TB treatment status recorded in the ART register despite being recorded as being on TB treatment in the DR-TB register, and 78% did not have an ART start date recorded in DR-TB register despite being on ART treatment as per the ART register. 11% of matched patients had a death recorded in one register but not the other, and of those with death recorded in both, 15% of dates differed by > 1 month.Conclusions: The underreporting of death and the lack of ART or TB status in the electronic DR-TB and ART registers could negatively impact monitoring efforts by downplaying the state of the TB/HIV epidemic. Improved recording of these data sources, and data integration across systems, could improve the accuracy of reporting for the national HIV/ART and TB programs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Adolescents experience disproportionately high rates of poor ART outcomes compared to adults despite prolonged use of antiretroviral therapy in Southern African treatment programs, presenting a significant challenge to national attempts to meet the UNAIDS 90-90-90 targets for 2020. This cohort study among adolescents aged 12–20 years accessing ART care at two urban public-sector clinics in Johannesburg between September and November 2013 aimed to identify factors potentially associated with poor attendance at clinic visits. Patients were followed up through routine medical records to identify missed visits (failing to attend clinic within 30 days of scheduled visit date) up to 2 years after enrolment. We enrolled 126 adolescents on ART for a median of 6.3 years (IQR: 2.7–8.4). A total of 47 (38%) adolescents missed a scheduled visit within 24 months of enrolment. Older adolescents (18–20 years) were more likely to miss a visit compared to adolescents aged 12–14 years (risk ratio (RR) = 1.72; 95% CI: 1.00–2.95). Those who were identified to have difficulty in taking medication (RR = 1.57; 95% CI: 1.13–2.18) as a barrier to care were more likely to miss a visit compared to adolescents who did not. Awareness of treatment fatigue, challenges to taking ART, and caregiver difficulties is important when considering interventions to improve treatment outcomes among adolescents. [ABSTRACT FROM AUTHOR]