Search

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]

While the diagnostic properties of the TB LAM urine assay (LAM) have been well-described, little is known about its predictive and prognostic properties at ART initiation in a routine clinic setting. We describe the predictive and prognostic properties of LAM in HIV-positive patients initiating ART at an urban hospital in Johannesburg, South Africa. Retrospective study of HIV-positive adults (>18 years) who initiated standard first-line ART between February 2012 and April 2013 and had a LAM test at initiation. In HIV-positive patients with no known TB at ART initiation, we assessed the sensitivity, specificity and positive/negative likelihood ratios of LAM to predict incident TB within 6 months of ART initiation. In addition, in patients with a TB diagnosis and on TB treatment <3 months at ART initiation, we measured the CD4 response at 6 months on ART. Of the 274 patients without TB at ART initiation, 65% were female with median CD4 count of 213 cells/mm³. Among the 14 (5.1%) patients who developed active TB, none were urine LAM +ve at baseline. LAM had poor sensitivity (0.0 % 95 % CI 0.00-23.2) to predict incident TB within 6 months of initiation. We analyzed 22 patients with a confirmed TB diagnosis at initiation separately. Of these, LAM +ve patients (27%) showed lower CD4 gains compared to LAM negative patients (median increase 103 vs 199 cells/mm³; p=0.08). LAM has limited value for accurately predicting incident TB in patients with higher CD4 counts after ART initiation. LAM may help identify TB/HIV co-infected patients at ART initiation who respond more slowly to treatment and require targeted interventions to improve treatment outcomes. Larger studies with longer patient follow-up are needed. [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]

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. [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: According to the World Health Organization, South Africa ranks as one of the highest burden of TB, TB/HIV co-infection, and drug-resistant TB (DR-TB) countries. DR-TB treatment is complicated to administer and relies on the use of multiple toxic drugs, with potential for severe adverse drug reactions. We report the occurrence of adverse events (AEs) during a standardised DR-TB treatment regimen at two outpatient, decentralized, public-sector sites in Johannesburg, South Africa. Methods: We reviewed medical records of the six-month intensive treatment phase for rifampicin-resistant (RR) TB patients registered May 2012 - December 2014. Patients contributed follow-up time until death, loss from treatment, censoring (6 months) or data extraction. A standardized regimen of kanamycin, moxifloxacin, ethionamide, terizidone, and pyrazinamide was used according to national guidelines. AEs were graded using the AIDS Clinical Trial Group scale. We present subhazard ratios from competing risk analysis for time to severe AE, accounting for mortality and loss from treatment. Results: Across the two sites, 578 eligible patient files were reviewed. 36.7% were categorized as low weight (=50 kg) at DR-TB initiation. 76.0% had no history of TB treatment prior to the current episode of RR TB. 26.8% were diagnosed with RR TB while hospitalized, indicating poor clinical condition. 82.5% of patients were also HIV positive, of whom 43. 8% were on ART prior to RR TB treatment and 32.1% initiated ART with or after RR TB treatment. Median CD4 count was 114.5 (IQR: 45-246.5). Overall, 578 reports of AEs were captured for 204 patients (35.3%) and 110 patients (19.0%) had at least one severe AE reported. Patients with at least one AE experienced a median of 3 (IQR: 2-4) AEs per patient. HIV-positive patients with CD4 counts =100 cells/mm³ and those newly initiating ART were more likely to experience a severe AE (sHR: 2.76, 95% CI: 1.30-5.84 and sHR: 3.07, 95% CI: 1.46-6.46, respectively). Conclusion: Severe AE are common during the first 6 months of RR TB treatment and HIV-positive patients newly initiating ART have the highest subdistribution hazard ratio for severe AE, accounting for the competing risks of death and loss from treatment. [ABSTRACT FROM AUTHOR]

Objective: In resource-limited settings, where genotypic drug resistance testing is rarely performed and poor adherence is the most common reason for treatment failure, programmatic approaches to handling treatment failure are essential. This study was performed to describe one such approach to adherence optimisation.Methods: This was a single-arm study of patients on second-line protease inhibitor (PI)-based antiretroviral therapy (ART) with a HIV-1 RNA ≥400 copies/ml in Johannesburg, South Africa, between 1 March 2012 and 1 December 2013. Patients underwent enhanced adherence counselling. Those with improved adherence and a repeat viral load of >1000 copies/ml underwent HIV-1 drug resistance testing. We describe results using simple proportions and 95% confidence intervals.Results: Of the 400 patients who underwent targeted adherence counselling after an elevated viral load on second-line ART, 388 (97%) underwent repeat viral load testing. Most of these (n = 249; 64%, 95% CI 59-69) resuppressed (<400 copies/ml) on second line. By the end of follow-up (1 March 2014), among the 139 (36%, 95% CI: 31-41%), who did not initially resuppress after being targeted, 106 had a viral load >400 copies/ml, 11 switched to third line, 5 were awaiting third line, 4 had died and 13 were lost to follow-up. Among the unsuppressed, 48 successfully underwent resistance testing with some resistance detected in most (41/48).Conclusions: Most (64%) second-line treatment failure in this clinic is related to adherence and can be overcome with careful adherence support. Controlled interventions are needed to determine what the optimal approach is to improving second-line outcomes and reducing the need for third-line ART. [ABSTRACT FROM AUTHOR]

Background: While most HIV care is provided on an outpatient basis, hospitals continue to treat serious HIV-related admissions, which is relatively resource-intensive and expensive. This study reports the primary reasons for HIV-related admission at a regional, urban hospital in Johannesburg, South Africa and estimates the associated lengths of stay and costs. Methods and Findings: A retrospective cohort study of adult, medical admissions was conducted. Each admission was assigned a reason for admission and an outcome. The length of stay was calculated for all patients (N = 1,041) and for HIV-positive patients (n = 469), actual utilization and associated costs were also estimated. Just under half were known to be HIV-positive admissions. Deaths and transfers were proportionately higher amongst HIV-positive admissions compared to HIV-negative and unknown. The three most common reasons for admission were tuberculosis and other mycobacterial infections (18%, n = 187), cardiovascular disorders (12%, n = 127) and bacterial infections (12%, n = 121). The study sample utilized a total of 7,733 bed days of those, 55% (4,259/7,733) were for HIV-positive patients. The average cost per admission amongst confirmed HIV-positive patients, which was an average of 9.3 days in length, was $1,783 (United States Dollars). Conclusions: Even in the era of large-scale antiretroviral treatment, inpatient facilities in South Africa shoulder a significant HIV burden. The majority of this burden is related to patients not on ART (298/469, 64%), and accounts for more than half of all inpatient resources. Reducing the costs of inpatient care is thus another important benefit of expanding access to ART, promoting earlier ART initiation, and achieving rates of ART retention and adherence. [ABSTRACT FROM AUTHOR]