Lawrence Long

Early loss to follow up after enrolment in pre-ART care at a large public clinic in Johannesburg, South Africa

Objective  To estimate loss to follow up (LTFU) between initial enrolment and the first scheduled return medical visit of a pre‐antiretroviral therapy (ART) care program for patients not eligible for ART.

The Impact and Cost of Scaling up GeneXpert MTB/RIF in South Africa

Objective We estimated the incremental cost and impact on diagnosis and treatment uptake of national rollout of Xpert MTB/RIF technology (Xpert) for the diagnosis of pulmonary TB above the cost of current guidelines for the years 2011 to 2016 in South Africa. Methods We parameterised a population-level decision model with data from national-level TB databases (n = 199,511) and implementation studies. The model follows cohorts of TB suspects from diagnosis to treatment under current diagnostic guidelines or an algorithm that includes Xpert. Assumptions include the number of TB suspects, symptom prevalence of 5.5%, annual suspect growth rate of 10%, and 2010 public-sector salaries and drug and service delivery costs. Xpert test costs are based on data from an in-country pilot evaluation and assumptions about when global volumes allowing cartridge discounts will be reached. Results At full scale, Xpert will increase the number of TB cases diagnosed per year by 30%–37% and the number of MDR-TB cases diagnosed by 69%–71%. It will diagnose 81% of patients after the first visit, compared to 46% currently. The cost of TB diagnosis per suspect will increase by 55% to USD 60–61 and the cost of diagnosis and treatment per TB case treated by 8% to USD 797–873. The incremental capital cost of the Xpert scale-up will be USD 22 million and the incremental recurrent cost USD 287–316 million over six years. Conclusion Xpert will increase both the number of TB cases diagnosed and treated and the cost of TB diagnosis. These results do not include savings due to reduced transmission of TB as a result of earlier diagnosis and treatment initiation.

Treatment outcomes and cost-effectiveness of shifting management of stable ART patients to nurses in South Africa: an observational cohort.

Lawrence Long and colleagues report that “down-referring” stable HIV patients from a doctor-managed, hospital-based ART clinic to a nurse-managed primary health facility provides good health outcomes and cost-effective treatment for patients.

The high cost of second-line antiretroviral therapy for HIV/AIDS in South Africa

Objective:The present article estimates the cost and outcomes of second-line antiretroviral therapy. The cost of second-line drugs is generally higher than that of first-line drugs and it is expected that the absolute number of patients on second-line antiretroviral therapy will increase over time. This information is crucial for planning and budgeting. Methods:Resource utilization and outcome data were extracted for patients who initiated standard second-line therapy. Resource usage was measured from second-line initiation for 12 months and outcomes were determined at 12 months. Unit costs were applied to resource usage using standard costing techniques. Costs were classified into drug, laboratory, visit, and fixed costs. Outcomes at 12 months were determined using attendance status, diagnostic results, and treatment status. Average cost per patient and average cost per outcome were reported. Results:Of the 293 participants in the study cohort, 58% remained in care and responding, 15% were in care but not responding, and 26% were no longer in care. During the 12 months following second-line initiation, the average cost per participant was

The outcomes and outpatient costs of different models of antiretroviral treatment delivery in South Africa

1037. Most of the cost per patient was attributable to drugs (71%), 13% to laboratory tests, 10% to clinic and pharmacy visits, and 6% to infrastructure and other fixed costs. Second-line therapy was 2.4 times more expensive per year in care than first-line therapy. Conclusion:The gradual increase in second-line numbers that can be expected as treatment programs mature may cause a meaningful increase in the overall average cost per patient treated.

Rapid point-of-care CD4 testing at mobile HIV testing sites to increase linkage to care: an evaluation of a pilot program in South Africa.

Objective  Estimate the average outpatient cost per patient in care and responding to treatment 1 year after initiation of antiretroviral therapy (ART) under different models of treatment delivery in South Africa.

Outcomes of stable HIV-positive patients down-referred from a doctor-managed antiretroviral therapy clinic to a nurse-managed primary health clinic for monitoring and treatment.

Background:A mobile HIV counseling and testing (HCT) program around Johannesburg piloted the integration of point-of-care (POC) CD4 testing, using the Pima analyzer, to improve linkages to HIV care. We report results from this pilot program for patients testing positive (n = 508) from May to October 2010. Methods:We analyzed 3 primary outcomes: assignment to testing group (offered POC CD4 or not), successful follow-up (by telephone), and completed the referral visit for HIV care within 8 weeks after HIV testing if successfully followed up. Proportions for each outcome were calculated, and relative risks were estimated using a modified Poisson approach. Results:Three hundred eleven patients were offered the POC CD4 test, and 197 patients were not offered the test. No differences in patient characteristics were observed between the 2 groups. Approximately 62.7% of patients were successfully followed up 8 weeks after HIV testing, with no differences observed between testing groups. Among those followed up, 54.4% reported completing their referral visit. Patients offered the POC CD4 test were more likely to complete the referral visit for further HIV care (relative risk 1.25, 95% confidence interval: 1.00 to 1.57). Conclusions:In this mobile HCT setting, patients offered POC CD4 testing as part of the HCT services were more likely to visit a referral clinic after testing, suggesting that rapid CD4 testing technology may improve linkage to HIV care. Future research can evaluate options for adjusting HCT services if POC CD4 testing was included permanently and the cost-effectiveness of the POC CD4 testing compared with other approaches for improving linkage of care.

High rates of survival, immune reconstitution, and virologic suppression on second-line antiretroviral therapy in South Africa.

Objective:To compare clinical, immunologic and virologic outcomes among stable HIV-positive patients down-referred to a nurse-managed primary healthcare clinic (PHC) for treatment maintenance to those who remained at a doctor-managed treatment-initiation site. Design:We conducted a matched cohort analysis among stable HIV patients at the Themba Lethu Clinic in Johannesburg, South Africa. Eligible patients met the criteria for down-referral [undetectable viral load <10 months, antiretroviral therapy (ART) >11 months, CD4 cell count ≥200 cells/&mgr;l, stable weight and no opportunistic infections], regardless of whether they were down-referred to a PHC for treatment maintenance between February 2008 and January 2009. Patients were matched 1 : 3 (down-referred : treatment-initiation) using propensity scores. Methods:We calculated rates and hazard ratios (HRs) for the effect of down-referral on loss to follow-up (LTFU) and mortality and the relative risk of down-referral on viral rebound by 12 months of follow-up. Results:Six hundred and ninety-three down-referred patients were matched to 2079 treatment-initiation patients. Two (0.3%) down-referred and 32 (1.5%) treatment-initiation patients died, 10 (1.4%) down-referred and 87 (4.2%) treatment-initiation patients were lost, and 22 (3.3%) down-referred and 100 (5.6%) treatment-initiation patients experienced viral rebound by 12 months of follow-up. After adjustment, patients down-referred were less likely to die [hazard ratio (HR) 0.2, 95% confidence interval (CI) 0.04–0.8], become LTFU (HR 0.3, 95% CI 0.2–0.6) or experience viral rebound (relative risk 0.6, 95% CI 0.4–0.9) than treatment-initiation patients during follow-up. Conclusion:The utilization of nurse-managed PHCs for treatment maintenance of stable patients could decrease the burden on specialized doctor-managed ART clinics. Patient outcomes for down-referred patients at PHCs appear equal, if not better, than those achieved at ART clinics among stable patients.

Lost opportunities to complete CD4+ lymphocyte testing among patients who tested positive for HIV in South Africa

To determine rates of survival, viral suppression, and immunologic change after 1 year on second-line antiretroviral therapy, we conducted a cohort study among 328 patients initiated on zidovudine, didanosine, and lopinavir/ritonavir. All patients who switched to standard second-line therapy at a large urban public-sector clinic in Johannesburg, South Africa, were included. A year after initiating second-line therapy 243/313 [78%; 95% confidence interval (CI) 73%-82%], subjects were alive and in care. Further, 203/262 (77%; 95% CI: 72%-82%) had a suppressed viral load by 1 year. Mean CD4 gain by 12 months was 133 cells/μL (95% CI: 106-160). Patients on second-line therapy had a small decreased likelihood of being alive and in care by 1 year [hazard ratio (HR) 0.84; 95% CI: 0.73-0.97] as time-matched comparisons on first-line antiretroviral therapy (ART). Patients switched before 2 viral loads >1000 (HR 1.68; 95% CI: 1.08-2.61), and those switched for reasons not related to noncompliance with first-line (HR 1.83; 95% CI: 1.14-2.93) were more likely to achieve virologic suppression by 1 year on second-line ART. As rates of treatment failure over the first year on second-line therapy were low, provision of second-line treatment to patients who fail their first-line ART should be considered a high priority in resource-poor settings.

Cohort Profile: The Themba Lethu Clinical Cohort, Johannesburg, South Africa

OBJECTIVE To estimate rates of completion of CD4+ lymphocyte testing (CD4 testing) within 12 weeks of testing positive for human immunodeficiency virus (HIV) at a large HIV/AIDS clinic in South Africa, and to identify clinical and demographic predictors for completion. METHODS In our study, CD4 testing was considered complete once a patient had retrieved the test results. To determine the rate of CD4 testing completion, we reviewed the records of all clinic patients who tested positive for HIV between January 2008 and February 2009. We identified predictors for completion through multivariate logistic regression. FINDINGS Of the 416 patients who tested positive for HIV, 84.6% initiated CD4 testing within the study timeframe. Of these patients, 54.3% were immediately eligible for antiretroviral therapy (ART) because of a CD4 cell count ≤ 200/µl, but only 51.3% of the patients in this category completed CD4 testing within 12 weeks of HIV testing. Among those not immediately eligible for ART (CD4 cells > 200/µl), only 14.9% completed CD4 testing within 12 weeks. Overall, of HIV+ patients who initiated CD4 testing, 65% did not complete it within 12 weeks of diagnosis. The higher the baseline CD4 cell count, the lower the odds of completing CD4 testing within 12 weeks. CONCLUSION Patient losses between HIV testing, baseline CD4 cell count and the start of care and ART are high. As a result, many patients receive ART too late. Health information systems that link testing programmes with care and treatment programmes are needed.