Health Economics and Epidemiology Research Office

Johannesburg, South Africa

Health Economics and Epidemiology Research Office

Johannesburg, South Africa

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Fox M.P.,Boston University | Fox M.P.,Health Economics and Epidemiology Research Office | Fox M.P.,University of Witwatersrand | Sanne I.M.,University of Witwatersrand | And 9 more authors.
AIDS | Year: 2010

Objectives: To compare treatment outcomes by starting CD4 cell counts using data from the Comprehensive International Program of Research on AIDS-South Africa trial. DESIGN: An observational cohort study. Methods: Patients presenting to primary care clinics with CD4 cell counts below 350 cells/μl were randomized to either doctor or nurse-managed HIV care and followed for at least 2 years after antiretroviral therapy (ART) initiation. Clinical and laboratory outcomes were compared by baseline CD4 cell counts. Results: Eight hundred and twelve patients were followed for a median of 27.5 months and 36% initiated ART with a CD4 cell count above 200 cells/μl. Although 10% of patients failed virologically, the risk was nearly double among those with a CD4 cell count of 200 cells/μl or less vs. above 200 cells/μl (12.2 vs. 6.8%). Twenty-one deaths occurred, with a five-fold increased risk for the low CD4 cell count group (3.7 vs. 0.7%). After adjustment, those with a CD4 cell count of 200 cells/μl had twice the risk of death/virologic failure [hazard ratio 1.9; 95% confidence interval (CI), 1.1-3.3] and twice the risk of incident tuberculosis (hazard ratio 1.90; 95% CI, 0.89-4.04) as those above 200 cells/μl. Those with either a CD4 cell count of 200 cells/μl or less (hazard ratio 2.1; 95% CI, 1.2-3.8) or a WHO IV condition (hazard ratio 2.9; 95% CI, 0.93-8.8) alone had a two-to-three-fold increased risk of death/virologic failure vs. those with neither, but those with both conditions had a four-fold increased risk (hazard ratio 3.9; 95% CI, 1.9-8.1). We observed some decreased loss to follow-up among those initiating ART at less than 200 cells/μl (hazard ratio 0.79; 95% CI, 0.50-1.25). Conclusion: Patients initiating ART with higher CD4 cell counts had reduced mortality, tuberculosis and less virologic failure than those initiated at lower CD4 cell counts. Our data support increasing CD4 cell count eligibility criteria for ART initiation. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Brennan A.,Boston University | Brennan A.,Health Economics and Epidemiology Research Office | Brennan A.,University of Witwatersrand | Evans D.,Health Economics and Epidemiology Research Office | And 11 more authors.
AIDS | Year: 2011

Objective: In April 2010, the South African government added tenofovir disoproxil fumarate to its first-line antiretroviral therapy (ART) for HIV patients. We analyzed the relationship between renal dysfunction at tenofovir initiation, nephrotoxicity and mortality. Design: Cohort analysis of HIV-infected adults who received tenofovir and had a creatinine clearance done at initiation at the Themba Lethu Clinic, Johannesburg, South Africa, between April 2004 and September 2009. Methods: We estimated the relationship between renal dysfunction, nephrotoxicity [any decline in kidney function from baseline (acute or chronic) that is secondary to a toxin (including drugs)] and mortality for patients initiated onto tenofovir-containing regimens using marginal structural models and inverse probability of treatment weights to correct estimates for lost to follow-up and confounding. Results: Of 890 patients initiated onto tenofovir, 573 (64.4%) had normal renal function (≥90 ml/min), 271 (30.4%) had mild renal dysfunction (60-89 ml/min) and 46 (5.2%) had moderate renal dysfunction (30-59 ml/min). A total of 2.4% experienced nephrotoxicity, 7.8% died and 9.7% were lost during 48 months of follow-up. Patients with mild [hazard ratio 4.8; 95% confidence interval (CI) 1.5-15.2] or moderate (hazard ratio 15.0; 95% CI 3.4-66.5) renal dysfunction were at greatest risk of nephrotoxicity, whereas those with mild (hazard ratio 1.2; 95% CI 0.7-2.3) or moderate (hazard ratio 3.2; 95% CI 1.3-7.8) renal dysfunction vs. normal renal function were at highest risk of death by 48 months. Conclusion: Much of the incident renal dysfunction in tenofovir patients is likely related to preexisting renal disorder, which may be exacerbated by tenofovir. With expanded use of tenofovir, screening for renal dysfunction prior to initiation and dose adjustment is necessary to help improve ART outcomes. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Rosen S.,Boston University | Rosen S.,Health Economics and Epidemiology Research Office | Rosen S.,University of Witwatersrand | Ketlhapile M.,Health Economics and Epidemiology Research Office
Tropical Medicine and International Health | Year: 2010

Objective To evaluate a pilot intervention to engage a patient tracer to follow up lost patients at a large public clinic in South Africa. Methods A social worker spent 4 months contacting by telephone a random sample of patients who had initiated antiretroviral therapy (ART) at least 6 months earlier and were ≥1 month late for a scheduled visit. The tracer was authorized to assist patients to return to care if needed. Cost was calculated from the perspective of the clinic. Results The tracer was able to determine the final status of 260 of a sample of 493 lost patients. Of the 260, 55 (21%) had died, 56 (21%) were still on ART at the same site, 79 (30%) reported transferring to another site and 70 (27%) had discontinued treatment. Among those discontinuing, commonly cited reasons were relocation (n = 18, 26%), traditional medicine or religious beliefs (n = 11, 16%), fear of disclosure or other family barriers (n = 9, 13%), and employment obstacles (n = 7, 10%). Twenty patients returned to care at the original site as a result of the intervention, at an average cost of $432 per patient returned. Conclusions A patient tracer was an effective way to determine the final status of lost patients and succeeded in returning some to care, but the cost per patient returned was high. Better information systems allowing sites to track deaths and transfers would greatly improve the efficiency of loss to follow-up interventions. © 2010 Blackwell Publishing Ltd.


Fox M.P.,Crosstown Center | Fox M.P.,Boston University | Fox M.P.,Health Economics and Epidemiology Research Office | Rosen S.,Crosstown Center | Rosen S.,Health Economics and Epidemiology Research Office
AIDS | Year: 2015

OBJECTIVES:: There are several published systematic reviews of adult retention in care after antiretroviral therapy (ART) initiation among adults, but limited information on pediatric retention. DESIGN:: Systematic review of pediatric retention on ART in low and middle-income countries during 2008-2013. METHODS:: We estimated all-cause attrition (death and loss to follow-up) and retention for pediatric patients receiving first-line ART in routine settings. We searched PubMed, Embase, Cochrane Register, and ISI Web of Science (January 2008-January 2014) and abstracts from AIDS and IAS (2008-2013). We estimated mean retention across cohorts using simple averages; interpolated any time period not reported to, up to the last period reported; summarized total retention in the population using Kaplan-Meier survival curves; and compared pediatric to adult retention. RESULTS:: We found 39 reports of retention in 45 patient cohorts and 55904 patients in 23 countries. Among them, 37% of patients not retained in care were known to have died and 63% were lost to follow-up. Unweighted averages of reported retention were 85, 81, and 81% at 12, 24, and 36 months after ART initiation. From life-table analysis, we estimated retention at 12, 24, and 36 months at 88, 72, and 67%. We estimated 36-month retention at 66% in Africa and 74% in Asia. CONCLUSION:: Pediatric ART retention was similar to that among adults. There were limited data from Asia, only one study from Latin America and the Caribbean, and no data from Eastern Europe, Central Asia, or the Middle East.. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Maskew M.,University of Witwatersrand | Maskew M.,Health Economics and Epidemiology Research Office | Westreich D.,Duke University | Fox M.P.,University of Witwatersrand | And 3 more authors.
Journal of the International AIDS Society | Year: 2012

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. © 2012 Maskew et al; licensee BioMed Central Ltd.


Miller C.M.,Boston University | Ketlhapile M.,Health Economics and Epidemiology Research Office | Rybasack-Smith H.,Boston University | Rosen S.,Boston University | Rosen S.,Health Economics and Epidemiology Research Office
Tropical Medicine and International Health | Year: 2010

Objectives To better understand the reasons why patients default from antiretroviral treatment (ART) programmes to help design interventions that improve treatment retention and ultimately, patient outcomes. Methods Prospective cohort study at two treatment sites in South Africa followed by qualitative interviews with patients that had defaulted. Results Respondents overwhelmingly reported that ART improved their health status and quality of life. Nevertheless, despite improved health from taking ART and worse health when treatment is stopped, serious barriers to treatment remained: transport costs, time needed for treatment, and logistical challenges were barriers to treatment, whereas stigma around HIV/AIDS, and side effects associated with ART were less influential. Conclusion With a better understanding of the reasons for defaulting, interventions can be designed that improve treatment retention and ultimately, patient outcomes. This study argues for realistic interventions and policy changes designed to reduce the financial and time burden of ART and to reduce logistical barriers, such as simplifying the referral and transfer process, employing patient advocates, and adopting extended and weekend clinic hours. © 2010 Blackwell Publishing Ltd.


Long L.,Health Economics and Epidemiology Research Office | Long L.,University of Witwatersrand | Brennan A.,Health Economics and Epidemiology Research Office | Brennan A.,University of Witwatersrand | And 13 more authors.
PLoS Medicine | Year: 2011

Background: To address human resource and infrastructure shortages, resource-constrained countries are being encouraged to shift HIV care to lesser trained care providers and lower level health care facilities. This study evaluated the cost-effectiveness of down-referring stable antiretroviral therapy (ART) patients from a doctor-managed, hospital-based ART clinic to a nurse-managed primary health care facility in Johannesburg, South Africa. Methods and Findings: Criteria for down-referral were stable ART (≥11 mo), undetectable viral load within the previous 10 mo, CD4>200 cells/mm3, <5% weight loss over the last three visits, and no opportunistic infections. All patients down-referred from the treatment-initiation site to the down-referral site between 1 February 2008 and 1 January 2009 were compared to a matched sample of patients eligible for down-referral but not down-referred. Outcomes were assigned based on vital and health status 12 mo after down-referral eligibility and the average cost per outcome estimated from patient medical record data. The down-referral site (n = 712) experienced less death and loss to follow up than the treatment-initiation site (n = 2,136) (1.7% versus 6.2%, relative risk = 0.27, 95% CI 0.15-0.49). The average cost per patient-year for those in care and responding at 12 mo was US$492 for down-referred patients and US$551 for patients remaining at the treatment-initiation site (p<0.0001), a savings of 11%. Down-referral was the cost-effective strategy for eligible patients. Conclusions: Twelve-month outcomes of stable ART patients who are down-referred to a primary health clinic are as good as, or better than, the outcomes of similar patients who are maintained at a hospital-based ART clinic. The cost of treatment with down-referral is lower across all outcomes and would save 11% for patients who remain in care and respond to treatment. These results suggest that this strategy would increase treatment capacity and conserve resources without compromising patient outcomes. © 2011 Long et al.


Harries A.D.,International Union Against Tuberculosis and Lung Disease | Harries A.D.,London School of Hygiene and Tropical Medicine | Zachariah R.,Médecins Sans Frontières | Lawn S.D.,London School of Hygiene and Tropical Medicine | And 3 more authors.
Tropical Medicine and International Health | Year: 2010

The scale-up of antiretroviral therapy (ART) has been one of the success stories of sub-Saharan Africa, where coverage has increased from about 2% in 2003 to more than 40% 5 years later. However, tempering this success is a growing concern about patient retention (the proportion of patients who are alive and remaining on ART in the health system). Based on the personal experience of the authors, 10 key interventions are presented and discussed that might help to improve patient retention. These are (1) the need for simple and standardized monitoring systems to track what is happening, (2) reliable ascertainment of true outcomes of patients lost to follow-up, (3) implementation of measures to reduce early mortality in patients both before and during ART, (4) ensuring uninterrupted drug supplies, (5) consideration of simple, non-toxic ART regimens, (6) decentralization of ART care to health centres and the community, (7) a reduction in indirect costs for patients particularly in relation to transport to and from clinics, (8) strengthening links within and between health services and the community, (9) the use of ART clinics to deliver other beneficial patient or family-orientated packages of care such as insecticide-treated bed nets, and (10) innovative (thinking 'out of the box') interventions. High levels of retention on ART are vital for individual patients, for credibility of programmes and for on-going resource and financial support. © 2010 Blackwell Publishing Ltd.


Fox M.P.,Boston University | Fox M.P.,Health Economics and Epidemiology Research Office | Fox M.P.,University of Witwatersrand | Rosen S.,Boston University | And 2 more authors.
Tropical Medicine and International Health | Year: 2010

Objectives To estimate the proportion of all-cause adult patient attrition from antiretroviral therapy (ART) programs in service delivery settings in sub-Saharan Africa through 36 months on treatment. Methods We identified cohorts within Ovid Medline, ISI Web of Knowledge, Cochrane Database of Systematic Reviews and four conference abstract archives. We summarized retention rates from studies describing observational cohorts from sub-Saharan Africa reporting on adult HIV 1- infected patients initiating first-line three-drug ART. We estimated all-cause attrition rates for 6, 12, 18, 24, or 36 months after ART initiation including patients who died or were lost to follow-up (as defined by the author), but excluding transferred patients. Results We analysed 33 sources describing 39 cohorts and 226 307 patients. Patients were more likely to be female (median 65%) and had a median age at initiation of 37 (range 34-40). Median starting CD4 count was 109 cells/mm 3. Loss to follow-up was the most common cause of attrition (59%), followed by death (41%). Median attrition at 12, 24 and 36 months was 22.6% (range 7%-45%), 25% (range 11%-32%) and 29.5% (range 13%-36.1%) respectively. After pooling data in a random-effects meta-analysis, retention declined from 86.1% at 6 months to 80.2% at 12 months, 76.8% at 24 months and 72.3% at 36 months. Adjusting for variable follow-up time in a sensitivity analysis, 24 month retention was 70.0% (range: 66.7%-73.3%), while 36 month retention was 64.6% (range: 57.5%-72.1%). Conclusions Our findings document the difficulties in retaining patients in care for lifelong treatment, and the progress being made in raising overall retention rates. © 2010 Blackwell Publishing Ltd.


Fox M.P.,Boston University | Fox M.P.,Health Economics and Epidemiology Research Office | Shearer K.,Health Economics and Epidemiology Research Office | Maskew M.,Health Economics and Epidemiology Research Office | And 6 more authors.
PLoS ONE | Year: 2014

Introduction: While momentum for increasing treatment thresholds is growing, if patients cannot be retained in HIV care from the time of testing positive through long-term adherence to antiretroviral therapy (ART), such strategies may fall short of expected gains. While estimates of retention on ART exist, few cohorts have data on retention from testing positive through long-term ART care.Methods: We explored attrition (loss or death) at the Themba Lethu HIV clinic, Johannesburg, South Africa in 3 distinct cohorts enrolled at HIV testing, pre-ART initiation, and ART initiation.Results: Between March 2010 and August 2012 we enrolled 380 patients testing HIV+, 206 initiating pre-ART care, and 185 initiating ART. Of the 380 patients enrolled at testing HIV-positive, 38.7% (95%CI: 33.9-43.7%) returned for eligibility staging within ≤3 months of testing. Of the 206 enrolled at pre-ART care, 84.5% (95%CI: 79.0-88.9%) were ART eligible at their first CD4 count. Of those, 87.9% (95%CI: 82.4-92.2%) initiated ART within 6 months. Among patients not ART eligible at their first CD4 count, 50.0% (95%CI: 33.1-66.9%) repeated their CD4 count within one year of the first ineligible CD4. Among the 185 patients in the ART cohort, 22 transferred out and were excluded from further analysis. Of the remaining 163, 81.0% (95%CI: 74.4-86.5%) were retained in care through two years on treatment.Conclusions: Our findings from a well-resourced clinic demonstrate continual loss from all stages of HIV care and strategies to reduce attrition from all stages of care are urgently needed. © 2014 Fox et al.

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