Venessa Timmerman

Outcomes in patients waiting for antiretroviral treatment in the Free State Province, South Africa: prospective linkage study

Objective:In South Africa, many HIV-infected patients experience delays in accessing antiretroviral therapy (ART). We examined pretreatment mortality and access to treatment in patients waiting for ART. Design:Cohort of HIV-infected patients assessed for ART eligibility at 36 facilities participating in the Comprehensive HIV and AIDS Management (CHAM) program in the Free State Province. Methods:Proportion of patients initiating ART, pre-ART mortality and risk factors associated with these outcomes were estimated using competing risks survival analysis. Results:Forty-four thousand, eight hundred and forty-four patients enrolled in CHAM between May 2004 and December 2007, of whom 22 083 (49.2%) were eligible for ART; pre-ART mortality was 53.2 per 100 person-years [95% confidence interval (CI) 51.8–54.7]. Median CD4 cell count at eligibility increased from 87 cells/μl in 2004 to 101 cells/μl in 2007. Two years after eligibility an estimated 67.7% (67.1–68.4%) of patients had started ART, and 26.2% (25.6–26.9%) died before starting ART. Among patients with CD4 cell counts below 25 cells/μl at eligibility, 48% died before ART and 51% initiated ART. Men were less likely to start treatment and more likely to die than women. Patients in rural clinics or clinics with low staffing levels had lower rates of starting treatment and higher mortality compared with patients in urban/peri-urban clinics, or better staffed clinics. Conclusions:Mortality is high in eligible patients waiting for ART in the Free State Province. The most immunocompromised patients had the lowest probability of starting ART and the highest risk of pre-ART death. Prioritization of these patients should reduce waiting times and pre-ART mortality.

Innovating to improve primary care in less developed countries: towards a global model

One of the biggest problems in global health is the lack of well trained and supported health workers in less developed settings. In many rural areas there are no physicians, and it is important to find ways to support and empower nurses and other health workers. The Knowledge Translation Unit of the University of Cape Town Lung Institute has spent 14 years developing a series of innovative packages to support and empower nurses and other health workers. PACK (Practical Approach to Care Kit) Adult comprises policy-based and evidence-informed guidelines; onsite, team and case-based training; non-physician prescribing; and a cascade system of scaling up. A series of randomised trials has shown the effectiveness of the packages, and methods are now being developed to respond cost-effectively and sustainably to global demand for implementing PACK Adult. Global health would probably benefit from less time and money spent developing new innovations and more spent on finding ways to spread those we already have.

Cost-effectiveness of nurse-led versus doctor-led antiretroviral treatment in South Africa: pragmatic cluster randomised trial

To estimate the cost‐effectiveness of nurse‐led versus doctor‐led antiretroviral treatment (ART) for HIV‐infected people.

Differences in access and patient outcomes across antiretroviral treatment clinics in the Free State province: A prospective cohort study

OBJECTIVE To assess differences in access to antiretroviral treatment (ART) and patient outcomes across public sector treatment facilities in the Free State province, South Africa. DESIGN Prospective cohort study with retrospective database linkage. We analysed data on patients enrolled in the treatment programme across 36 facilities between May 2004 and December 2007, and assessed percentage initiating ART and percentage dead at 1 year after enrolment. Multivariable logistic regression was used to estimate associations of facility-level and patient-level characteristics with both mortality and treatment status. RESULTS Of 44 866 patients enrolled, 15 219 initiated treatment within 1 year; 8 778 died within 1 year, 7 286 before accessing ART. Outcomes at 1 year varied greatly across facilities and more variability was explained by facility-level factors than by patient-level factors. The odds of starting treatment within 1 year improved over calendar time. Patients enrolled in facilities with treatment initiation available on site had higher odds of starting treatment and lower odds of death at 1 year compared with those enrolled in facilities that did not offer treatment initiation. Patients were less likely to start treatment if they were male, severely immunosuppressed (CD4 count ≤50 cells/µl), or underweight (<50 kg). Men were also more likely to die in the first year after enrolment. CONCLUSIONS Although increasing numbers of patients started ART between 2004 and 2007, many patients died before accessing ART. Patient outcomes could be improved by decentralisation of treatment services, fast-tracking the most immunodeficient patients and improving access, especially for men.

Temporal Trends in the Characteristics of Children at Antiretroviral Therapy Initiation in Southern Africa: The IeDEA-SA Collaboration

Background Since 2005, increasing numbers of children have started antiretroviral therapy (ART) in sub-Saharan Africa and, in recent years, WHO and country treatment guidelines have recommended ART initiation for all infants and very young children, and at higher CD4 thresholds for older children. We examined temporal changes in patient and regimen characteristics at ART start using data from 12 cohorts in 4 countries participating in the IeDEA-SA collaboration. Methodology/Principal Findings Data from 30,300 ART-naïve children aged <16 years at ART initiation who started therapy between 2005 and 2010 were analysed. We examined changes in median values for continuous variables using the Cuzicks test for trend over time. We also examined changes in the proportions of patients with particular disease severity characteristics (expressed as a binary variable e.g. WHO Stage III/IV vs I/II) using logistic regression. Between 2005 and 2010 the number of children starting ART each year increased and median age declined from 63 months (2006) to 56 months (2010). Both the proportion of children <1 year and ≥10 years of age increased from 12 to 19% and 18 to 22% respectively. Children had less severe disease at ART initiation in later years with significant declines in the percentage with severe immunosuppression (81 to 63%), WHO Stage III/IV disease (75 to 62%), severe anemia (12 to 7%) and weight-for-age z-score<−3 (31 to 28%). Similar results were seen when restricting to infants with significant declines in the proportion with severe immunodeficiency (98 to 82%) and Stage III/IV disease (81 to 63%). First-line regimen use followed country guidelines. Conclusions/Significance Between 2005 and 2010 increasing numbers of children have initiated ART with a decline in disease severity at start of therapy. However, even in 2010, a substantial number of infants and children started ART with advanced disease. These results highlight the importance of efforts to improve access to HIV diagnostic testing and ART in children.

Educational Outreach with an Integrated Clinical Tool for Nurse-Led Non-communicable Chronic Disease Management in Primary Care in South Africa: A Pragmatic Cluster Randomised Controlled Trial

Background In many low-income countries, care for patients with non-communicable diseases (NCDs) and mental health conditions is provided by nurses. The benefits of nurse substitution and supplementation in NCD care in high-income settings are well recognised, but evidence from low- and middle-income countries is limited. Primary Care 101 (PC101) is a programme designed to support and expand nurses’ role in NCD care, comprising educational outreach to nurses and a clinical management tool with enhanced prescribing provisions. We evaluated the effect of the programme on primary care nurses’ capacity to manage NCDs. Methods and Findings In a cluster randomised controlled trial design, 38 public sector primary care clinics in the Western Cape Province, South Africa, were randomised. Nurses in the intervention clinics were trained to use the PC101 management tool during educational outreach sessions delivered by health department trainers and were authorised to prescribe an expanded range of drugs for several NCDs. Control clinics continued use of the Practical Approach to Lung Health and HIV/AIDS in South Africa (PALSA PLUS) management tool and usual training. Patients attending these clinics with one or more of hypertension (3,227), diabetes (1,842), chronic respiratory disease (1,157) or who screened positive for depression (2,466), totalling 4,393 patients, were enrolled between 28 March 2011 and 10 November 2011. Primary outcomes were treatment intensification in the hypertension, diabetes, and chronic respiratory disease cohorts, defined as the proportion of patients in whom treatment was escalated during follow-up over 14 mo, and case detection in the depression cohort. Primary outcome data were analysed for 2,110 (97%) intervention and 2,170 (97%) control group patients. Treatment intensification rates in intervention clinics were not superior to those in the control clinics (hypertension: 44% in the intervention group versus 40% in the control group, risk ratio [RR] 1.08 [95% CI 0.94 to 1.24; p = 0.252]; diabetes: 57% versus 50%, RR 1.10 [0.97 to 1.24; p = 0.126]; chronic respiratory disease: 14% versus 12%, RR 1.08 [0.75 to 1.55; p = 0.674]), nor was case detection of depression (18% versus 24%, RR 0.76 [0.53 to 1.10; p = 0.142]). No adverse effects of the nurses’ expanded scope of practice were observed. Limitations of the study include dependence on self-reported diagnoses for inclusion in the patient cohorts, limited data on uptake of PC101 by users, reliance on process outcomes, and insufficient resources to measure important health outcomes, such as HbA1c, at follow-up. Conclusions Educational outreach to primary care nurses to train them in the use of a management tool involving an expanded role in managing NCDs was feasible and safe but was not associated with treatment intensification or improved case detection for index diseases. This notwithstanding, the intervention, with adjustments to improve its effectiveness, has been adopted for implementation in primary care clinics throughout South Africa. Trial Registration The trial is registered with Current Controlled Trials (ISRCTN20283604)

Towards universal ARV access: achievements and challenges in Free State province, South Africa

OBJECTIVE To study the progress and challenges with regard to universal antiretroviral (ARV) access in Free State Province, South Africa. METHODS Data from the first 4 years of the public sector ARV roll-out and selected health system indicators were used. Data were collected from the public sector ARV database in Free State Province for new patients on ARVs, average waiting times and median CD4 counts at the start of treatment. Information on staff training, vacancy rates and funding allocations for the ARV roll-out was obtained from official government reports. Projections were made of expected new ARV enrolments for 2008 and 2009 and compared with goals set by the National Strategic Plan (NSP) to achieve universal access to ARVs by 2011. RESULTS New ARV enrolments increased annually to 25% of the estimated need by the end of 2007. Average waiting times to enrolment decreased from 5.82 months to 3.24 months. Median CD4 counts at enrolment increased from 89 to 124 cells/mm3. There is a staff vacancy rate of 38% in the ARV programme and an inadequate increase in budget allocations. CONCLUSION The current vertical model of ARV therapy delivery is unlikely to raise the number of new enrolments sufficiently to achieve the goals of universal access by 2011 as envisaged by the NSP. The Free State is implementing a project (STRETCH trial) to broaden the ARV roll-out in an attempt to increase access to ARVs.

Effect of antiretroviral treatment on the risk of tuberculosis during South Africa's programme expansion.

Objective:The objective of this study is to estimate the effectiveness of antiretroviral treatment (ART) in preventing tuberculosis (TB) in HIV-infected people during the first 6 years of ART programme expansion. Design:A cohort study comparing TB risk without ART and after ART initiation. Setting:Public sector HIV programme of the Free State province, South Africa. Participants:Seventy-four thousand and seventy-four HIV-infected people enrolled from 2004 until 2010, of whom 43 898 received ART and 30 176 did not. Intervention:Combination ART. Main outcome measures:Time to first TB diagnosis, adjusted for CD4+ cell count, weight, age, sex, previous TB, district and year, with ART, CD4+ cell count and weight as time-varying covariates and with death as a competing risk. Results:Three thousand eight hundred and fifty-eight first TB episodes occurred during 78 202 person-years at risk with ART and 5669 episodes occurred during 62 801 person-years without ART [incidence rates 4.9 and 9.0 per 100 person-years, crude incidence rate ratio 0.55 (95% confidence interval 0.52–0.57)]. The adjusted subhazard ratio (SHR) of time to first TB episode after starting ART, compared with follow-up without ART, was 0.67 (0.64–0.70). Within CD4+ cell count subgroups (<50, 50–199, 100–199, 200–349 and >350 cells/&mgr;l), the respective SHRs were 0.64 (0.57–0.71), 0.63 (0.57–0.70), 0.66 (0.61–0.72), 0.67 (0.62–0.72), 0.72 (0.63–0.83) and 0.97 (0.60–1.59). Adjusted SHRs for ART decreased with each year of enrolment, from 0.90 (0.77–1.04) in 2004 to 0.54 (0.43–0.67) in 2010. Conclusion:ART was effective in preventing TB in HIV-infected patients with CD4+ cell counts below 350 cells/&mgr;l, but less so than previously estimated. Effectiveness increased each year.