The effectiveness and determinants of effectiveness of antiretroviral therapy for adults in the Western Cape Province of South Africa

Antiretroviral therapy (ART) first became available in the public sector in the Western Cape Province in Khayelitsha in 2001. This thesis describes the effectiveness of ART in Khayelitsha and the Province, following adult patients for up to five years on ART, and examining temporal trends over seven years during which time the availability of ART in the Province increased dramatically. Associations are explored with a range of clinical outcomes, and regimen durability and tolerability are described, together with regimen effectiveness when ART is administered to patients co-infected with tuberculosis. The results chapters of the thesis are presented in the form of published or submitted papers. The first paper corrects for under-ascertainment of mortality through linkages with the death registry. After five years on ART, four out of five patients were still alive. Survival did not deteriorate in more recent years despite the large increase in patient numbers. Patients who remained virologically suppressed experienced on average continued CD4 count recovery throughout follow-up to five years. The second paper describes the tolerability of each commonly used first-line antiretroviral drug in two townships in the Western Cape. Treatment-limiting toxicities were frequent and continued throughout follow-up in patients on stavudine (21% by 3 years on ART). Symptomatic hyperlactataemia or lactic acidosis as well as lipodystrophy were strongly associated with women initiating ART with a high initial body mass. The third paper explores the effectiveness of ART when co-administered with tuberculosis treatment, identifying that co-infected patients initiating nevirapinebased ART may be at a higher risk of virological failure, but that concurrent tuberculosis treatment did not otherwise compromise ART outcomes. The fourth paper, based on a household survey, provides an in-depth description of the Khayelitsha population demonstrating comparability with many of the urban settings in which ART is provided in the region. The final paper demonstrates that outcomes have not been compromised by the wider availability of ART in the Western Cape Province. The thesis concludes that the Khayelitsha and Provincial analyses provide considerable reassurance that the anticipated benefits of ART have not to date been eroded by health system weaknesses or contextual challenges

The effeciveness and determinants of effectiveness of antiretroviral therapy for adults in the Western Cape Province, South Africa

Includes bibliographical references.Antiretroviral therapy (ART) first became available in the public sector in the Western Cape Province in Khayelitsha in 2001. This thesis describes the effectiveness of ART in Khayelitsha and the Province, following adult patients for up to five years on ART, and examining temporal trends over seven years during which time the availability of ART in the Province increased dramatically. Associations are explored with a range of clinical outcomes, and regimen durability and tolerability are described, together with regimen effectiveness when ART is administered to patients co-infected with tuberculosis. The results chapters of the thesis are presented in the form of published or submitted papers. The first paper corrects for under-ascertainment of mortality through linkages with the death registry. After five years on ART, four out of five patients were still alive. Survival did not deteriorate in more recent years despite the large increase in patient numbers. Patients who remained virologically suppressed experienced on average continued CD4 count recovery throughout follow-up to five years. The second paper describes the tolerability of each commonly used first-line antiretroviral drug in two townships in the Western Cape. Treatment-limiting toxicities were frequent and continued throughout follow-up in patients on stavudine (21% by 3 years on ART). Symptomatic hyperlactataemia or lactic acidosis as well as lipodystrophy were strongly associated with women initiating ART with a high initial body mass. The third paper explores the effectiveness of ART when co-administered with tuberculosis treatment, identifying that co-infected patients initiating nevirapinebased ART may be at a higher risk of virological failure, but that concurrent tuberculosis treatment did not otherwise compromise ART outcomes. The fourth paper, based on a household survey, provides an in-depth description of the Khayelitsha population demonstrating comparability with many of the urban settings in which ART is provided in the region. The final paper demonstrates that outcomes have not been compromised by the wider availability of ART in the Western Cape Province. The thesis concludes that the Khayelitsha and Provincial analyses provide considerable reassurance that the anticipated benefits of ART have not to date been eroded by health system weaknesses or contextual challenges

Twelve-year mortality in adults initiating antiretroviral therapy in South Africa

Introduction: South Africa has the largest number of individuals living with HIV and the largest antiretroviral therapy (ART) programme worldwide. In September 2016, ART eligibility was extended to all 7.1 million HIV-positive South Africans. To ensure that further expansion of services does not compromise quality of care, long-term outcomes must be monitored. Few studies have reported long-term mortality in resource-constrained settings, where mortality ascertainment is challenging. Combining site records with data linked to the national vital registration system, sites in the International Epidemiology Databases to Evaluate AIDS Southern Africa collaboration can identify >95% of deaths in patients with civil identification numbers (IDs). This study used linked data to explore long-term mortality and viral suppression among adults starting ART in South Africa

The cost-effectiveness of Antiretroviral Treatment in Khayelitsha, South Africa – a primary data analysis

BACKGROUND: Given the size of the HIV epidemic in South Africa and other developing countries, scaling up antiretroviral treatment (ART) represents one of the key public health challenges of the next decade. Appropriate priority setting and budgeting can be assisted by economic data on the costs and cost-effectiveness of ART. The objectives of this research were therefore to estimate HIV healthcare utilisation, the unit costs of HIV services and the cost per life year (LY) and quality adjusted life year (QALY) gained of HIV treatment interventions from a provider's perspective. METHODS: Data on service utilisation, outcomes and costs were collected in the Western Cape Province of South Africa. Utilisation of a full range of HIV healthcare services was estimated from 1,729 patients in the Khayelitsha cohort (1,146 No-ART patient-years, 2,229 ART patient-years) using a before and after study design. Full economic costs of HIV-related services were calculated and were complemented by appropriate secondary data. ART effects (deaths, therapy discontinuation and switching to second-line) were from the same 1,729 patients followed for a maximum of 4 years on ART. No-ART outcomes were estimated from a local natural history cohort. Health-related quality of life was assessed on a sub-sample of 95 patients. Markov modelling was used to calculate lifetime costs, LYs and QALYs and uncertainty was assessed through probabilistic sensitivity analysis on all utilisation and outcome variables. An alternative scenario was constructed to enhance generalizability. RESULTS: Discounted lifetime costs for No-ART and ART were US$2,743 and US$9,435 over 2 and 8 QALYs respectively. The incremental cost-effectiveness ratio through the use of ART versus No-ART was US$1,102 (95$984 (95% CI 913-1,078) per life year gained. In an alternative scenario where adjustments were made across cost, outcome and utilisation parameters, costs and outcomes were lower, but the ICER was similar. CONCLUSION: Decisions to scale-up ART across sub-Saharan Africa have been made in the absence of incremental lifetime cost and cost-effectiveness data which seriously limits attempts to secure funds at the global level for HIV treatment or to set priorities at the country level. This article presents baseline cost-effectiveness data from one of the longest running public healthcare antiretroviral treatment programmes in Africa that could assist in enhancing efficient resource allocation and equitable access to HIV treatment

Anticipating future challenges to ART provision in South Africa: reflections on the Khayelitsha ART programme

The Khayelitsha ART programme has been in existence for five years. The emerging challenges are indicative of challenges other districts will face in the future. The number of adult patients started on ART annually in Khayelitsha has increased from 80 to 1 500. The gap between need and provision has narrowed, with a concomitant increase in the baseline CD4 count at ART initiation. Over time, adherence preparation has become less intensive, but the patient-centred approach has been retained. Consultations and staffing (especially doctors and counsellors) have increased   substantially over four years, without deterioration in clinical outcomes. To keep up with projected demand, the service needs to quadruple enrolment over the next five years. This will only be possible by utilising the full breadth of the primary care system and by integrating TB/HIV/ART care at each service point

The Effect of Complete Integration of HIV and TB Services on Time to Initiation of Antiretroviral Therapy: A Before-After Study.

Studies have shown that early ART initiation in TB/HIV co-infected patients lowers mortality. One way to implement earlier ART commencement could be through integration of TB and HIV services, a more efficient model of care than separate, vertical programs. We present a model of full TB/HIV integration and estimate its effect on time to initiation of ART

Reduced referral and case fatality rates for severe symptomatic hyperlactataemia in a South African public sector antiretroviral programme: a retrospective observational study

<p>Abstract</p> <p>Background</p> <p>Interventions to promote prevention and earlier diagnosis of severe symptomatic hyperlactataemia (SHL) were implemented in the Western Cape provincial antiretroviral programme (South Africa) from 2004. Interventions included clinician education, point-of-care lactate meters, switch from stavudine to zidovudine in high risk patients and stavudine dose reduction. This study assessed trends in referral rate, severity at presentation and case fatality rate for severe SHL.</p> <p>Methods</p> <p>Retrospective study of severe SHL cases diagnosed at a referral facility from 1 January 2003 to 31 December 2008. Severe SHL was defined as patients with compatible symptoms and serum lactate ≥ 5 mmol/l attributable to antiretroviral therapy (ART). Cumulative ART exposure at referring ART clinics was used to calculate referral rates.</p> <p>Results</p> <p>There were 254 severe SHL cases. The referral rate (per thousand patient years [py] ART exposure) peaked in 2005 (20.4/1000py), but fell to 1.3/1000py by 2008 (incidence rate ratio [IRR] = 0.07, 95%CI 0.04-0.11). In 2003, 66.7% of cases presented with a standard bicarbonate (SHCO₃) level <15 mmol/l, but this fell to 12.5% by 2008 (p for trend < 0.001). Case fatality rate fell from a peak of 33.3% in 2004 to 0% in 2008 (p for trend = 0.002).</p> <p>Conclusions</p> <p>These trends suggest the interventions were associated with reduced referral, less severe metabolic acidosis at presentation and improved survival.</p

Effectiveness of the first district-wide programme for the prevention of mother-to-child transmission of HIV in South Africa

Objective: The aim of this study was to estimate the field efficacy of the first routine programme for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) initiated in South Africa, in the subdistrict of Khayelitsha. Methods: A consecutive sample of 658 mother–infant pairs, identified from the PMTCT register from 1 March to 30 November 2003, were identified for enrolment in this study. Details of the regimen received were established and HIV status of the infants at between 6 and 10 weeks of age was determined by qualitative DNA polymerase chain reaction. Zidovudine (AZT) was provided antenatally from week 34 of gestation and during labour. Infant formula milk was offered to mothers who chose not to breastfeed. The protocol was amended in July 2003 such that women who had received 25 years was the only significant independent risk factor for transmission (odds ratio, 2.12; 95% CI, 1.14–4.07). Conclusion: The results of this study demonstrate the feasibility and effectiveness of a large-scale PMTCT programme in an urban public-sector setting

Virologic failure and second-line antiretroviral therapy in children in South Africa--the IeDEA Southern Africa collaboration

Article approval pendingWith expanding pediatric antiretroviral therapy (ART) access, children will begin to experience treatment failure and require second-line therapy. We evaluated the probability and determinants of virologic failure and switching in children in South Africa