Models Of Antiretroviral Therapy Research Articles

Community-supported models of care for people on HIV treatment in sub-Saharan Africa.

Further scale-up of antiretroviral therapy (ART) to those in need while supporting the growing patient cohort on ART requires continuous adaptation of healthcare delivery models. We describe several approaches to manage stable patients on ART developed by Médecins Sans Frontières together with Ministries of Health in four countries in sub-Saharan Africa. Using routine programme data, four approaches to simplify ART delivery for stable patients on ART were assessed from a patient and health system perspective: appointment spacing for clinical and drug refill visits in Malawi, peer educator-led ART refill groups in South Africa, community ART distribution points in DRC and patient-led community ART groups in Mozambique. All four approaches lightened the burden for both patients (reduced travel and lost income) and health system (reduced clinic attendance). Retention in care is high: 94% at 36 months in Malawi, 89% at 12 months in DRC, 97% at 40 months in South Africa and 92% at 48 months in Mozambique. Where evaluable, service provider costs are reported to be lower. Separating ART delivery from clinical assessments was found to benefit patients and programmes in a range of settings. The success of community ART models depends on sufficient and reliable support and resources, including a flexible and reliable drug supply, access to quality clinical management, a reliable monitoring system and a supported lay workers cadre. Such models require ongoing evaluation and further adaptation to be able to reach out to more patients, including specific groups who may be challenged to meet the demands of frequent clinic visits and the integrated delivery of other essential chronic disease interventions.

Community-based antiretroviral therapy programs can overcome barriers to retention of patients and decongest health services in sub-Saharan Africa: a systematic review

In sub-Saharan Africa models of care need to adapt to support continued scale up of antiretroviral therapy (ART) and retain millions in care. Task shifting, coupled with community participation has the potential to address the workforce gap, decongest health services, improve ART coverage, and to sustain retention of patients on ART over the long-term. The evidence supporting different models of community participation for ART care, or community-based ART, in sub-Saharan Africa, was reviewed. In Uganda and Kenya community health workers or volunteers delivered ART at home. In Mozambique people living with HIV/AIDS (PLWHA) self-formed community-based ART groups to deliver ART in the community. These examples of community ART programs made treatment more accessible and affordable. However, to achieve success some major challenges need to be overcome: first, community programs need to be driven, owned by and embedded in the communities. Second, an enabling and supportive environment is needed to ensure that task shifting to lay staff and PLWHA is effective and quality services are provided. Finally, a long term vision and commitment from national governments and international donors is required. Exploration of the cost, effectiveness, and sustainability of the different community-based ART models in different contexts will be needed.

An empirical test of the information-motivation-behavioral skills model of ART adherence in a sample of HIV-positive persons primarily in out-of-HIV-care settings

The current body of evidence supporting the Information-Motivation-Behavioral Skills (IMB) model of antiretroviral therapy (ART) adherence rests exclusively on data collected from people living with HIV (PLWH) at point-of-HIV-care services. The aims of this study were to: (1) determine if the IMB model is a useful predictive model of ART adherence among PLWH who were primarily recruited in out-of-HIV-care settings; and (2) assess whether the theorized associations between IMB model constructs and adherence persist in the presence of depression and current drug use. PLWH (n = 312) responding to a one-time online survey completed the Life Windows IMB-ART-Adherence Questionnaire, and demographic, depression (CES-D 10), and drug use items. Path models were used to assess the fit of a saturated versus fully mediated IMB model of adherence and examined for moderating effects of depression and current drug use. Participants were on average 43 years of age, had been living with HIV for 9 or more years, and mostly male (84.0%), Caucasian (68.8%), and gay-identified (74.8%). The a priori measurement models for information and behavioral skills did not have acceptable fit to the data and were modified accordingly. Using the revised IMB scales, IMB constructs were associated with adherence as predicted by the theory in all but one model (i.e., the IMB model operated as predicted among nondrug users and those with and without depression). Among drug users, information exerted a direct effect on adherence but was not significantly associated with behavioral skills. Results of this study suggest that the fully or partially mediated IMB model is supported for use with samples of PLWH recruited primarily out-of-HIV-care service settings and is robust in the presence of depression and drug use.

Bringing antiretroviral therapy (ART) closer to the end‐user through mobile clinics and home‐based ART: systematic review shows more evidence on the effectiveness and cost effectiveness is needed

Home-based antiretroviral therapy (ART) and ART through mobile clinics can potentially increase access to ART for large numbers of people, including hard-to-reach populations. We reviewed literature on the effectiveness and cost implications of the home-based ART and mobile clinic ART models. We searched Medline, Embase, PsycInfo, CINAHL, Cochrane Library, Web of Knowledge and Current Controlled Trials Register for articles published up to March 2012. We included non-randomised and randomised controlled clinical trials that recruited HIV/AIDS positive adults with or without prior exposure to ART. Six studies were included in the review, with only four effectiveness studies (all evaluating home-based ART and none for mobile clinic ART) and four studies reporting on the cost implications. The evidence suggests home-based ART is as effective as health facility-based ART, including on clinical outcomes, viral load and CD4+ count. However, three of these studies were very small. Studies suggest health facility-based ART is the most cost-effective, followed by mobile-clinic ART, with home-based ART being the least cost-effective. Evidence on the effectiveness and cost implications of mobile clinic and home-based ART is currently limited. Although the few available studies suggest home-based ART can potentially be as effective as health facility-based ART, there is need for more research before robust conclusions can be made. Results from the few available studies also suggest that health facility-based ART is the most cost-effective.

Scaling Up Community ART Groups in Mozambique

Aims: To describe the stepwise implementation and roll out of Community ART Groups (CAG) in Mozambique. Study Design: Descriptive study Place and Duration of Study: Mozambique, between February 2008 and December 2011. Methodology: Description of the stepwise implementation of a model for Anti-Retroviral Therapy (ART) delivery based on the principles of peer support and self-management. The program data on CAG were obtained through a chart review and routine datacollection. Results: To overcome patient reported barriers to monthly drug refills for ART the Tete Provincial Directorate of Health and Medecins Sans Frontieres developed a communitybased ART model or patient-centered model, through peer support groups named CAG. The first CAG commenced in 2008, in rural health facility catchment areas, where members of CAG shared transport costs to overcome distances to the ART clinics. In 2009, lessons learnt were exported in Tete province and CAG model was launched in semi-urban contexts to decrease time spent in the clinics. In 2011, retention rates as high as 97,5 % convinced a joint task force that included Ministry of Health and major partners Original Research Article Decroo et al.; ISRR, Article no. ISRR.2013.001 50 to pilot the CAG strategy on a national scale. Conclusion: To respond to staggering attrition rates Ministry of Health in Mozambique and partners piloted an innovative patient-centered model for HIV care and exported good practices from local to provincial and national level. Success of scale up will depend on the collaboration and interaction between policymakers, donors, health-managers, caregivers, communities, and patients.

Projecting the Benefits of Antiretroviral Therapy for HIV Prevention: The Impact of Population Mobility and Linkage to Care

Recent mathematical models suggested that frequent human immunodeficiency virus (HIV) testing with immediate initiation of antiretroviral therapy (ART) to individuals with a positive test result could profoundly curb transmission. The debate about ART as prevention has focused largely on parameter values. We aimed to evaluate structural assumptions regarding linkage to care and population mobility, which have received less attention. We modified the linkage structure of published models of ART as prevention, such that individuals who decline initial testing or treatment do not link to care until late-stage HIV infection. We then added population mobility to the models. We populated the models with demographic, clinical, immigration, emigration, and linkage data from a South African township. In the refined linkage model, elimination of HIV transmission (defined as an incidence of <0.1%) did not occur by 30 years, even with optimistic assumptions about the linkage rate. Across a wide range of estimates, models were more sensitive to structural assumptions about linkage than to parameter values. Incorporating population mobility further attenuated the reduction in incidence conferred by ART as prevention. Linkage to care and population mobility are critical features of ART-as-prevention models. Clinical trials should incorporate relevant data on linkage to care and migration to evaluate the impact of this strategy.

Early and Late Direct Costs in a Southern African Antiretroviral Treatment Programme: A Retrospective Cohort Analysis

There is a paucity of data on the health care costs of antiretroviral therapy (ART) programmes in Africa. Our objectives were to describe the direct heath care costs and establish the cost drivers over time in an HIV managed care programme in Southern Africa. We analysed the direct costs of treating HIV-infected adults enrolled in the managed care programme from 3 years before starting non-nucleoside reverse transcriptase inhibitor-based ART up to 5 years afterwards. The CD4 cell count criterion for starting ART was <350 cells/microl. We explored associations between variables and mean total costs over time using a generalised linear model with a log-link function and a gamma distribution. Our cohort consisted of 10,735 patients (59.4% women) with 594,497 mo of follow up data (50.9% of months on ART). Median baseline CD4+ cell count and viral load were 125 cells/microl and 5.16 log(10) copies/ml respectively. There was a peak in costs in the period around ART initiation (from 4 mo before until 4 mo after starting ART) driven largely by hospitalisation, following which costs plateaued for 5 years. The variables associated with changes in mean total costs varied with time. Key early associations with higher costs were low baseline CD4+ cell count, high baseline HIV viral load, and shorter duration in HIV care prior to starting ART; whilst later associations with higher costs were lower ART adherence, switching to protease inhibitor-based ART, and starting ART at an older age. Drivers of mean total costs changed considerably over time. Starting ART at higher CD4 counts or longer pre-ART care should reduce early costs. Monitoring ART adherence and interventions to improve it should reduce later costs. Cost models of ART should take into account these time-dependent cost drivers, and include costs before starting ART. Please see later in the article for the Editors' Summary.

PIN36 MICROSIMULATION OR COHORT MODELING? A COMPARATIVE CASE STUDY IN HIV INFECTION

Background: A trade-off between validity and feasibility is inevitable in decision analytic modelling. In HIV infection, progression rates depend, inter alia, on individual case histories. Variability between individuals can conveniently be modelled using first-order Monte Carlo microsimulation. But this makes concurrent modelling of second-order uncertainty problematic, as probabilistic analysis is more readily applied to an aggregate cohort. Objective: The objectives of this study were to compare first-order Monte Carlo simulation to a cohort approach in modelling the cost-effectiveness of antiretroviral therapy (ART) in HIV infection, and to validate the two models against an existing published model (CEPAC). Methods: Two alternative Markov models were developed. Cost-effectiveness analyses (CEA) were performed with each model in which optimised background therapy (OBT) plus enfuvirtide was compared with OBT alone in treatment-experienced patients, from a US payer perspective using 2003 costs, discounting costs and effects at 3% per annum over a lifetime. Disease progression in both models was dependent on CD4 cell count, viral load set point, treatment, response, age, and opportunistic infections. The simulation model (ARAMIS) used tracker variables to accumulate individual case histories. Transition probabilities depended on this prognostic information and on elapsed time. The cohort model (CM) used more disease states than ARAMIS to model history and time dependency partially. Both models were populated with cohort data from the TORO-1 and TORO-2 trials; as distributions in ARAMIS and stratified according to disease states in the CM. Markov cycle lengths in ARAMIS and the CM were 1 and 3 months respectively. Results: Estimated mean total lifetime costs were as follows. For OBT, ARAMIS: $156,700; CM: $148,500 (CEPAC: $151,000), and for OBT + enfuvirtide ARAMIS: $201,600, CM: $180,100 (CEPAC: $205,900). Mean discounted quality adjusted life expectancy (in QALYs) for OBT was estimated as ARAMIS: 3.60; CM 3.64 (CEPAC: 3.78) and for OBT + enfuvirtide as ARAMIS:4.59 and CM: 4.29 (CEPAC: 4.58). Respective figures for undiscounted, unadjusted life expectancy (years) were ARAMIS: 4.90; CM: 4.77 (CEPAC: 4.64) for OBT and ARAMIS: 6.40; CM: 5.76 (CEPAC: 5.57) for OBT + enfuvirtide. Conclusions: For treatment-experienced patients, the new models generated comparable estimates of life expectancy and costs. These results were comparable to the current "gold standard" among models of ART. The cohort and simulation approaches have individual strengths and limitations. The cohort model minimises computing time and simplifies the incorporation of probabilistic analysis of uncertainty, an increasingly required feature. The microsimulation model allows a fuller set of model inputs and avoids over-simplifying assumptions, yet the use of individual case histories allows a more compact set of Markov states. Microsimulation may have greater face validity among clinicians, though technology assessors may see this as less important than probabilistic sensitivity analysis. Our results apply to relatively advanced disease and treatment-experienced patients.

Public health consequences of screening patients for adherence to highly active antiretroviral therapy.

Improvements in HIV antiretroviral therapy (ART) have been accompanied by increasing recognition of the importance of adherence to treatment regimens for maximizing patient benefits while minimizing the emergence of drug-resistant virus. Whether clinicians should screen patients for adherence and only administer therapy to those believed likely to adhere has not been resolved. We first examine the implications of data drawn from a recent study reporting physicians' ability to predict whether patients will adhere to highly active antiretroviral therapy (HAART) or not. We then extend previously developed mathematical models of ART to include screening for adherence and focus on resulting drug resistance as well as on HIV and AIDS incidence at the population level. We show that although screening for adherence is likely to reduce the level of drug resistance compared with a policy of treating all HIV patients with HAART, rates of new HIV infections and AIDS cases in the population would likely increase unless screening accuracy is extremely (perhaps implausibly) high.