Rapid antiretroviral therapy scale-up in Hubei Province, China

In 2003, physicians in China were unprepared to care for people with AIDS. Project HOPE partnered with Hubei Province health authorities to train and mentor doctors and build capacity for HIV care. From 2004 to 2006, seventy-eight Chinese "master trainers" were trained, who then trained and mentored 8,759 health workers. During this period, as the free antiretroviral therapy period began, measures of physician competence in HIV care improved significantly, and annual mortality from AIDS fell from 49 percent to 8.8 percent. This international partnership created a sustainable capacity for effective HIV prevention and care that could be replicable in other settings.     

Human resources requirements for highly active antiretroviral therapy scale-up in Malawi

Background  

Twelve percent of the adult population in Malawi is estimated to be HIV infected. About 15% to 20% of these are in need of life saving antiretroviral therapy. The country has a public sector-led antiretroviral treatment program both in the private and public health sectors. Estimation of the clinical human resources needs is required to inform the planning and distribution of health professionals.     

Monitoring the response to antiretroviral therapy in resource-poor settings: the Malawi model

With assistance from the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM), Malawi is scaling-up the delivery of antiretroviral (ARV) therapy to HIV-positive eligible patients. The country has developed National ARV Treatment Guidelines, which emphasize a structured and standardized approach for all aspects of ARV delivery, including monitoring and evaluation. Using the successful DOTS model adapted by National TB Control Programmes throughout the world, Malawi has developed a system of quarterly ARV cohort and cumulative ARV quarterly analyses. Thyolo district, in the southern region of Malawi, has been using this system since April 2003. This paper describes the standardized ARV treatment regimens and the treatment outcomes used in Thyolo to assess the impact of treatment, the registration and monitoring systems and how the cohort analyses are carried out. Data are presented for case registration and treatment outcome for the first quarterly cohort (April to June) and the combined cohorts (April to June and July to September). Such quarterly analyses may be useful for districts and Ministries of Health in assessing ARV delivery, although the burden of work involved in calculating the numbers may become large once ARV delivery systems have been established for several years.     

Supervision, monitoring and evaluation of nationwide scale-up of antiretroviral therapy in Malawi

OBJECTIVE: To describe the supervision, monitoring and evaluation strategies used to assess the delivery of antiretroviral therapy during nationwide scale-up of treatment in Malawi. METHODS: In the first quarter of 2005, the HIV Unit of the Ministry of Health and its partners (the Lighthouse Clinic; Médecins Sans Frontières-Belgium, Thyolo district; and WHO's Country Office) undertook structured supervision and monitoring of all public sector health facilities in Malawi delivering antiretroviral therapy. FINDINGS: Data monitoring showed that by the end of 2004, there were 13,183 patients (5274 (40%) male, 12 527 (95%) adults) who had ever started antiretroviral therapy. Of patients who had ever started, 82% (10 761/13,183) were alive and taking antiretrovirals; 8% (1026/13,183) were dead; 8% (1039/13,183) had been lost to follow up; <1% (106/13,183) had stopped treatment; and 2% (251/13,183) had transferred to another facility. Of those alive and on antiretrovirals, 98% (7098/7258) were ambulatory; 85% (6174/7258) were fit to work; 10% (456/4687) had significant side effects; and, based on pill counts, 96% (6824/7114) had taken their treatment correctly. Mistakes in the registration and monitoring of patients were identified and corrected. Drug stocks were checked, and one potential drug stock-out was averted. As a result of the supervisory visits, by the end of March 2005 recruitment of patients to facilities scheduled to start delivering antiretroviral therapy had increased. CONCLUSION: This report demonstrates the importance of early supervision for sites that are starting to deliver antiretroviral therapy, and it shows the value of combining data collection with supervision. Making regular supervisory and monitoring visits to delivery sites are essential for tracking the national scale-up of delivery of antiretrovirals.     

Decline in national tuberculosis notifications with national scale-up of antiretroviral therapy in Malawi

From 2000 to 2012, Malawi scaled up antiretroviral therapy (ART) from <3000 to 404 905 persons living with HIV/AIDS (human immunodeficiency virus/acquired immune-deficiency syndrome), representing an ART coverage of 40.6% among those living with HIV. During this time, annual tuberculosis (TB) notifications declined by 28%, from 28 234 to 20 463. Percentage declines in annual TB case notifications were as follows: new TB (26%), recurrent TB (40%), new smear-positive pulmonary TB (19%), new smear-negative pulmonary TB (42%), extra-pulmonary TB (19%), HIV-positive TB (30%) and HIV-negative TB (10%). The decline in TB notifications is associated with ART scale-up, supporting its value in controlling TB in high HIV prevalence areas in sub-Saharan Africa.     

Marginal structural models application to estimate the effects of antiretroviral therapy in 5 cohorts of HIV seroconverters

OBJECTIVES: Standard methods to evaluate population effectiveness of treatments in observational studies have important limitations to appropriately adjust for time-dependent confounders. In this paper, we describe a recently developed methodological approach, marginal structural models (MSM), and use it to estimate the effectiveness of highly active antiretroviral therapy (HAART) on AIDS or death incidence. SUBJECTS AND METHODS: We analyzed all subjects followed after 1997 as part of the GEMES project (comprised by several cohorts of HIV seroconverters in Spain) and who had not used HAART before the start of follow-up. To estimate the effect of HAART on AIDS or death incidence, we estimated the parameters of a marginal structural Cox model by fitting an inverse probability weighted logistic regression model. The estimation of the weights was based on CD4 count, time since seroconversion, sex, age, transmission category and previous treatment. RESULTS: 917 eligible subjects were followed for an average of 3.4 years and we observed 139 events. 42.1% of the participants received HAART during the study. The estimated rate ratio was 1.01 (95% confidence interval [CI], 0.68-1.49) using a Cox model without covariates and 0.90 (95% CI, 0.61-1.32) using a Cox model with time-dependent covariates. The causal rate ratio estimated for MSM was 0.74, (95% CI, 0.49-1.12). CONCLUSIONS: The beneficial effect of HAART estimated by the MSM, but largely missed by conventional methods, is consistent with the findings of previous randomized studies. The MSM appropriately adjusted for the time-dependent covariate CD4 count, which is both a time-varying confounder and is affected by prior treatment.     

The role of state and non-state actors in the policy process: the contribution of policy networks to the scale-up of antiretroviral therapy in Thailand

Antiretroviral therapy (ART) is difficult in poor settings. In 2001, the Thai government adopted the policy to scale-up its treatment initiative to meet the needs of all its people. Employing qualitative approaches, including in-depth interviews, document review and direct observation, this study examines the processes by which the universal ART policy developed between 2001 and 2007, with the focus on the connections between actors who shared common interests--so-called policy networks. Research findings illustrate the crucial contributions of non-state networks in the policy process. The supportive roles of public-civic networks could be observed at every policy stage, and at different levels of the health sector. Although this particular health policy may be unique in case and setting, it does suggest clearly that while the state dominated the policy process initially, non-state actors played extremely important roles. Their contribution was not simply at agenda-setting stages--for example by lobbying government--but in the actual development and implementation of health policy. Further it illustrates that these processes were dynamic, took place over long periods and were not limited to national borders, but extended beyond, to include global actors and processes.     

The parametric g-formula to estimate the effect of highly active antiretroviral therapy on incident AIDS or death

The parametric g‐formula can be used to contrast the distribution of potential outcomes under arbitrary treatment regimes. Like g‐estimation of structural nested models and inverse probability weighting of marginal structural models, the parametric g‐formula can appropriately adjust for measured time‐varying confounders that are affected by prior treatment. However, there have been few implementations of the parametric g‐formula to date. Here, we apply the parametric g‐formula to assess the impact of highly active antiretroviral therapy on time to acquired immune deficiency syndrome (AIDS) or death in two US‐based human immunodeficiency virus cohorts including 1498 participants. These participants contributed approximately 7300 person‐years of follow‐up (49% exposed to highly active antiretroviral therapy) during which 382 events occurred and 259 participants were censored because of dropout. Using the parametric g‐formula, we estimated that antiretroviral therapy substantially reduces the hazard of AIDS or death (hazard ratio = 0.55; 95% confidence limits [CL]: 0.42, 0.71). This estimate was similar to one previously reported using a marginal structural model, 0.54 (95% CL: 0.38, 0.78). The 6.5‐year difference in risk of AIDS or death was 13% (95% CL: 8%, 18%). Results were robust to assumptions about temporal ordering, and extent of history modeled, for time‐varying covariates. The parametric g‐formula is a viable alternative to inverse probability weighting of marginal structural models and g‐estimation of structural nested models for the analysis of complex longitudinal data. Copyright © 2012 John Wiley & Sons, Ltd.     

Trends in all-cause mortality during the scale-up of an antiretroviral therapy programme: a cross-sectional study in Lusaka,Zambia

Objective

To follow the trends in all-cause mortality in Lusaka, Zambia, during the scale-up of a national programme of antiretroviral therapy (ART).

Methods

Between November 2004 and September 2011, we conducted 12 survey rounds as part of a cross-sectional study in Lusaka, with independent sampling in each round. In each survey, we asked the heads of 3600 households to state the number of deaths in their households in the previous 12 months and the number of orphans aged less than 16 years in their households and investigated the heads’ knowledge, attitudes and practices related to human immunodeficiency virus (HIV).

Findings

The number of deaths we recorded – per 100 person–years – in each survey ranged from 0.92 (95% confidence interval, CI: 0.78–1.09) in September 2011, to 1.94 (95% CI: 1.60–2.35) in March 2007. We found that mortality decreased only modestly each year (mortality rate ratio: 0.98; 95% CI: 0.95–1.00; P = 0.093). The proportion of households with orphans under the age of 16 years decreased from 17% in 2004 to 7% in 2011. The proportions of respondents who had ever been tested for HIV, had a comprehensive knowledge of HIV, knew where to obtain free ART and reported that a non-pregnant household member was receiving ART gradually increased.

Conclusion

The expansion of ART services in Lusaka was not associated with a reduction in all-cause mortality. Coverage, patient adherence and retention may all have to be increased if ART is to have a robust and lasting impact at population level in Lusaka.     

Early loss of HIV-infected patients on potent antiretroviral therapy programmes in lower-income countries

OBJECTIVE: To analyse the early loss of patients to antiretroviral therapy (ART) programmes in resource-limited settings. METHODS: Using data on 5491 adult patients starting ART (median age 35 years, 46% female) in 15 treatment programmes in Africa, Asia and South America with (3) 12 months of follow-up, we investigated risk factors for no follow-up after treatment initiation, and loss to follow-up or death in the first 6 months. FINDINGS: Overall, 211 patients (3.8%) had no follow-up, 880 (16.0%) were lost to follow-up and 141 (2.6%) were known to have died in the first 6 months. The probability of no follow-up was higher in 2003-2004 than in 2000 or earlier (odds ratio, OR: 5.06; 95% confidence interval, CI: 1.28-20.0), as was loss to follow-up (hazard ratio, HR: 7.62; 95% CI: 4.55-12.8) but not recorded death (HR: 1.02; 95% CI: 0.44-2.36). Compared with a baseline CD4-cell count (3) 50 cells/microl, a count < 25 cells/microl was associated with a higher probability of no follow-up (OR: 2.49; 95% CI: 1.43-4.33), loss to follow-up (HR: 1.48; 95% CI: 1.23-1.77) and death (HR: 3.34; 95% CI: 2.10-5.30). Compared to free treatment, fee-for-service programmes were associated with a higher probability of no follow-up (OR: 3.71; 95% CI: 0.97-16.05) and higher mortality (HR: 4.64; 95% CI: 1.11-19.41). CONCLUSION: Early patient losses were increasingly common when programmes were scaled up and were associated with a fee for service and advanced immunodeficiency at baseline. Measures to maximize ART programme retention are required in resource-poor countries.     

Measuring adherence to antiretroviral therapy in northern Tanzania: feasibility and acceptability of the Medication Event Monitoring System

Background  

An often-used tool to measure adherence to antiretroviral therapy (ART) is the Medication Event Monitoring System (MEMS), an electronic pill-cap that registers date and time of pill-bottle openings. Despite its strengths, MEMS-data can be compromised by inaccurate use and acceptability problems due to its design. These barriers remain, however, to be investigated in resource-limited settings. We evaluated the feasibility and acceptability of using MEMS-caps to monitor adherence among HIV-infected patients attending a rural clinic in Tanzania's Kilimanjaro Region.     

Contrasting predictors of poor antiretroviral therapy outcomes in two South African HIV programmes: a cohort study

Background  

Many national antiretroviral therapy (ART) programmes encourage providers to identify and address baseline factors associated with poor treatment outcomes, including modifiable adherence-related behaviours, before initiating ART. However, evidence on such predictors is scarce, and providers judgement may often be inaccurate. To help address this evidence gap, this observational cohort study examined baseline factors potentially predictive of poor treatment outcomes in two ART programmes in South Africa, with a particular focus on determinants of adherence.     

Marginal structural models for case-cohort study designs to estimate the association of antiretroviral therapy initiation with incident AIDS or death

To estimate the association of antiretroviral therapy initiation with incident acquired immunodeficiency syndrome (AIDS) or death while accounting for time-varying confounding in a cost-efficient manner, the authors combined a case-cohort study design with inverse probability-weighted estimation of a marginal structural Cox proportional hazards model. A total of 950 adults who were positive for human immunodeficiency virus type 1 were followed in 2 US cohort studies between 1995 and 2007. In the full cohort, 211 AIDS cases or deaths occurred during 4,456 person-years. In an illustrative 20% random subcohort of 190 participants, 41 AIDS cases or deaths occurred during 861 person-years. Accounting for measured confounders and determinants of dropout by inverse probability weighting, the full cohort hazard ratio was 0.41 (95% confidence interval: 0.26, 0.65) and the case-cohort hazard ratio was 0.47 (95% confidence interval: 0.26, 0.83). Standard multivariable-adjusted hazard ratios were closer to the null, regardless of study design. The precision lost with the case-cohort design was modest given the cost savings. Results from Monte Carlo simulations demonstrated that the proposed approach yields approximately unbiased estimates of the hazard ratio with appropriate confidence interval coverage. Marginal structural model analysis of case-cohort study designs provides a cost-efficient design coupled with an accurate analytic method for research settings in which there is time-varying confounding.     

Monitoring communicable disease: vaccination programmes.

The success of vaccination as a means of disease prevention depends on its appropriate application and its reputation with the profession and the public. Surveillance, by providing accurate information on effectiveness and the frequency and nature of hazards, is essential to this purpose. Several factors that influence the success and safety of vaccination programmes are discussed. The essential elements of a vaccine surveillance scheme are outlined with special reference to experience derived from monitoring vaccines in current use.