Abstract

BACKGROUND:

Raltegravir is a potential treatment option for virologically suppressed HIV-1 infected patients on enfuvirtide with injection site reactions.

OBJECTIVES:

To characterize safety and efficacy of an enfuvirtide to raltegravir switch including changes in T-cells, quality of life, and residual viremia.

STUDY DESIGN:

In patients with viral load <50 copies/mL and injection site reactions, enfuvirtide was switched to raltegravir without additional changes to the antiretroviral regimen. Virologic failure was defined as a viral load >1000 copies/mL or two consecutive viral load measurements between 50 and 1000 copies/mL (low-level viremia). Over the 24 week study, we compared changes in T-cells, injection site reactions, quality of life, and residual viremia, as measured through the single-copy assay which can detect plasma virus down to a single copy, using paired t-tests.

RESULTS:

Fourteen patients with a median CD4+ T-cell count of 420 cells/microL were enrolled. After the switch, two patients experienced virologic failure due to confirmed low-level viremia. However, both patients subsequently were re-suppressed, one without any changes to his regimen. There was no change in CD4+ T-cell count. Injection site reactions resolved. However, there was little reported change in quality of life. The baseline median level of residual viremia was 6 copies/mL and did not change after the switch to raltegravir.

CONCLUSIONS:

A switch to raltegravir in virologically suppressed patients on enfuvirtide is effective in maintaining immunologic and virologic control at 24 weeks but did not result in a change in residual viremia.

Abstract 

Background

Adherence is crucial for public health program effectiveness, though the benefits of increasing adherence must ultimately be weighed against the associated costs. We sought to determine the relationship between investment in community health worker (CHW) home visits and increased attendance at cervical cancer screening appointments in Cape Town, South Africa.

Methodology/Principal Findings

We conducted an observational study of 5,258 CHW home visits made in 2003–4 as part of a community-based screening program. We estimated the functional relationship between spending on these visits and increased appointment attendance (adherence). Increased adherence was noted after each subsequent CHW visit. The costs of making the CHW visits was based on resource use including both personnel time and vehicle-related expenses valued in 2004 Rand. The CHW program cost R194,018, with 1,576 additional appointments attended. Adherence increased from 74% to 90%; 55% to 87%; 48% to 77%; and 56% to 80% for 6-, 12-, 24-, and 36-month appointments. Average per-woman costs increased by R14–R47. The majority of this increase occurred with the first 2 CHW visits (90%, 83%, 74%, and 77%; additional cost: R12–R26).

Conclusions/Significance

We found that study data can be used for program planning, identifying spending levels that achieve adherence targets given budgetary constraints. The results, derived from a single disease program, are retrospective, and should be prospectively replicated.

This paper develops a mathematical/economic framework to address the following question: Given a particular population, a specific HIV prevention program and a fixed amount of funds that could be invested in the program, how much money should be invested?

Aims The prevalence of Type 2 diabetes mellitus (DM) has grown rapidly, but little is known about the drivers of inpatient spending in low- and middle-income countries. This study aims to compare the clinical presentation and expenditure on hospital admission for inpatients with a primary diagnosis of Type 2 DM in India, China, Thailand and Malaysia.

Methods We analysed data on adult, Type 2 DM patients admitted between 2005 and 2008 to five tertiary hospitals in the four countries, reporting expenditures relative to income per capita in 2007.

Results Hospital admission spending for diabetic inpatients with no complications ranged from 11 to 75% of per-capita income. Spending for patients with complications ranged from 6% to over 300% more than spending for patients without complications treated at the same hospital. Glycated haemoglobin was significantly higher for the uninsured patients, compared with insured patients, in India (8.6 vs. 8.1%), Hangzhou, China (9.0 vs. 8.1%), and Shandong, China (10.9 vs. 9.9%). When the hospital admission expenditures of the insured and uninsured patients were statistically different in India and China, the uninsured always spent less than the insured patients.

Conclusions With the rising prevalence of DM, households and health systems in these countries will face greater economic burdens. The returns to investment in preventing diabetic complications appear substantial. Countries with large out-of-pocket financing burdens such as India and China are associated with the widest gaps in resource use between insured and uninsured patients. This probably reflects both overuse by the insured and underuse by the uninsured.

Despite recommendations for voluntary HIV screening, few medical centres have implemented screening programmes. The objective of the study was to determine whether an intervention with computer-based reminders and feedback would increase screening for HIV in a Department of Veterans Affairs (VA) health-care system. The design of the study was a randomized controlled trial at five primary care clinics at the VA Palo Alto Health Care System. All primary care providers were eligible to participate in the study. The study intervention was computer-based reminders to either assess HIV risk behaviours or to offer HIV testing; feedback on adherence to reminders was provided. The main outcome measure was the difference in HIV testing rates between intervention and control group providers. The control group providers tested 1.0% (n = 67) and 1.4% (n = 106) of patients in the preintervention and intervention period, respectively; intervention providers tested 1.8% (n = 98) and 1.9% (n = 114), respectively (P = 0.75).In our random sample of 753 untested patients, 204 (27%) had documented risk behaviours. Providers were more likely to adhere to reminders to test rather than with reminders to perform risk assessment (11% versus 5%, P < 0.01). Sixty-one percent of providers felt that lack of time prevented risk assessment. In conclusion, in primary care clinics in our setting, HIV testing rates were low. Providers were unaware of the high rates of risky behaviour in their patient population and perceived important barriers to testing. Low-intensity clinical reminders and feedback did not increase rates of screening.

Estimating the potential health benefits and expenditures of a partially effective HIV vaccine is an important consideration in the debate about whether HIV vaccine research should continue. We developed an epidemic model to estimate HIV prevalence, new infections, and the cost-effectiveness of vaccination strategies in the U.S. Vaccines with modest efficacy could prevent 300,000-700,000 HIV infections and save $30 billion in healthcare expenditures over 20 years. Targeted vaccination of high-risk individuals is economically efficient, but difficulty in reaching these groups may mitigate these benefits. Universal vaccination is cost-effective for vaccines with 50% efficacy and price similar to other infectious disease vaccines.

Objectives To assess the concurrent validity and responsiveness of the Health Utility Index 3 (HUI3) in patients with advanced HIV/AIDS, and to determine the responsiveness of this measure, the MOS-HIV and EQ-5D to HIV-related clinical events.

Methods Data from the OPTIMA (OPTions In Management with Antiretrovirals) trial was analyzed. Two aspects of the validity of the HUI3 were considered: concurrent validity was evaluated using Spearman correlations with MOS-HIV component and summary scores. Responsiveness to AIDS-defining events (ADE) and all adverse events (our external change criterion) was assessed using area under the receiver operating characteristic (AUROC) curves.

Results The study enrolled 368 patients (mean follow-up: 3.66 years); 82% had at least one severe adverse event and 27% had at least one ADE. The HUI3 scale and items showed good concurrent validity, with 85% of the expected relationships with the MOS-HIV subscales verified. The HUI3 was responsive to both adverse events (AUROC [95%CI]: 0.68 [0.57, 0.80]) and ADEs (0.62 [0.51, 0.74]). The EQ-5D was responsive to ADEs (0.66 [0.56, 0.76]), but not responsive to adverse events (0.56 [0.46, 0.68]).

Conclusion The HUI3 is a valid and responsive measure of the change in HRQoL associated with clinical events in an advanced HIV/AIDS population.

Background: Since 2003, the President's Emergency Plan for AIDS Relief (PEPFAR) has been the most ambitious initiative to address the global HIV epidemic. However, the effect of PEPFAR on HIV-related outcomes is unknown.

Objective: To assess the effect of PEPFAR on HIV-related deaths, the number of people living with HIV, and HIV prevalence in sub-Saharan Africa.

Design: Comparison of trends before and after the initiation of PEPFAR's activities.

Setting: 12 African focus countries and 29 control countries with a generalized HIV epidemic from 1997 to 2007 (451 country-year observations).

Intervention: A 5-year, $15 billion program for HIV treatment, prevention, and care that started in late 2003.

Measurements: HIV-related deaths, the number of people living with HIV, and HIV prevalence.

Results: Between 2004 and 2007, the difference in the annual change in the number of HIV-related deaths was 10.5% lower in the focus countries than the control countries (P = 0.001). The difference in trends between the groups before 2003 was not significant. The annual growth in the number of people living with HIV was 3.7% slower in the focus countries than the control countries from 1997 to 2002 (P = 0.05), but during PEPFAR's activities, the difference was no longer significant. The difference in the change in HIV prevalence did not significantly differ throughout the study period. These estimates were stable after sensitivity analysis.

Limitation: The selection of the focus countries was not random, which limits the generalizability of the results.

Conclusion: After 4 years of PEPFAR activity, HIV-related deaths decreased in sub-Saharan African focus countries compared with control countries, but trends in adult prevalence did not differ. Assessment of epidemiologic effectiveness should be part of PEPFAR's evaluation programs.

Primary Funding Source: Agency for Healthcare Research and Quality.

Background Current World Health Organization (WHO) guidelines for treatment of HIV in resource-limited settings call for 2 antiretroviral regimens. The effectiveness and cost-effectiveness of increasing the number of antiretroviral regimens is unknown.

Methods Using a simulation model, we compared the survival and costs of current WHO regimens with two 3-regimen strategies: an initial regimen of 3 nucleoside reverse transcriptase inhibitors followed by the WHO regimens and the WHO regimens followed by a regimen with a second-generation boosted protease inhibitor (2bPI). We evaluated monitoring with CD4 counts only and with both CD4 counts and viral load. We used cost and effectiveness data from Cape Town and tested all assumptions in sensitivity analyses.

Results Over the lifetime of the cohort, 25.6% of individuals failed both WHO regimens by virologic criteria. However, when patients were monitored using CD4 counts alone, only 6.5% were prescribed additional highly active antiretroviral therapy due to missed and delayed detection of failure. The life expectancy gain for individuals who took a 2bPI was 6.7-8.9 months, depending on the monitoring strategy. When CD4 alone was available, adding a regimen with a 2bPI was associated with an incremental cost-effectiveness ratio of $2581 per year of life gained, and when viral load was available, the ratio was $6519 per year of life gained. Strategies with triple-nucleoside reverse transcriptase inhibitor regimens in initial therapy were dominated. Results were sensitive to the price of 2bPIs.

Conclusions About 1 in 4 individuals who start highly active antiretroviral therapy in sub-Saharan Africa will fail currently recommended regimens. At current prices, adding a regimen with a 2bPI is cost effective for South Africa and other middle-income countries by WHO standards.