Background. The effect of antiretroviral therapy (ART) interruption or intensification on health-related quality of life (HRQoL) in advanced HIV patients is unknown.

Objective. To assess the impact of temporary treatment interruption and intensification of ART on HRQoL.

Design. A 2 x 2 factorial open label randomized controlled trial.

Setting. Hospitals in the United States, Canada, and the United Kingdom.

Patients. Multidrug resistant (MDR) HIV patients.

Intervention. Patients were randomized to receive a 12-wk interruption or not, and ART intensification or standard ART.

Measurements. The Health Utilities Index (HUI3), EQ-5D, standard gamble (SG), time tradeoff (TTO), visual analog scale (VAS), and the Medical Outcomes Study HIV Health Survey (MOS-HIV).

Results. There were no significant differences in HRQoL among the four groups during follow-up; however, there was a temporary significant decline in HRQoL on some measures within the interruption group during interruption (HUI3 −0.05, P = 0.03; VAS −5.9, P = 0.002; physical health summary −2.9, P = 0.001; mental health summary −1.9, P = 0.02). Scores declined slightly overall during follow-up. Multivariate analysis showed significantly lower HRQoL associated with some clinical events.

Limitations. The results may not apply to HIV patients who have not experienced multiple treatment failures or who have not developed MDR HIV.

Conclusions. Temporary ART interruption and ART intensification provided neither superior nor inferior HRQoL compared with no interruption and standard ART. Among surviving patients, HRQoL scores declined only slightly over years of follow-up in this advanced HIV cohort; however, approximately one-third of patients died during the trial follow up. Lower HRQoL was associated with adverse clinical events.

Background Injection drug use (IDU) and heterosexual virus transmission both contribute to the growing mixed HIV epidemics in Eastern Europe and Central Asia. In Ukraine—chosen in this study as a representative country—IDU-related risk behaviors cause half of new infections, but few injection drug users (IDUs) receive methadone substitution therapy. Only 10% of eligible individuals receive antiretroviral therapy (ART). The appropriate resource allocation between these programs has not been studied. We estimated the effectiveness and cost-effectiveness of strategies for expanding methadone substitution therapy programs and ART in mixed HIV epidemics, using Ukraine as a case study.

Methods and Findings We developed a dynamic compartmental model of the HIV epidemic in a population of non-IDUs, IDUs using opiates, and IDUs on methadone substitution therapy, stratified by HIV status, and populated it with data from the Ukraine. We considered interventions expanding methadone substitution therapy, increasing access to ART, or both. We measured health care costs, quality-adjusted life years (QALYs), HIV prevalence, infections averted, and incremental cost-effectiveness. Without incremental interventions, HIV prevalence reached 67.2% (IDUs) and 0.88% (non-IDUs) after 20 years. Offering methadone substitution therapy to 25% of IDUs reduced prevalence most effectively (to 53.1% IDUs, 0.80% non-IDUs), and was most cost-effective, averting 4,700 infections and adding 76,000 QALYs compared with no intervention at US$530/QALY gained. Expanding both ART (80% coverage of those eligible for ART according to WHO criteria) and methadone substitution therapy (25% coverage) was the next most cost-effective strategy, adding 105,000 QALYs at US$1,120/QALY gained versus the methadone substitution therapy-only strategy and averting 8,300 infections versus no intervention. Expanding only ART (80% coverage) added 38,000 QALYs at US$2,240/QALY gained versus the methadone substitution therapy-only strategy, and averted 4,080 infections versus no intervention. Offering ART to 80% of non-IDUs eligible for treatment by WHO criteria, but only 10% of IDUs, averted only 1,800 infections versus no intervention and was not cost effective.

Conclusions Methadone substitution therapy is a highly cost-effective option for the growing mixed HIV epidemic in Ukraine. A strategy that expands both methadone substitution therapy and ART to high levels is the most effective intervention, and is very cost effective by WHO criteria. When expanding ART, access to methadone substitution therapy provides additional benefit in infections averted. Our findings are potentially relevant to other settings with mixed HIV epidemics.

Background Guidance is needed on best medical management for advanced HIV disease with multidrug resistance (MDR) and limited retreatment options. We assessed two novel antiretroviral (ARV) treatment approaches in this setting.

Methods and Findings We conducted a 2×2 factorial randomized open label controlled trial in patients with a CD4 count ≤300 cells/µl who had ARV treatment (ART) failure requiring retreatment, to two options (a) re-treatment with either standard (≤4 ARVs) or intensive (≥5 ARVs) ART and b) either treatment starting immediately or after a 12-week monitored ART interruption. Primary outcome was time to developing a first AIDS-defining event (ADE) or death from any cause. Analysis was by intention to treat. From 2001 to 2006, 368 patients were randomized. At baseline, mean age was 48 years, 2% were women, median CD4 count was 106/µl, mean viral load was 4.74 log₁₀ copies/ml, and 59% had a prior AIDS diagnosis. Median follow-up was 4.0 years in 1249 person-years of observation. There were no statistically significant differences in the primary composite outcome of ADE or death between re-treatment options of standard versus intensive ART (hazard ratio 1.17; CI 0.86–1.59), or between immediate retreatment initiation versus interruption before re-treatment (hazard ratio 0.93; CI 0.68–1.30), or in the rate of non-HIV associated serious adverse events between re-treatment options.

Conclusions We did not observe clinical benefit or harm assessed by the primary outcome in this largest and longest trial exploring both ART interruption and intensification in advanced MDR HIV infection with poor retreatment options.

Abstract

BACKGROUND:

Although recent guidelines call for expanded routine screening for HIV, resources for antiretroviral therapy (ART) are limited, and all eligible persons are not currently receiving treatment.

OBJECTIVE:

To evaluate the effects on the U.S. HIV epidemic of expanded ART, HIV screening, or interventions to reduce risk behavior.

DESIGN:

Dynamic mathematical model of HIV transmission and disease progression and cost-effectiveness analysis.

DATA SOURCES:

Published literature.

TARGET POPULATION:

High-risk (injection drug users and men who have sex with men) and low-risk persons aged 15 to 64 years in the United States.

TIME HORIZON:

Twenty years and lifetime (costs and quality-adjusted life-years [QALYs]).

PERSPECTIVE:

Societal.

INTERVENTION:

Expanded HIV screening and counseling, treatment with ART, or both.

OUTCOME MEASURES:

New HIV infections, discounted costs and QALYs, and incremental cost-effectiveness ratios.

RESULTS OF BASE-CASE ANALYSIS:

One-time HIV screening of low-risk persons coupled with annual screening of high-risk persons could prevent 6.7% of a projected 1.23 million new infections and cost $22,382 per QALY gained, assuming a 20% reduction in sexual activity after screening. Expanding ART utilization to 75% of eligible persons prevents 10.3% of infections and costs $20,300 per QALY gained. A combination strategy prevents 17.3% of infections and costs $21,580 per QALY gained.

RESULTS OF SENSITIVITY ANALYSIS:

With no reduction in sexual activity, expanded screening prevents 3.7% of infections. Earlier ART initiation when a CD4 count is greater than 0.350 × 10(9) cells/L prevents 20% to 28% of infections. Additional efforts to halve high-risk behavior could reduce infections by 65%.

LIMITATION:

The model of disease progression and treatment was simplified, and acute HIV screening was excluded.

CONCLUSION:

Expanding HIV screening and treatment simultaneously offers the greatest health benefit and is cost-effective. However, even substantial expansion of HIV screening and treatment programs is not sufficient to markedly reduce the U.S. HIV epidemic without substantial reductions in risk behavior.

PRIMARY FUNDING SOURCE:

National Institute on Drug Abuse, National Institutes of Health, and Department of Veterans Affairs.

We explore whether HIV stigma is associated with seeking to conceal testing interest. We examine 86,899 outpatient visits in a 1993-1997 national survey and compare HIV testing to four non-stigmatized tests: spirometry, allergy testing, mammography, and colonoscopy. We explore whether people testing for HIV, compared to people receiving control services, listed reasons for visit (RFV) less related to the test performed, listed their interest in testing more frequently as a non-primary RFV, and received more services unrelated to testing. A total of 48.7% of people tested for HIV listed a reason unrelated to testing as their primary RFV (spirometry: 8.9%; allergy testing: 29.3%), and 69.9% of people asking to test requested HIV testing as a secondary RFV (spirometry: 52%; allergy testing: 0%). People who tested for HIV received more services (M=1.83 additional services) than non-testers (M=0.95) on an index of seven services. We did not find this association for spirometry, allergy testing, colonoscopy, or mammography. We interpret these results to indicate that stigma may have behavioral correlates and that people may attempt to avoid HIV stigma by seeking a psychological cover for HIV testing. To our knowledge, this is the first study to attempt to use observational data on health service usage for assessing stigma and people's attempts to deal with HIV testing stigma.

Chronic viral diseases such as human immunodeficiency virus (HIV) and hepatitis B virus (HBV) afflict millions of people worldwide. A key public health challenge in managing such diseases is identifying infected, asymptomatic individuals so that they can receive antiviral treatment. Such treatment can benefit both the treated individual (by improving quality and length of life) and the population as a whole (through reduced transmission). We develop a compartmental model of a chronic, treatable infectious disease and use it to evaluate the cost and effectiveness of different levels of screening and contact tracing.

We show that:

1. the optimal strategy is to get infected individuals into treatment at the maximal rate until the incremental health benefits balance the incremental cost of controlling the disease;
   
2. as one reduces the disease prevalence by moving people into treatment (which decreases the chance that they will infect others), one should increase the level of contact tracing to compensate for the decreased effectiveness of screening;
   
3. as the disease becomes less prevalent, it is optimal to spend more per case identified; and
   
4. the relative mix of screening and contact tracing at any level of disease prevalence is such that the marginal efficiency of contact tracing (cost per infected person found) equals that of screening if possible (e.g., when capacity limitations are not binding).
   

We also show how to determine the costeffective equilibrium level of disease prevalence (among untreated individuals), and we develop an approximation of the path of the optimal prevalence over time. Using this, one can obtain a close approximation of the optimal solution without having to solve an optimal control problem. We apply our methods to an example of hepatitis B virus.