Kelly A. Gebo

Effect of Early versus Deferred Antiretroviral Therapy for HIV on Survival

BACKGROUND The optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain. METHODS We conducted two parallel analyses involving a total of 17,517 asymptomatic patients with HIV infection in the United States and Canada who received medical care during the period from 1996 through 2005. None of the patients had undergone previous antiretroviral therapy. In each group, we stratified the patients according to the CD4+ count (351 to 500 cells per cubic millimeter or >500 cells per cubic millimeter) at the initiation of antiretroviral therapy. In each group, we compared the relative risk of death for patients who initiated therapy when the CD4+ count was above each of the two thresholds of interest (early-therapy group) with that of patients who deferred therapy until the CD4+ count fell below these thresholds (deferred-therapy group). RESULTS In the first analysis, which involved 8362 patients, 2084 (25%) initiated therapy at a CD4+ count of 351 to 500 cells per cubic millimeter, and 6278 (75%) deferred therapy. After adjustment for calendar year, cohort of patients, and demographic and clinical characteristics, among patients in the deferred-therapy group there was an increase in the risk of death of 69%, as compared with that in the early-therapy group (relative risk in the deferred-therapy group, 1.69; 95% confidence interval [CI], 1.26 to 2.26; P<0.001). In the second analysis involving 9155 patients, 2220 (24%) initiated therapy at a CD4+ count of more than 500 cells per cubic millimeter and 6935 (76%) deferred therapy. Among patients in the deferred-therapy group, there was an increase in the risk of death of 94% (relative risk, 1.94; 95% CI, 1.37 to 2.79; P<0.001). CONCLUSIONS The early initiation of antiretroviral therapy before the CD4+ count fell below two prespecified thresholds significantly improved survival, as compared with deferred therapy.

Workshop on HIV Infection and Aging: What Is Known and Future Research Directions

Highly active antiretroviral treatment has resulted in dramatically increased life expectancy among patients with HIV infection who are now aging while receiving treatment and are at risk of developing chronic diseases associated with advanced age. Similarities between aging and the courses of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome suggest that HIV infection compresses the aging process, perhaps accelerating comorbidities and frailty. In a workshop organized by the Association of Specialty Professors, the Infectious Diseases Society of America, the HIV Medical Association, the National Institute on Aging, and the National Institute on Allergy and Infectious Diseases, researchers in infectious diseases, geriatrics, immunology, and gerontology met to review what is known about HIV infection and aging, to identify research gaps, and to suggest high priority topics for future research. Answers to the questions posed are likely to help prioritize and balance strategies to slow the progression of HIV infection, to address comorbidities and drug toxicity, and to enhance understanding about both HIV infection and aging.

The lifetime cost of current human immunodeficiency virus care in the United States.

Objective:We sought to project the lifetime cost of medical care for human immunodefiency virus (HIV)-infected adults using current antiretroviral therapy (ART) standards. Methods:Medical visits and hospitalizations for any reason were from the HIV Research Network, a consortium of high-volume HIV primary care sites. HIV treatment drug regimen efficacies were from clinical guidelines and published sources; data on other drugs used were not available. In a computer simulation model, we projected HIV medical care costs in 2004 U.S. dollars. Results:From the time of entering HIV care, per person projected life expectancy is 24.2 years, discounted lifetime cost is

Risk of Anal Cancer in HIV-Infected and HIV-Uninfected Individuals in North America

385,200, and undiscounted cost is

Longitudinal assessment of the effects of drug and alcohol abuse on HIV-1 treatment outcomes in an urban clinic.

618,900 for adults who initiate ART with CD4 cell count <350/&mgr;L. Seventy-three percent of the cost is antiretroviral medications, 13% inpatient care, 9% outpatient care, and 5% other HIV-related medications and laboratory costs. For patients who initiate ART with CD4 cell count <200/&mgr;L, projected life expectancy is 22.5 years, discounted lifetime cost is

Racial and gender disparities in receipt of highly active antiretroviral therapy persist in a multistate sample of HIV patients in 2001

354,100 and undiscounted cost is

Late Presentation for Human Immunodeficiency Virus Care in the United States and Canada

567,000. Results are sensitive to drug manufacturers’ discounts, ART efficacy, and use of enfuvirtide for salvage. If costs are discounted to the time of infection, the discounted lifetime cost is

Incidence and outcomes of malignancy in the HAART era in an urban cohort of HIV-infected individuals.

303,100. Conclusions:Effective ART regimens have substantially improved survival and have increased the lifetime cost of HIV-related medical care in the U.S.

Racial and Sex Disparities in Life Expectancy Losses among HIV-Infected Persons in the United States: Impact of Risk Behavior, Late Initiation, and Early Discontinuation of Antiretroviral Therapy

BACKGROUND Anal cancer is one of the most common cancers affecting individuals infected with human immunodeficiency virus (HIV), although few have evaluated rates separately for men who have sex with men (MSM), other men, and women. There are also conflicting data regarding calendar trends. METHODS In a study involving 13 cohorts from North America with follow-up between 1996 and 2007, we compared anal cancer incidence rates among 34 189 HIV-infected (55% MSM, 19% other men, 26% women) and 114 260 HIV-uninfected individuals (90% men). RESULTS Among men, the unadjusted anal cancer incidence rates per 100 000 person-years were 131 for HIV-infected MSM, 46 for other HIV-infected men, and 2 for HIV-uninfected men, corresponding to demographically adjusted rate ratios (RRs) of 80.3 (95% confidence interval [CI], 42.7-151.1) for HIV-infected MSM and 26.7 (95% CI, 11.5-61.7) for other HIV-infected men compared with HIV-uninfected men. HIV-infected women had an anal cancer rate of 30/100 000 person-years, and no cases were observed for HIV-uninfected women. In a multivariable Poisson regression model, among HIV-infected individuals, the risk was higher for MSM compared with other men (RR, 3.3; 95% CI, 1.8-6.0), but no difference was observed comparing women with other men (RR, 1.0; 95% CI, 0.5-2.2). In comparison with the period 2000-2003, HIV-infected individuals had an adjusted RR of 0.5 (95% CI, .3-.9) in 1996-1999 and 0.9 (95% CI, .6-1.2) in 2004-2007. CONCLUSIONS Anal cancer rates were substantially higher for HIV-infected MSM, other men, and women compared with HIV-uninfected individuals, suggesting a need for universal prevention efforts. Rates increased after the early antiretroviral therapy era and then plateaued.

Hospital and outpatient health services utilization among HIV-infected adults in care 2000-2002.

Objective To assess the temporal association of changes in substance abuse with antiretroviral therapy use and adherence, HIV-1 RNA suppression, and CD4 cell count changes in patients attending an urban clinic. Design Prospective cohort study. Methods Six-hundred and ninety-five HIV-1-infected individuals, who completed two or more semi-annual standardized surveys and in whom antiretroviral therapy was indicated, were included in the analysis. Surveys addressed antiretroviral therapy use and adherence, and use of illicit drugs and alcohol. Substance abuse was defined as active heroin, cocaine, or heavy alcohol use in the 6 months preceding survey. The units of analysis were consecutive pairs of surveys (couplets) in individual participants. Couplets in which participants denied substance abuse in both surveys were compared to couplets in which participants switched from non-use to substance abuse, and couplets in which participants reported substance abuse in both surveys were compared to couplets where participants switched from substance abuse to non-use. Results Switching from non-use to substance abuse was strongly associated with worsening antiretroviral therapy use and adherence, less frequent HIV-1 RNA suppression, and blunted CD4 cell increases, compared to remaining free of substance abuse. Alternatively, switching from substance abuse to non-use was strongly associated with improvements in antiretroviral therapy use and adherence, and HIV-1 treatment outcomes, compared to persisting with substance abuse. Conclusions This longitudinal study highlights the dynamic nature of substance abuse and its temporal association with the effectiveness of HIV-1 treatment in patients attending an inner-city clinic.