French HIV experts on early antiretroviral treatment for prevention: uncertainty and heterogeneity.

Early use of highly active antiretroviral treatment (ART) in people living with HIV for HIV prevention has gained legitimacy but remains controversial. Nineteen French HIV experts with diverse specializations (over half of whom were clinicians) were qualitatively interviewed on their views about ART irrespective of CD4 count of more than 500 cells/mm3 for purposes of HIV prevention, which is not systematically recommended in France. Content analysis identified 2 broad categories: individual considerations (subcategories: patient health and well-being; patient preparedness and choice) and collective considerations (subcategories:HIV transmission risk; impact on the epidemic; cost). Uncertainty surrounded many experts' considerations, and unity was lacking on key issues (eg, candidacy for early preventive treatment, expected clinical- and population-level effects). An umbrella theme labeled "Weighing the merits of early ART in the face of uncertainties was identified. Our analyses raise doubts about the current acceptability of widespread implementation of early ART for HIV prevention in France.

Minimal interference: A basis for selecting ART for prevention with positives.

Given international interest in "treatment as prevention" (TasP) and the pertinence of optimizing antiretroviral treatment (ART) regimens for TasP, 19 French HIV experts were interviewed on their criteria for ART if used specifically for prevention with HIV-positive persons. Through content analysis of the interview material, nine criteria were identified. The most endorsed criteria, collectively, suggest a choice of treatment based on "minimal interference" where negative impacts of ART are minimized and ease of treatment integration maximized in the lives of people living with HIV/AIDS (PLHIV) for both the short and long term. These criteria were the tolerance, side effects, and/or toxicity profile of ART, simplicity (e.g., of treatment schedule, dosage form) and the individualization of treatment (e.g., adapted to lifestyle). While virologic efficacy (i.e., a durable, undetectable viral load) was also deemed important, several experts specified that it was virtually assured with current treatments. To a much lesser extent, experts endorsed diffusion of ART into the genital compartments, a strong genetic barrier (against resistance), validated treatments (as opposed to new classes of ART), a rapid reduction in HIV viral load, and treatment cost. Pharmacologically, minimal interference calls for further improvements in the tolerance, side effects and toxicity profile of ART and in the simplicity of ART administration. Clinically, it means avoiding a one-size-fits-all approach to ART in TasP and engagement with and of PLHIV in ART selection and side effects management. Strategically, it emphasises keeping the health and quality of life of PLHIV at the forefront of a TasP-oriented public health intervention.

Impact of dyslipidemia associated with Highly Active Antiretroviral Therapy (HAART) on cardiovascular risk and life expectancy.

We investigated the effect of dyslipidemia associated with highly active antiretroviral therapy on cardiovascular risk and life expectancy among patients who had the human immunodeficiency virus. Dyslipidemia estimates were based on results from a phase 2 randomized trial that compared lipid changes after 32 weeks of therapy with atazanavir with those with nelfinavir (each in combination with stavudine and lamivudine). The resultant increased coronary risk was estimated using Framingham risk equations, and change in life expectancy (after adjustment for mortality due to human immunodeficiency virus) was based on the cardiovascular life expectancy model, which is based on a published Markov's model. Levels of total cholesterol and low-density lipoprotein cholesterol increased significantly more among patients who used nelfinavir (+24% and +28%) than among those who used atazanavir (+4% and +1%). This dyslipidemia increased the risk of coronary disease by 50% over 10 years. The absence of dyslipidemia was estimated to preserve life expectancy 0.15 to 1.53 additional years depending on a patient's age, gender, and other risk factors. There are increasing reports of dyslipidemia and cardiovascular events associated with highly active antiretroviral therapy. Significant increases in blood lipid levels observed with some protease inhibitors are associated with an increase in calculated 10-year coronary risk. Accordingly, minimizing dyslipidemia associated with highly active antiretroviral therapy may preserve life expectancy among adults who have the human immunodeficiency virus.

The cost-effectiveness of highly active antiretroviral therapy, Canada 1991-2001.

AIM: To estimate the cost-effectiveness ratio of highly-active antiretroviral therapy (HAART) in Canada. DESIGN: A before-and-after analysis to calculate incremental cost of life year gained (LYG) between 1991 and 1995 (pre-HAART period) and between 1997 and 2001 (HAART period) for non-AIDS and AIDS groups (CDC stage of HIV infection). METHODS: For two Quebec HIV hospital clinics, mean inpatient (IP) days, outpatient (OP) visits and direct health care costs per patient-year (PPY) were calculated. Cox's proportional hazards models calculated disease progression, stratified by study periods and adjusted for gender, age at cohort entry, sexual orientation, injecting drug use and baseline CD4 cell count. RESULTS: For non-AIDS patients, mean IP days was 1.6 (pre-HAART period) compared with 0.8 PPY (HAART period); mean OP visits increased from 2.8 to 5.5 PPY. Total cost was US$ 4265 (pre-HAART period) and US$ 9445 PPY (HAART period) of which 66 and 84%, respectively were spent on antiretroviral drugs. Median progression time was 6.3 years in the pre-HAART period compared with 12.5 years in HAART period (log rank chi = 270, P < 0.0001). Incremental cost per LYG between periods was US$ 14 587. For AIDS patients, mean IP days decreased from 13.3 to 4.4 PPY between periods; OP visits increased from 8.3 to 9.2 PPY. Total costs increased from US$ 9099 to US$ 11 754 PPY, while expenditure on antiretroviral drugs increased from 29 to 72% of total cost. Median progression time was 3.8 years in the pre-HAART period, which increased to 13.3 years in the HAART period (log rank chi = 158, P < 0.0001); incremental cost per LYG between periods was US$ 12 813. CONCLUSION: HAART appeared a cost-effective intervention in Canada.