Factors Associated with Mortality in HIV Type 1-Infected Adults Initiating Protease Inhibitor-Containing Therapy: Role of Education Level and of Early Transaminase Level Elevation

Despite a dramatic decline in mortality among human immunodeficiency virus (HIV)-infected adults in industrialized countries since the advent of highly active antiretroviral therapy (HAART), mortality remains higher among HIV-infected adults than in the general population. Since the use of HAART began, the distribution of the causes of death has changed, and factors associated with mortality might also have changed. In this study, the authors attempted to identify factors associated with mortality among HIV-1-infected adults at initiation of protease inhibitor (PI)-containing HAART. They also assessed the impact of early effect of treatment up to 4 months after the initiation of treatment.

The total of 1,155 patients were drawn from the Antiprotéases Cohorte (APROCO) Agence Nationale de Recherches sur le SIDA EP11 study -- a French prospective multicentric cohort of HIV-1-infected adults (> 18 years old) starting PI-containing therapy for the first time. Subjects were consecutively enrolled in 47 clinical centers in France between May 1997 and June 1998. Exclusion criteria were primary infection and postexposure prophylaxis.

Patient follow-up was scheduled at months 1 and 4 after enrollment and every 4 months thereafter. Baseline data included in this study were: sex, age, birthplace (France, Africa, or other), HIV transmission category, HIV clinical stage, CD4 cell count, plasma HIV RNA level, hemoglobin level, body mass index (BMI), plasma creatinine level, hepatitis C virus (HCV) antibodies, hepatitis B virus surface antigenemia, prior antiretroviral therapy, type of PI prescribed, and the combination of nucleoside analogues prescribed. Other variables assessed by self- administered questionnaires included: highest diploma obtained, employment, type of residence, couple life, participation in a patient association, depression, smoking, alcohol consumption, and injection drug use. The following variables were measured at month 4: occurrence of an AIDS-defining event, CD4 cell count, plasma HIV RNA level, hemoglobin level, elevation of hepatic transaminase levels, and change of PI.

Clinical characteristics included a median age of 36 years, median baseline CD4 cell count of 288 cells/mm3, and median baseline plasma HIV RNA load of 4.4 log10 copies/mL. After a median follow-up of 27 months, 48 deaths had occurred, of which 44 percent were related to HIV. The mortality rate was 2.9 percent at 12 months. When both data at baseline and data at 4 months after the start of treatment were considered, factors independently associated with mortality (using the Cox model) were: low baseline plasma creatinine level, low school education level, low CD4 cell count at 4 months, low hemoglobin level, and elevated hepatic transaminase levels.

The authors did not find an association between HCV seropositivity and mortality. Although it was not significant, the authors did find a trend for a higher risk of death for women than for men. The trend might be explained by a difference in school education.

According to the authors, "The few factors associated with mortality in this cohort are easy to measure during routine patient treatment in industrialized countries. CD4 cell count, plasma creatinine level, and hemoglobin level are linked to disease progression. Toxicity of treatments, possibly reflected in this study by elevation of hepatic transaminase level and hemoglobin levels, seemed to play a role in midterm prognosis through a mechanism that remains to be clarified. The higher risk of death in patients with a low level of education needs to be further evaluated to identify potential reasons (e.g., difficulty in treatment adherence, social problems, or high-risk behavior."

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