CD4 cell count and viral load-specific rates of AIDS, non-AIDS and deaths according to current antiretroviral use

• Published in: AIDS (London) Vol. 27; no. 6; pp. 907 - 918
• Main Authors: MOCROFT, Amanda, PHILLIPS, Andrew N, GATELL, Jose, HORBAN, Andrej, LEDERGERBER, Bruno, ZILMER, Kai, JEVTOVIC, Djordje, MALTEZ, Fernando, PODLEKAREVA, Daria, LUNDGRENH, Jens D
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 27.03.2013
• Subjects: Acquired Immunodeficiency Syndrome - drug therapy; Acquired Immunodeficiency Syndrome - immunology; Acquired Immunodeficiency Syndrome - mortality; Acquired Immunodeficiency Syndrome - virology; Adult; AIDS/HIV; Anti-Retroviral Agents - administration & dosage; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; CD4 Lymphocyte Count; Cohort Studies; Female; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Incidence; Infectious diseases; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Prospective Studies; Survival Analysis; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Immunopathology; Antiretroviral agent; Drug combination; Prognosis; death; Mortality; AIDS; Immune deficiency; Infection; Numeration; CD4 cell count; Chemotherapy; Microbiological investigation; Treatment; Immunological investigation; non-AIDS; Viral disease; T-Lymphocyte; Antiviral; Combined treatment; Viral load; combination antiretroviral therapy
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/QAD.0b013e32835cb766

CD4 cell count and viral loads are used in clinical trials as surrogate endpoints for assessing efficacy of newly available antiretrovirals. If antiretrovirals act through other pathways or increase the risk of disease this would not be identified prior to licensing. The aim of this study was to investigate the CD4 cell count and viral load-specific rates of fatal and nonfatal AIDS and non-AIDS events according to current antiretrovirals. Poisson regression was used to compare overall events (fatal or nonfatal AIDS, non-AIDS or death), AIDS events (fatal and nonfatal) or non-AIDS events (fatal or nonfatal) for specific nucleoside pairs and third drugs used with more than 1000 person-years of follow-up (PYFU) after 1 January 2001. Nine thousand, eight hundred and one patients contributed 42372.5 PYFU, during which 1203 (437 AIDS and 766 non-AIDS) events occurred. After adjustment, there was weak evidence of a difference in the overall events rates between nucleoside pairs (global P-value = 0.084), and third drugs (global P-value = 0.031). As compared to zidovudine/lamivudine, patients taking abacavir/lamivudine [adjusted incidence rate ratio (aIRR) 1.22; 95% CI 0.99-1.49] and abacavir and one other nucleoside [aIRR 1.51; 95% CI 1.14-2.02] had an increased incidence of overall events. Comparing the third drugs, those taking unboosted atazanavir had an increased incidence of overall events compared with those taking efavirenz (aIRR 1.46; 95% CI 1.09-1.95). There was little evidence of substantial differences between antiretrovirals in the incidence of clinical disease for a given CD4 cell count or viral load, suggesting there are unlikely to be major unidentified adverse effects of specific antiretrovirals.