Could early antiretroviral therapy entail more risks than benefits in sub―Saharan African HIV―infected adults? A model―based analysis

• Published in: Antiviral therapy Vol. 18; no. 1; pp. 45 - 55
• Main Authors: ANGLARET, Xavier, SCOTT, Callie A, EHOLIE, Serge, FREEDBERG, Kenneth A, WALENSKY, Rochelle P, OUATTARA, Eric, LOSINA, Elena, MOH, Raoul, BECKER, Jessica E, UHLER, Lauren, DANEL, Christine, MESSOU, Eugene
• Format: Journal Article
• Language: English
• Published: London International Medical Press 01.01.2013
• Subjects: Adult; Africa South of the Sahara; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral Therapy, Highly Active - methods; Antiviral agents; Biological and medical sciences; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Drug Administration Schedule; Female; HIV Infections - drug therapy; HIV Infections - mortality; HIV Infections - transmission; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Male; Medical sciences; Models, Biological; Pharmacology. Drug treatments; Secondary Prevention - methods; Secondary Prevention - statistics & numerical data; Survival Rate; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Sub-Saharan Africa; Africa; Africa South of the Sahara; Human; Immunopathology; Antiretroviral agent; AIDS; Immune deficiency; Infection; Chemotherapy; Treatment; Viral disease; Analysis; Risk factor; Adult; Antiviral; Models
• ISSN: 1359-6535; 2040-2058
• DOI: 10.3851/IMP2231

Initiation of antiretroviral therapy (ART) in all HIV-infected adults, regardless of CD4⁺ T-cell count, is a proposed strategy for reducing HIV transmission. We investigated the conditions under which starting ART early could entail more risks than benefits for patients with high CD4⁺ T-cell counts. We used a simulation model to compare ART initiation upon entry to care ('immediate ART') to initiation at CD4⁺ T-cell count ≤ 350 cells/μl ('WHO 2010 ART') in African adults with CD4⁺ T-cell counts >500 cells/μl. We varied inputs to determine the combination of parameters (population characteristics, conditions of care, treatment outcomes) that would result in higher 15-year mortality with immediate ART. The 15-year mortality was 56.7% for WHO 2010 ART and 51.8% for immediate ART. In one-way sensitivity analysis, lower 15-year mortality was consistently achieved with immediate ART unless the rate of fatal ART toxicity was >1.0/100 person-years, the rate of withdrawal from care was >1.2-fold higher or the rate of ART failure due to poor adherence was >4.3-fold higher on immediate than on WHO 2010 ART. In multi-way sensitivity analysis, immediate ART led to higher mortality when moderate rates of fatal ART toxicity (0.25/100 person-years) were combined with rates of withdrawal from care >1.1-fold higher and rates of treatment failure >2.1-fold higher on immediate than on WHO 2010 ART. In sub-Saharan Africa, ART initiation at entry into care would improve long-term survival of patients with high CD4⁺ T-cell counts, unless it is associated with increased withdrawal from care and decreased adherence. In early ART trials, a focus on retention and adherence will be crucial.