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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
University of Bordeaux, ISPED, Bordeaux, France. Xavier.Anglaret@isped.u-bordeaux2.fr
Xavier
X
Anglaret
Callie A
CA
Scott
Rochelle P
RP
Walensky
Eric
E
Ouattara
Elena
E
Losina
Raoul
R
Moh
Jessica E
JE
Becker
Lauren
L
Uhler
Christine
C
Danel
Eugene
E
Messou
Serge
S
Eholié
Kenneth A
KA
Freedberg
D000328:Adult; D017954:Africa South of the Sahara; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality / Q000635:transmission; D006801:Humans; D008297:Male; D008954:Models, Biological; D055502:Secondary Prevention / Q000379:methods / Q000706:statistics & numerical data; D015996:Survival Rate
D019380:Anti-HIV Agents