Limiting Cumulative HIV Viremia Copy-Years by Early Treatment Reduces Risk of AIDS and Death.
Viremia copy-years (VCY), a time-updated measure of cumulative HIV exposure, predicts AIDS/death; although its utility in deciding when to start combination antiretroviral therapy (cART) remains unclear. We aimed to assess the impact of initiating versus deferring cART on risk of AIDS/death by levels of VCY both independent of and within CD4 cell count strata ≥500 cells per cubic millimeter.



Using Concerted Action on Seroconversion to AIDS and Death in Europe (CASCADE) data, we created a series of nested "trials" corresponding to consecutive months for individuals ≥16 years at seroconversion after 1995 who were cART-naive and AIDS-free. Pooling across all trials, time to AIDS/death by CD4, and VCY strata was compared in those initiating vs. deferring cART using Cox models adjusted for: country, sex, risk group, seroconversion year, age, time since last HIV-RNA, and current CD4, VCY, HIV-RNA, and mean number of previous CD4/HIV-RNA measurements/year.



Of 9353 individuals, 5312 (57%) initiated cART and 486 (5%) acquired AIDS/died. Pooling CD4 strata, risk of AIDS/death associated with initiating vs. deferring cART reduced as VCY increased. In patients with high CD4 cell counts, ≥500 cells per cubic millimeter, there was a trend for a greater reduction for those initiating vs. deferring with increasing VCY (P = 0.09), with the largest benefit in the VCY ≥100,000 copy-years/mL group [hazard ratio (95% CI) = 0.41 (0.19 to 0.87)].



For individuals with CD4 ≥500 cells per cubic millimeter, limiting the cumulative HIV burden to <100,000 copy-years/mL through cART may reduce the risk of AIDS/death.
*Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom; †South African Centre for Epidemiological Modelling and Analysis, University of Stellenbosch, South Africa; ‡Department of Infection and Population Health, University College London (UCL), London, United Kingdom; §Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland; ‖Red de Investigación en Sida, Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid, Spain; ¶CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; #Servicio de Enfermedades Infecciosas, Hospital Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, Spain; and **Unitat Suport Metodològic a l'Investigació Biomedica (USMIB), Vall d'Hebron Institut de Recerca (VHIR), Universidad Autónoma de Barcelona, Barcelona, Spain.
Ashley D
AD
Olson
A Sarah
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Walker
Amitabh B
AB
Suthar
Caroline
C
Sabin
Heiner C
HC
Bucher
Inma
I
Jarrin
Santiago
S
Moreno
Santiago
S
Perez-Hoyos
Kholoud
K
Porter
Deborah
D
Ford
D000163:Acquired Immunodeficiency Syndrome / Q000401:mortality / Q000517:prevention & control*; D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014766:Viremia / Q000188:drug therapy*; D055815:Young Adult