Summary
Background
Recommendations have differed nationally and internationally with respect to the best time to start antiretroviral therapy (cART). We compared effectiveness of three strategies for initiation of cART in high-income countries for HIV-positive individuals who do not have AIDS: immediate universal cART initiation, cART initiation at a CD4 cell count below 500, and cART initiation at a CD4 cell count below 350 cells/mm3.
Methods
We used data from the HIV-CAUSAL collaboration of cohorts in Europe and the United States. We included 55,826 individuals diagnosed with HIV between 2000-2013, ART naïve, AIDS-free, aged≥18 years and within 6 months of HIV diagnosis. We used the parametric g-formula to adjust for baseline and time-varying confounders to estimate the following quantities as would have been observed under each cART initiation strategy after 7 years of HIV diagnosis: relative risks of both death and of death or AIDS-defining illness, mean survival time, proportion in need of cART, and proportion with HIV RNA<50 copies/mL.
Findings
Median [interquantile range] CD4 at HIV diagnosis was 376 [222,551] cells/mm3. Compared with immediate initiation, the mortality risk ratio estimate (95% CI) was 1.02 (1.01,1.02) under initiation at CD4<500 cells/mm3, and 1.06 (1.04,1.08) under initiation at CD4<350 cells/mm3. The corresponding estimates were 1.06 (1.06,1.07) and 1.20 (1.17,1.23) for the combined endpoint. Compared with immediate initiation, the mean survival time at 7 years under initiation at CD4<500 cells/mm3 and at CD4<350 cells/mm3 was 2 (1,2) and 5 (4,6) days shorter. Seven years after HIV diagnosis, 100%, 99%, and 93% of individuals would have been in need of cART, and 87%, 87% and 84% would have HIV-RNA<50 copies/mL, under immediate initiation, initiation at CD4<500 and <350 cells/mm3, respectively.
Interpretation
The benefits of immediate initiation of cART, such as prolonged survival and AIDS-free survival and increased virological suppression, were small in this high-income setting with relatively low CD4 count at HIV diagnosis. The estimated beneficial effect on AIDS is less than in recently reported randomised trials. Increasing rates of HIV testing might be as important as a policy of early initiation of cART.