Comparative effectiveness of immediate antiretroviral therapy versus CD4-based initiation in HIV-positive individuals in high-income countries: observational cohort study

Abstract

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.

Effect of Immediate Initiation of Antiretroviral Treatment in HIV-Positive Individuals Aged 50 Years or Older

“…The reduction in absolute risk was smaller for non-AIDS mortality. While small, the estimated benefits of immediate initiation on the all-cause mortality of these older populations are larger than those estimated among all individuals in the HIV-CAUSAL Collaboration (median age 37 years) 22: the 7-year risk of all-cause mortality for immediate initiation was only 0.25% (95% CI 0.40,0.37) lower than the risk under initiation at CD4 count<350 cells/mm 3 . These findings suggest that in older HIV-positive patients the benefits of immediate ART initiation on mortality are not offset by age-related comorbidities and potential effects of polypharmacy.…”

How common and frequent is heterosexual anal intercourse among South Africans? A systematic review and meta‐analysis

“…only1[57]2[69,78]3Regional lang. & English17[40,41,43,44,47–49,53,54,56,59–62,73–75]7[40,41,70,76,77,79,80]22 b  Not stated11[42,45,50–52,55,58,63–66]5[46,67,68,71,72]16AI – anal intercourse, VI – vaginal intercourse, UAI – unprotected anal intercourse, UVI – unprotected vaginal intercourse, F – female, M – male, Mix – data available on mixed gender only, FSW – female sex worker, MSM – men who have sex with men, shebeen – an informal establishment serving alcohol, STI – sexually transmitted infection, VCT – voluntary counselling and testing, ACASI – audio computer-assisted self-interview, FTFI – face-to-face interview, SAQ – self-administered questionnaire, CRS – cluster random sample, SRS – simple random sample, RDS – respondent-driven sample, RCT – randomized controlled trial a Studies which reported AI prevalence for unprotected AI only. b Sum lower than expected as two studies report on both higher and general-risk populations. c Recall period referred to here as “general” when participants were asked “Do you practise anal sex”, or similar. d Defined by author as “high risk” but no definition provided; sample consists of 79% FSW [70]. …”

Optimal timing of antiretroviral treatment initiation in HIV-positive children and adolescents: a multiregional analysis from Southern Africa, West Africa and Europe

“…This yields similar interpretations to a recent causal modelling study conducted in over 50 000 adults in North America and Europe. 39 Preliminary findings from the START and TEMPRANO trials point towards a morbidity benefit of immediate ART initiation but, as Lodi et al 39 have also highlighted, different populations with different co-infections, different follow-up times and different assumptions complicate comparisons between different settings. Furthermore, findings from adults can likely not be transferred to adolescents due to different patient care systems, durations of infection, issues with nonadherence, drug combinations and lifestyle factors.…”