Effect Estimates in Randomized Trials and Observational Studies:Comparing Apples With Apples

Effect estimates from randomized trials and observational studies might not be directly comparable because of differences in study design, other than randomization, and in data analysis. We propose a 3-step procedure to facilitate meaningful comparisons of effect estimates from randomized trials and observational studies: 1) harmonization of the study protocols (eligibility criteria, treatment strategies, outcome, start and end of follow-up, causal contrast) so that the studies target the same causal effect, 2) harmonization of the data analysis to estimate the causal effect, and 3) sensitivity analyses to investigate the impact of discrepancies that could not be accounted for in the harmonization process. To illustrate our approach, we compared estimates of the effect of immediate with deferred initiation of antiretroviral therapy in individuals positive for the human immunodeficiency virus from the Strategic Timing of Antiretroviral Therapy (START) randomized trial and the observational HIV-CAUSAL Collaboration

Expert consensus statement on the science of HIV in the context of criminal law.

CAPRISA, 2018.Abstract available in pdf

The Protease Inhibitor Monotherapy Versus Ongoing Triple Therapy (PIVOT) trial : a randomised controlled trial of a protease inhibitor monotherapy strategy for long-term management of human immunodeficiency virus infection

Background Standard-of-care antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection uses a combination of drugs, until now considered essential to minimise treatment failure and development of drug resistance. Protease inhibitors (PIs) are potent with a high genetic barrier to resistance and have the potential for use as monotherapy after viral load (VL) suppression achieved on combination therapy. However, longer-term resistance and toxicity risks are uncertain. Objective To compare the effectiveness, toxicity profile and cost-effectiveness of PI monotherapy with those of standard-of-care triple therapy in a pragmatic long-term clinical trial. Design Open-label, parallel-group, randomised controlled trial. Setting Forty-three HIV clinical centres in the UK NHS. Participants HIV-positive adults taking standard combination ART with a suppressed VL for ≥ 6 months. Interventions Patients were randomised to maintain ongoing triple therapy (OT) or switch to a strategy of physician-selected ritonavir-boosted PI monotherapy (PI-mono), with prompt return to combination therapy in the event of VL rebound. Main outcome measures The primary outcome was reduction of future drug options, defined as new intermediate-/high-level resistance to one or more drugs to which the patient’s virus was considered to be sensitive at trial entry (non-inferiority comparison, 10% margin). Secondary outcomes included confirmed virological rebound, serious drug- or disease-related complications, total grade 3 or 4 adverse events (AEs), neurocognitive function change, cluster of differentiation 4 (CD4) cell count change, change in health-related quality of life, cardiovascular risk change, health-care costs and health economic analysis. Results In total, 587 participants were randomised (77% male, 68% white) to OT (n = 291) or PI-mono (n = 296) and followed for a median of 44 months, of whom 2.7% withdrew/were lost to follow-up. One or more episodes of confirmed VL rebound were observed in eight patients (Kaplan–Meier estimate 3.2%) in the OT group and 95 patients (35.0%) in the PI-mono group [absolute risk difference 31.8%, 95% confidence interval (CI) 24.6% to 39.0%; p < 0.001]. PI-mono patients who changed to ART after VL rebound all resuppressed (median 3.5 weeks). The proportions with loss of a future drug option at 3 years were 0.7% in the OT group and 2.1% in the PI-mono group (difference 1.4%, (95% CI –0.4% to 3.4%); non-inferiority demonstrated). There were no significant differences in serious disease complications between groups or in the frequency of grade 3 or 4 clinical AEs (16.8% OT group vs. 22% PI-mono group; absolute risk difference 5.1%, 95% CI –1.3% to 11.5%; p = 0.12). Overall, the PI-mono strategy was shown to be cost-effective compared with OT under most scenarios explored. PI-mono was cost saving because of the large savings in ART drug costs while being no less effective in terms of quality-adjusted life-years in the within-trial analysis and only marginally less effective when extrapolated to lifetime outcomes. Conclusions PI monotherapy, with prompt reintroduction of combination therapy for VL rebound, was non-inferior to combination therapy in preserving future treatment options and is an acceptable and cost-effective alternative for long-term management of HIV infection. Trial registration Current Controlled Trials ISRCTN04857074. Funding This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 21. See the NIHR Journals Library website for further project information

Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection

Presentes no The INSIGHT START Study Group: Beatriz Grinsztejn; Valdiléa Veloso; Sandra Wagner Cardoso (Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil)Submitted by Fábio Marques ([email protected]) on 2018-10-15T14:21:48Z No. of bitstreams: 1 Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection_Beatriz_Grinsztejn_etal_INI_Lapclin-AIDS_2015.pdf: 610432 bytes, checksum: b2ca3130269a736bda8e3527c830aeae (MD5)Approved for entry into archive by Regina Costa ([email protected]) on 2018-10-17T13:47:56Z (GMT) No. of bitstreams: 1 Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection_Beatriz_Grinsztejn_etal_INI_Lapclin-AIDS_2015.pdf: 610432 bytes, checksum: b2ca3130269a736bda8e3527c830aeae (MD5)Made available in DSpace on 2018-10-17T13:47:57Z (GMT). No. of bitstreams: 1 Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection_Beatriz_Grinsztejn_etal_INI_Lapclin-AIDS_2015.pdf: 610432 bytes, checksum: b2ca3130269a736bda8e3527c830aeae (MD5) Previous issue date: 2015Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter

Demographic and HIV-specific characteristics of participants enrolled in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial

Artículo de publicación ISIObjectives The risks and benefits of initiating antiretroviral treatment (ART) at high CD4 cell counts have not been reliably quantified. The Strategic Timing of AntiRetroviral Treatment (START) study is a randomized international clinical trial that compares immediate with deferred initiation of ART for HIV-positive individuals with CD4 cell counts above 500 cells/μL. We describe the demographics, HIV-specific characteristics and medical history of this cohort. Methods Data collected at baseline include demographics, HIV-specific laboratory values, prior medical diagnoses and concomitant medications. Baseline characteristics were compared by geographical region, gender and age. Results START enrolled 4685 HIV-positive participants from 215 sites in 35 countries. The median age is 36 years [interquartile range (IQR) 29–44 years], 27% are female, and 45% self-identify as white, 30% as black, 14% as Latino/Hispanic, 8% as Asian and 3% as other. The route of HIV acquisition is reported as men who have sex with men in 55% of participants, heterosexual sex in 38%, injecting drug use in 1% and other/unknown in 5%. Median time since HIV diagnosis is 1.0 year (IQR 0.4–3.0 years) and the median CD4 cell count and HIV RNA values at study entry are 651 cells/μL (IQR 584–765 cells/μL) and 12 754 HIV RNA copies/mL (IQR 3014–43 607 copies/mL), respectively. Conclusions START has enrolled a diverse group of ART-naïve individuals with high CD4 cell counts who are comparable to the HIV-positive population from the regions in which they were enrolled. The information collected with this robust study design will provide a database with which to evaluate the risks and benefits of early ART use for many important outcomes