ObjectiveTo systematically evaluate the efficacy and safety of early initiation of antiretroviral therapy (ART) in asymptomatic HIV-infected, treatment-naive adults and adolescents. To assess the evidence for the optimal time to initiate ART.
MethodsDatabases including PubMed, EMbase, The Cochrane Library (Issue 4, 2016), CBM, CNKI, VIP and WanFang Data were searched to collect randomized controlled trials (RCTs) about early initiation and optimal time to initiate ART in asymptomatic, treatment-naive HIV-infected patients from January 1996 to April 2016. Two review authors independently assessed study eligibility, extracted data and graded methodological quality. Data extraction and methodological quality were checked by a third author who resolved differences when these arose. We meta-analysed dichotomous outcomes using the risk ratio (RR) and report the 95% confidence intervals (95% CIs) by using RevMan 5.3 software.
ResultsA total of 4 RCTs involving 8 751 patients were included. The results of meta-analysis showed that initiating ART at CD4+ T-cell counts (CD4 counts) ≥350 cells/μL or 500 cells/μL, comparing to deferring initiation of ART to CD4 counts <350 cells/μL, would benefit patients more: (1) Risk of AIDS-defining illnesses which representing disease progression, reduced significantly when starting ART at higher CD4 counts (no less than 350 cells/μL) (RR=0.49, 95%CI 0.38 to 0.64, P<0.001). The reduction of risk was even more significant when initiating ART at CD4 counts of not less than 500 cells/μL (RR=0.38, 95%CI 0.24 to 0.59, P<0.001). (2) When initiating ART at CD4 counts of not less than 350 cells/μL, the risk of serious non-AIDS related events was significantly reduced by 42% (RR=0.58, 95%CI 0.40 to 0.83, P=0.003). When initiating ART at CD4 counts of not less than 500 cells/μL, according to START 2015, the risk of serious non-AIDS related events could be reduced by 39% (RR=0.61, P=0.04). (3) However, when initiating ART at CD4 counts of not less than 350 cells/μL or 500 cells/μL, comparing to deferring initiation, there were no statistically significant differences in death (RR=0.70, 95%CI 0.48 to 1.02, P=0.06) and serious adverse events (RR=0.67, 95%CI 0.38 to 1.20, P=0.18).
ConclusionOur findings contribute to the evidence base for recommending initiating ART at CD4 counts of 350-500 cells/μL compared to initiating it later when CD4 counts fall below 350 cells/μL. As for patients with CD4 counts of not less than 500 cells/μL, initiation of ART is also recommended.
ObjectiveTo systematically review the recommendations for antiretroviral therapy in the AIDS guidelines, and summarize the sources of evidence supporting the recommendations, the quality of the evidence and the strength of the recommendations, and the consistency of the recommendations. MethodsWe systematically searched for articles published before Dec 2024 in PubMed, Web of Science, Embase, CNKI, WanFang Data, VIP, CBM, and 9 guideline databases, websites, integrating recommendations. Quality and reporting practices were evaluated using AGREE Ⅱ and RIGHT tools respectively. ResultsThe average score of AGREE Ⅱ was 62 points, the overall reporting rate was 69.68%, and the quality of methodology and reporting specifications were low. Analysis of the recommendation results showed that a total of 57 recommendations for ART therapy were extracted from 18 guidelines, mainly recommending 2 NRTIs combined with third-category drugs. NRTI drugs are mainly based on TDF+FTC (3TC), TAF+FTC, and ABC+3TC. The third category of drugs recommended by various guidelines with relatively high frequency includes INSTI (DTG, BIC, RAL), NNRTI (EFV) and PIs (DRV/r). The third category of drugs recommended with relatively high frequency in alternative therapies includes INSTI (DTG, RAL), NNRTI (EFV, RPV) and PIs (DRV/c). ConclusionThe methodological quality and reporting specifications of the HIV clinical practice guidelines need to be improved. The evidence grading of the guidelines is not standardized, there are differences in the combination of drugs recommended by each guideline, the strength of recommendations and the quality of the evidence are inconsistent, and there are obvious differences in the sources of evidence to support the opinions. In the future, it is necessary to combine high-quality clinical trials or randomized controlled trials, adopt systematic and rigorous evidence level and recommendation grading standards when necessary, and provide high-quality evidence sources to formulate complete guidelines. Specific conditions such as the patient's biological indicators should also be fully considered to clarify which virological and biological indicators ART therapy is suitable for, so as to provide precise treatment.
