No less an organisation than the International AIDS Society has published this review of evidence for starting ART with a CD4 cell count between 350 and 500. There is not much evidence.
Did WHO jump the gun by recommending earlier ART? Time, and more studies, will tell.
Jamie
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http://www.iasociety.org/Default.aspx?pageId=5&elementId=15867
Benefits of Starting ART at 350-499 CD4s in WHO Review, Meta-Analysis
Mark Mascolini
10 June 2014
Starting antiretroviral therapy (ART) at a CD4 count between 350 and 499 cells/µL rather than below 350 cells/µL reduced the risk of AIDS or death as well as the risk of non-AIDS diseases in a 26-study systematic review and meta-analysis planned to inform World Health Organization (WHO) guidelines. Starting ART with 350 to 499 cells/µL (defined as early in this study) heightened the risk of grade 3 or 4 laboratory abnormalities but not other adverse outcomes.
For low- or middle-income countries, WHO currently recommends starting ART in adults and adolescents at a CD4 count of 350 to 499 cells/µL but not at a count of 500 cells/µL or higher, as in the United States. To inform review of WHO guidelines, researchers conducted this systematic review and meta-analysis, searching the literature for randomized controlled trials and cohort studies that evaluated progression to AIDS, death, CD4 recovery, and grade 3 or 4 lab abnormalities when starting treatment at 350 to 499 cells/µL rather than below 350 cells/µL.
The researchers identified 24 studies that met their criteria, including three randomized controlled trials (RCT). One RCT found that starting ART at 350 to 499 cells/µL rather than below reduced the risk of death almost 25% (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.34 to 1.76), while combined data from 13 cohort studies indicated that starting at 350 to 499 cells/µL lowered the risk of death by one third (HR 0.66, 95% CI 0.55 to 0.79).
Two RCTs indicated that starting ART at 350 to 499 cells/µL rather than lower halved the risk of progression to AIDS or death (RR 0.48, 95% CI 0.26 to 0.91), while nine cohort studies found a 30% lower risk of progression to AIDS or death (RR 0.70, 95% CI 0.40 to 1.24).
One RCT determined that starting ART at 350 to 499 cells/µL rather than below 350 cells/µL slashed the risk of non-AIDS-defining illness 86% (RR 0.14, 95% CI 0.03 to 0.64), while one cohort study found more than a 50% lower risk of a new non-AIDS illness (RR 0.47, 95% CI 0.23 to 0.98).
One cohort study found that earlier ART almost tripled chances of reaching a CD4 count of at least 800 cells/µL (HR 2.84, 95% CI 2.45 to 3.28), but two other cohort studies found no evidence that starting ART earlier raised chances of gaining at least 100 cells/µL during the study period.
One RCT determined that beginning ART with 350 to 499 cells/µL rather than at a lower count raised the risk of grade 3 or 4 lab abnormalities almost 50% (RR 1.49, 95% CI 1.25 to 1.77).
The researchers rated the quality of evidence low or very low for clinical outcomes (AIDS or death) because the studies included few cases of AIDS or death. Quality of evidence was high for adverse events.
The authors note that “apart from the laboratory abnormalities, early treatment does not appear to cause additional harms.” They add that “the literature for beginning ART at CD4+ T-cell counts of at least 500 cells/μl is much less robust and awaits new data from the large trials and combination cohort studies to provide additional evidence of the effectiveness of even earlier initiation.”
The authors stress that they eagerly await results of two ongoing trials, START and TEMPRANO, “in hopes that they will add additional high-quality evidence to answer the question of when to start ART definitively.”
Source: Andrew Anglemyer, George W. Rutherford, Philippa J. Easterbrook, Tara Horvath, Marco Vitória, Michael Jan, Meg C. Doherty. Early initiation of antiretroviral therapy in HIV-infected adults and adolescents: a systematic review. AIDS. 2014; 28: S105-S118.
http://www.iasociety.org/Default.aspx?pageId=5&elementId=15867
