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  IAS 2013: 7th IAS Conference on HIV
Pathogenesis Treatment and Prevention
June 30 - July 3 2013
Kuala Lumpur, Malaysia
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Systemic Review Sees Evidence for Advantage to Starting ART Above 500 CD4s
  7th IAS Conference on HIV Pathogenesis, Treatment and Prevention, June 30-July 3, 2013, Kuala Lumpur
Mark Mascolini
A systematic review of observational studies and randomized controlled trials confirmed advantages for starting antiretroviral therapy (ART) at a CD4 count above 350 rather than between 200 and 349 [1]. The review also found evidence from five observational studies suggesting a survival advantage for starting ART immediately rather than waiting for the count to fall below 500.
Three years ago the World Health Organization (WHO) revised its antiretroviral guidelines to recommend starting ART when the CD4 count dips below 350, but several countries now use a threshold of 500. United States guidelines recommend starting ART regardless of CD4 count. To inform evolution of WHO guidelines, WHO investigators and collaborators at other institutions conducted a systematic review of studies to estimate differences in risk of disease progression between people whose CD4 count lay at 350 or above when ART began ("early treatment") and people whose CD4 lay between 200 and 349 when they started ART ("deferred treatment"). The investigators also assessed risk of disease progression or death above versus below the 500-cell cutoff.
Their electronic database search yielded 13 observational studies comparing early and deferred treatment at the 350-cell threshold. All these studies found a lower death risk in people starting ART early. The pooled risk ratio (RR) indicated that early starters had a 34% lower risk of death (RR 0.66, 95% confidence interval 0.55 to 0.79). One randomized controlled trial did not find a significantly lower death risk with early ART (RR 0.77, 95% CI 0.34 to 1.75).
Nine observational studies assessing the risk of AIDS or death yielded a pooled 28% lower risk with ART started above the 350-cell cutoff (RR 0.72, 95% CI 0.65 to 0.81), while two randomized controlled trials found a 52% lower risk of AIDS or death with early treatment (RR 0.48, 95% CI 0.26 to 0.91). Four observational studies assessing only progression to clinical AIDS yielded a nonsignificant 30% lower pooled risk with early ART (RR 0.70, 95% CI 0.40 to 1.24). In one randomized controlled trial assessing this endpoint, risk of progression was significantly lower with early therapy (RR 0.31, 95% CI 0.10 to 0.96).
Four observational studies assessing the risk of AIDS or death in people who began ART at a CD4 count above or below 500 found no advantage to early therapy (RR 0.94, 95% CI 0.69 to 1.28). But five observational studies comparing starting ART immediately with waiting for a count below 500 yielded a pooled 22% lower risk of death, which approached statistical significance (RR 0.78, 95% CI 0.57 to 1.06).
The researchers concluded that AIDS and mortality risk appear to be lower in people who start ART before their CD4 count sinks below 350. They believe "subgroup analyses suggest a continued, attenuated mortality risk reduction using higher CD4 thresholds."
1. Anglemyer A, Rutherford G, Easterbrook P, et al. Early initiation of antiretroviral therapy (ART) for individuals with HIV infection: a systematic review. 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention, June 30-July 3, 2013, Kuala Lumpur. Abstract TUPE302.