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IAS 2013: Meta-analysis Finds Early HIV Treatment Reduces Risk of AIDS and Death

A meta-analysis of more than 30 studies found that starting antiretroviral therapy with a CD4 T-cell count above 350 cell/mm³ was associated with a lower risk of progression to AIDS or death, according to a poster presented at the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013) this month in Kuala Lumpur.

Current U.S. DHHS guidelines recommend that everyone diagnosed with HIV should initiate ART regardless of CD4 count, and the World Health Organization (WHO) released updated guidelines at the IAS meeting recommending that people worldwide should start treatment when CD4s fall below 500 cells/mm³.

There is clear evidence of the advantages of starting HIV treatment before one's CD4 count falls into the danger zone below 200 or 350 cells/mm³, but the benefits versus risks of starting at a higher level are less clear.

To inform the process of revising the WHO guidelines, researchers with WHO and the University of California at San Francisco performed a systematic literature review and meta-analysis -- using the methods of the Cochrane Collaboration -- to estimate differences in HIV disease progression and death between people who start ART with a baseline CD4 count of 350 cells/mm³ or higher (the WHO threshold in effect at the time of the analysis) and those who start with 200-349 cells/mm³.

Andrew Anglemyerand colleagues search electronic publication databases and abstracts in all languages for relevant randomized controlled trials (RCTs) and observational studies that assessed the risk of progression to AIDS, death, or both combined, according to early versus deferred antiretroviral treatment.

Results

• 13 observational studies comparing mortality among patients on early versus deferred treatment all found significantly reduced mortality for those who started ART above 350 cells/mm³ (pooled risk ratio [RR] 0.66, or 34% risk reduction).
• 1 RCT looking at mortality found a non-significant risk reduction (RR 0.77, or 23% reduction).
• 4 observational studies comparing progression to clinical AIDS alone saw a risk reduction, but results showed substantial heterogeneity, or inconsistency (RR 0.70, or 30% reduction).
• 1 RCT also found a significantly reduced risk of progression to AIDS alone (RR 0.31, or 69% reduction).
• 9 observational studies comparing combined rates of AIDS or death found significantly reduced risk for people who started ART early (RR 0.72, or 28% reduction).
• 2 RCTs looking at AIDS and death combined likewise saw a reduced risk associated with early treatment (RR 0.48, or 52% reduction).
• A smaller subgroup analysis compared people who started ART at or above 500 cells/mm³ -- essentially, immediately upon HIV diagnosis -- versus those who started below 500 cells/mm³ (no RCTs had adequate data for inclusion in this analysis):

o   4 observational studies saw a small but significant reduction in AIDS or death associated with earlier treatment (RR 0.94, or 6% reduction);

o   5 observational studies saw a borderline significant reduction in mortality (RR 0.78, or 22% reduction).

"Using [then] current WHO guidelines, mortality risk and risk for AIDS or death appear to be reduced in subjects who are treated early, compared to those who defer treatment to < 350 cells/[mm³]," the researchers concluded. "Subgroup analyses suggest a continued, attenuated mortality risk reduction using higher CD4 thresholds."

These findings provide support for the latest WHO revision calling for early treatment. The ongoing Strategic Timing of Antiretroviral Treatment -- or START -- trialis designed to collect the missing RCT data. This trial is currently enrolling people with CD4 counts greater than 500 cells/mm³ who will either start treatment immediately or wait until their CD4 level falls to 350 cells/mm³ or they develop AIDS symptoms.

7/24/13

Reference

A Anglemyer, G Rutherford, P Easterbrook, et al. Early initiation of antiretroviral therapy (ART) for individuals with HIV infection: a systematic review. 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Kuala Lumpur, June 30-July 3, 2013.  Abstract TUPE302.