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Early Time-limited Treatment Leads to Better Outcomes for Infants with HIV


Infants with HIV who start antiretroviral therapy (ART) immediately after birth had a lower risk of disease progression or death and were able to safely interrupt treatment longer than children who started ART later, according to findings from the long-running CHER study published in the August 22, 2013, advance online edition of The Lancet.

Mark Cotton from Stellenbosch Universityand fellow investigators with the CHER Study Team compared different treatment strategies for asymptomatic HIV-infected babies at 2 trial sites in South Africa.

This open-label trial included 377 infants age 12 weeks or younger (median 7.4 weeks). At baseline all had CD4 T-cell percentages of at least 25% (median 35%), indicating that they did not yet have severe immune deficiency. The median baseline HCV RNA viral load was 5.7 log copies/mL.

Participating infants were randomly allocated to 3 treatment arms, all receiving lopinavir/ritonavir (Kaletra or Aluvia) plus zidovudine/lamivudine (the drugs in Combivir) as first-line therapy:

  • Deferred ART starting when CD4 percentage fell below 25%;
  • Immediate ART for 40 weeks followed by treatment interruption;
  • Immediate ART for 96 weeks followed by treatment interruption.

Treatment interruptions lasted until a child's CD4 percentage fell below 20%-25% (depending on age) or they developed symptomatic HIV/AIDS (severe CDC stage B or stage C disease). The median duration of follow-up was 4.8 years, and the primary endpoint was time to death or immunological, virological, or clinical failure of first-line ART.

Previous findings from CHER, first reported in 2007, contributed to the World Health Organization's recommendation that all children with HIV should receive ART regardless of immune status.


  • A total of 34 infants (9%) were lost to follow-up during the study.
  • The median time to ART initiation in the deferred treatment group was 20 weeks.
  • Duration of treatment interruption before restarting ART was 33 weeks in the 40-week immediate treatment arm and 70 weeks in the 96-week immediate treatment arm.
  • At the end of the trial, 19% of infants in the 40-week arm and 32% in the 96-week arm remained well enough to stay off ART.
  • Overall, babies in the deferred treatment arm time spent 81% of follow-up time on ART, compared with 70% and 69%, respectively, in the 40-week and 96-week immediate treatment arms.
  • 38% of infants in the deferred treatment arm experienced ART failure or death during follow-up, compared with 25% and 21%, respectively, in the 40-week and 96-week immediate treatment arms.
  • Infants in the 40-week and 96-week immediate treatment arms were significantly less likely to reach the primary endpoint than those in the deferred treatment arm (hazard ratio 0.59 and 0.47, or about 40% and 50% less likely, respectively).
  • Looking at death alone, twice as many babies died in the deferred treatment arm (18%) than in either of the immediate treatment arms (9% each).
  • 3 children in deferred treatment arm, 3 in the 40-week immediate arm, and 1 in the 96-week immediate arm switched to a second-line ART regimen during the study period.

"Early time-limited ART had better clinical and immunological outcomes than deferred ART, with no evidence of excess disease progression during subsequent treatment interruption and less overall ART exposure than deferred ART," the researchers concluded. "Longer time on primary ART permits longer subsequent interruption, with marginally better outcomes."

Taking breaks from ART could reduce side effects, lower treatment cost, relieve drug shortages, and potentially reduce the likelihood of developing drug resistance, the study authors explained in their discussion. As a limitation, they noted that the trial did not compare children who received immediate treatment and stayed on continuous ART.

While these findings suggest that drug holidays may be safe for some children, Robert Colebunders from the Institute of Tropical Medicine in Belgium and Victor Musiime from Makerere University in Uganda cautioned in an accompanying commentary that, "Treatment interruption is a risky option in poor countries which lack laboratory facilities to monitor levels of CD4 immune cells" at frequent enough intervals.

On the other hand, they noted that a baby in Mississippi who started combination ART at just 31 hours after birth has been able to stay off treatment with no evidence of HIV rebound for 18 months and counting.

The SMART trial and other studies of HIV positive adults have shown that treatment interruption can by risky, leading to higher rates of opportunistic illness, death, and chronic non-AIDS conditions. Chronic heart, liver, and kidney disease may less of a concern for young children than for older adults, but further research is needed to look at long-term consequences.



MF Cotton, A Violari, K Otwombe, et al (CHER Study Team). Early time-limited antiretroviral therapy versus deferred therapy in South African infants infected with HIV: results from the children with HIV early antiretroviral (CHER) randomised trial. The Lancet. August 22, 2013 (Epub ahead of pront).

R Colebunders and V Musiime. Does the CHER trial open up new therapeutic perspectives? (Comment). The Lancet. August 22, 2013 (Epub ahead of print).

Other Source

Kaiser Family Foundation. Early Treatment of HIV-Positive Infants Might Allow Later Therapy Interruptions, Study Shows. Kaiser Daily Global Health Policy Report. August 23, 2013.