Emma Hitt, PhD

July 25, 2011

July 25, 2011 (Rome, Italy) — A 48-week short course of antiretroviral therapy (ART) initiated within 6 months of HIV seroconversion significantly delays the time until CD4 levels fall below 350 cells/mm3, as well as the need for long-term ART, compared with standard therapy, which is no treatment until the CD4 cell count drops below 350 cells/mm3, according to new findings from the Short Pulse Anti Retroviral Therapy at HIV Seroconversion (SPARTAC) trial.

Sarah J. Fidler, MBBS, MRCP, PhD, from Imperial College London, United Kingdom, and colleagues presented the findings here at the 6th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention, during a late-breaking session.

"SPARTAC is the largest ever randomized controlled trial in primary HIV infection, enrolling men and women in both developed and developing world settings," Dr. Fidler told Medscape Medical News.

According to Dr. Fidler, HIV-induced immunological destruction begins early and, despite later ART, is never completely reversed. "Observational studies have shown encouraging data to suggest potential immunological benefit for early ART," she added.

The SPARTAC trial was designed to evaluate whether ART initiated as near to HIV transmission as possible may protect against HIV-induced immune damage.

A total of 366 patients diagnosed with primary HIV infection were randomly assigned within 6 months of seroconversion to receive ART for 48 weeks, ART for 12 weeks, or no therapy (ie, standard of care). Participants were followed for an average of 4.2 years.

Only half of the 48-week ART group reached the primary endpoint (CD4 level < 350 cells/mm3 and long-term ART initiation) compared with 61% in both the 12-week ART group and the no-therapy group.

Participants receiving 48-week ART had long-term therapy delayed for a median of 65 weeks (range, 17 - 114 weeks) longer than those receiving no therapy, indicating an average hazard ratio of 0.63 (95% confidence interval, 0.45 - 0.90; P = .01); 48-week ART also conferred a higher average CD4 count of 138 cells over 4.5 years. In contrast, the delay with ART for 12 weeks was not significantly different from that observed with no therapy.

The researchers also found a trend for greater delay to primary endpoints the sooner ART was initiated after estimated seroconversion (P = .09).

ART given for 48 weeks reduced HIV RNA by 0.44 log10 copies/mL 36 weeks after interrupting therapy compared with no therapy. There was no significant difference among the 3 groups in terms of AIDS, deaths, or serious adverse events, and virological failure on long-term ART was similar across groups.

"In contrast to the SMART study, there was no rebound in [interleukin] 6 and a drop in d-dimer compared with baseline levels 4 weeks after stopping ART," Dr. Fidler said during her talk. She added that "interruption of ART in primary HIV infection showed no evidence of harm, development of drug resistance, or CD4 recovery after starting long-term ART."

"It is reassuring to see that there is no apparent harm in starting and stopping early ART, as this regimen might allow us to treat initial acute sickness and then give patients a drug-free break for a year or 2," said independent commentator Myron S. Cohen, MD, the J. Herbert Bate Distinguished Professor of Medicine, Microbiology and Immunology, and Public Health at the University of North Carolina at Chapel Hill. Dr. Cohen is also associate vice chancellor of Global Health and the director of the Institute for Global Health and Infectious Diseases at the University of North Carolina at Chapel Hill and serves as chief of the Division of Infectious Diseases.

"It's clear that ART alone in early HIV does not change the course of the disease, and adjunctive intervention is needed," he told Medscape Medical News. "However, we do see less HIV rebound and some sparing of immune function," he added.

The study was not commercially supported. Abbott Laboratories Limited supplied the study drug. Dr. Fidler and Dr. Cohen have disclosed no relevant financial relationships.

6th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention: Abstract WELBX06. Presented July 20, 2011.

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