When to Start ART, Redux
Two new studies strongly suggest that early ART initiation is associated with significant improvements in CD4-cell count and HIV viral load.
Management of recently acquired HIV infection has long been controversial, with the risks and benefits of treatment versus observation debated now for nearly 2 decades. On the risk side is the toxicity of lifelong treatment, especially because patients may have normal or near-normal CD4-cell counts after recovery from acute HIV infection and may remain asymptomatic for many years. Benefits include preservation of immunologic function, reduction in transmission risk to others, and perhaps reduction in the HIV reservoir. Now, findings from two new studies strongly suggest that we manage early HIV infection the same way we do long-established disease — with antiretroviral therapy (ART).
Le and colleagues conducted a prospective, observational study involving 468 patients (95% men) in San Diego with acute or early HIV infection — 213 who initiated ART within 4 months after HIV acquisition and 384 who did not receive it until later. Sixty-four percent of patients treated early achieved the primary endpoint (CD4 recovery to 900 cells/mm3 during 48 months of observation) versus 34% of those treated later (P<0.001). For those treated later, the median time to CD4 count <500 cells/mm3 — a threshold at which the clinical evidence of treatment benefit becomes much stronger — was only 12 months, suggesting that even if treatment is not started early, it is likely to be needed relatively soon.
In the open-label SPARTAC trial, conducted at sites in Europe, South America, Australia, and Africa, 371 patients (60% men) with primary HIV infection (variously defined) were randomized to receive 12 weeks of ART, 48 weeks of ART, or no ART (standard of care). The primary endpoint was either a CD4 count <350 cells/mm3 or initiation of long-term ART. During a median follow-up of 4.2 years, only the 48-week treatment group demonstrated a delay in reaching a CD4 count <350 cells/mm3, with 28% falling to this level versus 40% of the 12-week group and 39% of the no-ART group. The proportion of patients requiring long-term ART initiation was similar among groups. In addition, 36 weeks after the end of short-course therapy, the mean change in HIV RNA level from baseline was significantly greater in the 48-week group than in the no-ART group (difference, –0.44 log copies/mL). Among participants in the 48-week group, treatment started closer to the time of HIV acquisition appeared to confer greater benefit.
Comment: These studies have substantial limitations, most notably the nonrandomized design and skewed demographics in the first, and the fact that treatment interruption makes both treatment strategies in the second study of limited relevance today. Furthermore, the various definitions of early HIV infection — a problem that has plagued this field from the outset — imply a very heterogeneous patient population: In the SPARTAC study, some participants had acute symptomatic HIV infection pre-seroconversion and others were enrolled based solely on newly positive HIV-antibody results. In both studies, follow-up was too short to provide hard clinical endpoints showing the benefits of early treatment.
These limitations notwithstanding, there is a consistent message in the aggregate results: Treatment of early HIV infection — the earlier the better — is associated with significant improvements in the most important surrogate markers of HIV disease, CD4-cell count and HIV viral load. For these outcomes alone, prompt treatment is warranted.
Published in Journal Watch HIV/AIDS Clinical Care January 18, 2013
Le T et al. Enhanced CD4+ T-cell recovery with earlier HIV-1 antiretroviral therapy. N Engl J Med 2013 Jan 17; 368:218.
- Medline abstract (Free)
SPARTAC Trial Investigators. Short-course antiretroviral therapy in primary HIV infection. N Engl J Med 2013 Jan 17; 368:207.
- Medline abstract (Free)
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