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Treating Acute HIV Infection and Treatment Interruptions to Boost Immune Control: an experiment comes to an end
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Written by David Margolis, MD, University of Texas, Southwastern Medical Center Dallas
Walker (Abstract 24) presented long-term follow-up of a select cohort of patients in whom symptomatic early HIV infection had been detected, and ART given followed by supervised treatment interruptions. Initial reports generated great excitement in the field as it was suggested that this strategy resulted in improved immune control of viremia. Initially, 7 of 8 patients maintained stable CD4 counts and low viral loads without therapy.
However, 14 subjects have now been enrolled and treated in this protocol for up to 5.3 years with sobering results. Subjects have undergone initial ART and subsequently subjected to up to 4 supervised treatment interruptions. Re-treatment was required if viral load remained above 5000 copies for longer than 3 consecutive weeks, or was in excess of 50,000 copies on any single occasion.
11 of 14 subjects were able to maintain control of viremia by these criteria for at least 90 days, but only 6 of 14 at 1 year, and 3 of 14 at 3 years. Over the course of the study, a gradual increase in viremia and decline in CD4 cell counts was observed in most individuals, with a significant decline of CD4 cell count in 1 of the remaining 3 patients with controlled viremia. This pattern was not influenced by treatment interruptions.
The total magnitude and breadth of HIV-specific CD8 T-cell responses increased during the first, second, and third supervised treatment interruptions, as the intact immune system was exposed to repeated to HIV antigen. However, the extent of these increases in anti-HIV immune response did not correlate with subsequent viral control. Other factors that may correlate with disease progression, such as HLA type, baseline viral load, chemokine receptor alleles, extent of HIV antibody production, did not correlate with viral control in this protocol.
These findings were echoed in European studies (Abstracts 396 and 397), which also did not demonstrate a beneficial effect on HIV-specific immune control or level of viremia after early therapy or treatment interruption. These data indicate that despite initial control of viremia, durable immune control in persons following treated acute infection occurs infrequently. Unfortunately, it appears that the immune system, even when protected by ART, does not learn how to better control HIV on its repeated encounters with the virus. These data highlight the challenges to current efforts to develop an AIDS vaccine designed to retard disease progression rather than prevent infection.
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