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Abstract
BackgroundEarly treatment of acute HIV infection with highly active antiretroviral therapy, followed by supervised treatment interruption (STI), has been associated with at least transient control of viremia. However, the durability of such control remains unclear. Here we present longitudinal follow-up of a single-arm, open-label study assessing the impact of STI in the setting of acute HIV-1 infection.Methods and FindingsFourteen patients were treated during acute HIV-1 infection and subsequently subjected to an STI protocol that required retreatment if viral load exceeded 50,000 RNA copies/ml plasma or remained above 5,000 copies/ml for more than three consecutive weeks. Eleven of 14 (79%) patients were able to achieve viral loads of less than 5,000 RNA copies/ml for at least 90 d following one, two, or three interruptions of treatment. However, a gradual increase in viremia and decline in CD4+ T cell counts was observed in most individuals. By an intention-to-treat analysis, eight (57%), six (43%), and three (21%) of 14 patients achieved a maximal period of control of 180, 360, and 720 d, respectively, despite augmentation of HIV-specific CD4+ and CD8+ T cell responses. The magnitude of HIV-1-specific cellular immune responses before treatment interruption did not predict duration of viremia control. The small sample size and lack of concurrent untreated controls preclude assessment of possible clinical benefit despite failure to control viremia by study criteria.ConclusionsThese data indicate that despite initial control of viremia, durable viral control to less than 5,000 RNA copies/ml plasma in patients following treated acute HIV-1 infection occurs infrequently. Determination of whether early treatment leads to overall clinical benefit will require a larger and randomized clinical trial. These data may be relevant to current efforts to develop an HIV-1 vaccine designed to retard disease progression rather than prevent infection since they indicate that durable maintenance of low-level viremia may be difficult to achieve.
Highlights
The use of highly active antiretroviral therapy (HAART) can dramatically prolong the life of individuals infected by human immunodeficiency virus 1 (HIV-1) [1], but early hopes for virus eradication have not been realized [2]
The small sample size and lack of concurrent untreated controls preclude assessment of possible clinical benefit despite failure to control viremia by study criteria. These data indicate that despite initial control of viremia, durable viral control to less than 5,000 RNA copies/ml plasma in patients following treated acute HIV-1 infection occurs infrequently
These data may be relevant to current efforts to develop an HIV-1 vaccine designed to retard disease progression rather than prevent infection since they indicate that durable maintenance of low-level viremia may be difficult to achieve
Summary
The use of highly active antiretroviral therapy (HAART) can dramatically prolong the life of individuals infected by human immunodeficiency virus 1 (HIV-1) [1], but early hopes for virus eradication have not been realized [2]. The successful use of HAART is limited by drug-related toxicities, high costs, and drug resistance [3], factors which have led to the development of alternative therapeutic strategies, including the use of supervised, or structured, treatment interruption (STI) This approach, involving recurrent limited exposure to autologous virus, has not been successful in chronic infection [4,5], but has been shown to lead to at least transient containment of viremia after intervention in the acute phase of infection in humans and animals exposed to AIDS-associated retroviruses [6,7,8,9]. The. Early treatment of acute HIV infection with highly active antiretroviral therapy, followed by supervised treatment interruption (STI), has been associated with at least transient control of viremia. In other words, giving patients ‘‘drug holidays’’ did not help to keep the virus at bay for long periods of time
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