How does the timing of antiretroviral therapy initiation in acute infection affect HIV reservoirs?

Abstract

Purpose of review The long-lived viral reservoir is a major obstacle to achieving a cure for HIV. Therapeutic strategies, such as early antiretroviral therapy (ART), may be a prerequisite to achieving long-term control of viral replication upon ART withdrawal. Recent findings HIV persistence is established early in acute HIV infection (AHI) with infection in long-lived memory CD4+ T cells. Studies conducted in nonhuman primates have suggested that this could occur as early as 3 days postinfection; however, the timing in humans is uncertain. ART during AHI significantly restricts the HIV reservoirs as compared with later treatment. Early ART, particularly prior to the detection of HIV immunoglobulin M, may also reduce the contribution of the long-lived central memory CD4+ T cells to the total HIV reservoir, a profile observed in individuals who naturally control HIV without ART. Summary It is clear that early ART has a greater impact in limiting the HIV reservoirs than later treatment. However, latently infected long-lived memory CD4+ T cells persist in most early treated individuals. Therefore, additional interventions will likely be required to eliminate all cells capable of producing replication-competent virus but treatment in AHI may be the critical first step in containing the HIV reservoirs.

HIV-1 RNA testing of pooled dried blood spots is feasible to diagnose acute HIV infection in resource limited settings

“…4,5,21,22 Patients treated during acute infection are also ideal candidates for curative interventions as early therapy prevents immune damage and limits seeding of reservoirs. 23,24 According to the 2012 Human Science Research Council South African National HIV Prevalence, Incidence and Behaviour Survey, the overall HIV incidence in 2 -49-year-old individuals was 1.07%. However, as the epidemic is generalised, it is difficult to define risk groups, apart from a higher incidence among young black female survey participants.…”

Primary HIV infection: a medical and public health emergency requiring rapid specialist management

“…21,32,37,40 Duration of ART at PHI Three randomised controlled trials in PHI reported a modest benefit (delaying the decline in CD4 cell count, or time from PHI, to requiring lifelong ART) following a 48-week 38 or 60-week 39,40 course of ART. Interruption of therapy even if started close to the time of PHI is no longer recommended.…”

“…[24][25][26] > Reduction in the enhanced risk of onward transmission of HIV associated with PHI. [27][28][29][30][31][32] > Limitation in the size of latent pool of HIV-infected cells; the viral reservoir, 33,35 which has been associated with risk of missed diagnoses of acute HIV infection, the presence of certain indicator diseases should trigger the offer of HIV testing, 16,17 for individuals presenting with signs or symptoms of Epstein-Barr virus, cytomegalovirus, secondary syphilis, tuberculosis and bacterial pneumonia. As a result of the challenges with current technology at accurately diagnosing acute HIV infection, encouraging both access and increasing the frequency of HIV testing among those at highest risk are key to improving timely identification of PHI.…”

Multifarious immunotherapeutic approaches to cure HIV-1 infection

“…17 On an individual patient basis, those demonstrating the greatest benefit from immunotherapy (with improved clinical and immunological parameters) received cART at earlier stages following infection, which concurs with a number of reports. 18,19 There is an emerging consensus that early initiation of cART is an essential aspect of long-term control of HIV-1 and likely to be critical in future latency reversal approaches. 19 …”

“…18,19 There is an emerging consensus that early initiation of cART is an essential aspect of long-term control of HIV-1 and likely to be critical in future latency reversal approaches. 19 …”