The HIV treatment cascade in acutely infected people

Abstract

Purpose of Review Acute and early HIV (AHI) is a pivotal time during HIV infection, yet there remain major shortfalls in diagnosis, linkage to care, and antiretroviral therapy (ART) initiation during AHI. We introduce an AHI-specific cascade, review recent evidence pertaining to the unique challenges of AHI, and discuss strategies for improving individual and public health outcomes. Recent Findings Presentation during AHI is common. Expanding use of 4th generation testing and pooled nucleic acid amplification testing (NAT) has led to improved AHI detection in resource-wealthy settings. Technologies capable of AHI diagnosis are rare in resource-limited settings; further development of point-of-care devices and utilization of targeted screening is needed. Rapid ART initiation during AHI limits reservoir seeding, preserves immunity, and prevents transmission. Reporting of AHI cascade outcomes is limited, but new evidence suggests that impressive rates of diagnosis, linkage to care, rapid ART initiation, and viral suppression can be achieved. Summary With advancements in AHI diagnostics and strong evidence for the therapeutic and prevention benefits of ART initiated during AHI, improving AHI cascade outcomes is both crucial and feasible. HIV guidelines should recommend diagnostic algorithms capable of detecting AHI and prescribe rapid, universal ART initiation during AHI.

Viral kinetics in untreated versus treated acute HIV infection in prospective cohort studies in Thailand

“…This provides a strong rationale for studying immunotherapeutics in early treated individuals who have little or no viral escape, less CD4 depletion and more preserved memory T cells in order to improve HIV-specific immune responses and possibly enhancing the chance for HIV remission (i.e. undetectable plasma VL levels following ART discontinuation) [26][27][28]. High VL during acute infection increases the risk for onward transmission [24,[29][30][31][32]; therefore, modifying the trajectory of VL with early ART could have an important public health implication for HIV prevention.…”

“…Fiebig stages at AHI diagnosis were categorized according to Fiebig and Busch: Fiebig I/II: HIV RNA+, p24 antigen±, HIV IgM− and Fiebig III/IV: HIV IgM+, Western blot-/indeterminate [13]. The follow-up assessments for VL in RV217 were on days 3,7,10,14,17,21,24,28,35,42,56 and 84 and then every three months. In RV254, these were performed on days 3, 5 and 7 and then at weeks 2,4,8,12,16,20,24,36 and 48.…”

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

“…Interventions to consider at this time include ART, screening and treatment of concomitant STI, and the promotion of immediate changes in sexual behaviour. 21 These include consistent condom use, limiting drug and alcohol intake (which may impair the ability CMV = cytomegalovirus; CRP = C-reactive protein; EBV = Epstein-Barr virus; FBC = full blood count; HSV = herpes simplex virus; LFT = liver function test; MCS = microscopy, culture and sensitivities; OCP = ova, cysts and parasites; PCR = polymerase chain reaction; PHI = primary HIV infection; STS = syphilis serology; VZV = varicella zoster virus. …”

“…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.…”

“…Interruption of therapy even if started close to the time of PHI is no longer recommended. 21 Therefore, once started, ART should be taken lifelong.…”