Absence of Detectable HIV-1 Viremia after Treatment Cessation in an Infant

Abstract

SUMMARY An infant born to a woman with human immunodeficiency virus type 1 (HIV-1) infection began receiving antiretroviral therapy (ART) 30 hours after birth owing to high-risk exposure. ART was continued when detection of HIV-1 DNA and RNA on repeat testing met the standard diagnostic criteria for infection. After therapy was discontinued (when the child was 18 months of age), levels of plasma HIV-1 RNA, proviral DNA in peripheral-blood mononuclear cells, and HIV-1 antibodies, as assessed by means of clinical assays, remained undetectable in the child through 30 months of age. This case suggests that very early ART in infants may alter the establishment and long-term persistence of HIV-1 infection.

Predicting the outcomes of treatment to eradicate the latent reservoir for HIV-1

“…From left to right, they represent a case of early ART initiation in an adult [the "Chun patient" (C.) (36)], two cases of hematopoietic stem cell transplant with wild-type donor cells [the two Boston patients (Bo.1 and Bo.2) (23)], a case of early ART initiation in an infant [the Mississippi baby (Mi.) (25), assuming, as recently reported, rebound after 27 mo], and a case of hematopoietic stem cell transplant with Δ32 CCR5 donor cells [the Berlin patient (Be.) (22,37)].…”

“…We predict that much higher efficacy will be required for eradication, which may be achieved by multiple rounds of LRA therapy, a combination of therapies, or development of therapies to which a greater fraction of the LR is susceptible. Though we have focused on LRA therapy, our findings also serve to interpret infection eradication or delays in rebound caused by early treatment (24,25,57) or stem cell transplantation (22,23), both of which also reduce the LR. In both of these cases, however, additional immunological dynamics likely play a major role and will need to be incorporated into future models.…”

“…The feasibility of reservoir reduction as a method of HIV-1 cure is supported by case studies of stem cell transplantation (22,23) and, more recently, early treatment initiation (24,25), which have allowed patients to interrupt treatment for months or years without viral rebound. The dramatic reductions in reservoir size accompanying these strategies stands in stark contrast to the actions of current LRAs, which induce only a fraction of latent virus in vitro (26,27) and have not produced a measurable decrease in LR size in vivo (12,13,28).…”

Prevalence and outcomes of HIV‐1 diagnostic challenges during universal birth testing – an urban South African observational cohort

“…As a collective, the diagnostic challenges described in this study raise important questions concerning EID, including the potential for antiretroviral prophylaxis to be associated with virological control and even “functional-cure”-type scenarios [9]. Furthermore, infants with multiple indeterminate virological results followed by loss of detectability raise fundamental questions regarding the mechanism of post-exposure prophylaxis and the possibility of transient or abortive infectious processes.…”

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

“…In addition to these adult studies, there is a case report of ART‐free ‘HIV remission’ for over 2 years in a child who was started on ART at 36 hours after birth 214, and a more recent report of an infected infant on continuous ART treatment from 4 hours of age with undetectable proviral DNA by 6 days of life 215. Although the first patient has now been reported as having detectable VL and has commenced ART 216, these reports together provide a proof of concept that in some individuals, after early treatment of primary infection, a prolonged treatment interruption may be possible with preservation of control of HIV replication.…”