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In 2013, researchers announced that a newborn child from Mississippi, USA might have been functionally cured of HIV by being given combination antiretroviral therapy within hours of birth. Public and media attention has since been captured by the possibility of finding a cure for HIV transmitted from mother to child. Research into the strategy used for the Mississippi patient is crucially important to establish whether it can be replicated and shown to work in diverse populations. At the same time, any ethical issues likely to arise in such studies should be addressed and not ignored in the pursuit of a functional cure. In this Personal View we identify ethical issues that could arise in research towards achievment of a functional cure for HIV in neonates, including difficult trade-offs associated with choosing the study population and questions about the broader social implications of the research, and propose ways to resolve them., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

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.

Pyomyositis is a musculoskeletal infection with formation of an intramuscular abscess. Endemic in tropical climates, it is being reported with increasing frequency in temperate climates such as the United States. The most common causative organism is Staphylococcus aureus, present in greater than 90% of reported cases. Risk factors include underlying chronic illness, malnutrition, immunocompromised state, and muscle trauma. We present a case in which Streptococcus agalactae was the causative agent of myositis in a child with a history of perinatally derived human immunodeficiency virus infection.

Objective: To determine zidovudine pharmacokinetics and tolerance in premature human human immunodeficiency virus-exposed infants., Study Design: Pediatric AIDS Clinical Trials Group Study 331 was a multicentered prospective, open-label study of the use of zidovudine in premature infants. Thirty-eight infants <35 weeks' gestational age (GA) were studied while receiving zidovudine 1.5 mg/kg every 12 hours until 2 weeks of age, then 2.0 mg/kg every 8 hours until 6 weeks of age. Population pharmacokinetics were evaluated at 1, 2, and 4 weeks' postnatal age; zidovudine doses were adjusted to maintain troughs <3 microM., Results: Zidovudine clearance was lower than reported in term infants at similar postnatal ages. Nine premature infants required dose reduction because of high levels (7/19 <30 weeks' and 2/19 >/=30 weeks' GA). Postnatal age, GA, serum creatinine, and furosemide use independently predicted zidovudine clearance. Zidovudine was generally well tolerated in this high-risk population., Conclusions: Zidovudine clearance is greatly reduced in premature infants. We recommend the following zidovudine dosing schedule in this population: 1.5 mg/kg (intravenous) or 2.0 mg/kg (oral) every 12 hours increased to every 8 hours at 2 weeks of age (>/=30 weeks' GA) or at 4 weeks (<30 weeks' GA).

BackgroundThis study measured serial plasma human immunodeficiency virus (HIV)-1-specific antibody (Ab) levels in children who initiated antiretroviral therapy (ART) prior to 2 years of age, and evaluated their relationship to peripheral blood HIV-1 RNA and DNA levels.MethodsWe studied 46 HIV-1-infected children, stratified by age at ART initiation (3 mo-2 years, late therapy [LT]) and by virologic response (R) or non-response (NR), before and up to 4 years following ART. We studied 20 HIV-1-uninfected children born to HIV-1-infected mothers (seroreverters [SR]) as controls. Plasma immunoglobulin G (IgG) Ab levels directed against HIV-1 envelope (gp160, gp41), gag (capsid, p24; matrix, p17), reverse transcriptase (p66/51), and integrase (p31) were serially measured using quantitative enzyme-linked immunosorbent assays. HIV-1 Ab rates of decline were estimated over the first 15 months of the study.ResultsThe HIV-1 Ab rates of decline in the ET-R group were similar to those in the SR group for all Ab specificities, except for p17 (P = .01). Ab decline rates in the LT-R group and the NR group were significantly slower than in the SR group for all tested Ab specificities. After 1 year of age, Ab levels to p31 and p17 were significantly associated with HIV-1 RNA levels (P < .001); Ab levels to gp160 (P < .001) and gp41 (P < .001) were significantly associated with cell-associated HIV-1 DNA levels.ConclusionsQuantitative HIV-1-specific Ab levels may be useful for screening children on ART for viral suppression or for residual, cell-associated HIV-1 DNA levels.Clinical trials registrationNCT00000872.