The last and first frontier – emerging challenges for HIV treatment and prevention in the first week of life with emphasis on premature and low birth weight infants

Abstract

IntroductionThere is new emphasis on identifying and treating HIV in the first days of life and also an appreciation that low birth weight (LBW) and preterm delivery (PTD) frequently accompany HIV-related pregnancy. Even in the absence of HIV, PTD and LBW contribute substantially to neonatal and infant mortality. HIV-exposed and -infected infants with these characteristics have received little attention thus far. As HIV programs expand to meet the 90-90-90 target for ending the HIV pandemic, attention should focus on newborn infants, including those delivered preterm or of LBW.DiscussionIn high prevalence settings, infant diagnosis of HIV is usually undertaken after the neonatal period. However, as in utero infection may be diagnosed at birth, earlier initiation of therapy may limit viral replication and prevent early damage. Globally, there is growing awareness that preterm and LBW infants constitute a substantial proportion of births each year. Preterm infants are at high risk for vertical transmission. Feeding difficulties, apnoea of prematurity and vulnerability to sepsis occur commonly. Feeding intolerance, a frequent occurrence, may compromise oral administration of medications. Although there is growing experience with post-exposure prophylaxis for HIV-exposed term newborn infants, there is less experience with preterm and LBW infants. For treatment, there are even fewer options for preterm infants. Only zidovudine has adequate dosing recommendations for treating term and preterm infants and has an intravenous formulation, essential if feeding intolerance occurs. Nevirapine dosing for prevention, but not treatment, is well established for both term and preterm infants.HIV diagnosis at birth is likely to be extremely stressful for new parents, more so if caring for preterm or LBW infants. Programs need to adapt to support the medical and emotional needs of young infants and their parents, where interventions may be lifesaving.ConclusionsNew focus is required for the newborn baby, including those born preterm, with LBW or small for gestational age to consolidate gains already made in early diagnosis and treatment of young children.

Targeting 90–90–90 – don't leave children and adolescents behind

“…There is no randomized controlled trial evidence of the benefit of starting ART within the first few weeks of life as addressed by Cotton et al . [ 24 ]. However, arguments in favour of diagnosing and treating paediatric HIV soon after birth include the rapid disease progression in early infancy and the potential to lower viral reservoirs with possible later treatment-sparing options [ 25 – 27 ].…”

“…While paediatric HIV research is not easy for a number of reasons, including the developmental biology of children, decreased number of new paediatric infections, and complex but important regulatory and ethical requirements, it is essential if we are to achieve the 90–90–90 targets. Both clinical and implementation science research is needed to identify more effective and safer ways of treating children, especially newborns [ 24 ], adolescents [ 65 ] and those failing therapy [ 64 ], as well as how best to operationalize and deliver interventions at scale in a range of settings [ 66 ].…”

“The right time is just after birth”: acceptability of point-of-care birth testing in Eswatini: qualitative results from infant caregivers, health care workers, and policymakers

“…However, for some infants -many infected in utero -waiting until 6 weeks is too late as they will have already developed advanced disease or not survived. The consequences of untreated HIV are especially severe among preterm and low birth weight infants [4]. Testing immediately after birth is essential for identifying infants infected in utero and starting them on treatment as soon as possible.…”

Propelling the Pediatric HIV Therapeutic Agenda With Science, Innovation, and Collaboration

“…Currently, there are only 5 ARVs with appropriate formulations, dosing, and safety data to recommend their use in full-term neonates [zidovudine, lamivudine, nevirapine, lopinavir/ritonavir (at 2 weeks of age), and raltegravir]. 72 , 73 The dosage and therapeutic use of nevirapine in newborns is investigational. However, important strides are being made to accelerate the development, study, and availability of the most potent ARVs to treat young babies.…”

“…Investigators are now using sophisticated modeling and simulation techniques using data from older children and adults to inform dosing strategies for neonates and infants. 72 , 73 Washout pharmacokinetic studies, measuring newborn blood levels during the first days to weeks of life of transplacentally transferred maternal ARVs, have also given insight into the behavior of specific agents during this period of rapid physiologic change. Raltegravir, available in a chewable tablet and a granule formulation, was recently approved for use in full-term neonates and is an excellent example of optimizing data sources to inform pediatric dosing.…”