Page 75 - SAHCS HIVMed Journal Vol 20 No 1 2019

Page 3 of 5 Opinion Paper

The ADVANCE study randomised 1053 adolescents and Data from the International epidemiologic Databases to
adults to receiving a DTG-based regimen with either TAF or Evaluate AIDS Southern Africa collaboration (IeDEA-SA)
TDF and emtricitabine (FTC), compared to standard of care showed that between 2004 and 2017 perinatally HIV-infected
efavirenz/FTC/TDF. The study reported non-inferiority for children and adolescents had suboptimal retention in care,
DTG-based regimens at 48 weeks, with the primary endpoint suboptimal VL suppression rates and mortality, with
of viral load (VL) < 50 copies/mL in an intention to treat particular risk for those who initiate ART at older ages and
analysis. Toxicity was low overall across the study arms; more severe immunosuppression. Adolescents, especially
however, significant weight gain particularly in black South those at high risk, require additional support and follow-up
African women occurred in those receiving DTG/TAF/FTC to prevent morbidity and mortality. 24
(median 10 kg increase), compared to DTG/TDF/FTC
(median 5 kg increase) and EFV/TDF/FTC (median 3 kg Fifth workshop on children who
increase) were randomised to DTG/TDF/FTC versus
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EFV(400 mg)/TDF/FTC. Although this weight gain or the are HIV-exposed and uninfected
20
implications thereof are currently not well understood, The fifth workshop on children who are HIV-exposed and
further evaluation of this finding is warranted. However, as uninfected (CHEU) was themed around the first 1000 days
participants enrolled were relatively well, this raises concern of life (conception to age 2 years), with presentations
regarding long-term risks for cardiovascular disease in
women receiving DTG and TAF combination ART. Sixty-five spanning basic and clinical science, policy, programmatic
women conceived on the study with no increased risk for and research considerations. According to the Joint United
adverse pregnancy outcomes in women receiving DTG at Nations Programme on HIV and AIDS (UNAIDS) estimates,
conception. globally there were 14.8 million CHEU (age 0–14 years) in
2018, with 3.5 million (24%) living in South Africa. The
A study in Johannesburg and Tshwane, South Africa, offered prevalence of CHEU exceeded 20% in four southern African
point-of-care maternal VL and early infant diagnosis HIV countries: Eswatini (32%), Botswana (27%), South Africa
testing around the time of delivery only during ‘office hours’. (22%) and Lesotho (21%). 25
Of 1762 valid VLs, around 36.4% were unsuppressed at
delivery with a VL > 50 copies/mL). Fortunately, infant The HIV-exposed in utero environment
HIV infection rates were low (65/4333; 1.5%); however, this
highlights gaps in optimised maternal ART coverage and Untangling the mechanisms of adverse birth outcomes in
uptake of VL testing at delivery, with potential risk of HIV pregnant women living with HIV (pWLHIV) and the role
transmission. 21 that HIV, specific antiretroviral drugs or other maternal
factors play is crucial to securing optimal outcomes for
HIV treatment and treatment outcomes CHEU. In pWLHIV cohorts on non-PI-based ART in Cape
in children and adolescents Town, timing of ART initiation either preconception or
during pregnancy had no influence on placental pathology.
As guidelines move to a universal regimen for all HIV-positive
persons, children lag behind in the era of DTG. Data However, T-regulatory cells were significantly lower at
were presented from the ODYSSEY trial, regarding the birth in CHEU than children HIV unexposed and
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pharmacokinetics (PK) of 5 mg DTG dispersible tablets in 28 uninfected (CHUU). In a Canadian cohort of pWLHIV,
children weighing 6 kg to < 20 kg (in three weight bands: 6 kg PI-based ART was associated with lower progesterone and
to < 10 kg, 10 kg to < 14 kg and 14 kg to < 20 kg) from Zimbabwe prolactin levels, altered placental morphology and
and Uganda. In the weight bands between 10 kg to < 14 kg and inefficient or over-worked placentas compared to pWLHIV
14 kg to < 20kg, PK data were similar to the published data in on non-PI-based ART and pregnant women without
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adults, older children and younger children. However, as in HIV. In a mouse model, normal placental spiral artery
the 6 to < 10 kg group, some children had low trough remodelling and trophoblast invasion, controlled by
concentration (C trough ) levels with high inter-participants progesterone and prolactin, were inhibited by lopinavir/
variability; further PK data are required for this group and ritonavir but not atazanavir/ritonavir or darunavir/
children weighed between 3 kg and < 6 kg, highlighting ritonavir. Further work is needed to determine whether
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complexities of HIV treatment in younger age groups. 22 these endocrine and placental alterations are associated
with preterm birth and intrauterine growth restriction in
A study from Zimbabwe analysed results of genotypic pWLHIV.
resistance testing in 160 of 185 children with virological
failure on first and second line regimens, and calculated a Solutions to children who are HIV-exposed and
total genotypic susceptibility score (tGSS) for a switch to uninfected vulnerabilities in early childhood
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protease inhibitor (PI)- or DTG-based regimens, respectively.
The tGSS demonstrated that therapy with the tenofovir– In a Belgian cohort of CHEU compared to HIV-unexposed
lamivudine–dolutegravir (TLD) combination tablet may children, neonatal immune parameters as well as infectious
result in DTG monotherapy, due to dual NRTI resistance morbidity risk differed by timing of initiation of maternal
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with associated risks of virologic failure and future DTG ART. Infants of mothers on preconception ART had
resistance. 23 immune and infectious morbidity profiles similar to

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