Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children

BACKGROUND Children with human immunodeficiency virus type 1 (HIV-1) infection have limited options for effective antiretroviral treatment (ART). METHODS We conducted an open-label, randomized, noninferiority trial comparing three-drug ART based on the HIV integrase inhibitor dolutegravir with standard care (non–dolutegravir-based ART) in children and adolescents starting first- or second-line ART. The primary end point was the proportion of participants with virologic or clinical treatment failure by 96 weeks, as estimated by the Kaplan–Meier method. Safety was assessed. RESULTS From September 2016 through June 2018, a total of 707 children and adolescents who weighed at least 14 kg were randomly assigned to receive dolutegravir-based ART (350 participants) or standard care (357). The median age was 12.2 years (range, 2.9 to 18.0), the median weight was 30.7 kg (range, 14.0 to 85.0), and 49% of the participants were girls. By design, 311 participants (44%) started first-line ART (with 92% of those in the standard-care group receiving efavirenz-based ART), and 396 (56%) started second-line ART (with 98% of those in the standard-care group receiving boosted protease inhibitor–based ART). The median followup was 142 weeks. By 96 weeks, 47 participants in the dolutegravir group and 75 in the standard-care group had treatment failure (estimated probability, 0.14 vs. 0.22; difference, –0.08; 95% confidence interval, −0.14 to −0.03; P=0.004). Treatment effects were similar with first- and second-line therapies (P=0.16 for heterogeneity). A total of 35 participants in the dolutegravir group and 40 in the standard-care group had at least one serious adverse event (P=0.53), and 73 and 86, respectively, had at least one adverse event of grade 3 or higher (P=0.24). At least one ART-modifying adverse event occurred in 5 participants in the dolutegravir group and in 17 in the standard-care group (P=0.01). CONCLUSIONS In this trial involving children and adolescents with HIV-1 infection who were starting first- or second-line treatment, dolutegravir-based ART was superior to standard care. (Funded by ViiV Healthcare; ODYSSEY ClinicalTrials.gov number, NCT02259127; EUDRACT number, 2014-002632-14; and ISRCTN number, ISRCTN91737921.

Optimizing the World Health Organization algorithm for HIV vertical transmission risk assessment by adding maternal self-reported antiretroviral therapy adherence

Background The World Health Organization (WHO) risk assessment algorithm for vertical transmission of HIV (VT) assumes the availability of maternal viral load (VL) result at delivery and early viral control 4 weeks after initiating antiretroviral treatment (ART). However, in many low-and-middle-income countries, VL is often unavailable and mothers' ART adherence may be suboptimal. We evaluate the inclusion of the mothers' self-reported adherence into the established WHO-algorithm to identify infants eligible for enhanced post-natal prophylaxis when mothers' VL result is not available at delivery. Methods We used data from infants with perinatal HIV infection and their mothers enrolled from May-2018 to May-2020 in Mozambique, South Africa, and Mali. We retrospectively compared the performance of the WHO-algorithm with a modified algorithm which included mothers' adherence as an additional factor. Infants were considered at high risk if born from mothers without a VL result in the 4 weeks before delivery and with adherence Results At delivery, 143/184(78%) women with HIV knew their status and were on ART. Only 17(12%) obtained a VL result within 4 weeks before delivery, and 13/17(76%) of them had VL >= 1000 copies/ml. From 126 women on ART without a recent VL result, 99(79%) had been on ART for over 4 weeks. 45/99(45%) women reported suboptimal (< 90%) adherence. A total of 81/184(44%) infants were classified as high risk of VT as per the WHO-algorithm. The modified algorithm including self-adherence disclosure identified 126/184(68%) high risk infants. Conclusions In the absence of a VL result, mothers' self-reported adherence at delivery increases the number of identified infants eligible to receive enhanced post-natal prophylaxis