CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

961

Resistance in Young Children Newly-Diagnosed With HIV in Western Cape, South Africa Kim Anderson 1 , Gert U. van Zyl 2 , Nei-Yuan Hsiao 1 , Vanessa Mudaly 3 , Jacqueline Voget 3 , Alexa Heekes 1 , Emma Kalk 1 , Florence Phelanyane 3 , Andrew Boulle 1 , Gayathri Sridhar 4 , Leigh Ragone 4 , Vani Vannappagari 4 , Mary-Ann Davies 1 1 University of Cape Town, Cape Town, South Africa, 2 Stellenbosch University, Stellenbosch, South Africa, 3 Western Cape Provincial Department of Health, Cape Town, South Africa, 4 ViiV Healthcare, Research Triangle Park, NC, USA Background: Pretreatment drug resistance among children living with HIV (CLHIV) can potentially compromise antiretroviral therapy (ART) effectiveness. Drug resistant HIV may be directly transmitted during vertical acquisition or resistance may be acquired in infants with HIV following exposure to antiretrovirals consumed through breastfeeding or administered as prophylaxis. Methods: We performed resistance testing in young CLHIV (age <3 years) newly diagnosed with HIV in Western Cape, South Africa (July 2021 to October 2022) who either (1) acquired HIV via possible breastfeeding transmission from mothers who received ART (any regimen) during pregnancy/postpartum and/ or (2) were exposed to protease inhibitors (PIs) or integrase strand transfer inhibitors (INSTIs) in utero. Possible breastfeeding transmission was defined as a positive HIV-PCR test at age >28 days, which occurred after a previous negative HIV-PCR test. We limited mutations included to those recommended for surveillance of transmitted drug resistance. Results: We included 135 newly diagnosed CLHIV for resistance testing, of whom 91% (123) had possible breastfeeding transmission. Most mothers started ART before pregnancy (77%) and were exposed to ≥3 classes of ART prior to infant diagnosis (66%). Overall, 58% of CLHIV (78/135) had resistance mutations detected and 15% of those with mutations (12/78) had mutations to more than one class. Non-nucleoside reverse transcriptase inhibitor (NNRTI)-associated mutations were common (73/78; 94%). Nucleoside reverse transcriptase inhibitor-, INSTI- and PI-associated mutations were found in 18% (14/78), 3% (2/78) and 1% (1/78) of CLHIV with mutations, respectively. One child with breastfeeding transmission of HIV, had high-level INSTI and NNRTI resistance detected at age 18 months at HIV diagnosis (E138K, G118R and K103N mutations). The mother had changed from efavirenz- to dolutegravir-based ART 13 months after delivery. Conclusion: NNRTI-associated mutations are common and may be transmitted or arise from exposure to NNRTIs as prophylaxis or in breastmilk. Dolutegravir is the preferred first-line treatment for both adults and CLHIV older than 4 weeks and very low INSTI resistance levels have been observed in adults, but limited data exist on genotyping the integrase region in CLHIV. The prevalence of pretreatment INSTI resistance in CLHIV is likely to be very small but future surveillance is necessary. There is a need for further, longitudinal studies with paired mother-infant resistance results.

960

Rapid Antiretroviral Therapy Initiation Following Point-of-Care Early Infant Diagnosis in Uganda Stella M. Migamba 1 , Tamara N Nyombi 2 , Edirisa Nsubuga 1 , Andrew Kwiringira 1 , Benon Kwesiga 1 , Steven N. Kabwama 2 , Mary Nakafeero 3 , Daniel Kadobera 1 , Phoebe Mayambala 4 , Lilian Bulage 1 , Alex Ario 1 , Julie Harris 4 1 Uganda National Institute of Public Health, Kampala, Uganda, 2 Other Institution – Follow-up needed, Uganda, 3 Makerere University, Kampala, Uganda, 4 Centers for Disease Control and Prevention, Kampala, Uganda Background: Uganda Ministry of Health recommends a first HIV DNA-PCR test at 4-6 weeks for early infant diagnosis (EID) of HIV-exposed infants (HEIs), immediate results return and initiation of antiretroviral therapy (ART) for infants with HIV infection. In 2019, MOH introduced point-of-care (POC) whole-blood EID testing in 33 health facilities and scaled up to 133 in 2020. We assessed turnaround time for test results and ART linkage before and after implementation of POC testing. Methods: We evaluated EID register data for HEI at 10 health facilities with POC and minimum EID testing volume of 12 infants per month from 2018-2021. At each facility, we abstracted data for 12 months before and after POC rollout. We compared time to sample collection, results receipt, and ART initiation between periods using medians, Wilcoxon rank-sum, and log-rank tests. Results: Data for 4,004 HEI were extracted, including 1,688 (42%) pre-POC and 2,316 (58%) during POC. Ninety-four percent of infants (3,762/4,004) had a first EID test. Median age at sample collection was 44 (IQR 38-52) days pre-POC and 42 (IQR 38-52) days during POC (p<0.001). Of 3,762 HEIs tested, 3,667 (97%) had test results. For infants with HIV infection (n=69), median age at sample collection was 92 (IQR 45-120) days pre-POC and 127 (IQR 74-206) days during POC (p=0.03). For all infants, median days from sample collection to results receipt by infants' caregivers were 29 (IQR 16-54) pre-POC and 1 (IQR 0-28) during POC (p<0.001); among infants with HIV infection, median days were 22 (IQR 4-30) pre-POC and 0 (0-3) during POC (p<0.001). Pre-POC, 0% (0/23) infants with HIV infection started ART on the sample collection day compared to 40% (17/42) during POC; ART linkage by 7 days after HIV diagnosis was 78% (21/27) pre-POC and 95% (40/42) during POC (p<0.001). Conclusion: POC testing improved EID results turnaround time and ART initiation for infants with HIV infection. Later age at testing among infants diagnosed with HIV suggests missed opportunities in identifying HIV-exposed infants. While POC expansion could further improve ART linkage and loss to follow-up, there's need to examine barriers surrounding the POC target of initiating ART on the sample collection day.

Poster Abstracts

962

CMV Viraemia Is Associated With Mortality Among Children With HIV Starting ART in Sub-Saharan Africa Temitope Fisayo 1 , Ceri Evans 2 , Kuda Mutasa 2 , Moira Spyer 3 , Sandra Rukobo 2 , Dagmar Alber 4 , Mutsawashe Bwakura-Dangarembizi 5 , Victor Musiime 6 , Kusum Nathoo 5 , Adeodata R. Kekitiinwa 7 , Cissy Kityo 8 , Diana Gibb 4 , Nigel Klein 4 , Sarah Walker 4 , Andrew Prendergast 1 1 Queen Mary University of London, London, United Kingdom, 2 Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe, 3 UCL Great Ormond Street Institute of Child Health, London, United Kingdom, 4 University College London, London, United Kingdom, 5 University of Zimbabwe, Harare, Zimbabwe, 6 Makerere University, Kampala, Uganda, 7 Baylor College of Medicine Children's Foundation, Kampala, Uganda, 8 Joint Clinical Research Centre, Kampala, Uganda Background: Cytomegalovirus (CMV) co-infection is associated with mortality in adults with HIV, but the association between CMV viraemia and mortality in children with HIV is uncertain. Methods: In 497 children enrolled in the ARROW trial (registry number ISRCTN24791884) in Uganda and Zimbabwe, CMV was quantified using real-

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