CROI 2020 Abstract eBook

Abstract eBook

Oral Abstracts

Conclusion: Age at starting ART, combined with other maternal and infant factors, predict the size of the pool of proviral DNA in very early-treated infants during the first year of ART.

137 ANTIMICROBIAL PROPHYLAXIS AMONG AFRICAN ADULTS ON ART: RESULTS OF A RANDOMIZED TRIAL Randy G. Mungwira 1 , Nginache Nampota 2 , Osward M. Nyirenda 2 , Titus H. Divala 2 , Maxwell M. Kanjala 2 , Felix A. Mkandawire 2 , Lufina Tsirizani 2 , Wongani Nyangulu 3 , Edson Mwinjiwa 3 , Terrie Taylor 4 , Jane E. Mallewa 2 , Christopher V. Plowe 5 , Joep J. van Oosterhout 6 , Miriam K. Laufer 5 , Matthew B. Laurens 5 1 WHO, Lilongwe, Malawi, 2 University of Malawi, Blantyre, Malawi, 3 Dignitas International, Blantyre, Malawi, 4 Blantyre Malaria Project, Blantyre, Malawi, 5 University of Maryland, Baltimore, MD, USA, 6 Dignitas International, Zomba, Malawi prophylaxis reduced morbidity and mortality among HIV-infected adults, predominantly by preventing malaria and diarrhea in this population. Routine administration of TS prophylaxis has continued with expanded access to ART throughout sub-Saharan Africa. However, the public health benefit has not been definitively evaluated. We designed a clinical trial to evaluate the impact of TS prophylaxis on morbidity and mortality among HIV-infected Malawian adults following good response to ART. If beneficial, we also aimed to determine if this is due to TS antibacterial and/or antimalarial properties Methods: We conducted a randomized, controlled, open label, phase 3 trial of continued standard of care prophylaxis with daily TS compared to discontinuation of TS and starting weekly chloroquine (CQ) prophylaxis or discontinuation of TS prophylaxis. The study randomized 1,499 HIV-infected adults (1:1:1 ratio) with nondetectable viral load and CD4 count >250/mm 3 . The primary endpoint events were death and WHO Stage 3 and 4 events. We compared virologic, immunologic and clinical responses to ART among study arms. Results: Among 2219 persons screened, 1499 were enrolled. 4958 pyo were accrued, and 1249 (83%) completed the study. 24 deaths were reported, 10 in TS group, 6 in CQ group, and 8 in no prophylaxis group. The primary endpoint rate was lower in TS group compared to no prophylaxis, but this result was not significant (Table 1). When WHO Stage 2 events are added to the primary endpoint rate per 100 pyo for each group, TS group had a lower rate of events compared to no prophylaxis and to CQ. Groups did not differ regarding secondary endpoints of virologic failure, low CD4 cell count, or adverse events. Participants on TS prophylaxis experienced fewer malaria episodes than those on no prophylaxis and equivalent episodes compared to CQ prophylaxis. Participants on TS experienced fewer suspected or confirmed bacterial infections than those on no prophylaxis or CQ. Conclusion: Following immune reconstitution, TS prophylaxis continued to provide benefit in terms of prevention of non-severe bacterial infections and malaria, and was safe and well tolerated. Continuation of TS prophylaxis should be considered based on comprehensive analyses of cost and risk/benefit alongside other public health interventions aimed to improve outcomes in this population. Background: Before widespread antiretroviral therapy (ART) use in sub-Saharan Africa, studies demonstrated that daily trimethoprim-sulfamethoxazole (TS)

136 LONG-TERM TREATMENT OUTCOMES: EARLY VERSUS DEFERRED ART IN CHILDREN LIVING WITH HIV Thanyawee Puthanakit 1 , Jiratchaya Sophonphan 2 , Wipaporn Natalie Songtaweesin 1 , Thidarat Jupimai 1 , Ly Penh Sun 3 , Pope Kosalaraksa 4 , Rawiwan Hansudewechakul 5 , Suparat Kanjanavanit 6 , Chettra Kea 3 , Chaiwat Ngampiyaskul 7 , Tuangtip Theerawit 1 , Stephen J. Kerr 2 , Claude A. Mellins 8 , Jintanat Ananworanich 9 , for the PREDICT and Resilience Study Group 1 Chulalongkorn University, Bangkok, Thailand, 2 HIV–NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand, 3 National Centre for HIV/AIDS Dermatology and STDs, Phnom Penh, Cambodia, 4 Khon Kaen University, Khon Kaen, Thailand, 5 Chiang Rai Prachanukroh Hospital, Chiang Rai, Thailand, 6 Nakornping Hospital, Chiang Mai, Thailand, 7 Prapokklao Hospital, Chanthaburi, Thailand, 8 New York State Psychiatric Institute, New York, NY, USA, 9 Henry M Jackson Foundation, Bethesda, MD, USA Background: WHO antiretroviral treatment (ART) guidelines currently recommend initiating ART in HIV infected children at any CD4 count, as soon as possible after diagnosis. The objective of this study was to describe long term treatment outcomes after a decade of follow up, among children in the PREDICT study who did not have rapidly progressive HIV, and were randomized to early versus deferred treatment strategies. Methods: The PREDICT study was a multicentre, randomisedtrial in Thailand and Cambodia. ART-naïve HIV-infected children aged 1-12 years with CD4 15-24% and no advanced HIV symptoms were randomly assigned (1:1) to start ART at study entry (early treatment) or when CD4 < 15% (deferred treatment, standard of care at that time). The long-term endpoints were virological suppression, cumulative probability of virological treatment failure,defined as plasma HIV RNA> 1000 copies/mL, and immunological status. Cumulative failure probability was calculated using the Kaplan-Meier method; formal comparisons between group were made using chi-square, log rank test, Mann_Whitney U tests. Results: FromMarch 2006 to September 2008, 300 Thai and Cambodian children were enrolled, with a median age of 6•4 (IQR 3•9-8•4) years, and median baseline CD4 of 19% (IQR 16-22). As of July 2019, 230 (77%) participants remained in the study (132 Thai, 98 Cambodian), 19 withdrew, 2 died and 47 were lost or referred out at median age of 12.9 (10.4-15.4) years. The median age at last visit was 16.7 years (IQR 14.3-18.6). Current antiretroviral regimens were 75.2% NNRTI-based, 20.4% PI-based and 4.4% others. Among adolescents with HIV, 86.3% in the early arm and 77.9% in the deferred arm had plasma HIV RNA <50 copies/mL (p=0.09); 88.9% in the early arm and 76.1% in the deferred arm had CD4 > 500 cells/mm 3 (p=0.01). However, the 10 year cumulative probability of virologic failure was higher among adolescents in the deferred (34.3(95%CI 24.8-46.1)) versus early treatment group 22.8(95%CI 16.1-31.7) [P=0.07]. Conclusion: Leveraging this randomized study conducted when early ART was not the standard of care, it demonstrates that amongst children with slow progressor, a decade of ART could not overcome the lower CD4 count at ART start. The long lasting poorer CD4 recovery and higher virological failure mandates prompt diagnosis and ART initiation in children.

Oral Abstracts

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CROI 2020