{"doi":"10.1038/s41591-024-03105-4","title":"Sustained aviremia despite anti-retroviral therapy non-adherence in male children after in utero HIV transmission","abstract":"After sporadic reports of post-treatment control of HIV in children who initiated combination anti-retroviral therapy (cART) early, we prospectively studied 284 very-early-cART-treated children from KwaZulu-Natal, South Africa, after vertical HIV transmission to assess control of viremia. Eighty-four percent of the children achieved aviremia on cART, but aviremia persisting to 36 or more months was observed in only 32%. We observed that male infants have lower baseline plasma viral loads (P = 0.01). Unexpectedly, a subset (n = 5) of males maintained aviremia despite unscheduled complete discontinuation of cART lasting 3-10 months (n = 4) or intermittent cART adherence during 17-month loss to follow-up (n = 1). We further observed, in vertically transmitted viruses, a negative correlation between type I interferon (IFN-I) resistance and viral replication capacity (VRC) (P < 0.0001) that was markedly stronger for males than for females (r = -0.51 versus r = -0.07 for IFN-α). Although viruses transmitted to male fetuses were more IFN-I sensitive and of higher VRC than those transmitted to females in the full cohort (P < 0.0001 and P = 0.0003, respectively), the viruses transmitted to the five males maintaining cART-free aviremia had significantly lower replication capacity (P < 0.0001). These data suggest that viremic control can occur in some infants with in utero-acquired HIV infection after early cART initiation and may be associated with innate immune sex differences.","journal":"Nature Medicine","year":2024,"id":425089,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9609,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":951177,"name":"Gabriela Cromhout","orcid":"0000-0003-2748-1572","position":1,"is_corresponding":false},{"id":464783,"name":"Emily Adland","orcid":null,"position":2,"is_corresponding":false},{"id":463976,"name":"Katya Govender","orcid":"0000-0001-5753-0107","position":3,"is_corresponding":false},{"id":709765,"name":"Nicholas Herbert","orcid":"0000-0002-3708-694X","position":4,"is_corresponding":false},{"id":555615,"name":"Nicholas Lim","orcid":"0000-0001-9261-7726","position":5,"is_corresponding":false},{"id":464780,"name":"Rowena Fillis","orcid":null,"position":6,"is_corresponding":false},{"id":496301,"name":"Kenneth Sprenger","orcid":"0000-0002-5460-1675","position":7,"is_corresponding":false},{"id":463971,"name":"Vinícius Vieira","orcid":"0000-0002-4901-0424","position":8,"is_corresponding":false},{"id":1223222,"name":"Samantha Kannie","orcid":null,"position":9,"is_corresponding":false},{"id":496885,"name":"Jeroen van Lobenstein","orcid":null,"position":10,"is_corresponding":false},{"id":496303,"name":"Kogielambal Chinniah","orcid":"0009-0006-3869-8071","position":11,"is_corresponding":false},{"id":496887,"name":"Constant Kapongo","orcid":null,"position":12,"is_corresponding":false},{"id":496888,"name":"Roopesh Bhoola","orcid":null,"position":13,"is_corresponding":false},{"id":496889,"name":"Malini Krishna","orcid":null,"position":14,"is_corresponding":false},{"id":1223223,"name":"Noxolo Mchunu","orcid":null,"position":15,"is_corresponding":false},{"id":380955,"name":"Giuseppe Rubens Pascucci","orcid":"0000-0002-5978-1193","position":16,"is_corresponding":false},{"id":380953,"name":"Nicola Cotugno","orcid":"0000-0002-7748-1581","position":17,"is_corresponding":false},{"id":373975,"name":"Paolo Palma","orcid":"0000-0002-3066-4719","position":18,"is_corresponding":false},{"id":724407,"name":"Alfredo Tagarro","orcid":"0000-0003-2860-3455","position":19,"is_corresponding":false},{"id":724408,"name":"Pablo Rojo","orcid":"0000-0002-0197-5462","position":20,"is_corresponding":false},{"id":406970,"name":"Julia Roider","orcid":"0000-0002-1347-2838","position":21,"is_corresponding":false},{"id":676415,"name":"Maria C. 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