Pub Date : 2025-11-01Epub Date: 2025-08-27DOI: 10.1016/S2352-3018(25)00184-5
Melanie A Gasper, Anna-Ursula Happel, Sonwabile Dzanibe, Jennifer Slyker, Heather B Jaspan
The introduction and programmatic scale-up of universal antiretroviral therapy in pregnancy (option B and option B+) and the subsequent universal test-and-treat approaches have dramatically reduced infant HIV-1 acquisitions globally, with a parallel increase in the number of infants who are HIV-exposed uninfected (HEU). Although infants who are HEU have historically had higher risk of morbidity and mortality than infants who are HIV unexposed, effective parental viral suppression has enabled people living with HIV to carry healthier pregnancies and realise the benefits of optimised feeding practices that support the transfer of key nutrients and immune factors through their parent's own milk. However, residual, heightened inflammation, altered gut microbiome, and differences in innate and adaptive immunology in infants who are HEU remain, and might contribute to persistent, heightened infectious morbidity. Parental HIV infection continues to influence child health in the option B and option B+ era; future research is needed to uncover underlying mechanisms and long-term implications of these strategies.
{"title":"Immunology of infants who are HIV-exposed uninfected in the parental combination antiretroviral therapy era.","authors":"Melanie A Gasper, Anna-Ursula Happel, Sonwabile Dzanibe, Jennifer Slyker, Heather B Jaspan","doi":"10.1016/S2352-3018(25)00184-5","DOIUrl":"10.1016/S2352-3018(25)00184-5","url":null,"abstract":"<p><p>The introduction and programmatic scale-up of universal antiretroviral therapy in pregnancy (option B and option B+) and the subsequent universal test-and-treat approaches have dramatically reduced infant HIV-1 acquisitions globally, with a parallel increase in the number of infants who are HIV-exposed uninfected (HEU). Although infants who are HEU have historically had higher risk of morbidity and mortality than infants who are HIV unexposed, effective parental viral suppression has enabled people living with HIV to carry healthier pregnancies and realise the benefits of optimised feeding practices that support the transfer of key nutrients and immune factors through their parent's own milk. However, residual, heightened inflammation, altered gut microbiome, and differences in innate and adaptive immunology in infants who are HEU remain, and might contribute to persistent, heightened infectious morbidity. Parental HIV infection continues to influence child health in the option B and option B+ era; future research is needed to uncover underlying mechanisms and long-term implications of these strategies.</p>","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":" ","pages":"e789-e801"},"PeriodicalIF":13.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/s2352-3018(25)00304-2
The Lancet Hiv
{"title":"A field of possibilities for paediatric HIV.","authors":" The Lancet Hiv","doi":"10.1016/s2352-3018(25)00304-2","DOIUrl":"https://doi.org/10.1016/s2352-3018(25)00304-2","url":null,"abstract":"","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":"27 23 1","pages":"e737"},"PeriodicalIF":16.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145411584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-29DOI: 10.1016/s2352-3018(25)00261-9
Lee Fairlie, Daniel W Szydlo, Ashley Mayo, Katie Bunge, Felix Mhlanga, Jeanna Piper, Sufia Dadabhai, Vanessa M Gatsi, Elizea Horne, Phionah Kibalama Ssemambo, Vitumbiko Mandiwa, Nyaradzo M Mgodi, Maxensia Owor, Peter L Anderson, Mark A Marzinke, Clemensia Nakabiito, Rachel Scheckter, Catherine Chappell, Sharon L Hillier, Bonus Makanani, Luis Gadama, Linly Seyama, Taha E Taha, Mary Glenn Fowler, Carlotta Mabuza, Hermien Gous, Petina Musara, Z Mike Chirenje, Naana Cleland, Roberta Black, Nahida Chakhtoura, Dianne M Rausch, Teri Senn, James F Rooney, Zeda Rosenberg, Craig Hendrix, Lisa Noguchi, Abraham Johnson, Cheryl Blanchette, Jontraye Davis, Tara McClure, Lisa Levy, Richard H Beigi, Sharon A Riddler, Devika Singh, Edward Livant, Lisa Rossi, Luis Duran, Mei Song, Ariana Katz, Alinda Young, Elizabeth Montgomery, Imogen Hawley, Marie Stoner, Ariane van der Straten, Ivan Balan, Barbra Richardson, Jennifer Balkus, Lena Kemel, Maricel Manalo, Tanya Harrell, Amanda Brown
{"title":"Safety outcomes among infants whose mothers used the dapivirine vaginal ring or oral PrEP during pregnancy (MTN-042/DELIVER): a randomised phase 3b study","authors":"Lee Fairlie, Daniel W Szydlo, Ashley Mayo, Katie Bunge, Felix Mhlanga, Jeanna Piper, Sufia Dadabhai, Vanessa M Gatsi, Elizea Horne, Phionah Kibalama Ssemambo, Vitumbiko Mandiwa, Nyaradzo M Mgodi, Maxensia Owor, Peter L Anderson, Mark A Marzinke, Clemensia Nakabiito, Rachel Scheckter, Catherine Chappell, Sharon L Hillier, Bonus Makanani, Luis Gadama, Linly Seyama, Taha E Taha, Mary Glenn Fowler, Carlotta Mabuza, Hermien Gous, Petina Musara, Z Mike Chirenje, Naana Cleland, Roberta Black, Nahida Chakhtoura, Dianne M Rausch, Teri Senn, James F Rooney, Zeda Rosenberg, Craig Hendrix, Lisa Noguchi, Abraham Johnson, Cheryl Blanchette, Jontraye Davis, Tara McClure, Lisa Levy, Richard H Beigi, Sharon A Riddler, Devika Singh, Edward Livant, Lisa Rossi, Luis Duran, Mei Song, Ariana Katz, Alinda Young, Elizabeth Montgomery, Imogen Hawley, Marie Stoner, Ariane van der Straten, Ivan Balan, Barbra Richardson, Jennifer Balkus, Lena Kemel, Maricel Manalo, Tanya Harrell, Amanda Brown","doi":"10.1016/s2352-3018(25)00261-9","DOIUrl":"https://doi.org/10.1016/s2352-3018(25)00261-9","url":null,"abstract":"","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":"54 1","pages":""},"PeriodicalIF":16.1,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145382817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-29DOI: 10.1016/s2352-3018(25)00264-4
Sean D Young
{"title":"Artificial intelligence in HIV research, policy, and clinical care","authors":"Sean D Young","doi":"10.1016/s2352-3018(25)00264-4","DOIUrl":"https://doi.org/10.1016/s2352-3018(25)00264-4","url":null,"abstract":"","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":"60 1","pages":""},"PeriodicalIF":16.1,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145382821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-21DOI: 10.1016/s2352-3018(25)00265-6
Joseph N Jarvis,Peter Ehrenkranz,David S Lawrence,Claire M Keene,Michael J Reid,Ingrid T Katz,Daniel Shodell,Carmen Pérez-Casas,Kennedy Mupeli,Suilanji Sivile,Aleny M Couto,Meg Doherty,Ajay Rangaraj,Nathan Ford
HIV programmes globally continue to face two persistent challenges: advanced HIV disease and high HIV incidence. These issues are often viewed separately, with advanced HIV disease viewed as a late-stage clinical failure and high HIV incidence as a failure of early prevention. However, these issues are closely linked at the individual and population level; both reflect the inability of current care models to engage and sustain viral suppression among a sizeable subgroup of people living with HIV who initiate antiretroviral therapy late or cycle in and out of care. In sub-Saharan Africa, where the HIV burden is highest, most individuals with advanced HIV disease are people who have previously initiated antiretroviral therapy and subsequently disengaged, often multiple times. This type of interruption in care has substantial implications for immune decline, viral rebound, and mortality. As donor funding decreases, there is a risk that global HIV responses will revert focus to maintaining aggregate antiretroviral therapy coverage, overlooking harder-to-reach populations with persistent viraemia.
{"title":"Reducing HIV incidence and mortality: two sides of the same coin in the approach to ending AIDS.","authors":"Joseph N Jarvis,Peter Ehrenkranz,David S Lawrence,Claire M Keene,Michael J Reid,Ingrid T Katz,Daniel Shodell,Carmen Pérez-Casas,Kennedy Mupeli,Suilanji Sivile,Aleny M Couto,Meg Doherty,Ajay Rangaraj,Nathan Ford","doi":"10.1016/s2352-3018(25)00265-6","DOIUrl":"https://doi.org/10.1016/s2352-3018(25)00265-6","url":null,"abstract":"HIV programmes globally continue to face two persistent challenges: advanced HIV disease and high HIV incidence. These issues are often viewed separately, with advanced HIV disease viewed as a late-stage clinical failure and high HIV incidence as a failure of early prevention. However, these issues are closely linked at the individual and population level; both reflect the inability of current care models to engage and sustain viral suppression among a sizeable subgroup of people living with HIV who initiate antiretroviral therapy late or cycle in and out of care. In sub-Saharan Africa, where the HIV burden is highest, most individuals with advanced HIV disease are people who have previously initiated antiretroviral therapy and subsequently disengaged, often multiple times. This type of interruption in care has substantial implications for immune decline, viral rebound, and mortality. As donor funding decreases, there is a risk that global HIV responses will revert focus to maintaining aggregate antiretroviral therapy coverage, overlooking harder-to-reach populations with persistent viraemia.","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":"52 1","pages":""},"PeriodicalIF":16.1,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-21DOI: 10.1016/s2352-3018(25)00273-5
{"title":"Correction to Lancet HIV 2025; 12: e691-700.","authors":"","doi":"10.1016/s2352-3018(25)00273-5","DOIUrl":"https://doi.org/10.1016/s2352-3018(25)00273-5","url":null,"abstract":"","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":"15 1","pages":""},"PeriodicalIF":16.1,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-08DOI: 10.1016/s2352-3018(25)00274-7
Kimesh Loganathan Naidoo,Moherndran Archary
{"title":"Dolutegravir in neonates: finally we are getting there!","authors":"Kimesh Loganathan Naidoo,Moherndran Archary","doi":"10.1016/s2352-3018(25)00274-7","DOIUrl":"https://doi.org/10.1016/s2352-3018(25)00274-7","url":null,"abstract":"","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":"12 1","pages":""},"PeriodicalIF":16.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-08DOI: 10.1016/s2352-3018(25)00239-5
Adrie Bekker,Nicolas Salvadori,Helena Rabie,Samantha du Toit,Kanchana Than-In-At,Maria Groenewald,Shaun Barnabas,Lindee Ganger,Thanchanok Luangcharoenkul,Sirikanya Pingkarawat,Edmund V Capparelli,Andrew Owen,Ratchada Cressey,Samantha Fry,Geraldine Le Roux,Yardpiroon Tawon,Jutatip Kaewmalee,Thamonphat Phitak,Marc Lallemant,Mark F Cotton,Tim R Cressey
BACKGROUNDDolutegravir is not recommended for neonates (age 28 days or younger) due to the absence of dosing guidelines and safety information. We evaluated the multidose pharmacokinetics and safety of two paediatric dolutegravir formulations in neonates: a scored dispersible tablet and a novel oral dispersible film.METHODSWe did a phase 1/2, open-label, single-centre, two-stage, randomised trial in neonates at Tygerberg Hospital, South Africa, who were born at term (≥37 weeks gestational age, birthweights ≥2 kg) to pregnant women on dolutegravir-based antiretroviral therapy. Neonates in stage two were randomly assigned (1:1) to receive 5 mg dolutegravir either as half of a scored dispersible tablet (10 mg) or one oral dispersible film (5 mg), administered every 48 h for the first 2 weeks of life, followed by daily up to day 28 of life. Plasma pharmacokinetic samples were collected during three visits: at entry (before and 1-3 h after the first dolutegravir dose); at any time from the third dolutegravir dose but before week 4 of life (before and 1, 2, 4, 6, and 48 h after the dolutegravir dose); and during week 4 of life (before and 1-3 h after the dolutegravir dose). The primary outcomes were dolutegravir pharmacokinetic parameters of area under the concentration time curve (AUC), maximum plasma concentration (Cmax), apparent clearance (CL/F), and trough concentration (Ctrough) in participants who completed intensive pharmacokinetic sampling and occurrence of non-treatment-related and treatment-related adverse events of grade 3 or higher and any adverse events in participants who received at least one dose of dolutegravir. Target pharmacokinetic criteria were geometric mean Ctrough higher than 0·67 μg/mL and individual Cmax lower than 17·0 μg/mL. The trial is registered with ClinicalTrials.gov, NCT05590325.FINDINGSBetween Sept 15, 2023, and Nov 6, 2024, 41 neonates were enrolled, randomly assigned, and received dolutegravir (21 [51%] received dispersible tablets and 20 [49%] received dolutegravir films); 25 (61%) neonates were male and 16 (39%) were female. Median birthweight was 3235 g (range 2365-4330) and the first dolutegravir dose was administered at median 47 h (range 22-78) after birth. Intensive dolutegravir pharmacokinetic profiles sampled after at least three doses of dolutegravir (range 6-10 days of life) were similar between the dolutegravir dispersible tablet and the dolutegravir film and the dolutegravir geometric mean area under the concentration time curve (AUC0-48), and CL/F were 193·2 μg x h/mL and 0·026 L/h, respectively. Both formulations attained a dolutegravir geometric mean Ctrough higher than 0·67 μg/mL. All neonates had a dolutegravir Cmax lower than 17·0 μg/mL at every pharmacokinetic visit. No adverse events were related to dolutegravir. Two grade 3 adverse events, the highest severity observed, occurred in one neonate with pneumonia. A total of 22 adverse events occurred in 12 (57%) of the 21 neonates receiving dolute
{"title":"Safety and pharmacokinetics of dolutegravir dispersible tablets and oral films in term neonates exposed to HIV in South Africa (PETITE-DTG study): an open-label, randomised, phase 1/2 trial.","authors":"Adrie Bekker,Nicolas Salvadori,Helena Rabie,Samantha du Toit,Kanchana Than-In-At,Maria Groenewald,Shaun Barnabas,Lindee Ganger,Thanchanok Luangcharoenkul,Sirikanya Pingkarawat,Edmund V Capparelli,Andrew Owen,Ratchada Cressey,Samantha Fry,Geraldine Le Roux,Yardpiroon Tawon,Jutatip Kaewmalee,Thamonphat Phitak,Marc Lallemant,Mark F Cotton,Tim R Cressey","doi":"10.1016/s2352-3018(25)00239-5","DOIUrl":"https://doi.org/10.1016/s2352-3018(25)00239-5","url":null,"abstract":"BACKGROUNDDolutegravir is not recommended for neonates (age 28 days or younger) due to the absence of dosing guidelines and safety information. We evaluated the multidose pharmacokinetics and safety of two paediatric dolutegravir formulations in neonates: a scored dispersible tablet and a novel oral dispersible film.METHODSWe did a phase 1/2, open-label, single-centre, two-stage, randomised trial in neonates at Tygerberg Hospital, South Africa, who were born at term (≥37 weeks gestational age, birthweights ≥2 kg) to pregnant women on dolutegravir-based antiretroviral therapy. Neonates in stage two were randomly assigned (1:1) to receive 5 mg dolutegravir either as half of a scored dispersible tablet (10 mg) or one oral dispersible film (5 mg), administered every 48 h for the first 2 weeks of life, followed by daily up to day 28 of life. Plasma pharmacokinetic samples were collected during three visits: at entry (before and 1-3 h after the first dolutegravir dose); at any time from the third dolutegravir dose but before week 4 of life (before and 1, 2, 4, 6, and 48 h after the dolutegravir dose); and during week 4 of life (before and 1-3 h after the dolutegravir dose). The primary outcomes were dolutegravir pharmacokinetic parameters of area under the concentration time curve (AUC), maximum plasma concentration (Cmax), apparent clearance (CL/F), and trough concentration (Ctrough) in participants who completed intensive pharmacokinetic sampling and occurrence of non-treatment-related and treatment-related adverse events of grade 3 or higher and any adverse events in participants who received at least one dose of dolutegravir. Target pharmacokinetic criteria were geometric mean Ctrough higher than 0·67 μg/mL and individual Cmax lower than 17·0 μg/mL. The trial is registered with ClinicalTrials.gov, NCT05590325.FINDINGSBetween Sept 15, 2023, and Nov 6, 2024, 41 neonates were enrolled, randomly assigned, and received dolutegravir (21 [51%] received dispersible tablets and 20 [49%] received dolutegravir films); 25 (61%) neonates were male and 16 (39%) were female. Median birthweight was 3235 g (range 2365-4330) and the first dolutegravir dose was administered at median 47 h (range 22-78) after birth. Intensive dolutegravir pharmacokinetic profiles sampled after at least three doses of dolutegravir (range 6-10 days of life) were similar between the dolutegravir dispersible tablet and the dolutegravir film and the dolutegravir geometric mean area under the concentration time curve (AUC0-48), and CL/F were 193·2 μg x h/mL and 0·026 L/h, respectively. Both formulations attained a dolutegravir geometric mean Ctrough higher than 0·67 μg/mL. All neonates had a dolutegravir Cmax lower than 17·0 μg/mL at every pharmacokinetic visit. No adverse events were related to dolutegravir. Two grade 3 adverse events, the highest severity observed, occurred in one neonate with pneumonia. A total of 22 adverse events occurred in 12 (57%) of the 21 neonates receiving dolute","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":"105 1","pages":""},"PeriodicalIF":16.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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