Pub Date : 2025-03-14DOI: 10.1016/S2352-3018(25)00075-X
{"title":"Correction to Lancet HIV 2024; 11: e31-41.","authors":"","doi":"10.1016/S2352-3018(25)00075-X","DOIUrl":"https://doi.org/10.1016/S2352-3018(25)00075-X","url":null,"abstract":"","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665183","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 : 2025-03-13DOI: 10.1016/S2352-3018(25)00073-6
Ed Holt
{"title":"Tajikistan faces a crucial moment in HIV/AIDS response.","authors":"Ed Holt","doi":"10.1016/S2352-3018(25)00073-6","DOIUrl":"https://doi.org/10.1016/S2352-3018(25)00073-6","url":null,"abstract":"","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639811","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}
{"title":"Long-acting PrEP for adolescent girls and young women.","authors":"Wipaporn Natalie Songtaweesin, Thanyawee Puthanakit","doi":"10.1016/S2352-3018(25)00042-6","DOIUrl":"https://doi.org/10.1016/S2352-3018(25)00042-6","url":null,"abstract":"","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634880","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 : 2025-03-12DOI: 10.1016/S2352-3018(24)00310-2
Lynda Stranix-Chibanda, Erica L Hamilton, Julie Ngo, Yuqing Jiao, Brett Hanscom, Rahul Paul Choudhury, Yaw Agyei, Estelle Piwowar-Manning, Mark Marzinke, Sinead Delany-Moretlwe, Nyaradzo Mgodi, Bekezela Siziba, Ishana Naidoo, Brenda Gati Mirembe, Betty Kamira, Cynthia McCoig, Adeola Adeyeye, Hans M L Spiegel, Sybil Hosek
<p><strong>Background: </strong>Long-acting formulations of HIV pre-exposure prophylaxis (PrEP) appear particularly well suited to adolescents. We aimed to establish the safety, tolerability, and acceptability of long-acting injectable cabotegravir as PrEP in cisgender adolescent girls.</p><p><strong>Methods: </strong>HPTN 084-01 is a single-arm, open-label, phase 2b trial conducted at three clinical research sites in South Africa, Uganda, and Zimbabwe. Girls were recruited via community study-outreach teams, reproductive health clinics, and peer referral. Sexually active adolescent girls (younger than 18 years) willing to use long-acting contraception, weighing at least 35 kg, and able to participate with parental or guardian consent (unless an emancipated minor) were eligible. After an oral lead-in, if no adverse events occurred, participants received a 3 mL intramuscular gluteal injection (long-acting injectable cabotegravir 600 mg) at weeks 5, 9, 17, 25, and 33. The product was discontinued for grade 3 or higher toxic effects or pregnancy. The primary outcomes were safety, tolerability, and acceptability. Safety (ie, proportions of grade 2 or higher clinical and laboratory events) was assessed at weeks 6, 10, 18, 26, and 34 in all enrolled participants. Injection tolerability (ie, proportions of premature discontinuation due to intolerability, frequency of injections, or burden of study procedures) and product acceptability (ie, proportions of scheduled injections completed and participants preferring long-acting injectable cabotegravir for future use) were assessed in all participants who received at least one injection at study end. The trial was registered with ClinicalTrials.gov (NCT04824131) and is completed.</p><p><strong>Findings: </strong>Between Nov 1, 2020, and Aug 31, 2021, 69 participants were assessed for eligibility and 55 met inclusion criteria. The mean age was 16·0 years (SD 1·1), 39 (71%) had a recent primary sexual partner, 12 (22%) reported transactional sex, and 22 (40%) had sexually transmitted infections at baseline. Two participants dropped out and did not initiate long-acting injectable cabotegravir due to adverse events unrelated to the study drug during the oral lead-in. One participant stopped long-acting injectable cabotegravir after three injections due to pregnancy. 51 (93%) participants reported at least one adverse event of grade 2 or higher, mostly unrelated, transient laboratory abnormalities. There were no long-acting injectable cabotegravir discontinuations due to intolerability. Of the 52 participants who completed step 2, all scheduled injections were completed and 32 (62%) participants reported they would consider using long-acting injectable cabotegravir for HIV prevention in the future.</p><p><strong>Interpretation: </strong>Long-acting injectable cabotegravir is a safe, tolerable, and acceptable option for the prevention of HIV in adolescent girls. Our study findings expand the HIV prevention options
{"title":"Safety, tolerability, and acceptability of long-acting injectable cabotegravir for HIV prevention in cisgender female adolescents (HPTN 084-01): a single-arm, open-label, phase 2b trial.","authors":"Lynda Stranix-Chibanda, Erica L Hamilton, Julie Ngo, Yuqing Jiao, Brett Hanscom, Rahul Paul Choudhury, Yaw Agyei, Estelle Piwowar-Manning, Mark Marzinke, Sinead Delany-Moretlwe, Nyaradzo Mgodi, Bekezela Siziba, Ishana Naidoo, Brenda Gati Mirembe, Betty Kamira, Cynthia McCoig, Adeola Adeyeye, Hans M L Spiegel, Sybil Hosek","doi":"10.1016/S2352-3018(24)00310-2","DOIUrl":"https://doi.org/10.1016/S2352-3018(24)00310-2","url":null,"abstract":"<p><strong>Background: </strong>Long-acting formulations of HIV pre-exposure prophylaxis (PrEP) appear particularly well suited to adolescents. We aimed to establish the safety, tolerability, and acceptability of long-acting injectable cabotegravir as PrEP in cisgender adolescent girls.</p><p><strong>Methods: </strong>HPTN 084-01 is a single-arm, open-label, phase 2b trial conducted at three clinical research sites in South Africa, Uganda, and Zimbabwe. Girls were recruited via community study-outreach teams, reproductive health clinics, and peer referral. Sexually active adolescent girls (younger than 18 years) willing to use long-acting contraception, weighing at least 35 kg, and able to participate with parental or guardian consent (unless an emancipated minor) were eligible. After an oral lead-in, if no adverse events occurred, participants received a 3 mL intramuscular gluteal injection (long-acting injectable cabotegravir 600 mg) at weeks 5, 9, 17, 25, and 33. The product was discontinued for grade 3 or higher toxic effects or pregnancy. The primary outcomes were safety, tolerability, and acceptability. Safety (ie, proportions of grade 2 or higher clinical and laboratory events) was assessed at weeks 6, 10, 18, 26, and 34 in all enrolled participants. Injection tolerability (ie, proportions of premature discontinuation due to intolerability, frequency of injections, or burden of study procedures) and product acceptability (ie, proportions of scheduled injections completed and participants preferring long-acting injectable cabotegravir for future use) were assessed in all participants who received at least one injection at study end. The trial was registered with ClinicalTrials.gov (NCT04824131) and is completed.</p><p><strong>Findings: </strong>Between Nov 1, 2020, and Aug 31, 2021, 69 participants were assessed for eligibility and 55 met inclusion criteria. The mean age was 16·0 years (SD 1·1), 39 (71%) had a recent primary sexual partner, 12 (22%) reported transactional sex, and 22 (40%) had sexually transmitted infections at baseline. Two participants dropped out and did not initiate long-acting injectable cabotegravir due to adverse events unrelated to the study drug during the oral lead-in. One participant stopped long-acting injectable cabotegravir after three injections due to pregnancy. 51 (93%) participants reported at least one adverse event of grade 2 or higher, mostly unrelated, transient laboratory abnormalities. There were no long-acting injectable cabotegravir discontinuations due to intolerability. Of the 52 participants who completed step 2, all scheduled injections were completed and 32 (62%) participants reported they would consider using long-acting injectable cabotegravir for HIV prevention in the future.</p><p><strong>Interpretation: </strong>Long-acting injectable cabotegravir is a safe, tolerable, and acceptable option for the prevention of HIV in adolescent girls. Our study findings expand the HIV prevention options","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634884","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 : 2025-03-11DOI: 10.1016/S2352-3018(25)00011-6
Anneli Uusküla, Anna Tisler, Jack DeHovitz, Gad Murenzi, Philip E Castle, Gary Clifford
The advent of effective antiretroviral therapy (ART) has increased the lifespan of many people living with HIV. As a result, cancers driven by high-risk human papillomavirus (HPV) infection have emerged as an increasingly important cause of mortality in this population. The complex interplay between HIV and HPV necessitates a deep understanding of the HPV-related cancer burden in people living with HIV and the integration of effective prevention strategies into their care. Although cervical cancer is a global concern, anal cancer is more important among people living with HIV in settings where HIV is more concentrated among men who have sex with men. High HPV prevalence, coupled with resource constraints, particularly in sub-Saharan Africa, where the majority of people living with HIV reside, creates substantial barriers to successful prevention and management of HPV-related malignancies. Implementing preventive measures, such as HPV vaccination and comprehensive screening programmes, is crucial and will require addressing existing health inequities and developing tailored interventions for people living with HIV. The development of enhanced secondary prevention tools and innovative treatment modalities is essential to mitigate the burden of HPV-associated cancers and improve the overall health outcomes for this vulnerable population.
{"title":"Prevention and control of HPV-related cancers in people living with HIV.","authors":"Anneli Uusküla, Anna Tisler, Jack DeHovitz, Gad Murenzi, Philip E Castle, Gary Clifford","doi":"10.1016/S2352-3018(25)00011-6","DOIUrl":"https://doi.org/10.1016/S2352-3018(25)00011-6","url":null,"abstract":"<p><p>The advent of effective antiretroviral therapy (ART) has increased the lifespan of many people living with HIV. As a result, cancers driven by high-risk human papillomavirus (HPV) infection have emerged as an increasingly important cause of mortality in this population. The complex interplay between HIV and HPV necessitates a deep understanding of the HPV-related cancer burden in people living with HIV and the integration of effective prevention strategies into their care. Although cervical cancer is a global concern, anal cancer is more important among people living with HIV in settings where HIV is more concentrated among men who have sex with men. High HPV prevalence, coupled with resource constraints, particularly in sub-Saharan Africa, where the majority of people living with HIV reside, creates substantial barriers to successful prevention and management of HPV-related malignancies. Implementing preventive measures, such as HPV vaccination and comprehensive screening programmes, is crucial and will require addressing existing health inequities and developing tailored interventions for people living with HIV. The development of enhanced secondary prevention tools and innovative treatment modalities is essential to mitigate the burden of HPV-associated cancers and improve the overall health outcomes for this vulnerable population.</p>","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630955","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 : 2025-03-03DOI: 10.1016/S2352-3018(25)00045-1
Caroline A Bulstra, Felix Teufel, Pooja Joshi, Rifat Atun
{"title":"Unified health surveys for integrated health systems.","authors":"Caroline A Bulstra, Felix Teufel, Pooja Joshi, Rifat Atun","doi":"10.1016/S2352-3018(25)00045-1","DOIUrl":"https://doi.org/10.1016/S2352-3018(25)00045-1","url":null,"abstract":"","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573993","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 : 2025-03-01Epub Date: 2025-02-12DOI: 10.1016/S2352-3018(24)00306-0
Lisa M Noguchi, Maxensia Owor, Nyaradzo M Mgodi, Brenda Gati Mirembe, Sufia Dadabhai, Elizea Horne, Holly Gundacker, Barbra A Richardson, Katherine Bunge, Rachel Scheckter, Mei Song, Mark A Marzinke, Peter L Anderson, Edward Livant, Cindy Jacobson, Jeanna M Piper, Nahida Chakhtoura, Sharon L Hillier, Jennifer E Balkus
<p><strong>Background: </strong>In 2021, WHO recommended dapivirine vaginal rings (DVRs) for HIV prevention, but noted evidence gaps for breastfeeding populations. This trial aimed to describe safety profiles associated with DVRs and oral pre-exposure prophylaxis (PrEP) use during breastfeeding and to summarise study-drug quantification and concentrations for mothers and infants.</p><p><strong>Methods: </strong>Microbicide Trials Network (MTN)-043 was a phase 3b, open-label, randomised trial in which mother-infant pairs were recruited from local health facilities and enrolled at four HIV clinical trial sites in Malawi, South Africa, Uganda, and Zimbabwe. Eligible mothers (aged ≥18 years) were HIV-negative, exclusively breastfeeding one infant (aged 6-12 weeks, birthweight ≥2000 g), and had not been exposed to HIV post-exposure prophylaxis in the previous 6 months. Mother-infant pairs were randomly assigned (3:1) via a computer-generated sequence to 12 weeks of 25 mg monthly DVR or daily oral PrEP (200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate), with stratification by site using a permuted block design. Participants and staff were aware of study product assignment. Primary outcomes were maternal and infant safety (all serious adverse events and grade 3 or worse adverse events) and drug concentrations, which were measured in maternal plasma, maternal blood, breastmilk, infant plasma, and infant blood. All mother-infant pairs who received at least one dose of study product were included in the primary safety analysis, and those with at least one post-enrolment drug concentration result were included in the drug quantification analysis. The trial was registered at ClinicalTrials.gov (NCT04140266).</p><p><strong>Findings: </strong>Between Sept 24, 2020, and July 29, 2021, 197 mother-infant pairs enrolled (148 on DVR and 49 on PrEP), all of whom received at least one dose of study product and were included in the primary safety analysis. Two (1%) of 148 mothers in the DVR group had serious adverse events, and three (2%) in the DVR group and two (4%) in the oral PrEP group had a grade 3 or worse adverse event; four (3%) of 148 infants in the DVR group had a serious adverse event, and ten (7%) in the DVR group and one (2%) in the oral PrEP group had a grade 3 or worse adverse event. No mother or infant in the oral PrEP group had a serious adverse event. No HIV infections were detected. 144 participants in the DVR group and 48 in the oral PrEP group had at least one post-enrolment drug concentration result. Quantifiable median dapivirine concentrations ranged from 656·0 (IQR 407·0-878·0) pg/mL at week 1 to 558·5 (282·0-778·0) pg/mL at month 3, but were observed infrequently (5-15%) in specimens from infants, with median concentrations below the limit of quantification at all visits. Median tenofovir diphosphate concentrations ranged from 263·0 (193·0-363·0) fmol/punch at week 1 to 777·0 (381·0-1241·0) fmol/punch at month 3, but were not ob
{"title":"Safety and drug quantification of the dapivirine vaginal ring and oral pre-exposure prophylaxis in breastfeeding mother-infant pairs (MTN-043): a phase 3B, open-label, randomised trial.","authors":"Lisa M Noguchi, Maxensia Owor, Nyaradzo M Mgodi, Brenda Gati Mirembe, Sufia Dadabhai, Elizea Horne, Holly Gundacker, Barbra A Richardson, Katherine Bunge, Rachel Scheckter, Mei Song, Mark A Marzinke, Peter L Anderson, Edward Livant, Cindy Jacobson, Jeanna M Piper, Nahida Chakhtoura, Sharon L Hillier, Jennifer E Balkus","doi":"10.1016/S2352-3018(24)00306-0","DOIUrl":"10.1016/S2352-3018(24)00306-0","url":null,"abstract":"<p><strong>Background: </strong>In 2021, WHO recommended dapivirine vaginal rings (DVRs) for HIV prevention, but noted evidence gaps for breastfeeding populations. This trial aimed to describe safety profiles associated with DVRs and oral pre-exposure prophylaxis (PrEP) use during breastfeeding and to summarise study-drug quantification and concentrations for mothers and infants.</p><p><strong>Methods: </strong>Microbicide Trials Network (MTN)-043 was a phase 3b, open-label, randomised trial in which mother-infant pairs were recruited from local health facilities and enrolled at four HIV clinical trial sites in Malawi, South Africa, Uganda, and Zimbabwe. Eligible mothers (aged ≥18 years) were HIV-negative, exclusively breastfeeding one infant (aged 6-12 weeks, birthweight ≥2000 g), and had not been exposed to HIV post-exposure prophylaxis in the previous 6 months. Mother-infant pairs were randomly assigned (3:1) via a computer-generated sequence to 12 weeks of 25 mg monthly DVR or daily oral PrEP (200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate), with stratification by site using a permuted block design. Participants and staff were aware of study product assignment. Primary outcomes were maternal and infant safety (all serious adverse events and grade 3 or worse adverse events) and drug concentrations, which were measured in maternal plasma, maternal blood, breastmilk, infant plasma, and infant blood. All mother-infant pairs who received at least one dose of study product were included in the primary safety analysis, and those with at least one post-enrolment drug concentration result were included in the drug quantification analysis. The trial was registered at ClinicalTrials.gov (NCT04140266).</p><p><strong>Findings: </strong>Between Sept 24, 2020, and July 29, 2021, 197 mother-infant pairs enrolled (148 on DVR and 49 on PrEP), all of whom received at least one dose of study product and were included in the primary safety analysis. Two (1%) of 148 mothers in the DVR group had serious adverse events, and three (2%) in the DVR group and two (4%) in the oral PrEP group had a grade 3 or worse adverse event; four (3%) of 148 infants in the DVR group had a serious adverse event, and ten (7%) in the DVR group and one (2%) in the oral PrEP group had a grade 3 or worse adverse event. No mother or infant in the oral PrEP group had a serious adverse event. No HIV infections were detected. 144 participants in the DVR group and 48 in the oral PrEP group had at least one post-enrolment drug concentration result. Quantifiable median dapivirine concentrations ranged from 656·0 (IQR 407·0-878·0) pg/mL at week 1 to 558·5 (282·0-778·0) pg/mL at month 3, but were observed infrequently (5-15%) in specimens from infants, with median concentrations below the limit of quantification at all visits. Median tenofovir diphosphate concentrations ranged from 263·0 (193·0-363·0) fmol/punch at week 1 to 777·0 (381·0-1241·0) fmol/punch at month 3, but were not ob","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":" ","pages":"e180-e190"},"PeriodicalIF":12.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426463","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 : 2025-03-01Epub Date: 2025-02-17DOI: 10.1016/S2352-3018(24)00155-3
Ellen White, Cissy Kityo, Moira J Spyer, Hilda A Mujuru, Immaculate Nankya, Adeodata R Kekitiinwa, Abbas Lugemwa, Elizabeth Kaudha, Afaaf Liberty, Haseena Cassim, Moherndran Archary, Mark F Cotton, Grace Miriam Ahimbisibwe, Tim R Cressey, Chaiwat Ngampiyaskul, Ussanee Srirompotong, Osee Behuhuma, Yacine Saidi, Alasdair Bamford, Robin Kobbe, Eleni Nastouli, Pablo Rojo, Carlo Giaquinto, Diana M Gibb, Deborah Ford, Anna Turkova
<p><strong>Background: </strong>ODYSSEY showed superior efficacy for dolutegravir-based antiretroviral therapy (ART) versus standard of care (SOC) in children living with HIV starting first-line or second-line ART aged 4 weeks or older. Here, we aim to compare virological outcomes and resistance in the dolutegravir group versus SOC for first-line and second-line ART up to 96 weeks.</p><p><strong>Methods: </strong>ODYSSEY was an open-label, multicentre, randomised, non-inferiority trial done in 29 centres in seven countries (Germany, Spain, South Africa, Thailand, the UK, Uganda, and Zimbabwe). ODYSSEY recruited children living with HIV aged at least 28 days and younger than 18 years, weighing at least 3 kg, starting first-line ART (ODYSSEY A), or switching to second-line therapy after treatment failure (ODYSSEY B). Children were randomly assigned (1:1) to dolutegravir plus two nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs; dolutegravir group) versus the SOC group (non-nucleoside reverse transcriptase inhibitor [NNRTI], boosted protease inhibitor, or non-dolutegravir integrase strand-transfer inhibitor, plus two NRTIs). Two randomised cohorts were combined in this exploratory analysis: children weighing at least 14 kg were enrolled between Sept 20, 2016, and June 22, 2018, and children weighing less than 14 kg were enrolled between July 5, 2018, and Aug 26, 2019. Virological failure was defined as an inadequate virological response at week 24 with an ART switch or confirmed HIV-1 RNA viral load of at least 400 copies per mL after week 36. Virological suppression was defined as two consecutive viral loads of less than 400 copies per mL and was compared between groups, including an ART switch and death as competing risks. Children with virological failure were tested for post-failure genotypic resistance, with baseline results used to identify emergent resistance. Development of emergent resistance was a secondary trial outcome and all other outcomes are exploratory. ODYSSEY was registered with ClinicalTrials.gov (NCT02259127), EUDRACT (2014-002632-14), and ISRCTN (ISRCTN91737921).</p><p><strong>Findings: </strong>In ODYSSEY at enrolment, 381 participants started first-line ART (ODYSSEY A: 189 in the dolutegravir group and 192 in the SOC group) and 407 participants started second-line ART (ODYSSEY B: 202 in the dolutegravir group and 205 in the SOC group). 72 participants in ODYSSEY A and 13 participants in ODYSSEY B weighed less than 14 kg. 401 (51%) of 788 participants were female and 387 (49%) were male. Virological suppression occurred significantly earlier in the dolutegravir group (adjusted [cause-specific] hazard ratio [HR] 1·57 [95% CI 1·35 to 1·83]; p<0·0001). Overall, 51 (13%) participants had virological failure by 96 weeks in the dolutegravir group versus 86 (22%) in the SOC group (including 18 [10%] vs 43 [22%] in ODYSSEY A and in 33 [16%] vs 43 [21%] in ODYSSEY B; adjusted HR 0·56 [0·40 to 0·79]; p=0·0011). Among ODY
背景：ODYSSEY显示，在开始接受一线或二线抗逆转录病毒疗法（ART）的4周或4周以上的艾滋病病毒感染儿童中，基于多罗替拉韦的抗逆转录病毒疗法（ART）与标准护理（SOC）相比疗效更佳。在此，我们旨在比较多罗替拉韦组与标准疗法组在长达 96 周的一线和二线抗逆转录病毒疗法中的病毒学结果和耐药性：ODYSSEY 是一项开放标签、多中心、随机、非劣效试验，在七个国家（德国、西班牙、南非、泰国、英国、乌干达和津巴布韦）的 29 个中心进行。ODYSSEY 试验招募了年龄至少 28 天、小于 18 岁、体重至少 3 公斤、开始接受一线抗逆转录病毒疗法（ODYSSEY A）或治疗失败后转为二线疗法（ODYSSEY B）的艾滋病病毒感染儿童。儿童被随机分配（1:1）至多罗替拉韦+两种核苷或核苷酸逆转录酶抑制剂（NRTIs；多罗替拉韦组）与SOC组（非核苷酸逆转录酶抑制剂[NNRTI]、增强型蛋白酶抑制剂或非多罗替拉韦整合酶链转移抑制剂+两种NRTIs）。本次探索性分析合并了两个随机队列：体重至少14公斤的儿童在2016年9月20日至2018年6月22日期间入组，体重小于14公斤的儿童在2018年7月5日至2019年8月26日期间入组。病毒学失败的定义是：第24周病毒学应答不充分，需要更换抗逆转录病毒疗法，或第36周后证实HIV-1 RNA病毒载量至少为400拷贝/毫升。病毒学抑制的定义是病毒载量连续两次低于每毫升 400 拷贝，并在各组间进行比较，包括 ART 转换和死亡作为竞争风险。对病毒学检测失败的儿童进行失败后基因型耐药性检测，并根据基线结果确定新出现的耐药性。出现耐药性是次要试验结果，所有其他结果均为探索性结果。ODYSSEY已在ClinicalTrials.gov（NCT02259127）、EUDRACT（2014-002632-14）和ISRCTN（ISRCTN91737921）上注册：在ODYSSEY中，381名参与者在入组时开始一线抗逆转录病毒疗法（ODYSSEY A：多替拉韦组189人，SOC组192人），407名参与者开始二线抗逆转录病毒疗法（ODYSSEY B：多替拉韦组202人，SOC组205人）。72 名 ODYSSEY A 参与者和 13 名 ODYSSEY B 参与者体重不足 14 千克。788 名参与者中有 401 人（51%）为女性，387 人（49%）为男性。多鲁曲韦组的病毒抑制发生时间明显更早（调整后[特定原因]危险比[HR] 1-57 [95% CI 1-35 to 1-83]；p解释：与 NNRTIs 和基于增强蛋白酶抑制剂的 SOC 相比，多罗替拉韦能更快地抑制病毒，降低病毒学失败的风险。与开始接受齐多夫定治疗的患者相比，开始接受以阿巴卡韦或替诺福韦为骨干、基于多罗替拉韦的二线抗逆转录病毒疗法的患者出现病毒学失败的风险更低。在一线治疗期间，多鲁曲韦能防止出现耐药性；在开始二线治疗时，在二线治疗方案中使用多鲁曲韦的参与者与主要使用蛋白酶抑制剂的SOC的参与者出现核苷类逆转录酶抑制剂骨架和锚定药物耐药性的风险相似：资金来源：Penta 基金会、ViiV Healthcare 和英国医学研究委员会。
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