Browsing by Author "Desmonde, Sophie"

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    Age-specific mortality rate ratios in adolescents and youth aged 10–24 years living with perinatally versus nonperinatally acquired HIV
    (Wolters Kluwer, 2021) Desmonde, Sophie; Ciaranello, Andrea L.; Malateste, Karen; Musick, Beverly; Patten, Gabriela; Thien Vu, An; Edmonds, Andrew; Neilan, Anne M.; Duda, Stephany N.; Wools-Kaloustian, Kara; Davies, Mary-Ann; Leroy, Valériane; Biostatistics and Health Data Science, School of Medicine
    Objective: To measure mortality incidence rates and incidence rate ratios (IRR) in adolescents and youth living with perinatally acquired HIV (YPHIV) compared with those living with nonperinatally acquired HIV (YNPHIV), by region, by sex, and during the ages of 10-14, 15-19, and 20-24 years in IeDEA. Design and methods: All those with a confirmed HIV diagnosis, antiretroviral therapy (ART)-naive at enrollment, and who have post-ART follow-up while aged 10-24 years between 2004 and 2016 were included. We estimated post-ART mortality incidence rates and 95% confidence intervals (95% CI) per 100 person-years for YPHIV (enrolled into care <10 years of age) and YNPHIV (enrolled ≥10 years and <25 years). We estimate mortality IRRs in a negative binomial regression model, adjusted for sex, region time-varying age, CD4+ cell count at ART initiation (<350 cells/μl, ≥350 cells/μl, unknown), and time on ART (<12 and ≥12 months). Results: Overall, 104 846 adolescents and youth were included: 21 340 (20%) YPHIV (50% women) and 83 506 YNPHIV (80% women). Overall mortality incidence ratios were higher among YNPHIV (incidence ratio: 2.3/100 person-years; 95% CI: 2.2-2.4) compared with YPHIV (incidence ratio: 0.7/100 person-years; 95% CI: 0.7-0.8). Among adolescents aged 10-19 years, mortality was lower among YPHIV compared with YNPHIV (all IRRs <1, ranging from 0.26, 95% CI: 0.13-0.49 in 10-14-year-old boys in the Asia-Pacific to 0.51, 95% CI: 0.30-0.87 in 15-19-year-old boys in West Africa). Conclusion: We report substantial amount of deaths occurring during adolescence. Mortality was significantly higher among YNPHIV compared to YPHIV. Specific interventions including HIV testing and early engagement in care are urgently needed to improve survival among YNPHIV.
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    Global estimates of viral suppression in children and adolescents and adults on antiretroviral therapy adjusted for missing viral load measurements: a multiregional, retrospective cohort study in 31 countries
    (Elsevier, 2021) Han, Win Min; Law, Matthew G.; Egger, Matthias; Wools-Kaloustian, Kara; Moore, Richard; McGowan, Catherine; Kumarasamy, Nagalingesawaran; Desmonde, Sophie; Edmonds, Andrew; Davies, Mary-Ann; Yiannoutsos, Constantin; Althoff, Keri N.; Cortes, Claudia P.; Mohamed, Thahira Jamal; Jaquet, Antoine; Anastos, Kathryn; Euvrard, Jonathan; Castelnuovo, Barbara; Salters, Kate; Esteves Coelho, Lara; Ekouevi, Didier K.; Eley, Brian; Diero, Lameck; Zaniewski, Elizabeth; Ford, Nathan; Sohn, Annette H.; Kariminia, Azar; IeDEA collaboration; Medicine, School of Medicine
    Background: As countries move towards the UNAIDS's 95-95-95 targets and with strong evidence that undetectable equals untransmittable, it is increasingly important to assess whether those with HIV who are receiving antiretroviral therapy (ART) achieve viral suppression. We estimated the proportions of children and adolescents and adults with viral suppression at 1, 2, and 3 years after initiating ART. Methods: In this retrospective cohort study, seven regional cohorts from the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium contributed data from individuals initiating ART between Jan 1, 2010, and Dec 31, 2019, at 148 sites in 31 countries with annual viral load monitoring. Only people with HIV who started ART after the time a site started routine viral load monitoring were included. Data up to March 31, 2020, were analysed. We estimated the proportions of children and adolescents (aged <18 years at ART initiation) and adults (aged ≥18 years at ART initiation) with viral suppression (viral load <1000 copies per mL) at 1, 2, and 3 years after ART initiation using an intention-to-treat approach and an adjusted approach that accounted for missing viral load measurements. Findings: 21 594 children and adolescents (11 812 [55%] female, 9782 [45%] male) from 106 sites in 22 countries and 255 662 adults (163 831 [64%] female, 91 831 [36%] male) from 143 sites in 30 countries were included. Using the intention-to-treat approach, the proportion of children and adolescents with viral suppression was 7303 (36%) of 20 478 at 1 year, 5709 (30%) of 19 135 at 2 years, and 4287 (24%) of 17 589 at 3 years after ART initiation; the proportion of adults with viral suppression was 106 541 (44%) of 240 600 at 1 year, 79 141 (36%) of 220 925 at 2 years, and 57 970 (29%) of 201 124 at 3 years after ART initiation. After adjusting for missing viral load measurements among those who transferred, were lost to follow-up, or who were in follow-up without viral load testing, the proportion of children and adolescents with viral suppression was 12 048 (64% [plausible range 43-81]) of 18 835 at 1 year, 10 796 (62% [41-77]) of 17 553 at 2 years, and 9177 (59% [38-91]) of 15 667 at 3 years after ART initiation; the proportion of adults with viral suppression was 176 964 (79% [53-80]) of 225 418 at 1 year, 145 552 (72% [48-79]) of 201 238 at 2 years, and 115 260 (65% [43-69]) of 178 458 at 3 years after ART initiation. Interpretation: Although adults with HIV are approaching the global target of 95% viral suppression, progress among children and adolescents is much slower. Substantial efforts are still needed to reach the viral suppression target for children and adolescents.
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    Global HIV mortality trends among children on antiretroviral treatment corrected for under‐reported deaths: an updated analysis of the International epidemiology Databases to Evaluate AIDS collaboration
    (Wiley, 2021-09) Kassanjee, Reshma; Johnson, Leigh F.; Zaniewski, Elizabeth; Ballif, Marie; Christ, Benedikt; Yiannoutsos, Constantin T.; Nyakato, Patience; Desmonde, Sophie; Edmonds, Andrew; Sudjaritruk, Tavitiya; Pinto, Jorge; Vreeman, Rachel; Dahourou, Désiré Lucien; Twizere, Christelle; Kariminia, Azar; Carlucci, James G.; Kasozi, Charles; Davies, Mary-Ann; Biostatistics, School of Public Health
    Introduction: The Joint United Nations Programme on HIV/AIDS (UNAIDS) projections of paediatric HIV prevalence and deaths rely on the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium for mortality estimates among children living with HIV (CHIV) receiving antiretroviral therapy (ART). Previous estimates, based on data through 2014, may no longer be accurate due to expanded paediatric HIV care and treatment eligibility, and the possibility of unreported deaths in CHIV considered lost to follow-up (LTFU). We therefore estimated all-cause mortality and its trends in CHIV (<15 years old) on ART using extended and new IeDEA data. Methods: We analysed (i) IeDEA observational data from CHIV in routine care globally, and (ii) novel data from an IeDEA tracing study that determined outcomes in a sample of CHIV after being LTFU in southern Africa. We included 45,711 CHIV on ART during 2004 to 2017 at 72 programmes in Africa, Asia-Pacific and Latin America. We used mixed effects Poisson regression to estimate mortality by age, sex, CD4 at ART start, time on ART, region and calendar year. For Africa, in an adjusted analysis that accounts for unreported deaths among those LTFU, we first modified the routine data by simulating mortality outcomes within six months after LTFU, based on a Gompertz survival model fitted to the tracing data (n = 221). Results: Observed mortality rates were 1.8 (95% CI: 1.7 to 1.9) and 9.4 (6.3 to 13.4) deaths per 100 person-years in the routine and tracing data, respectively. We found strong evidence of higher mortality at shorter ART durations, lower CD4 values, and in infancy. Averaging over covariate patterns, the adjusted mortality rate was 54% higher than the unadjusted rate. In unadjusted analyses, mortality reduced by an average 60% and 73% from 2005 to 2017, within and outside of Africa, respectively. In the adjusted analysis for Africa, this temporal reduction was 42%. Conclusions: Mortality rates among CHIV have decreased substantially over time. However, when accounting for worse outcomes among those LTFU, mortality estimates increased and temporal improvements were slightly reduced, suggesting caution in interpreting analyses based only on programme data. The improved and updated IeDEA estimates on mortality among CHIV on ART support UNAIDS efforts to accurately model global HIV statistics.
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    Incidence of switching to second-line antiretroviral therapy and associated factors in children with HIV: an international cohort collaboration
    (Elsevier, 2019-02) Collins, Intira J.; Wools-Kaloustian, Kara; Goodall, Ruth; Smith, Colette; Abrams, Elaine J.; Ben-Farhat, Jihane; Balkan, Suna; Davies, Mary-Ann; Edmonds, Andrew; Leroy, Valériane; Nuwagaba-Biribonwoha, Harriet; Patel, Kunjal; Paul, Mary E.; Pinto, Jorge; Conejo, Pablo Rojo; Sohn, Annette; Van Dyke, Russell; Vreeman, Rachel; Maxwell, Nicky; Timmerman, Venessa; Duff, Charlotte; Judd, Ali; Seage, George, III; Williams, Paige; Gibb, Diana M.; Bekker, Linda-Gail; Mofenson, Lynne; Vicari, Marissa; Essajee, Shaffiq; Mohapi, Edith Q.; Kazembe, Peter N.; Hlatshwayo, Makhosazana; Lumumba, Mwita; Kekitiinwa-Rukyalekere, Adeodata; Wanless, Sebastian; Matshaba, Mogomotsi S.; Goetghebuer, Tessa; Thorne, Claire; Warszawski, Josiane; Galli, Luisa; Geelen, Sybil; Giaquinto, Carlo; Marczynska, Magdalena; Marques, Laura; Prata, Filipa; Ene, Luminita; Okhonskaia, Liubov; Noguera-Julian, Antoni; Naver, Lars; Rudin, Christoph; Jourdain, Gonzague; Volokha, Alla; Rouzier, Vanessa; Succi, Regina; Chokephaibulkit, Kulkanya; Kariminia, Azar; Yotebieng, Marcel; Lelo, Patricia; Lyamuya, Rita; Marete, Irene; Oyaro, Patrick; Boulle, Andrew; Malisita, Kennedy; Fatti, Geoffrey; Haas, Andreas D.; Desmonde, Sophie; Dicko, Fatoumata; Abzug, Mark J.; Levin, Myron; Oleske, James; Chernoff, Miriam; Traite, Shirley; Purswani, Murli; Teasdale, Chloe; Chadwick, Ellen; Pediatrics, School of Medicine
    Background: Estimates of incidence of switching to second-line antiretroviral therapy (ART) among children with HIV are necessary to inform the need for paediatric second-line formulations. We aimed to quantify the cumulative incidence of switching to second-line ART among children in an international cohort collaboration. Methods: In this international cohort collaboration study, we pooled individual patient-level data for children younger than 18 years who initiated ART (two or more nucleoside reverse-transcriptase inhibitors [NRTI] plus a non-NRTI [NNRTI] or boosted protease inhibitor) between 1993 and 2015 from 12 observational cohort networks in the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration. Patients who were reported to be horizontally infected with HIV and those who were enrolled in trials of treatment monitoring, switching, or interruption strategies were excluded. Switch to second-line ART was defined as change of one or more NRTI plus either change in drug class (NNRTI to protease inhibitor or vice versa) or protease inhibitor change, change from single to dual protease inhibitor, or addition of a new drug class. We used cumulative incidence curves to assess time to switching, and multivariable proportional hazards models to explore patient-level and cohort-level factors associated with switching, with death and loss to follow-up as competing risks. Findings: At the data cutoff of Sept 16, 2015, 182 747 children with HIV were included in the CIPHER dataset, of whom 93 351 were eligible, with 83 984 (90·0%) from sub-Saharan Africa. At ART initiation, the median patient age was 3·9 years (IQR 1·6-6·9) and 82 885 (88·8%) patients initiated NNRTI-based and 10 466 (11·2%) initiated protease inhibitor-based regimens. Median duration of follow-up after ART initiation was 26 months (IQR 9-52). 3883 (4·2%) patients switched to second-line ART after a median of 35 months (IQR 20-57) of ART. The cumulative incidence of switching at 3 years was 3·1% (95% CI 3·0-3·2), but this estimate varied widely depending on the cohort monitoring strategy, from 6·8% (6·5-7·2) in settings with routine monitoring of CD4 (CD4% or CD4 count) and viral load to 0·8% (0·6-1·0) in settings with clinical only monitoring. In multivariable analyses, patient-level factors associated with an increased likelihood of switching were male sex, older age at ART initiation, and initial NNRTI-based regimen (p<0·0001). Cohort-level factors that increased the likelihood of switching were higher-income country (p=0·0017) and routine or targeted monitoring of CD4 and viral load (p<0·0001), which was associated with a 166% increase in likelihood of switching compared with CD4 only monitoring (subdistributional hazard ratio 2·66, 95% CI 2·22-3·19). Interpretation: Our global paediatric analysis found wide variations in the incidence of switching to second-line ART across monitoring strategies. These findings suggest the scale-up of viral load monitoring would probably increase demand for paediatric second-line ART formulations.