Introduction
The HIV pandemic continues to be a global health challenge; 36.9 million persons were estimated to be living with HIV in 2017 [1]. Women account for over half of the adults living with HIV worldwide and up to 60% of persons from low-income and middle-income settings, where health needs are the most pressing [1,2].
Access to healthcare and life-saving antiretroviral therapy (ART) varies greatly across regions and depends on structural and individual factors [1–3]. Access to HIV testing is a prerequisite to ART initiation, but delayed HIV diagnosis and linkage to care are major barriers to timely access to ART, and thus, its clinical benefits [3–6]. Largely a consequence of increases in the uptake of universal HIV screening during pregnancy to prevent mother-to-child HIV transmission over the last decade, women from most geographical regions are diagnosed with HIV earlier and have higher CD4+ cell counts at diagnosis than heterosexually infected men [1,3–6]. These factors underlie some of the reported mortality differences between women and men favoring women [7–11]. However, no study has so far specifically compared early and late mortality differences among women living with HIV (WLWH) across different geographical regions worldwide.
Globally, WLWH differ in their age distribution, HIV transmission routes, socioeconomic status and viral and tuberculosis co-infection rates, and risk factors for non-HIV mortality [1,3–11]. Wide variations exist between countries and regions of the world in terms of access to HIV testing, ART regimens, and CD4+ cell counts at ART initiation, along with HIV testing policies and guidelines for treatment. Many of these factors may be because of healthcare systems and resource availability for healthcare within the individual country. In turn, this may impact mortality rates for WLWH [1,2,12]. Finally, background mortality rates in different regions have striking variations that, together with the previously mentioned aspects, shape the mortality rates of WLWH [13]. Collaboration between large multiregional cohorts from different regions of the world provides an opportunity to describe geographic disparities in mortality. In this work, we estimate all-cause mortality after ART initiation, overall and by duration of ART use, among WLWH in Europe, the Americas and Sub-Saharan Africa up to 48 months after ART initiation, in order to help to understand key underlying drivers of mortality in women from different settings.
Methods
Setting and data sources
We merged databases from HIV cohorts in the International Epidemiology Databases to Evaluate AIDS (IeDEA) Collaboration and the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord (merger 2015). These collaborations have been described elsewhere [14–19].
IeDEA is an international research consortium that collects HIV/AIDS data through seven international regional centers, four in Africa and one each in the Asia-Pacific region; the Caribbean, Central and South America region; and North America. Five IeDEA regions contributed data to this study: the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) [14], the Caribbean, Central and South America network for HIV epidemiology (CCASAnet) [15] and IeDEA East [16], Southern [16] and West Africa [16]. COHERE is a collaboration of HIV cohorts across Europe constituting 40 cohorts and cohort collaborations from 34 countries [17]. COHERE includes other collaborations, such as CASCADE [18] and EuroSIDA [19].
Institutional review boards approved the pooling of data and their use in collaborative analyses, and ethics permission was granted.
Study population and inclusion criteria
Eligible individuals were ART-naïve women, 18–80 years old at ART initiation, who started their first ART regimen between 1 January 2000 and 31 December 2014. North American participants were required to have a second visit within 12 months of enrollment, regardless of ART initiation status, so that anyone who died soon after enrollment would not have been included in NA-ACCORD. In Southern Africa, analyses were restricted to cohorts from the Republic of South Africa where patient records could be linked to the vital registry. We excluded individuals from the Asia-Pacific region [20] (N = 849) as the number of deaths was very low, those from Mexico because of having too few eligible participants (N = 100) and those from Argentina (N = 545) as mortality was reported to be under-ascertained and no further corrections could be applied.
Ascertainment of mortality
The primary outcome was death because of any cause in the 48 months after ART initiation. To address concerns regarding death under-ascertainment, a survey addressing ascertainment and matching with external mortality registries was distributed. Seventy-five percent of cohorts in Europe reported good or very good death ascertainment, but only 40% conducted cross-checks with mortality registries. Cumulative mortality in the European cohorts did not vary significantly according to self-assessment of mortality ascertainment (data not shown). Death ascertainment was reported to be poor in East and West Africa. To correct mortality estimates for East Africa, we used an inverse-probability-weighted estimator of the mortality rate where weights are constant and equal to the inverse ratio of the patients who could be traced out of all patients who were lost to follow-up [21]. For corrections of under-ascertainment in West Africa, we used a modification of the approach by Brinkhof et al.[22], which uses inflation factors to account for mortality under-reporting, under the assumption that mortality under-ascertainment was similar in the two regions [21]. Death rates based on observed data were estimated for different participant subgroups. These ‘passive’ mortality estimates were then multiplied by a group-specific inflation factor determined as the ratio of the lost-to-follow-up-adjusted death rates over the observed rates estimated within East African cohorts [21,22]. For the Republic of South Africa cohort, civil identification numbers, wherever available, were cross-checked with national population registers prior to data transfer to confirm dates of death. All sites in the Caribbean, Central and South America region, except for Argentina, reported ascertaining deaths with population-based mortality registries. North American cohorts link to a population-based death registry at least annually.
Statistical methods
Data-contributing regions were categorized as Europe; East Africa; West Africa; Southern Africa; South America; North America; and Central America and the Caribbean. The countries in each region are shown in Supplemental Table 1, https://links.lww.com/QAD/B551.
Participant characteristics at ART initiation by region were described using frequency tables for categorical variables and medians and interquartile ranges for continuous variables. Differences in sociodemographic and clinical characteristics by region were assessed with Kruskal–Wallis test for continuous variables and the chi-squared test for independence for categorical variables. We assumed that women from Haiti, Republic of South Africa, West Africa and East Africa with unknown transmission mode were infected through heterosexual contact [1].
Mortality rates were calculated by region for the intervals 0–3, 3–6, 6–12, 12–24 and 24–48 months after ART initiation. Mortality rate ratios, compared with Europe, were estimated at each interval using a piecewise exponential parametric survival model fit through Poisson regression. The use of a piecewise exponential parametric survival model fit through Poisson regression simplified the prediction of mortality rate ratios for each duration interval on ART, whereas the implicit assumption of constant hazards within each interval produced almost identical inter-regional comparative mortality rate ratio estimates when compared with a piecewise spline-based flexible parametric survival model [23,24]. Parametric survival models offer alternatives and may be more appropriate than semi-parametric techniques, such a Cox regression when the proportional hazards assumption is in question [25].
Multivariable models were adjusted for baseline age (<30, 30–44, 45–59, ≥60 years), CD4+ cell counts within 6 months prior to ART initiation (0–24, 25–49, 50–99, 100–199, 200–349, ≥350 cells/μl, unknown) and period of ART initiation (2000–2003, 2004–2007, 2008–2011, 2012–2014). As the HIV epidemics in East, West and South Africa, the Caribbean, South and Central America are predominantly heterosexual epidemics, no adjustment for transmission category could be applied for comparisons between these regions and Europe or North America. Neither adjustment for HIV-RNA nor AIDS prior to ART initiation were included because of the high percentage of missing values in these regions. For comparisons between North America and Europe, multivariable models were additionally adjusted for transmission category, HIV-RNA, AIDS at ART initiation, and race/ethnicity in the subset of participants with available information for these variables.
A set of sensitivity analyses were undertaken. Analyses were repeated restricting to patients with documented or presumed heterosexual transmission, patients starting ART post2004, cohorts with more than 50% of data on CD4+ cell counts at baseline and cohorts with ‘very good’ self-reported mortality ascertainment.
Statistical analyses were performed using Stata 14 (StataCorp, College Station, Texas, USA).
Results
A total of 190 175 women (16% Europe, 47% East Africa, 13% West Africa, 19% South Africa, 1% South America, 3% North America and 2% Central America/Caribbean) were included. Median age at ART initiation ranged from 33 years in South Africa to 40 years in North America. The proportion of persons who injected drugs was highest in North America (18%) and Europe (7%). Only 16% of the women in North America were of white race/ethnicity, whereas 63 and 17% were of black race and Hispanic ethnicity, respectively. Race/ethnicity data were available for 45% of European women, 26% of whom were black, largely migrants from sub-Saharan Africa. Of ART initiators, median CD4+ cell counts at initiation were close to 250 cells/μl in Europe and North America, 141 cells/μl in South Africa and 170–190 cells/μl in other regions (Table 1).
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Table 1: Characteristics of 190 175 women living with HIV in Europe, sub-Saharan Africa and the Americas who initiated ART 2000–2014.
In all regions except for North America, because of cohort inclusion criteria in that region, the highest death rates occurred during the first 3 months after starting ART and declined thereafter (Fig. 1). Women from Europe had the lowest death rates across the study period, whereas the highest were observed among women from Central America and the Caribbean between 0 and 3 months, in East Africa between 3 and 6 months and West Africa between 6 and 48 months from ART initiation.
Fig. 1: Crude mortality rates per 100 person-years for women initiating antiretroviral theray by global region.
Mortality rates in women from Europe were significantly lower than rates in women from all other regions during the first 48 months after starting ART, except for North American women, whose rates were similar for the first 6 months and significantly higher thereafter (Table 2). The greatest differences were observed in the first 3 months and attenuated thereafter. Taking into account differences in baseline age, CD4+ cell count and period of ART initiation, differences in mortality were attenuated although still of large magnitude and statistically significant. After additional adjustments for transmission category, HIV-RNA and AIDS prior to ART initiation for comparisons between North America and Europe, differences in mortality were reduced, but still present. Further adjustment for race/ethnicity in the subset of patients with available information for this variable contributed to reduction of differences between 6 and 48 months on ART.
Table 2: Mortality rate ratios (95% confidence interval) compared with Europe by duration on antiretroviral therapy.
Sensitivity analyses yielded results consistent with the main analyses (Supplemental Table 2, https://links.lww.com/QAD/B551).
Discussion
This large collaborative study found that there was significant variability in all-cause mortality among WLWH in Europe, the Americas and sub-Saharan Africa up to 48 months after ART initiation, with distinct geographical patterns for short-term, midterm and long-term mortality. The highest mortality was observed in WLWH in Central America and the Caribbean and sub-Saharan Africa, who also had the lowest CD4+ cell counts at ART initiation. The lowest mortality was reported in women living in Europe, who had, together with women from North America, the highest CD4+ cell counts; women living in South America had intermediate mortality. These differences were apparent after correcting for under-ascertainment in mortality in most of the African sites. Mortality was highest in the first 3 months after ART initiation in all evaluable regions, and decreased from then onwards to reach stable rates from the first until the fourth year following ART, when inter-regional differences were attenuated.
The baseline differences of WLWH explained some of the relative differences encountered but did not fully explain the higher mortality observed in women from sub-Saharan African and American regions compared with the women on ART living in Europe. Indeed, women from sub-Saharan Africa and from Central America and the Caribbean had the lowest CD4+ cell counts at ART initiation, a strong predictor of subsequent HIV-related, mortality [8–11,26]. Median CD4+ cell counts at ART initiation were close to 250 cells/μl in women living in North America and Europe, but mortality rates differed substantially. The lower mortality of WLWH in Europe compared with women in North America has been previously reported [8,9] and attributed to the accessibility and equity of health services, to background mortality rates, to causes of death of populations affected by HIV in the different settings, and to near complete death ascertainment in North America [27]. Our findings build on these explanations expanding comparisons to East and West Africa, the Caribbean, Central and South and America.
Most of the European countries included in this study have universal healthcare systems, which grant free access to HIV testing, HIV care and ART medications, and this may account for some of the better HIV-related outcomes observed among women in European cohorts. However, not all countries in Europe provide free access to ART for undocumented migrants, a nonnegligible proportion of WLWH in Europe [28,29]. Even for documented migrant women, barriers to access care because of socioeconomic, gender, ethnic and cultural factors exist and may have a negative impact on survival [30]. Barriers to accessing adequate healthcare have been consistently reported in black and Latina women and First Nations/indigenous women in North America, irrespective of HIV status [10,30–33]. In addition, access to HIV testing and life-saving ART among women from low-income and middle-income settings is considerably lower than in Western Europe and North America [1,2,34]. These health inequities may lead to lower CD4+ cell counts at ART initiation, which likely account for the exceedingly high early and overall mortality observed in the women in sub-Saharan Africa and Central and South America and the Caribbean.
Our findings need to be placed in the context of background mortality rates of women from the general population living in geographical regions with generalized HIV epidemics, together with mortality patterns of racial and ethnic minorities in North America and Europe, with concentrated HIV epidemics [1,35,36]. Globally, all-cause mortality in women living in sub-Saharan Africa, the Caribbean, and Central and South America is also higher than among the women from Europe and North America [13]. Within North America, African-American and Latina women have higher mortality rates than white women, both in general [35,36] and from HIV-infection [31], but patterns have been described to be complex and evolve over time [37]. Conversely, migrant women in Europe have lower all-cause mortality relative to general population women, consistent with healthy migrant selection bias [38].
For all regions analyzed, and with different magnitudes, mortality was highest in the initial 3 months following ART. The exception to this pattern was North America given NA-ACCORD's inclusion criteria, as anyone who died very soon after enrollment (including those who initiated ART) was excluded, thereby artificially reducing early mortality in North America. Higher mortality soon after ART has been well described and attributed to late ART initiation and is largely caused by AIDS-defining conditions preventable with ART [39–42]. Failures in earlier HIV testing and/or linkage to care to commence ART represent a clear opportunity for intervention. Unfortunately, cause of death was not available in our dataset for most settings, but studies that have analyzed causes of death patterns report that, for both AIDS and non-AIDS defining causes of death, rates are lower in WLWH in Europe than in North America [10].
These analyses have been performed in the largest and most globally representative sample assembled to date of WLWH. Data from 56 countries in seven multisite cohort collaborations have been harmonized to reach a final sample of nearly 200 000 women initiating ART and under follow-up. Inevitably, selection and information biases were likely to be present, and multiple strategies were used to minimize their effects. Stringent inclusion criteria were required leading to the exclusion of Asia Pacific cohort, Central Africa and some countries within Central and South America [14–19]. Under-ascertainment of mortality at clinical sites in East and West Africa were partially corrected by a modification of Brinkhof and colleagues’ approach [21,22,43,44]. However, under-reporting is likely to be time-sensitive in sites in sub-Saharan Africa and is also likely to increase overtime.
Sensitivity analyses to account for potential selection biases derived from lack of cross-checks with mortality registries in some of the European cohorts, and of differential data availability to characterize losses to follow-up were also performed. Unfortunately, having missing data was inevitable in such an ambitious data collection and harmonization exercise. For example, information on CD4+ cell count and HIV-RNA viral load was missing for a large proportion of the women from lower income settings and reveals the lack of availability of clinical monitoring tools in those regions. Type of ART regimen was not available from all sites, and given that the study period started in 2000, we assumed all the women to be on at least three antiretroviral drugs. Although mortality of women living with HIV in Europe may be under-ascertained, this was assessed through sensitivity analyses that excluded cohorts that did not perform cross-checks with mortality registries and/or reported incomplete or poor death ascertainment, and the main findings did not significantly change. A recent publication highlights that European cohort participants were generally representative of the national HIV-diagnosed population reported by surveillance systems, but that PWID, migrants, persons with low CD4+ cell counts and those over 55 years of age are generally under-represented in European cohorts [45]. Finally, as of today, national ART guidelines have expanded in most settings to ’Treat All’ patients with HIV, regardless of CD4+ cell count or clinical stage, as recommended by WHO in 2015. Although we have controlled for baseline AIDS status and CD4+ cell count, it is possible that differences in ART guidelines between regions, which in part determine who initiates ART, could explain some of the differences observed.
The global health inequalities highlighted in this study pertain to women who have accessed health services and have started ART, so they are likely to underestimate overall gaps for women living with HIV, particularly those not yet diagnosed or linked to care. Voluntary antenatal HIV testing, widely implemented in most countries included in these analyses, has been a major step forward in increasing access to health services, but requires expansion and improvement. The data presented can support the development of context-specific interventions to help countries reach their 2020 targets and improve the life expectancies of HIV-positive women at the global level.
Acknowledgements
∗The ‘Differences in all-cause mortality after ART initiation in HIV-positive women from Europe, Sub-Saharan Africa and the Americas’ Project Working Group for The IeDEA and COHERE in EuroCoord Cohort Collaboration.
Project writing committee working group: Inma Jarrín (CASCADE, COHERE), David B. Hanna (IeDEA-CA), Denis Nash (IeDEA-CA), Constantin T. Yiannoutsos (IeDEA-EA), Kholoud Porter (CASCADE, COHERE), Morna Cornell (IeDEA-SA), Francois Dabis (IeDEA-WA, COHERE), Beverly Musick (IeDEA-EA), Andrew Phillips (COHERE), Amanda Mocroft (EuroSIDA, COHERE), Antoine Jaquet (IeDEA-WA), Peter Rebeiro (CCASAnet), Paula Luz (CCASAnet), Michelle Giles (IeDEA Asia-Pacific), Annette Sohn (IeDEA Asia-Pacific), Keri Althoff (NA-ACCORD), Richard Moore (NA-ACCORD), Kara Wools-Kaloustian (IeDEA-EA), Matthias Egger (IeDEA-SA, COHERE), Kathryn Anastos (IeDEA-CA), Julia del Amo (CASCADE, COHERE).
Data coordinating centers: COHERE Regional Coordinating Centres (RCC), IeDEA data coordination; Bordeaux RCC: Diana Barger, Christine Schwimmer, Monique Termote, Linda Wittkop; Copenhagen RCC: Maria Campbell, Casper M. Frederiksen, Nina Friis-Møller, Jesper Kjaer, Dorthe Raben, Rikke Salbøl Brandt. IeDEA: Don Hoover and Qiuhu Shi.
COHERE
Steering Committee - Contributing Cohorts: Ali Judd (AALPHI), Robert Zangerle (AHIVCOS),Giota Touloumi (AMACS), Josiane Warszawski (ANRS CO1 EPF/ANRS CO11 OBSERVATOIRE EPF), Laurence Meyer (ANRS CO2 SEROCO), François Dabis (ANRS CO3 AQUITAINE), Murielle Mary Krause (ANRS CO4 FHDH), Jade Ghosn (ANRS CO6 PRIMO), Catherine Leport (ANRS CO8 COPILOTE), Linda Wittkop (ANRS CO13 HEPAVIH), Peter Reiss (ATHENA), Ferdinand Wit (ATHENA), Maria Prins (CASCADE), Heiner Bucher (CASCADE), Diana Gibb (CHIPS), Gerd Fätkenheuer (Cologne-Bonn), Julia Del Amo (CoRIS), Niels Obel (Danish HIV Cohort), Claire Thorne (ECS, NSHPC), Amanda Mocroft (EuroSIDA), Ole Kirk (EuroSIDA), Christoph Stephan (Frankfurt), Santiago Pérez-Hoyos (GEMES-Haemo), Osamah Hamouda (German ClinSurv), Barbara Bartmeyer (German ClinSurv), Nikoloz Chkhartishvili (Georgian National HIV/AIDS), Antoni Noguera-Julian (CORISPE-cat), Andrea Antinori (ICC), Antonella d’Arminio Monforte (ICONA), Norbert Brockmeyer (KOMPNET), Luis Prieto (Madrid PMTCT Cohort), Pablo Rojo Conejo (CORISPES-Madrid), Antoni Soriano-Arandes (NENEXP), Manuel Battegay (SHCS), Roger Kouyos (SHCS), Cristina Mussini (Modena Cohort), Jordi Casabona (PISCIS), Jose M. Miró (PISCIS), Antonella Castagna (San Raffaele), Deborah_Konopnick (St. Pierre Cohort), Tessa Goetghebuer (St Pierre Paediatric Cohort), Anders Sönnerborg (Swedish InfCare), Carlo Torti (The Italian Master Cohort), Caroline Sabin (UK CHIC), Ramon Teira (VACH), Myriam Garrido (VACH). David Haerry (European AIDS Treatment Group).
Executive Committee: Stéphane de Wit (Chair, St. Pierre University Hospital), Jose Mª Miró (PISCIS), Dominique Costagliola (FHDH), Antonella d’Arminio-Monforte (ICONA), Antonella Castagna (San Raffaele), Julia del Amo (CoRIS), Amanda Mocroft (EuroSida), Dorthe Raben (Head, Copenhagen Regional Coordinating Centre), Geneviève Chêne (Head, Bordeaux Regional Coordinating Centre). Paediatric Cohort Representatives: Ali Judd, Pablo Rojo Conejo.
Regional Coordinating Centres: Bordeaux RCC: Diana Barger, Christine Schwimmer, Monique Termote, Linda Wittkop; Copenhagen RCC: Casper M. Frederiksen, Dorthe Raben, Rikke Salbøl Brandt.
Project Leads and Statisticians: Juan Berenguer, Julia Bohlius, Vincent Bouteloup, Heiner Bucher, Alessandro Cozzi-Lepri, François Dabis, Antonella d’Arminio Monforte, Mary-Anne Davies, Julia del Amo, Maria Dorrucci, David Dunn, Matthias Egger, Hansjakob Furrer, Marguerite Guiguet, Sophie Grabar, Ali Judd, Ole Kirk, Olivier Lambotte, Valériane Leroy, Sara Lodi, Sophie Matheron, Laurence Meyer, Jose Mª Miró, Amanda Mocroft, Susana Monge, Fumiyo Nakagawa, Roger Paredes, Andrew Phillips, Massimo Puoti, Eliane Rohner, Michael Schomaker, Colette Smit, Jonathan Sterne, Rodolphe Thiebaut, Claire Thorne, Carlo Torti, Marc van der Valk, Linda Wittkop.
Funding: The COHERE study group has received unrestricted funding from: Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (ANRS), France; HIV Monitoring Foundation, The Netherlands; and the Augustinus Foundation, Denmark. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under EuroCoord grant agreement n° 260694. A list of the funders of the participating cohorts can be found at www.COHERE.org.
IeDEA-SA Steering Group
Matthias Egger, Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland; Mary-Ann Davies, Centre for Infectious Disease Epidemiology and Research (CIDER), University of Cape Town, South Africa; Gary Maartens, Aid for AIDS, Cape Town, South Africa; Carolyn Bolton and Michael Vinikoor, Centre for Infectious Disease Research (CIDRZ), Lusaka, Zambia; Monique van Lettow, Dignitas International, Lusaka, Zambia; Robin Wood, Gugulethu (Desmond Tutu HIV Foundation), Cape Town, South Africa; Nosisa Sipambo, Harriet Shezi Clinic, Johannesburg, South Africa; Frank Tanser, Hlabisa (Africa Health Research Institute), Cape Town, South Africa; Andrew Boulle, Khayelitsha ART Programme, Cape Town, South Africa; Geoffrey Fatti, Kheth’Impilo, Cape Town, South Africa; Sam Phiri, Lighthouse Trust, Lilongwe, Malawi; Cleophas Chimbetete, Newlands Clinic, Harare, Zimbabwe; Karl Technau, Rahima Moosa Mother and Child Hospital, Johannesburg, South Africa; Brian Eley, Red Cross Hospital, Cape Town, South Africa, Cape Town, South Africa; Josephine Muhairwe, SolidarMed Lesotho, Maseru, Lesotho; Juan Burgos-Soto, SolidarMed Mozambique, Cabo Delgado, Mozambique; Cordelia Kunzekwenyika, SolidarMed Zimbabwe, Masvingo, Zimbabwe; Matthew Fox, Themba Lethu Clinic, Johannesburg, South Africa; Hans Prozesky, Tygerberg Academic Hospital, Stellenbosch, South Africa.
Funding: Research reported in this publication was supported by the National Institute of Allergy And Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD), National Institute On Drug Abuse (NIDA), National Cancer Institute (NCI), and the National Institute of Mental Health (NIMH), in accordance with the regulatory requirements of the National Institutes of Health under Award Number U01AI069924 Southern Africa IeDEA Consortium. IeDEA Southern Africa is also supported by special project funding (Grant No. 174281) from the Swiss National Science Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Swiss National Science Foundation.
IeDEA-EA Executive Committee: Lameck Diero [Academic Model Providing Access to Healthcare (AMPATH), Eldoret, Kenya], Elizabeth Bukusi [Family Family AIDS Care & Education Services (FACES), Kisumu, Kenya], John Ssali (Masaka Regional Referral Hospital, Masaka, Uganda), Mwebesa Bosco Bwana [Mbarara University of Science and Technology (MUST), Mbarara, Uganda], Barbara Castelnuovo [Infectious Diseases Institute (IDI), Kampala, Uganda], Fred Nalugoda [Rakai Health Sciences Program (RHSP), Kalisizo, Uganda], Geoffrey Somi [National AIDS Control Program (NACP) Dar es Salaam, Tanzania], and Mark Urassa [National Institute for Medical Research (NIMR), Mwanza, Tanzania], Batya Elul (Columbia University, New York, USA), Jennifer Syvertsen (University of California Riverside, California, USA) Rami Kantor (Brown University, Providence, USA), Jeff Martin (University of California, San Francisco, USA), Craig Cohen (University of California, San Fransisco, USA), Paula Braitstein (University of Toronto, Toronto, Canada) East African IeDEA Regional Data Center, Indiana University: Kara Wools-Kaloustian, Constantin Yiannoutsos, and Beverly Musick.
Funding: Research reported in this publication was supported by the National Institute Of Allergy And Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD), National Institute On Drug Abuse (NIDA), National Cancer Institute (NCI), and the National Institute of Mental Health (NIMH), in accordance with the regulatory requirements of the National Institutes of Health under Award Number U01AI069911 East Africa IeDEA Consortium. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
IeDEA-WA Steering Group
Site investigators and cohorts: Adult cohorts: Marcel Djimon Zannou, CNHU, Cotonou, Benin; Armel Poda, CHU Souro Sanou, Bobo Dioulasso, Burkina Faso; Fred Stephen Sarfo and Komfo Anokeye Teaching Hospital, Kumasi, Ghana; Eugene Messou, ACONDA CePReF, Abidjan, Cote d’Ivoire; Henri Chenal, CIRBA, Abidjan, Cote d’Ivoire; Kla Albert Minga, CNTS, Abidjan, Cote d’Ivoire; Emmanuel Bissagnene, and Aristophane Tanon, CHU Treichville, Cote d’Ivoire; Moussa Seydi, CHU de Fann, Dakar, Senegal; Akessiwe Akouda Patassi, CHU Sylvanus Olympio, Lomé, Togo. Pediatric cohorts: Sikiratou Adouni Koumakpai-Adeothy,_CNHU, Cotonou, Benin; Lorna Awo Renner, Korle Bu Hospital, Accra, Ghana; Sylvie Marie N’Gbeche, ACONDA CePReF, Abidjan, Ivory Coast; Clarisse Amani Bosse, ACONDA_MTCT+, Abidjan, Ivory Coast; Kouadio Kouakou, CIRBA, Abidjan, Cote d’Ivoire; Madeleine Amorissani Folquet, CHU de Cocody, Abidjan, Cote d’Ivoire; François Tanoh Eboua, CHU de Yopougon, Abidjan, Cote d’Ivoire; Fatoumata Dicko Traore, Hopital Gabriel Toure, Bamako, Mali; Elom Takassi, CHU Sylvanus Olympio, Lomé,Togo; Coordinators and data centers: François Dabis, Elise Arrive, Eric Balestre, Renaud Becquet, Charlotte Bernard, Shino Chassagne Arikawa, Alexandra Doring, Antoine Jaquet, Karen Malateste, Elodie Rabourdin, Thierry Tiendrebeogo, ADERA, Isped & INSERM U1219, Bordeaux, France. Sophie Desmonde, Julie Jesson, Valeriane Leroy, Inserm 1027, Toulouse, France. Didier Koumavi Ekouevi, Jean-Claude Azani, Patrick Coffie, Abdoulaye Cissé, Guy Gnepa, Apollinaire Horo, Christian Kouadio, Boris Tchounga, PACCI, CHU Treichville, Abidjan, Côte d’Ivoire.
Funding: The IeDEA West Africa collaboration was supported by the National Institute of Mental Health (NIMH), National Cancer Institute (NCI), the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), and the National Institute of Allergy and Infectious Diseases (NIAID) of the U.S. National Institutes of Health (NIH) under Award Number U01AI069919. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
IeDEA-CA Steering Group
Nimbona Pélagie, ANSS, Burundi; Patrick Gateretse, Jeanine Munezero, Valentin Nitereka, Théodore Niyongabo, Christelle Twizere, Centre National de Reference en Matiere de VIH/SIDA, Burundi; Hélène Bukuru, Thierry Nahimana, CHUK, Burundi; Jérémie Biziragusenyuka, Risase Scholastique Manyundo, HPRC, Burundi; Tabeyang Mbuh, Kinge Thompson Njie, Edmond Tchassem, Kien-Atsu Tsi, Bamenda Hospital, Cameroon; Rogers Ajeh, Mark Benwi, Anastase Dzudie, Akindeh Mbuh, Marc Lionel Ngamani, Victorine Nkome, CRENC & Douala General Hospital, Cameroon; Djenabou Amadou, Eric Ngassam, Eric Walter Pefura Yone, Jamot Hospital, Cameroon; Alice Ndelle Ewanoge, Norbert Fuhngwa, Chris Moki, Denis Nsame Nforniwe, Limbe Regional Hospital, Cameroon; Catherine Akele, Faustin Kitetele, Patricia Lelo, Martine Tabala, Kalembelembe Pediatric Hospital, Democratic Republic of Congo; Emile Wemakoy Okitolonda, Landry Wenzi, Kinshasa School of Public Health, Democratic Republic of Congo; Merlin Diafouka, Martin Herbas Ekat, Dominique Mahambou Nsonde, CTA Brazzaville, Republic of Congo; Adolphe Mafou, CTA Pointe-Noire, Republic of Congo; Fidele Ntarambirwa, Bethsaida Hospital, Rwanda; Yvonne Tuyishimire, Busanza Health Center, Rwanda; Theogene Hakizimana, Gahanga Health Center, Rwanda; Josephine Ayinkamiye, Gikondo Health Center, Rwanda; Sandrine Mukantwali, Kabuga Health Center, Rwanda; Henriette Kayitesi, Olive Uwamahoro, Kicukiro Health Center, Rwanda; Viateur Habumuremyi, Jules Ndumuhire, Masaka Health Center, Rwanda; Joyce Mukamana, Yvette Ndoli, Oliver Uwamahoro, Nyarugunga Health Center, Rwanda; Gallican Kubwimana, Pacifique Mugenzi, Benjamin Muhoza, Athanase Munyaneza, Emmanuel Ndahiro, Diane Nyiransabimana, Jean d’Amour Sinayobye, Vincent Sugira, Rwanda Military Hospital, Rwanda; Chantal Benekigeri, Gilbert Mbaraga, WE-ACTx Health Center, Rwanda.
Coordinating and Data Centers:
Adebola Adedimeji, Kathryn Anastos, Madeline Dilorenzo, Lynn Murchison, Jonathan Ross, Albert Einstein College of Medicine, USA; Diane Addison, Margaret Baker, Ellen Brazier, Heidi Jones, Elizabeth Kelvin, Sarah Kulkarni, Grace Liu, Denis Nash, Matthew Romo, Olga Tymejczyk, Institute for Implementation Science in Population Health, Graduate School of Public Health and Health Policy, City University of New York (CUNY), USA; Batya Elul, Columbia University, USA; Xiatao Cai, Don Hoover, Hae-Young Kim, Chunshan Li, Qiuhu Shi, Data Solutions, USA; Robert Agler, Kathryn Lancaster, Marcel Yotebieng, Ohio State University, USA; Mark Kuniholm, University at Albany, State University of New York, USA; Andrew Edmonds, Angela Parcesepe, University of North Carolina at Chapel Hill, USA; Olivia Keiser, University of Geneva; Stephany Duda; Vanderbilt University School of Medicine, USA; April Kimmel, Virginia Commonwealth University School of Medicine, USA; Margaret McNairy, Weill Cornell Medical Center.
Funding: National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number U01AI096299 (PI: Anastos and Nash).
IeDEA-Asia Pacific Steering Group
P.S. Ly (TAHOD Steering Committee member) and V. Khol, National Center for HIV/AIDS, Dermatology & STDs, Phnom Penh, Cambodia; F.J. Zhang (TAHOD Steering Committee member), H.X. Zhao and N. Han, Beijing Ditan Hospital, Capital Medical University, Beijing, China; M.P. Lee (TAHOD Steering Committee member), P.C.K. Li, W. Lam and Y.T. Chan, Queen Elizabeth Hospital, Hong Kong, China; N. Kumarasamy (TAHOD Steering Committee member; co-Chair), S. Saghayam and C. Ezhilarasi, Chennai Antiviral Research and Treatment Clinical Research Site (CART CRS), YRGCARE Medical Centre, VHS, Chennai, India; S. Pujari (TAHOD Steering Committee member), K. Joshi, S. Gaikwad and A. Chitalikar, Institute of Infectious Diseases, Pune, India; T.P. Merati (TAHOD Steering Committee member), D.N. Wirawan and F. Yuliana, Faculty of Medicine Udayana University & Sanglah Hospital, Bali, Indonesia; E. Yunihastuti (TAHOD Steering Committee member), D. Imran and A. Widhani, Faculty of Medicine Universitas Indonesia - Dr Cipto Mangunkusumo General Hospital, Jakarta, Indonesia; J. Tanuma (TAHOD Steering Committee member), S Oka and T Nishijima, National Center for Global Health and Medicine, Tokyo, Japan; J.Y. Choi (TAHOD Steering Committee member), S. Na and J.H. Kim, Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea; B.L.H. Sim (TAHOD Steering Committee member), Y.M. Gani, and R. David, Hospital Sungai Buloh, Sungai Buloh, Malaysia; A. Kamarulzaman (TAHOD Steering Committee member), S.F. Syed Omar, S. Ponnampalavanar and I. Azwa, University Malaya Medical Centre, Kuala Lumpur, Malaysia; R. Ditangco (TAHOD Steering Committee member), M. Pasayan and R. Bantique, Research Institute for Tropical Medicine, Manila, Philippines; Y.J. Chan (TAHOD Steering Committee member), W.W. Ku and P.C. Wu, Taipei Veterans General Hospital, Taipei, Taiwan; O.T. Ng (TAHOD Steering Committee member; Steering Committee Chair), P.L. Lim, L.S. Lee and Z. Ferdous, Tan Tock Seng Hospital, Singapore; A. Avihingsanon (TAHOD Steering Committee member), S. Gatechompol, P. Phanuphak and C. Phadungphon, HIV-NAT/Thai Red Cross AIDS Research Centre, Bangkok, Thailand; S. Kiertiburanakul (TAHOD Steering Committee member), A. Phuphuakrat, L. Chumla and N. Sanmeema, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; R. Chaiwarith (TAHOD Steering Committee member), T. Sirisanthana, W. Kotarathititum and J. Praparattanapan, Research Institute for Health Sciences, Chiang Mai, Thailand; S. Khusuwan (TAHOD Steering Committee member) and P. Kambua, Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand; K.V. Nguyen (TAHOD Steering Committee member), H.V. Bui, D.T.H. Nguyen and D.T. Nguyen, National Hospital for Tropical Diseases, Hanoi, Vietnam; D.D. Cuong (TAHOD Steering Committee member), N.V. An and N.T. Luan, Bach Mai Hospital, Hanoi, Vietnam; A.H. Sohn (TAHOD Steering Committee member), J.L. Ross (TAHOD Steering Committee member) and B. Petersen, TREAT Asia, amfAR - The Foundation for AIDS Research, Bangkok, Thailand; M.G. Law (TAHOD Steering Committee member), A. Jiamsakul (TAHOD Steering Committee member) and R. Bijker, The Kirby Institute, UNSW Australia, Sydney, Australia.
The TREAT Asia HIV Observational Database is an initiative of TREAT Asia, a program of amfAR, The Foundation for AIDS Research, with support from the US National Institutes of Health's National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Cancer Institute, the National Institute of Mental Health, and the National Institute on Drug Abuse, as part of the International Epidemiology Databases to Evaluate AIDS (IeDEA; U01AI069907). The Kirby Institute is funded by the Australian Government Department of Health and Ageing, and is affiliated with the Faculty of Medicine, UNSW Sydney. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of any of the governments or institutions mentioned above.
IeDEA Caribbean, Central, and South America (CCASAnet) Steering Group
Fundación Huésped, Argentina: Pedro Cahn, Carina Cesar, Valeria Fink, Omar Sued, Emanuel Dell’Isola, Hector Perez, Jose Valiente, Cleyton Yamamoto. Instituto Nacional de Infectologia-Fiocruz, Brazil: Beatriz Grinsztejn, Valdilea Veloso, Paula Luz, Raquel de Boni, Sandra Cardoso Wagner, Ruth Friedman, Ronaldo Moreira. Universidade Federal de Minas Gerais, Brazil: Jorge Pinto, Flavia Ferreira, Marcelle Maia. Universidade Federal de São Paulo, Brazil: Regina Célia de Menezes Succi, Daisy Maria Machado, Aida de Fátima Barbosa Gouvêa. Fundación Arriarán, Chile: Marcelo Wolff, Claudia Cortes, Maria Fernanda Rodriguez, Gladys Allendes. Les Centres GHESKIO, Haiti: Jean William Pape, Vanessa Rouzier, Adias Marcelin, Christian Perodin. Hospital Escuela Universitario, Honduras: Marco Tulio Luque. Instituto Hondureño de Seguridad Social, Honduras: Denis Padgett. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico: Juan Sierra Madero, Brenda Crabtree Ramirez, Paco Belaunzaran, Yanink Caro Vega. Instituto de Medicina Tropical Alexander von Humboldt, Peru: Eduardo Gotuzzo, Fernando Mejia, Gabriela Carriquiry. Vanderbilt University Medical Center, USA: Catherine C McGowan, Bryan E Shepherd, Timothy Sterling, Karu Jayathilake, Anna K Person, Peter F Rebeiro, Jessica Castilho, Stephany N Duda, Fernanda Maruri, Hilary Vansell, Cathy Jenkins, Ahra Kim, Sarah Lotspeich.
Funding: IeDEA CCASAnet: This work was supported by the NIH-funded Caribbean, Central and South America network for HIV epidemiology (CCASAnet), a member cohort of the International Epidemiologic Databases to Evaluate AIDS (leDEA) (U01AI069923). This award is funded by the following institutes: Eunice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD), Office Of The Director, National Institutes Of Health (OD), National Institute Of Allergy And Infectious Diseases (NIAID), National Cancer Institute (NCI), and the National Institute Of Mental Health (NIMH). Peter Rebeiro is supported by K01AI131895, ‘The HIV Care Continuum and Health Policy: Changes Through Context and Geography’ Paula Luz is supported by funding from the National Council of Technological and Scientific Development (CNPq) and the Research Funding Agency of the State of Rio de Janeiro (FAPERJ).
NA-ACCORD Steering Group
Executive Committee: Richard D. Moore, Michael S. Saag, Stephen J. Gange, Mari M. Kitahata, Keri N. Althoff, Michael A. Horberg, Marina B. Klein, Rosemary G. McKaig and Aimee M. Freeman Data Management Core: Mari M. Kitahata, Stephen E. Van Rompaey, Heidi M. Crane, Daniel R. Drozd, Liz Morton, Justin McReynolds and William B. Lober.
Epidemiology and Biostatistics Core: Stephen J. Gange, Keri N. Althoff, Jennifer S. Lee, Bin You, Brenna Hogan, Jinbing Zhang, Jerry Jing, Elizabeth Humes, and Sally Coburn. AIDS Clinical Trials Group Longitudinal Linked Randomized Trials: Constance A. Benson and Ronald J. Bosch. AIDS Link to the IntraVenous Experience: Gregory D. Kirk. Fenway Health HIV Cohort: Kenneth H. Mayer and Chris Grasso. HAART Observational Medical Evaluation and Research: Robert S. Hogg, P. Richard Harrigan, Julio SG Montaner, Benita Yip, Julia Zhu, Kate Salters and Karyn Gabler. HIV Outpatient Study: Kate Buchacz and Jun Li. HIV Research Network: Kelly A. Gebo and Richard D. Moore. Johns Hopkins HIV Clinical Cohort: Richard D. Moore. John T. Carey Special Immunology Unit Patient Care and Research Database, Case Western Reserve University: Benigno Rodriguez. Kaiser Permanente Mid-Atlantic States: Michael A. Horberg. Kaiser Permanente Northern California: Michael J. Silverberg.
Longitudinal Study of Ocular Complications of AIDS: Jennifer E. Thorne. Multicenter Hemophilia Cohort Study–II: Charles Rabkin. Multicenter AIDS Cohort Study: Joseph B. Margolick, Lisa P. Jacobson and Gypsyamber D'Souza. Montreal Chest Institute Immunodeficiency Service Cohort: Marina B. Klein. Ontario HIV Treatment Network Cohort Study: Abigail Kroch, Ann Burchell, Adrian Betts and Joanne Lindsay. Retrovirus Research Center, Bayamon Puerto Rico: Robert F. Hunter-Mellado and Angel M. Mayor. Southern Alberta Clinic Cohort: M. John Gill. Study of the Consequences of the Protease Inhibitor Era: Steven G. Deeks and Jeffrey N. Martin. Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy: Jun Li and John T. Brooks.
University of Alabama at Birmingham 1917 Clinic Cohort: Michael S. Saag, Michael J. Mugavero and James Willig. University of California at San Diego: William C. Mathews. University of North Carolina at Chapel Hill HIV Clinic Cohort: Joseph J. Eron and Sonia Napravnik. University of Washington HIV Cohort: Mari M. Kitahata, Heidi M. Crane and Daniel R. Drozd. Vanderbilt Comprehensive Care Clinic HIV Cohort: Timothy R. Sterling, David Haas, Peter Rebeiro and Megan Turner. Veterans Aging Cohort Study: Amy C. Justice, Robert Dubrow, and David Fiellin. Women's Interagency HIV Study: Stephen J. Gange and Kathryn Anastos.
Funding: This work was supported by National Institutes of Health grants U01AI069918, F31AI124794, F31DA037788,G12MD007583,1AI093197, K01AI131895, K23EY01370, K24AI065298, K24AI118591, K24DA000432, KL2TR000421,M01RR000052,N01CP01004,N02CP055504, N02CP91027, P30AI027757, P30AI027763, P30AI027767, P30AI036219, P30AI050410, P30AI094189, P30AI110527, P30MH62246, R01AA016893, R01CA165937, R01DA011602, R01DA012568, R01 AG053100, R24AI067039, U01AA013566, U01AA020790, U01AI031834, U01AI034989, U01AI034993, U01AI034994, U01AI035004, U01AI035039,U01AI035040, U01AI035041, U01AI035042, U01AI037613, U01AI037984, U01AI038855, U01AI038858, U01AI042590, U01AI068634, U01AI068636, U01AI069432, U01AI069434, U01AI103390, U01AI103397, U01AI103401, U01AI103408, U01DA03629, U01DA036935, U01HD032632, U10EY008057, U10EY008052, U10EY008067, U24AA020794,U54MD007587, UL1RR024131, UL1TR000004, UL1TR000083, UL1TR000454, UM1AI035043, Z01CP010214 and Z01CP010176; contracts CDC-200-2006-18797 and CDC-200-2015-63931 from the Centers for Disease Control and Prevention, USA; contract 90047713 from the Agency for Healthcare Research and Quality, USA; contract 90051652 from the Health Resources and Services Administration, USA; grants CBR-86906, CBR-94036, HCP-97105 and TGF-96118 from the Canadian Institutes of Health Research, Canada; Ontario Ministry of Health and Long Term Care; and the Government of Alberta, Canada. Additional support was provided by the National Cancer Institute, National Institute for Mental Health and National Institute on Drug Abuse.
Conflicts of interest
There are no conflicts of interest.
