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AbstractIntroductionImmune reconstitution following antiretroviral therapy (ART) initiation is crucial to prevent AIDS and non‐AIDS‐related comorbidities. Patients with suppressed viraemia who fail to restore cellular immunity are exposed to an increased risk of morbidity and mortality during long‐term follow‐up, although the underlying mechanisms remain poorly understood. We aim to describe clinical outcomes and factors associated with the worse immune recovery and all‐cause mortality in people living with HIV (PLWH) from Latin America following ART initiation.MethodsRetrospective cohort study using the CCASAnet database: PLWH ≥18 years of age at ART initiation using a three drug‐based combination therapy and with medical follow‐up for ≥24 months after ART initiation and undetectable viral load were included. Patients were divided into four immune recovery groups based on rounded quartiles of increase in CD4 T‐cell count at 2 years of treatment (<150, [150, 250), [250, 350] and >350 cells/mm3). Primary outcomes included all‐cause mortality, AIDS‐defining events and non‐communicable diseases that occurred >2 years after ART initiation. Factors associated with an increase in CD4 T‐cell count at 2 years of treatment were evaluated using a cumulative probability model with a logit link.ResultsIn our cohort of 4496 Latin American PLWH, we found that patients with the lowest CD4 increase (<150) had the lowest survival probability at 10 years of follow‐up. Lower increase in CD4 count following therapy initiation (and remarkably not a lower baseline CD4 T‐cell count) and older age were risk factors for all‐cause mortality. We also found that older age, male sex and higher baseline CD4 T‐cell count were associated with lower CD4 count increase following therapy initiation.ConclusionsOur study shows that PLWH with lower increases in CD4 count have lower survival probabilities. CD4 increase during follow‐up might be a better predictor of mortality in undetectable PLWH than baseline CD4 count. Therefore, it should be included as a routine clinical variable to assess immune recovery and overall survival.

AbstractIntroductionThe "greying" of the HIV epidemic necessitates a better understanding of the healthcare needs of older HIV‐positive adults. As these individuals age, it is unclear whether comorbidities and their associated therapies or the ageing process itself alter the response to antiretroviral therapy (ART). In this study, HIV treatment outcomes and corresponding risk factors were compared between older ART initiators and those who were younger using data from the Caribbean, Central and South America Network for HIV Epidemiology (CCASAnet).MethodsHIV‐positive adults (≥18 years) initiating ART at nine sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru were included. Patients were classified as older (≥50 years) or younger (<50 years) based on age at ART initiation. ART effectiveness was measured using three outcomes: death, virologic failure and ART treatment modification. Cox regression models for each outcome compared risk between older and younger patients, adjusting for other covariates.ResultsAmong 26,311 patients initiating ART between 1996 and 2016, 3389 (13%) were ≥50 years. The majority of patients in both ≥50 and <50 age groups received a non‐nucleoside reverse transcriptase inhibitor‐based regimen (89% vs. 87%), did not have AIDS at baseline (63% vs. 62%), and were male (59% vs. 58%). Older patients had a higher risk of death (adjusted hazard ratio (aHR) 1.64; 95% confidence intervals (CI): 1.48 to 1.83) and a lower risk of virologic failure (aHR: 0.73; 95% CI: 0.63 to 0.84). There was no difference in risk of ART modification (aHR: 1.00; 95% CI: 0.94 to 1.06). Risk factors for death, virologic failure and treatment modification were similar for each group.ConclusionsOlder age at ART initiation was associated with increased mortality and decreased risk of virologic failure in our cohort of more than 26,000 ART initiators in Latin America and the Caribbean. To the best of our knowledge this is the first study from the region to evaluate ART outcomes in this growing and important population. Given the complexity of issues related to ageing with HIV, a greater understanding is needed in order to properly respond to this shifting epidemic.

Background: Having 90% of patients on antiretroviral therapy (ART) and achieving an undetectable viral load (VL) is 1 of the 90: 90: 90 by 2020 targets. In this global analysis, we investigated the proportions of adult and paediatric patients with VL suppression in the first 3 years after ART initiation. Methods: Patients from the IeDEA cohorts who initiated ART between 2010 and 2014 were included. Proportions with VL suppression (<1000 copies/ mL) were estimated using (1) strict intention to treat (ITT)-loss to follow-up (LTFU) and dead patients counted as having detectable VL; and (2) modified ITT-LTFU and dead patients were excluded. Logistic regression was used to identify predictors of viral suppression at 1 year after ART initiation using modified ITT. Results: A total of 35,561 adults from 38 sites/16 countries and 2601 children from 18 sites/6 countries were included. When comparing strict with modified ITT methods, the proportion achieving VL suppression at 3 years from ART initiation changed from 45.1% to 90.2% in adults, and 60.6% to 80.4% in children. In adults, older age, higher CD4 count preART, and homosexual/bisexual HIV exposure were associated with VL suppression. In children, older age and higher CD4 percentage pre-ART showed significant associations with VL suppression. Conclusions: Large increases in the proportion of VL suppression in adults were observed when we excluded those who were LTFU or had died. The increases were less pronounced in children. Greater emphasis should be made to minimize LTFU and maximize patient retention in HIV-infected patients of all age groups. ; U.S. National Institutes of Health's National Institute of Allergy and Infectious Diseases ; Eunice Kennedy Shriver National Institute of Child Health and Human Development ; National Cancer Institute ; Centers for Disease Control and Prevention, USA ; Agency for Healthcare Research and Quality, USA ; Health Resources and Services Administration, USA ; Canadian Institutes of Health Research, Canada ; Ontario Ministry of Health and Long Term Care ; Government of Alberta, Canada ; Intramural Research Program of the National Cancer Institute ; Australian Government Department of Health and Ageing ; UNSW, Kirby Inst, Sydney, NSW 2052, Australia ; Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA ; Fdn Huesped, Buenos Aires, DF, Argentina ; Univ Chile, Sch Med, Santiago, Chile ; Fdn Arriaran, Santiago, Chile ; Univ Cape Town, Sch Publ Hlth & Family Med, Cape Town, South Africa ; Childrens Hosp 2, Ho Chi Minh City, Vietnam ; Univ Cape Town, Dept Paediat & Child Hlth, Cape Town, South Africa ; Univ Calgary, Calgary, AB, Canada ; YRGCARE Med Ctr, Madras, Tamil Nadu, India ; Univ Fed Sao Paulo, Pediat Infect Dis Div, Escola Paulista Med, Sao Paulo, Brazil ; Johns Hopkins Univ, Dept Med, Div Infect Dis, Baltimore, MD USA ; Univ Stellenbosch, Dept Med, Div Infect Dis, Cape Town, South Africa ; Tygerberg Hosp, Cape Town, South Africa ; Univ Bern, Inst Social & Prevent Med, Bern, Switzerland ; Univ Fed Sao Paulo, Pediat Infect Dis Div, Escola Paulista Med, Sao Paulo, Brazil ; NCI: U01AI035004 ; NCI: U01AI035039 ; NCI: U01AI035040 ; NCI: U01AI035041 ; NCI: U01AI035042 ; NCI: U01AI037613 ; NCI: U01AI037984 ; NCI: U01AI038855 ; NCI: U01AI038858 ; NCI: U01AI042590 ; NCI: U01AI068634 ; NCI: U01AI068636 ; NCI: U01AI069432 ; NCI: U01AI069434 ; Centers for Disease Control and Prevention, USA: CDC-200-2006-18797 ; Centers for Disease Control and Prevention, USA: CDC-200-2015-63931 ; Agency for Healthcare Research and Quality, USA: 90047713 ; Health Resources and Services Administration, USA: 90051652 ; Canadian Institutes of Health Research, Canada: CBR-86906 ; Canadian Institutes of Health Research, Canada: CBR-94036 ; Canadian Institutes of Health Research, Canada: HCP-97105 ; Canadian Institutes of Health Research, Canada: TGF-96118 ; NCI: P30AI027757 ; NCI: P30AI027763 ; NCI: P30AI027767 ; NCI: P30AI036219 ; NCI: P30AI050410 ; NCI: P30AI094189 ; NCI: P30AI110527 ; NCI: P30MH62246 ; NCI: R01AA016893 ; NCI: R01CA165937 ; NCI: R01DA004334 ; NCI: R01DA011602 ; NCI: R01DA012568 ; NCI: R24AI067039 ; NCI: U01AA013566 ; NCI: U01AA020790 ; NCI: U01AI1031834 ; NCI: U01AI034989 ; NCI: U01AI034993 ; NCI: U01AI034994 ; NCI: M01RR000052 ; NCI: U54MD007587 ; NCI: UL1RR024131 ; NCI: UL1TR000004 ; NCI: UL1TR000083 ; NCI: UL1TR000454 ; NCI: UM1AI035043 ; NCI: Z01CP010214 ; NCI: Z01CP010176 ; NCI: U01AI069907 ; NCI: U01AI069923 ; NCI: U01AI069924 ; NCI: U01AI069918 ; NCI: F31DA037788 ; NCI: G12MD007583 ; NCI: K01A1093197 ; NCI: K23EY013707 ; NCI: K24DA000432 ; NCI: K24AI065298 ; NCI: KL2TR000421 ; NCI: N02CP055504 ; NCI: U01AI103390 ; NCI: U01AI103397 ; NCI: U01AI103401 ; NCI: U01AI103408 ; NCI: U01DA036935 ; NCI: U01HD032632 ; NCI: U10EY008057 ; NCI: U10EY008052 ; NCI: U10EY008067 ; NCI: U24AA020794 ; Web of Science

AbstractIntroductionIn 2013, the World Health Organization (WHO) recommended initiating combination ART (cART) in all adults with HIV and CD4+ lymphocyte counts (CD4) <500 cells/mm3. In 2015, this was updated to recommend cART initiation in all patients with HIV, regardless of CD4 count. Implementation of these guidelines in real‐world settings has not been evaluated in Latin America. To assess changes in time to cART initiation during routine care, we estimated trends in time from enrolment in care to cART initiation in HIV‐positive adults with high CD4 counts in the Caribbean, Central and South America network for HIV Epidemiology (CCASAnet) during 2003 to 2017.MethodsAll cART‐naive individuals ≥18 years of age from 2003 to 2017 with CD4 ≥350 cells/mm3 and without AIDS at enrolment at five CCASAnet sites (Brazil, Chile, Honduras, Mexico and Peru) were included. Patients without information regarding AIDS‐defining events were excluded. We estimated unadjusted median time from enrolment to cART initiation by calendar year using Kaplan‐Meier methods and calculated adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for trends in cART initiation using Cox models and restricted cubic splines for continuous variables, accounting for age, sex, CD4 at enrolment, route of HIV transmission and clinic site.ResultsOf the 3171 patients included, 1,650 (52%) had CD4 ≥500 cells/mm3 at enrolment. Median time to cART initiation after 2013 was 6.21 weeks (interquartile range (IQR): 1.89, 23.21), and 4.71 weeks (IQR: 1.43, 9.57) after 2015. Among 763 (24%) patients who never initiated cART, 33 (4.3%) were reported as deceased, 481 (63%) were lost to follow‐up, and 249 (33%) were administratively censored before initiation. Adjusted probability of cART initiation greatly increased in recent years, in particular after 2013 and 2015 (2013 vs. 2003: HR = 7.14; 95% CI: 5.84 to 8.73, and 2015 vs. 2003: HR = 12.60; 95% CI: 10.37 to 15.32).ConclusionsTime to cART initiation decreased substantially, roughly following changes in WHO guidelines in this real‐world setting in Latin America. However, a very high proportion of patients never started cART, compromising retention in care and survival, as shown by their higher proportion of LTFU and death, which reinforce the notion that earlier treatment implementation strategies are needed.

AbstractIntroductionKaposi's sarcoma (KS) remains the most frequent malignancy in persons living with HIV (PWH) in Latin America. We examined KS trends and outcomes from Latin American clinical sites in the era of increased access to antiretroviral therapy (ART).MethodsCohorts in Brazil, Peru, Mexico, Honduras, Argentina and Chile contributed clinical data of PWH ≥16 years old from 2000 to 2017, excluding patients with KS diagnosed before clinic enrolment. We compared KS incidence over time using multivariable incidence rate ratios. Predictors of KS before/at or after ART initiation and of mortality after KS were examined using Cox regression.ResultsOf 25 981 PWH, 481 had incident KS, including 200 ART‐naïve and 281 ART‐treated patients. From 2000 to 2017, the incidence of KS decreased from 55.1 to 3.0 per 1000 person‐years. In models adjusting for CD4 and other factors, the relative risk for KS decreased from 2000 to 2008. Since 2010, the adjusted risk of KS increased in the periods before and ≤90 days after ART initiation but decreased >90 days after ART. In addition to low CD4 and male‐to‐male sex, KS risk after ART was associated with age and history of other AIDS‐defining illnesses. Mortality after KS (approximately 25% after five years) was not associated with either year of KS diagnosis nor timing of diagnosis relative to ART initiation.ConclusionsKS incidence in Latin America has remained stable in recent years and risk is highest before and shortly after ART initiation. Early diagnosis of HIV and ART initiation remain critical priorities in the region.