The impact of earthquakes in Latin America on the continuity of HIV care: A retrospective observational cohort study.

Objectives: As earthquakes occur frequently in Latin America and can cause significant disruptions in HIV care, we sought to analyze patterns of HIV care for adults at Latin American clinical sites experiencing a significant earthquake within the past two decades. Study design: Retrospective clinical cohort study. Methods: Adults receiving HIV care at sites experiencing at least a "moderate intensity" (Modified Mercalli scale) earthquake in the Caribbean, Central and South America network for HIV epidemiology (CCASAnet) contributed data from 2003 to 2017. Interrupted Time Series models were fit with discontinuities at site-specific earthquake dates (Sept. 16, 2015 in Chile; Apr. 18, 2014 and Sept. 19, 2017 in Mexico; and Aug. 15, 2007 in Peru) to assess clinical visit, CD4 measure, viral load lab, and ART initiation rates 3- and 6-months after versus before earthquakes. Results: Comparing post-to pre-earthquake periods, there was a sharp drop in median visit (incidence rate ratio [IRR] = 0.79, 95% confidence interval [CI]: 0.68-0.91) and viral load lab (IRR = 0.78, 95% CI: 0.62-0.99) rates per week, using a 3-month window. CD4 measurement rates also decreased (IRR = 0.43; 95% CI: 0.37-0.51), though only using a 6-month window. Conclusions: Given that earthquakes occur frequently in Latin America, disaster preparedness plans must be more broadly implemented to avoid disruptions in HIV care and attendant poor outcomes.

Lessons learned from over a decade of data audits in international observational HIV cohorts in Latin America and East Africa.

Introduction: Routine patient care data are increasingly used for biomedical research, but such "secondary use" data have known limitations, including their quality. When leveraging routine care data for observational research, developing audit protocols that can maximize informational return and minimize costs is paramount. Methods: For more than a decade, the Latin America and East Africa regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium have been auditing the observational data drawn from participating human immunodeficiency virus clinics. Since our earliest audits, where external auditors used paper forms to record audit findings from paper medical records, we have streamlined our protocols to obtain more efficient and informative audits that keep up with advancing technology while reducing travel obligations and associated costs. Results: We present five key lessons learned from conducting data audits of secondary-use data from resource-limited settings for more than 10 years and share eight recommendations for other consortia looking to implement data quality initiatives. Conclusion: After completing multiple audit cycles in both the Latin America and East Africa regions of the IeDEA consortium, we have established a rich reference for data quality in our cohorts, as well as large, audited analytical datasets that can be used to answer important clinical questions with confidence. By sharing our audit processes and how they have been adapted over time, we hope that others can develop protocols informed by our lessons learned from more than a decade of experience in these large, diverse cohorts.

Cryptococcal Meningitis and Clinical Outcomes in Persons With Human Immunodeficiency Virus: A Global View.

BACKGROUND: Cryptococcal meningitis (CM) is a major cause of morbidity and mortality in persons with human immunodeficiency virus (HIV; PWH). Little is known about CM outcomes and availability of diagnostic and treatment modalities globally. METHODS: In this retrospective cohort study, we investigated CM incidence and all-cause mortality in PWH in the International Epidemiology Databases to Evaluate AIDS cohort from 1996 to 2017. We estimated incidence using quasi-Poisson models adjusted for sex, age, calendar year, CD4 cell count (CD4), and antiretroviral therapy (ART) status. Mortality after CM diagnosis was examined using multivariable Cox models. A site survey from 2017 assessed availability of CM diagnostic and treatment modalities. RESULTS: Among 518 852 PWH, there were 3857 cases of CM with an estimated incidence of 1.54 per 1000 person-years. Mortality over a median of 2.6 years of post-CM diagnosis follow-up was 31.6%, with 29% lost to follow-up. In total, 2478 (64%) were diagnosed with CM after ART start with a median of 253 days from ART start to CM diagnosis. Older age (hazard [HR], 1.31 for 50 vs 35 years), lower CD4 (HR, 1.15 for 200 vs 350 cells/mm3), and earlier year of CM diagnosis (HR, 0.51 for 2015 vs 2000) were associated with higher mortality. Of 89 sites, 34% reported access to amphotericin B; 12% had access to flucytosine. CONCLUSIONS: Mortality after CM diagnosis was high. A substantial portion of CM cases occurred after ART start, though incidence and mortality may be higher than reported due to ascertainment bias. Many sites lacked access to recommended CM treatment.

Site-Level Comprehensiveness of Care Is Associated with Individual Clinical Retention Among Adults Living with HIV in International Epidemiology Databases to Evaluate AIDS, a Global HIV Cohort Collaboration, 2000-2016.

Retention in care (RIC) reduces HIV transmission and associated morbidity and mortality. We examined whether delivery of comprehensive services influenced individual RIC within the International epidemiology Databases to Evaluate AIDS (IeDEA) network. We collected site data through IeDEA assessments 1.0 (2000-2009) and 2.0 (2010-2016). Each site received a comprehensiveness score for service availability (1 = present, 0 = absent), with tallies ranging from 0 to 7. We obtained individual-level cohort data for adults with at least one visit from 2000 to 2016 at sites responding to either assessment. Person-time was recorded annually, with RIC defined as completing two visits at least 90 days apart in each calendar year. Multivariable modified Poisson regression clustered by site yielded risk ratios and predicted probabilities for individual RIC by comprehensiveness. Among 347,060 individuals in care at 122 sites with 1,619,558 person-years of follow-up, 69.8% of person-time was retained in care, varying by region from 53.8% (Asia-Pacific) to 82.7% (East Africa); RIC improved by about 2% per year from 2000 to 2016 (p = 0.012). Every site provided CD4+ count testing, and >90% of individuals received care at sites that provided combination antiretroviral therapy adherence measures, prevention of mother-to-child transmission, tuberculosis screening, HIV-related prevention, and community tracing services. In adjusted models, individuals at sites with more comprehensive services had higher probabilities of RIC (0.71, 0.74, and 0.83 for scores 5, 6, and 7, respectively; p = 0.019). Within IeDEA, greater site-level comprehensiveness of services was associated with improved individual RIC. Much work remains in exploring this relationship, which may inform HIV clinical practice and health systems planning.

Late-onset opportunistic infections while receiving anti-retroviral therapy in Latin America: burden and risk factors.

OBJECTIVES: The aim of this study was to describe the incidence, clinical characteristics, and risk factors of late-onset opportunistic infections (LOI) in people who live with HIV (PWLHA) within the Caribbean, Central and South America network for HIV epidemiology. METHODS: We performed a retrospective cohort study including treatment-naive PWLHA enrolled at seven sites (Argentina, Brazil, Chile, Peru, Mexico, and two sites in Honduras). Follow-up began at 6 months after treatment started. Outcomes were LOI, loss to follow-up, and death. We used a Cox proportional hazards model and a competing risks model to evaluate risk factors. RESULTS: A total of 10,583 patients were included. Median follow up was at 5.4 years. LOI occurred in 895 (8.4%) patients. Median time to opportunistic infection was 2.1 years. The most common infections were tuberculosis (39%), esophageal candidiasis (10%), and Pneumocystis jirovecii (P. jirovecii) pneumonia (10%). Death occurred in 576 (5.4%) patients, and 3021 (28.5%) patients were lost to follow-up. A protease inhibitor-based regimen (hazard ratio 1.25), AIDS-defining events during the first 6 months of antiretroviral-treatment (hazard ratio 2.12), starting antiretroviral-treatment in earlier years (hazard ratio 1.52 for 2005 vs 2010), and treatment switch (hazard ratio 1.31) were associated with a higher risk of LOI. CONCLUSION: LOI occurred in nearly one in 10 patients. People with risk factors could benefit from closer follow-up.

Clinical effects of durability of immunosuppression in virologically suppressed ART-initiating persons with HIV in Latin America. A retrospective cohort study.

Background: Clinical outcomes are rarely studied in virologically suppressed people living with HIV (PWH) and incomplete CD4 recovery. To explore whether time living with severe immunosuppression predict clinical outcomes better than baseline or time updated CD4, we estimated the association between cumulative percentage of time with CD4 <200 cells/µL during viral suppression (VS) (%tCD4<200), and mortality and comorbidities during 2000-2019. Methods: In a retrospective cohort analysis, we followed PWH initiating ART in Latin America from first VS (HIV-RNA<200 copies/µL) to death, virological failure or loss to follow-up. We fit Cox models to estimate risk of death and/or AIDS-defining and serious non-AIDS-defining events (ADE and SNADE -cancer, cardiovascular, liver, and renal diseases) by %tCD4<200 (continuous variable). We predicted survival probabilities for each event and calculated risks of hypothetical cases of different %tCD4<200. Findings: In 8,369 patients with 34·9 months of follow-up (median, IQR: 16·7, 69·1), 4,274 (51%) started ART with CD4<200 cells/µL. Median %tCD4<200 was 0% (IQR: 0, 15%). We identified 195 (2·3%) deaths and 584 (7·2%) patients with ADE/SNADE. For an increased %tCD4<200 of 15% (e.g., 15% vs. 0%), the adjusted relative hazard (aHR) of death was 1·27 (95% confidence interval [CI]: 1·19 - 1·35), of ADE/SNADE was 1·13 (95%CI: 1·09 - 1·17), of SNADE was 0·96 (95%CI: 0·89 - 1·02) and of death/ADE/SNADE was 1·11 (95%CI: 1·07 - 1·14). Estimates were similar after adjusting for time updated CD4 count. Interpretation: In virologically suppressed PWH, increased time living with severe immunosuppression had an increased risk of death and ADE/SNADE in this Latin American cohort, independently of time updated CD4 count. Funding: This work was supported by the NIH-funded Caribbean, Central and South America network for HIV epidemiology (CCASAnet, U01AI069923), a member cohort of the International Epidemiologic Databases to Evaluate AIDS (leDEA). This award is funded by the following institutes: Eunice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD), National Cancer Institute (NCI), National Institute Of Allergy And Infectious Diseases (NIAID), National Institute Of Mental Health (NIMH), the National Heart, Lung, and Blood Institute (NHLBI), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the Fogarty International Center (FIC). Specific funding was provided from the Fogarty International Center (FIC) for lead author, Yanink Caro-Vega, for the Fogarty-IeDEA Mentorship Program (FIMP).

Timing of HIV diagnosis relative to pregnancy and postpartum HIV care continuum outcomes among Latin American women, 2000 to 2017.

BACKGROUND: HIV incidence among women of reproductive age and vertical HIV transmission rates remain high in Latin America. We, therefore, quantified HIV care continuum barriers and outcomes among pregnant women living with HIV (WLWH) in Latin America. METHODS: WLWH (aged ≥16 years) enrolling at Caribbean, Central and South America network for HIV epidemiology (CCASAnet) sites from 2000 to 2017 who had HIV diagnosis, pregnancy and delivery dates contributed. Logistic regression produced adjusted odds ratios (aOR) and 95% confidence intervals (CI) for retention in care (≥2 visits ≥3 months apart) and virological suppression (viral load <200 copies/mL) 12 months after pregnancy outcome. Cumulative incidences of loss to follow-up (LTFU) postpartum were estimated using Cox regression. Evidence of HIV status at pregnancy confirmation was the exposure. Covariates included pregnancy outcome (born alive vs. others); AIDS diagnosis prior to delivery; CD4, age, HIV-1 RNA and cART regimen at first delivery and CCASAnet country. RESULTS: Among 579 WLWH, median postpartum follow-up was 4.34 years (IQR 1.91, 7.35); 459 (79%) were HIV-diagnosed before pregnancy confirmation, 445 (77%) retained in care and 259 (45%) virologically suppressed at 12 months of postpartum. Cumulative incidence of LTFU was 21% by 12 months and 40% by five years postpartum. Those HIV-diagnosed during pregnancy had lower odds of retention (aOR = 0.58, 95% CI: 0.35 to 0.97) and virological suppression (aOR = 0.50, 95% CI: 0.31 to 0.82) versus those HIV-diagnosed before. CONCLUSION: HIV diagnosis during pregnancy was associated with poorer 12-month retention and virological suppression. Young women should be tested and linked to HIV care earlier to narrow these disparities.

Estimated life expectancy gains with antiretroviral therapy among adults with HIV in Latin America and the Caribbean: a multisite retrospective cohort study.

BACKGROUND: There are few data on life expectancy gains among people living with HIV in low-income and middle-income settings where antiretroviral therapy (ART) is increasingly available. We aimed to analyse life expectancy trends from 2003 to 2017 among people with HIV beginning treatment with ART within the Caribbean, central America, and South America. METHODS: We did a multisite retrospective cohort study and included people with HIV who had started treatment with ART and were aged 16 years or older between Jan 1, 2003, and Dec 31, 2017, from Caribbean, Central and South America network for HIV epidemiology (CCASAnet) sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru, who contributed person-time data from the age of 20 years until date of death, last contact, database closure, or Dec 31, 2017. We used the Chiang method of abridged life tables to estimate life expectancy at age 20 years for three eras (2003-08, 2009-12, and 2013-17) overall and by demographic and clinical characteristics at ART initiation. We used Poisson regression models to weight mortality rates to account for informative censoring. FINDINGS: 30 688 people with HIV were included in the study; 17 491 (57·0%) were from the Haiti site and 13 197 (43·0%) were from all other sites. There were 2637 deaths during the study period: 1470 in Haiti and 1167 in other sites. Crude and weighted mortality rates decreased among all age groups over calendar eras. From 2003-08 to 2013-17, overall life expectancy for people with HIV at age 20 years increased from 13·9 years (95% CI 12·5-15·2) to 61·2 years (59·0-63·4) in Haiti and from 31·0 years (29·3-32·8) to 69·5 years (67·2-71·8) in other sites. Life expectancies at the end of the study period were within 10 years of those of the general population (69·9 years in Haiti and 78·0 years in all other sites in 2018). Disparities in life expectancy among people with HIV by sex or HIV transmission risk factor, CD4 cell count, level of education, and history of tuberculosis at or before ART initiation persisted across calendar eras. INTERPRETATION: Life expectancy among people with HIV receiving ART has significantly improved in Latin America and the Caribbean. Persistent disparities in life expectancy among people with HIV by demographic and clinical factors at ART initiation highlight vulnerable populations in the region. FUNDING: National Institutes of Health. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Outcomes After Second-Line Antiretroviral Therapy in Children Living With HIV in Latin America.

BACKGROUND: Little is known about the long-term outcomes of children living with HIV in Latin America. Few studies have examined antiretroviral therapy (ART) regimen switches in the years after the introduction of ART in this population. This study aimed to assess clinical outcomes among children who started second-line ART in the Caribbean, Central and South America network for HIV epidemiology. METHODS: Children (<18 years old) with HIV who switched to second-line ART at sites within Caribbean, Central and South America network for HIV epidemiology were included. The cumulative incidence and relative hazards of virologic failure while on second-line ART, loss to follow-up, additional major ART regimen changes, and all-cause mortality were evaluated using competing risks methods and Cox models. RESULTS: A total of 672 children starting second-line ART were included. Three years after starting second-line ART, the cumulative incidence of death was 0.10 [95% confidence interval (CI) 0.08 to 0.13], loss to follow-up was 0.14 (95% CI: 0.11 to 0.17), and major regimen change was 0.19 (95% CI: 0.15 to 0.22). Of those changing regimens, 35% were due to failure and 11% due to toxicities/side effects. Among the 312 children with viral load data, the cumulative incidence of virologic failure at 3 years was 0.62 (95% CI: 0.56 to 0.68); time to virologic failure and regimen change were uncorrelated (rank correlation -0.001; 95% CI -0.18 to 0.17). CONCLUSIONS: Poor outcomes after starting second-line ART in Latin America were common. The high incidence of virologic failure and its poor correlation with changing regimens was particularly worrisome. Additional efforts are needed to ensure children receive optimal ART regimens.

Improving Methods to Classify Perinatal versus Nonperinatal HIV Acquisition in Young Adolescents 10-14 Years of Age.

Mode of HIV acquisition for adolescents with HIV is often not recorded within routine healthcare databases. Hence, age at enrollment in HIV care is often used as a proxy for perinatal versus nonperinatal infection. Using routine cohort data from adolescents presenting for HIV care 10-14 years of age, we developed logistic regression models to predict likely mode of infection.

Antiretroviral therapy and Kaposi's sarcoma trends and outcomes among adults with HIV in Latin America.

INTRODUCTION: Kaposi'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). METHODS: Cohorts 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. RESULTS: Of 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. CONCLUSIONS: KS 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.

Dolutegravir and pregnancy outcomes in women on antiretroviral therapy in Brazil: a retrospective national cohort study.

BACKGROUND: Dolutegravir has been widely available in Brazil since 2017. Following the signal that infants born to women with dolutegravir exposure at conception in Botswana had a higher risk of neural tube defects (NTDs), public health leaders initiated a national investigation to evaluate periconception dolutegravir exposure among all pregnant Brazilian women with HIV and its potential association with risk of NTDs, stillbirth, or miscarriage before 22 weeks (also called spontaneous abortion). METHODS: In this retrospective, observational, national, cohort study, we identified all women with pregnancies and possible dolutegravir exposure within 8 weeks of estimated date of conception between Jan 1, 2017, and May 31, 2018, and approximately 3:1 matched pregnant women exposed to efavirenz between Jan 1, 2015, and May 31, 2018, using the Brazilian antiretroviral therapy database. We did detailed chart reviews for identified women. The primary outcomes were NTD and a composite measure of NTD, stillbirth, or miscarriage. NTD incidences were calculated with 95% CI. The composite outcome was examined with logistic regression using propensity score matching weights to balance confounders. FINDINGS: Of 1427 included women, 382 were exposed to dolutegravir within 8 weeks of estimated date of conception. During pregnancy, 183 (48%) of 382 dolutegravir-exposed and 465 (44%) of 1045 efavirenz-exposed women received folic acid supplementation. There were 1452 birth outcomes. There were no NTDs in either dolutegravir-exposed (0, 95% CI 0-0·0010) or efavirenz-exposed groups (0, 95% CI 0-0·0036). There were 23 (6%) stillbirths or miscarriages in 384 dolutegravir-exposed fetuses and 28 (3%) in the 1068 efavirenz-exposed fetuses (p=0·0037). Logistic regression models did not consistently indicate an association between dolutegravir exposure and risk of stillbirths or miscarriages. After study closure, two confirmed NTD outcomes in fetuses with periconception dolutegravir exposure were reported to public health officials. An updated estimate of NTD incidence incorporating these cases and the estimated number of additional dolutegravir-exposed pregnancies between Jan 1, 2015 and Feb 28, 2019, is 0·0018 (95% CI 0·0005-0·0067). INTERPRETATION: Neither dolutegravir nor efavirenz exposure was associated with NTDs in our national cohort; incidence of NTDs is probably well under 1% in dolutegravir-exposed HIV-positive women but still slightly above HIV-uninfected women (0·06%) in Brazil. FUNDING: The Brazilian Ministry of Health and the United States' National Institutes of Health.

Raltegravir use and outcomes among children and adolescents living with HIV in the IeDEA global consortium.

INTRODUCTION: As integrase inhibitors become available in low- and middle-income countries (LMICs), they offer the potential to expand extremely limited treatment options available to children and adolescents. In LMICs, only small numbers have used raltegravir, primarily as part of third-line regimens. Using data from the IeDEA global consortium, we aimed to describe the characteristics of children on raltegravir-containing regimens and their outcomes. METHODS: We included data from 1994 to 2017 from children (age <18 years), from East and Southern Africa, Asia and South America, who received cART regimens containing raltegravir for ≥90 days. We describe their characteristics at raltegravir start, and their immunological and virological outcomes. RESULTS AND DISCUSSION: In total, 62 children were included, with median age at raltegravir initiation of 14.3 years (IQR 11.2 to 15.8) and median CD4 count of 276 cells/µL (IQR 68 to 494). Among 40 (65%) with drug resistance testing prior to raltegravir, 71% were resistant to at least one protease inhibitor (PI), and 32% had high-level resistance to at least one drug class. Most (n = 50; 81%) received raltegravir as part of third-line cART following PI-based regimens, and were on regimens containing four or more drugs (n = 47, 76%). By database closure, median duration on raltegravir was 2.0 years (IQR 0.8 to 3.0), 1 (1.6%) patient had died, 6 (9.7%) were lost to follow-up and 21 (34%) had discontinued raltegravir. Among 15 patients reporting reasons for stopping raltegravir, six discontinued because it was no longer available. Within one year of starting raltegravir, among 53 patients with VL measures, 40 (75%) had VL < 1000 copies/mL, and among 54 with a reported CD4 count, 45 (83%) and 36 (67%) were ≥350 and ≥500 cells/µL, respectively, with median CD4 count increasing to 517.5 cells/µL (IQR 288 to 810). CONCLUSIONS: Among children in LMICs, the initial use of raltegravir has been primarily for post PI-based cART. We found good virological and immunological outcomes despite frequent prior triple-class failure and high levels of drug resistance. Both access to raltegravir and long-term adherence to regimens with large pill-burdens remain challenging. Policies which promote earlier access to new drugs and simplify daily regimens for children and adolescents in LMICs are needed.

Frequency of non-communicable diseases in people 50 years of age and older receiving HIV care in Latin America.

BACKGROUND: A growing population of older adults with HIV will increase demands on HIV-related healthcare. Nearly a quarter of people receiving care for HIV in Latin America are currently 50 years or older, yet little is known about the frequency of comorbidities in this population. We estimated the prevalence and incidence of non-communicable diseases (NCDs) among people 50 years of age or older (≥50yo) receiving HIV care during 2000-2015 in six centers affiliated with the Caribbean, Central and South American network for HIV epidemiology (CCASAnet). METHODS: We estimated the annual prevalence, and overall prevalence and incidence of cardiovascular diseases, diabetes, hypertension, dyslipidemia, psychiatric disorders, chronic liver and renal diseases, and non-AIDS-defining cancers, and multimorbidity (more than one NCD) of people ≥50yo receiving care for HIV. Analyses were performed according to age at enrollment into HIV care (<50yo and ≥50yo). RESULTS: We included 3,415 patients ≥50yo, of whom 1,487(43%) were enrolled at age ≥50 years. The annual prevalence of NCDs increased from 32% to 68% and multimorbidity from 30% to 40% during 2000-2015. At the last registered visit, 53% of patients enrolled <50yo and 50% of those enrolled ≥50yo had at least one NCD. Most common NCDs at the last visit in each age-group at enrollment were dyslipidemia (36% in <50yo and 28% in ≥50yo), hypertension (17% and 18%), psychiatric disorders (15% and 10%), and diabetes (11% and 12%). CONCLUSIONS: The prevalence of NCDs and multimorbidity in people ≥50 years receiving care for HIV in CCASAnet centers in Latin America increased substantially in the last 15 years. Our results make evident the need of planning for provision of complex, primary care for aging adults living with HIV.

Self-audits as alternatives to travel-audits for improving data quality in the Caribbean, Central and South America network for HIV epidemiology.

INTRODUCTION: Audits play a critical role in maintaining the integrity of observational cohort data. While previous work has validated the audit process, sending trained auditors to sites ("travel-audits") can be costly. We investigate the efficacy of training sites to conduct "self-audits." METHODS: In 2017, eight research groups in the Caribbean, Central, and South America network for HIV Epidemiology each audited a subset of their patient records randomly selected by the data coordinating center at Vanderbilt. Designated investigators at each site compared abstracted research data to the original clinical source documents and captured audit findings electronically. Additionally, two Vanderbilt investigators performed on-site travel-audits at three randomly selected sites (one adult and two pediatric) in late summer 2017. RESULTS: Self- and travel-auditors, respectively, reported that 93% and 92% of 8919 data entries, captured across 28 unique clinical variables on 65 patients, were entered correctly. Across all entries, 8409 (94%) received the same assessment from self- and travel-auditors (7988 correct and 421 incorrect). Of 421 entries mutually assessed as "incorrect," 304 (82%) were corrected by both self- and travel-auditors and 250 of these (72%) received the same corrections. Reason for changing antiretroviral therapy (ART) regimen, ART end date, viral load value, CD4%, and HIV diagnosis date had the most mismatched corrections. CONCLUSIONS: With similar overall error rates, findings suggest that data audits conducted by trained local investigators could provide an alternative to on-site audits by external auditors to ensure continued data quality. However, discrepancies observed between corrections illustrate challenges in determining correct values even with audits.

Cardiovascular disease among people living with HIV in Brazil.

OBJECTIVES: There is a paucity of data on cardiovascular disease (CVD) among people living with HIV (PLHIV) in resource-limited countries. We assessed factors associated with CVD and the impact of prevalent CVD on all-cause mortality in PLHIV on antiretroviral therapy in Brazil. METHODS: Competing risk regression to assess factors associated with CVD and all-cause mortality in the HIV-Brazil Cohort Study between 2003 and 2014. RESULTS: Among 5614 patients, the rate of CVD was 3.5 (95% confidence interval [95% CI] 2.9-4.3) per 1000 person-years. CVD was associated with older age (adjusted hazard ratio [aHR] 6.4 for ≥55 years vs. <35 years, 95% CI: 2.5-16.3, P < 0.01), black race (aHR 1.8 vs. white race, 95% CI: 1.0-3.1, P = 0.04), past CVD (aHR 3.0 vs. no past CVD, 95% CI: 1.4-6.2, P < 0.01), hypertension (aHR 1.8 vs. no hypertension, 95% CI: 1.0-3.1, P = 0.04), high-grade dyslipidemia (aHR 9.3 vs. no high-grade dyslipidemia, 95% CI: 6.0-14.6, P < 0.01), ever smoking (aHR 2.4 vs. never, 95% CI: 1.2-5.0, P = 0.02) and low nadir CD4 cell count (aHR 1.8 for 100-250 cells/mm3 vs. >250 cells/mm3 , 95% CI: 1.0-3.2, P = 0.05). The rate of death was 16.6 (95% CI: 15.1-18.3) per 1000 person-years. Death was strongly associated with having had a past CVD event (aHR 1.7 vs. no past CVD event, 95% CI: 1.1-2.7, P = 0.01). CONCLUSIONS: Traditional and HIV-specific factors associated with CVD among PLHIV in Brazil are similar to those identified among PLHIV in high-income countries. PLHIV in Brazil with a history of CVD have a high risk of death. CVD care and treatment remain priorities for PLHIV in Brazil as this population ages and antiretroviral therapy use expands.

OBJECTIFS: Il existe peu de données sur les maladies cardiovasculaires (MCV) chez les personnes vivant avec le VIH (PVVIH) dans les pays à ressources limitées. Nous avons évalué les facteurs associés aux MCV et l'impact des MCV prévalentes sur la mortalité toutes causes confondues des PVVIH sous le traitement antirétroviral au Brésil. MÉTHODES: Régression des risques concurrente pour évaluer les facteurs associés aux MCV et à la mortalité toutes causes confondues dans l'étude de cohorte VIH-Brésil entre 2003 et 2014. RÉSULTATS: Parmi 5.614 patients, le taux de MCV était de 3,5 (intervalle de confiance à 95% [IC95%] 2,9-4,3) pour 1.000 personnes-années. Les MCV étaient associées à un âge plus avancé (rapport de risque ajusté [aHR] 6,4 chez les ≥55 ans versus chez les <35 ans, IC95%: 2,5-16,3 ; p <0,01), race noire (aHR: 1,8 versus race blanche, IC95%: 1,0-3,1 ; p = 0,04), MCV passée (aHR: 3,0 versus pas de MCV passée, IC95%: 1,4-6,2 ; p <0,01), hypertension (aHR: 1,8 versus pas d'hypertension, IC95%: 1,0-3,1 ; p = 0,04), dyslipidémie de grade élevé (aHR 9,3 versus absence de dyslipidémie de grade élevé, IC95%: 6,0-14,6 ; p <0,01), tabagisme (aHR 2,4 versus n'avoir jamais fumé, IC95%: 1,2-5,0 ; p = 0,02) et faible nombre de CD4 au nadir (aHR: 1,8 pour 100-250 cellules/mm3 versus >250 cellules/mm3 , IC95%: 1,0-3,2 ; p = 0,05). Le taux de décès était de 16,6 (IC95%: 15,1-18,3) pour 1.000 personnes-années. Le décès était fortement associé à un événement MCV antérieur (aHR: 1,7 versus aucun événement MCV antérieur, IC95%: 1,1-2,7 ; p = 0,01). CONCLUSIONS: Les facteurs traditionnels et spécifiques au VIH associés aux MCV chez les PVVIH au Brésil sont similaires à ceux identifiés chez les PVVIH dans les pays à revenu élevé. Les PVVIH au Brésil ayant des antécédents de MCV ont un risque élevé de décès. Les soins et le traitement des MCV restent des priorités pour les PVVIH au Brésil à mesure que cette population vieillit et que l'utilisation des thérapies antirétrovirales augmente.

Increased Mortality After Tuberculosis Treatment Completion in Persons Living With Human Immunodeficiency Virus in Latin America.

We assessed the association between cured tuberculosis (TB) and mortality among persons living with human immunodeficiency virus (HIV) in Latin America. We compared survival among persons with and without TB at enrollment in HIV care, starting 9 months after clinic enrollment. In multivariable analysis, TB was associated with higher long-term mortality (hazard ratio, 1.57; 95% confidence interval, 1.25-1.99).

The Population Impact of Late Presentation With Advanced HIV Disease and Delayed Antiretroviral Therapy in Adults Receiving HIV Care in Latin America.

Late presentation to care and antiretroviral therapy (ART) initiation with advanced human immunodeficiency virus (HIV) disease are common in Latin America. We estimated the impact of these conditions on mortality in the region. We included adults enrolled during 2001-2014 at HIV care clinics. We estimated the adjusted attributable risk (AR) and population attributable fraction (PAF) for all-cause mortality of presentation to care with advanced HIV disease (advanced LP), ART initiation with advanced HIV disease, and not initiating ART. Advanced HIV disease was defined as CD4 of <200 cells/µL or acquired immune deficiency syndrome. AR and PAF were derived using marginal structural models. Of 9,229 patients, 56% presented with advanced HIV disease. ARs of death for advanced LP were 86%, 71%, and 58%, and PAFs were 78%, 58%, and 43% at 1, 5, and 10 years after enrollment. Among people without advanced LP, ARs of death for delaying ART were 39%, 32%, and 37% at 1, 5, and 10 years post-enrollment and PAFs were 20%, 14%, and 15%. Among people with advanced LP, ART decreased the hazard of death by 63% in the first year after enrollment, but 93% of these started ART; thus universal ART among them would reduce mortality by only 10%. Earlier presentation to care and earlier ART initiation would prevent most HIV deaths in Latin America.

Temporal changes in ART initiation in adults with high CD4 counts in Latin America: a cohort study.

INTRODUCTION: In 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. METHODS: All 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. RESULTS: Of 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). CONCLUSIONS: Time 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.

Stunting and growth velocity of adolescents with perinatally acquired HIV: differential evolution for males and females. A multiregional analysis from the IeDEA global paediatric collaboration.

INTRODUCTION: Stunting is a key issue for adolescents with perinatally acquired HIV (APH) that needs to be better understood. As part of the IeDEA multiregional consortium, we described growth evolution during adolescence for APH on antiretroviral therapy (ART). METHODS: We included data from sub-Saharan Africa, the Asia-Pacific, and the Caribbean, Central and South America regions collected between 2003 and 2016. Adolescents on ART, reporting perinatally acquired infection or entering HIV care before 10 years of age, with at least one height measurement between 10 and 16 years of age, and followed in care until at least 14 years of age were included. Characteristics at ART initiation and at 10 years of age were compared by sex. Correlates of growth defined by height-for-age z-scores (HAZ) between ages 10 and 19 years were studied separately for males and females, using linear mixed models. RESULTS: Overall, 8737 APH were included, with 46% from Southern Africa. Median age at ART initiation was 8.1 years (interquartile range (IQR) 6.1 to 9.6), 50% were females, and 41% were stunted (HAZ<-2 SD) at ART initiation. Males and females did not differ by age and stunting at ART initiation, CD4 count over time or retention in care. At 10 years of age, 34% of males were stunted versus 39% of females (p < 0.001). Females had better subsequent growth, resulting in a higher prevalence of stunting for males compared to females by age 15 (48% vs. 25%) and 18 years (31% vs. 15%). In linear mixed models, older age at ART initiation and low CD4 count were associated with poor growth over time (p < 0.001). Those stunted at 10 years of age or at ART initiation had the greatest growth improvement during adolescence. CONCLUSIONS: Prevalence of stunting is high among APH worldwide. Substantial sex-based differences in growth evolution during adolescence were observed in this global cohort, which were not explained by differences in age of access to HIV care, degree of immunosuppression or region. Other factors influencing growth differences in APH, such as differences in pubertal development, should be better documented, to guide further research and inform interventions to optimize growth and health outcomes among APH.