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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., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Some tuberculosis (TB) treatment guidelines recommend daily TB treatment in both the intensive and continuation phases of treatment in HIV-positive persons to decrease the risk of relapse and acquired drug resistance. However, guidelines vary across countries, and treatment is given 7, 5, 3, or 2 days/week. The effect of TB treatment intermittency in the continuation phase on mortality in HIV-positive persons on antiretroviral therapy (ART), is not well-described., Methods: We conducted an observational cohort study among HIV-positive adults treated for TB between 2000 and 2018 and after enrollment into the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet; Brazil, Chile, Haiti, Honduras, Mexico and Peru). All received standard TB therapy (2-month initiation phase of daily isoniazid, rifampin or rifabutin, pyrazinamide ± ethambutol) and continuation phase of isoniazid and rifampin or rifabutin, administered concomitantly with ART. Known timing of ART and TB treatment were also inclusion criteria. Kaplan-Meier and Cox proportional hazards methods compared time to death between groups. Missing model covariates were imputed via multiple imputation., Results: 2303 patients met inclusion criteria: 2003(87%) received TB treatment 5-7 days/week and 300(13%) 2-3 days/week in the continuation phase. Intermittency varied by site: 100% of patients from Brazil and Haiti received continuation phase treatment 5-7 days/week, followed by Honduras (91%), Peru (42%), Mexico (7%), and Chile (0%). The crude risk of death was lower among those receiving treatment 5-7 vs. 2-3 days/week (HR = 0.68; 95% CI = 0.51-0.91; P = 0.008). After adjusting for age, sex, CD4, ART use at TB diagnosis, site of TB disease (pulmonary vs. extrapulmonary), and year of TB diagnosis, mortality risk was lower, but not significantly, among those treated 5-7 days/week vs. 2-3 days/week (HR 0.75, 95%CI 0.55-1.01; P = 0.06). After also stratifying by study site, there was no longer a protective effect (HR 1.42, 95%CI 0.83-2.45; P = 0.20)., Conclusions: TB treatment 5-7 days/week was associated with a marginally decreased risk of death compared to TB treatment 2-3 days/week in the continuation phase in multivariable, unstratified analyses. However, little variation in TB treatment intermittency within country meant the results could have been driven by other differences between study sites. Therefore, randomized trials are needed, especially in heterogenous regions such as Latin America., (© 2022. The Author(s).)

Due to a huge crisis extensive to health services many Venezuelan people living with HIV (PLWH) had migrated abroad, including Peru where favorable laws were in place until June 2019. We describe the health status and epidemiological trends of PLWH from Venezuela at an HIV program in Lima. We analyzed baseline and follow-up data of all Venezuelan PLWH enrolled in our HIV program from January 2017 to December 2019. A cross-sectional study in a subsample served to describe ARV adherence and context of migration. Between 2017-2019 our HIV Program registered 398 Venezuelan PLWH, representing 20% of the 2018 annual enrollments; numbers decreased since mid-2019. The median age was 30 years (IQR 26;37) and 90.5% were men. Between 2017 and 2019, the proportion with diagnosis in Peru increased from 14.3% to 60.9%; of AIDS stage at entry, from 8.8% to 27.2%. By December 2019, 182/250 (72.8%) were still in care, and 43 (10.8%) had not started ART. Viral suppression evaluated in 195, was achieved in 71.8%. From 2017 to 2019, migrant PLWH arrived in worsened clinical conditions, with increasing diagnosis in Peru; the flow of migrant PLWH entering care diminished with less favorable laws. Viral suppression rates were suboptimal.

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., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This study was carried out to describe and compare the demographic, clinical, and therapeutic characteristics of HIV patients who developed some cancer. We identified 276 cancer cases diagnosed at Hospital Cayetano Heredia between 2000 and 2018. 80,8% (223/276) had AIDS-defining-cancers (ADCs), being Kaposi's Sarcoma the most frequent type; meanwhile, among non-AIDS-defining-cancers (NADCs), the most frequent was Hodgkin lymphoma. The median age was 36,5 years, being highest among the cases diagnosed with NADCs. Concerning CD4 lymphocyte counts, the median among ADCs was much lower than NADCs, 87,5 cells/µl and 216 cells/µl, respectively. Therefore, NADCs cases have a longer history of HIV infection, and an older age at cancer diagnosis, as well as higher CD4 cells counts.

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., (© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

We analyzed 312 drug-resistant genomes of Mycobacterium tuberculosis isolates collected from HIV-coinfected and HIV-negative TB patients from nine countries with a high tuberculosis burden. We found that rifampicin-resistant M. tuberculosis strains isolated from HIV-coinfected patients carried disproportionally more resistance-conferring mutations in rpoB that are associated with a low fitness in the absence of the drug, suggesting these low-fitness rpoB variants can thrive in the context of reduced host immunity., (Copyright © 2020 Loiseau et al.)

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 Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Tuberculosis (TB) is a leading cause of mortality among people living with HIV (PLHIV). An invigorated global END TB Strategy seeks to increase efforts in scaling up TB preventive therapy (TPT) as a central intervention for HIV programmes in an effort to contribute to a 90% reduction in TB incidence and 95% reduction in mortality by 2035. TPT in PLHIV should be part of a comprehensive approach to reduce TB transmission, illness and death that also includes TB active case-finding and prompt, effective and timely initiation of anti-TB therapy among PLHIV. However, the use and implementation of preventive strategies has remained deplorably inadequate and today TB prevention among PLHIV has become an urgent priority globally., Discussion: We present a summary of the current and novel TPT regimens, including current evidence of use with antiretroviral regimens (ART). We review challenges and opportunities to scale-up TB prevention within HIV programmes, including the use of differentiated care approaches and demand creation for effective TB/HIV services delivery. TB preventive vaccines and diagnostics, including optimal algorithms, while important topics, are outside of the focus of this commentary., Conclusions: A number of new tools and strategies to make TPT a standard of care in HIV programmes have become available. The new TPT regimens are safe and effective and can be used with current ART, with attention being paid to potential drug-drug interactions between rifamycins and some classes of antiretrovirals. More research and development is needed to optimize TPT for small children, pregnant women and drug-resistant TB (DR-TB). Effective programmatic scale-up can be supported through context-adapted demand creation strategies and the inclusion of TPT in client-centred services, such as differentiated service delivery (DSD) models. Robust collaboration between the HIV and TB programmes represents a unique opportunity to ensure that TB, a preventable and curable condition, is no longer the number one cause of death in PLHIV., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

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/mm 3 . 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/mm 3 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/mm 3 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., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Tuberculosis (TB) diagnosis in human immunodeficiency virus (HIV) positive persons is difficult, particularly in resource-limited settings. The relationship between TB culture status and mortality in HIV-positive persons treated for TB is unclear., Methods: We evaluated HIV-positive adults treated for TB at or after their first HIV clinic visit in Argentina, Brazil, Chile, Honduras, Mexico or Peru from 2000 to 2015. Anti-tuberculosis treatment included 2 months of isoniazid, rifampicin (RMP)/rifabutin (RBT), pyrazinamide ± ethambutol, followed by continuation phase treatment with isoniazid + RMP/RBT., Results: Of 759 TB-HIV patients, 238 (31%) were culture-negative, 228 (30%) had unknown culture status or did not undergo culture and 293 (39%) were culture-positive. The median CD4 at TB diagnosis was 96 (interquartile range 40-228); 636 (84%) received concurrent antiretroviral therapy (ART) and anti-tuberculosis treatment. There were 123 (16%) deaths: 90/466 (19%) with TB culture-negative, unknown or not performed vs. 33/293 (11%) who were TB culture-positive ( P = 0.005). In Kaplan-Meier analysis, mortality in TB patients without culture-confirmed disease was higher ( P = 0.002). In a Cox model adjusted for age, sex, CD4, ART timing, disease site and stratified by study site, mortality in persons without culture-confirmed TB was not significantly increased compared to those with culture-positive TB (hazard ratio 1.39, 95%CI 0.89-2.16, P = 0.15)., Conclusion: Most HIV-positive patients treated for TB did not have culture-confirmed TB, and mortality tended to be higher in patients without culture-confirmed disease, although the association was not statistically different after adjusting for other variables. Accurate TB diagnosis in HIV-positive persons is crucial.

Patient-nominated supporters can potentially improve the continuum of HIV care. We retrospectively determined factors associated with having a patient-nominated supporter among people living with HIV (PLWH), and its association with retention in care and viral suppression. We analysed registries of adults evaluated by social workers (n = 1345) at a referral hospital in Peru between 2011-2014. Nondisclosure of HIV status was associated with lacking supporters (aPR: 5.41, 95% CI: 3.83-7.64). Retention in care was 76.4% and 34.2% after one and two years of enrolment, respectively. PLWH with supporters were more likely to be retained in care after two years (aRR = 1.36, 95% CI: 1.02-1.81), but not after one year (aRR = 1.10, 95% CI: 0.98-1.23) compared to PLWH without supporters. Having supporters who were parents or friends was associated with an increased probability of being retained in care after one and two years of enrolment. Viral suppression after one year of enrolment was 58.7%. Having a supporter was not associated with viral suppression (aRR = 1.18, 95% CI: 0.99-1.41), but PLWH with supporters were more likely to have viral load measurements (p = 0.005). Patient-nominated supporters appear beneficial for engagement in HIV care; these benefits may be related to the nature of their relationship with PLWH.

Background: Since 2006, the Peruvian National TB program (NTP) recommends voluntary counseling and testing (VCT) for all tuberculosis (TB) patients. Responding to the differential burden of both diseases in Peru, TB is managed in peripheral health facilities while HIV is managed in referral centers. This study aims to determine the coverage of HIV screening among TB patients and the characteristics of persons not screened., Methods: From March 2010 to December 2011 we enrolled new smear-positive pulmonary TB adults in 34 health facilities in a district in Lima. NTP staff offered VCT to all TB patients. Patients with an HIV positive result were referred for confirmation tests and management. We interviewed patients to collect their demographic and clinical characteristics and registered if patients opted in or out of the screening., Results: Of the 1295 enrolled TB patients, nine had a known HIV diagnosis. Of the remaining, 76.1% (979) were screened for HIV. Among the 23.9% (307) not screened, 38.4% (118) opted out of the screening. TB patients at one of the health care facilities of the higher areas of the district (OR = 3.38, CI 95% 2.17-5.28 for the highest area and OR = 2.82, CI 95% 1.78-4.49 for the high area) as well as those reporting illegal drug consumption (OR = 1.65, CI 95% 1.15-2.37) were more likely not to be screened. Twenty-four were HIV positive (1.9% of all patients 1295, or 2.4% of those screened). Of 15 patients diagnosed with HIV during the TB episode, ten were enrolled in an HIV program. The median time between the result of the HIV screening and the first consultation at the HIV program was 82 days (IQR, 32-414). The median time between the result of the HIV screening and antiretroviral initiation was 148.5 days (IQR 32-500)., Conclusions: An acceptable proportion of TB patients were screened for HIV in Lima. Referral systems of HIV positive patients should be strengthened for timely ART initiation.

Background: The HIV care cascade has improved in Latin America over the last decade. However, the influence of alcohol and noninjected drug use (NIDU) on cascade outcomes is mostly unknown. This study estimated the association of alcohol and NIDU with retention in care, loss to follow up (LTFU), and virologic failure (VF)., Methods: Individuals ≥18 years attending routine HIV clinic visits and completing the Rapid Screening Tool (RST; evaluating NIDU and ART adherence in 7-day recall period) during 2012-13 were followed up to 2015 in the Caribbean, Central and South America network for HIV epidemiology. Adjusted odds ratios (aOR) were calculated for the association of alcohol consumption and NIDU with retention in care by logistic regression; adjusted hazard ratios (aHR) were estimated for the associations with LTFU and VF by Cox regression., Results: Among 3604 individuals, the proportions retained in care for one year were 84%, 79%, 72%, and 69% for patients reporting non-use, alcohol use, NIDU, and both alcohol and NIDU, respectively. For the same patient groups, the proportions LTFU over 18 months were 6%, 8%, 12%, and 13%, respectively. There were 1901 patients (53%) with HIV RNA results; VF proportions were similar between users and nonusers (ranging from 14-16%). After controlling for age, sex, study site, HIV transmission mode, time on ART, AIDS status, and CD4 count, neither alcohol use (aOR = 1.1, CI = 0.9-1.4; aHR = 1.0, CI = 0.8-1.3) nor NIDU (aOR = 1.3, CI = 0.9-1.8; aHR = 1.4, CI = 0.9-2.1) were significantly associated with retention or VF, respectively. However, both alcohol use (aHR = 1.2, CI = 1.02-1.4) and NIDU (aHR = 1.3, CI = 1.00-1.8) were associated with increased LTFU., Conclusion: Alcohol use and NIDU in a 7-day recall period increased the risk of being LTFU during the next 18 months, highlighting the need for routine screening and targeted interventions to keep these individuals in care and on ART.

Introduction: The "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)., Methods: HIV-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., Results: Among 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., Conclusions: Older 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., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.)

Introduction: Based on the hypothesis that HIV programs struggle to deliver health services that harmonize necessities of treatment and prevention, we described the outcomes of routinely provided HIV testing to partners of people living with HIV (PLWH) through a secondary analysis of routine data collected at a public hospital in Lima, Peru., Methods: Among PLWH enrolled in the study center's HIV program between 2005 and 2014, we identified index cases (IC): PLWH who reported a unique partner not previously enrolled. We grouped partners according to their HIV status as reported by IC and collected data on HIV testing, clinical characteristics and admissions. The main outcome was the frequency of HIV testing among partners with reported unknown/seronegative HIV status., Results: Out of 1586 PLWH who reported a unique partner at enrollment, 171 had a previously enrolled partner, leaving 1415 (89%) IC. HIV status of the partner was reported as unknown in 571 (40%), seronegative in 325 (23%) and seropositive in 519 (37%). Out of 896 partners in the unknown/seronegative group, 72 (8%) had HIV testing, 42/72 (58%) tested within three months of IC enrollment. Among the 49/72 (68%) who tested positive for HIV, 33 (67%) were enrolled in the HIV program. The proportion in WHO clinical stage IV was lower in enrolled partners compared to IC (37% vs 9%, p = 0.04). Non-tested partners (824) were likely reachable by the hospital, as 297/824 (36%) of their IC were admitted in the study center at least once, 51/243 (21%) female IC had received pregnancy care at the study center, and 401/692 (64%) of IC on antiretroviral therapy had achieved viral suppression, implying frequent visits to the hospital for pill pick-up., Conclusion: In this setting, HIV testing of partners of PLWH was suboptimal, illustrating missed opportunities for HIV control. Integration of HIV strategies in primarily clinical-oriented services is a challenging need.

Objectives: International health agencies have promoted nontargeted universal (opt-out) HIV screening tests in different settings, including emergency departments (EDs). We performed a systematic review and meta-analysis to assess the testing uptake of strategies (opt-in targeted, opt-in nontargeted and opt-out) to detect new cases of HIV infection in EDs., Methods: We searched the Pubmed and Embase databases, from 1984 to April 2015, for opt-in and opt-out HIV diagnostic strategies used in EDs. Randomized controlled or quasi experimental studies were included. We assessed the percentage of positive individuals tested for HIV infection in each programme (opt-in and opt-out strategies). The mean percentage was estimated by combining studies in a random-effect meta-analysis. The percentages of individuals tested in the programmes were compared in a random-effect meta-regression model. Data were analysed using stata version 12. Quality assessments were performed using the Newcastle-Ottawa Scale., Results: Of the 90 papers identified, 28 were eligible for inclusion. Eight trials used opt-out, 18 trials used opt-in, and two trials used both to detect new cases of HIV infection. The test was accepted and taken by 75 155 of 172 237 patients (44%) in the opt-out strategy, and 73 581 of 382 992 patients (19%) in the opt-in strategy. The prevalence of HIV infection detected by the opt-out strategy was 0.40% (373 cases), that detected by the opt-in nontargeted strategy was 0.52% (419 cases), and that detected by the opt-in targeted strategy was 1.06% (52 cases)., Conclusions: In this meta-analysis, the testing uptake of the opt-out strategy was not different from that of the opt-in strategy to detect new cases of HIV infection in EDs., (© 2016 British HIV Association.)

Background: In Latin America, the first wave of HIV-infected patients initiated highly active antiretroviral therapy (HAART) 10 or more years ago. Characterizing their treatment experience and corresponding outcomes across a decade of HAART may yield insights relevant to the ongoing care of such patients and those initiating HAART more recently in similar clinical settings., Methods: This retrospective study included adults initiating HAART before 2004 at 8 sites in Argentina, Brazil, Chile, Haiti, Honduras, and Mexico. Patient status (in care, dead, or lost to follow-up [LTFU]) was assessed at 6-month intervals for 10 years, along with CD4 count and HIV-1 viral load (VL) for patients in care., Results: 4,975 patients (66% male) started HAART prior to 2004; 45% were not antiretroviral-naïve. At 1, 5, and 10 years, rates of mortality were 4.2%, 9.0%, and 13.6% respectively. LTFU rates for the same periods were 2.4%, 10.9%, and 24.2%. Among patients remaining in care at 10 years, 84.4% were estimated to have VL≤400 copies/mL (Haiti excluded) and median baseline CD4 increased from 158 to 525 cells/mm3. Only 11.4% of all patients remained on their first regimen, 12.6% were on their second, 11.5% were on their third, and 23.0% were on their fourth or subsequent regimen. Outcomes were generally better for patients who were not antiretroviral-naïve, except for viral suppression. Heterogeneity among sites was substantial., Conclusions: Despite advanced disease and predominant use of older antiretrovirals, a large percentage of early HAART initiators in this Latin American cohort were alive and in care with sustained virologic suppression and progressive immune recovery after 10 years.

This cross-sectional study describes substance use prevalence and its association with combination antiretroviral therapy (cART) adherence among 3343 individuals receiving care at HIV clinics in Argentina, Brazil, Chile, Honduras, Mexico, and Peru. A rapid screening tool evaluated self-reported 7-day recall of alcohol, marijuana, cocaine, heroin, and methamphetamine use, and missed cART doses. Overall, 29.3 % individuals reported having ≥1 alcoholic drinks, 5.0 % reported any illicit drug use and 17.0 % reported missed cART doses. In the logistic regression model, compared to no substance use, alcohol use [adjusted odds ratio (AOR) = 2.46, 95 % confidence interval (CI): 1.99-3.05], illicit drug use (AOR = 3.57, 95 % CI: 2.02-6.30), and using both alcohol and illicit drugs (AOR = 4.98, 95 % CI: 3.19-7.79) were associated with missed cART doses. The associations between substance use and likelihood of missing cART doses point to the need of targeting alcohol and illicit drug use to improve adherence among people living with HIV in Latin America.

We investigate mutations and correlates according to HIV-1 subtype after virological failure (VF) of standard first-line antiretroviral therapy (ART) (non-nucleoside/nucleotide reverse transcriptase inhibitor [NNRTI] +2 nucleoside/nucleotide reverse transcriptase inhibitor [N(t)RTI]). SECOND-LINE study participants were assessed at baseline for HIV-1 subtype, demographics, HIV-1 history, ART exposure, viral load (VL), CD4(+) count, and genotypic ART resistance. We used backward stepwise multivariate regression (MVR) to assess associations between baseline variables and presence of ≥3 N(t)RTI mutations, ≥1 NNRTI mutation, ≥3 thymidine analog-N(t)RTI [ta-N(t)RTI] mutations (TAMs), the K65/K70 mutation, and predicted etravirine (ETV)/rilpivirine (RPV) activity. The inclusion p-value for MVR was p < .2. The exclusion p-value from stepwise elimination was p > .05. Of 541 participants, 491 (91%) had successfully characterized baseline viral isolates. Subtype distribution: B (n = 123, 25%), C (n = 202, 41%), CRF01&#95;AE (n = 109, 22%), G (n = 25, 5%), and CRF02&#95;AG (n = 27, 5%). Baseline CD4(+) 200-394 cells/mm(3) were associated with <3 N(t)RTI mutations (OR = 0.47; 95% CI 0.29-0.77; p = .003), absence of the K65/K70 mutation (OR = 0.43; 95% CI 0.26-0.73; p = .002), and higher ETV sensitivity (OR = 0.52; 95% CI 0.35-0.78; p = .002). Recent tenofovir (TDF) use was associated with K65/K70 mutations (OR = 8.91; 95% CI 5.00-15.85; p < .001). Subtype CRF01&#95;AE was associated with ≥3 N(t)RTI mutations (OR = 2.34; 95% CI 1.31-4.17; p = .004) and higher RPV resistance (OR = 2.13; 95% CI 1.30-3.49; p = .003), and subtype C was associated with <3 TAMs (OR = 0.45; 95% CI 0.21-0.99; p = .015). Subtypes CRF01&#95;AE (OR = 2.46; 95% CI 1.26-4.78; p = .008) and G (OR = 4.77; 95% CI 1.44-15.76; p = .01) were associated with K65/K70 mutations. Higher VL at confirmed first-line VF was associated with ≥3 N(t)RTI mutations (OR = 1.39; 95% CI 1.07-1.78; p = .013) and ≥3 TAMs (OR = 1.62; 95% CI 1.15-2.29; p = .006). The associations of first-line resistance mutations across the HIV-1 subtypes in this study are consistent with knowledge derived from subtype B, with some exceptions. Patterns of resistance after failure of a first-line ta-N(t)RTI regimen support using TDF in N(t)RTI-containing second-line regimens, or using N(t)RTI-sparing regimens.

Introduction: Latinos living with HIV in the Americas share a common ethnic and cultural heritage. In North America, Latinos have a relatively high rate of new HIV infections but lower rates of engagement at all stages of the care continuum, whereas in Latin America antiretroviral therapy (ART) services continue to expand to meet treatment needs. In this analysis, we compare HIV treatment outcomes between Latinos receiving ART in North America versus Latin America., Methods: HIV-positive adults initiating ART at Caribbean, Central and South America Network for HIV (CCASAnet) sites were compared to Latino patients (based on country of origin or ethnic identity) starting treatment at North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) sites in the United States and Canada between 2000 and 2011. Cox proportional hazards models compared mortality, treatment interruption, antiretroviral regimen change, virologic failure and loss to follow-up between cohorts., Results: The study included 8400 CCASAnet and 2786 NA-ACCORD patients initiating ART. CCASAnet patients were younger (median 35 vs. 37 years), more likely to be female (27% vs. 20%) and had lower nadir CD4 count (median 148 vs. 195 cells/µL, p<0.001 for all). In multivariable analyses, CCASAnet patients had a higher risk of mortality after ART initiation (adjusted hazard ratio (AHR) 1.61; 95% confidence interval (CI): 1.32 to 1.96), particularly during the first year, but a lower hazard of treatment interruption (AHR: 0.46; 95% CI: 0.42 to 0.50), change to second-line ART (AHR: 0.56; 95% CI: 0.51 to 0.62) and virologic failure (AHR: 0.52; 95% CI: 0.48 to 0.57)., Conclusions: HIV-positive Latinos initiating ART in Latin America have greater continuity of treatment but are at higher risk of death than Latinos in North America. Factors underlying these differences, such as HIV testing, linkage and access to care, warrant further investigation.

Objective: To determine the prevalence of adequate monitoring and the costs of measuring CD4+ T-lymphocytes (CD4+ cell) and human immunodeficiency virus (HIV) viral load in people receiving antiretroviral therapy (ART) in seven countries in the WHO Region of the Americas., Methods: We obtained retrospective, longitudinal data for 14 476 adults who started a first ART regimen at seven HIV clinics in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru between 2000 and 2011. We estimated the proportion of 180-day periods with adequate monitoring, which we defined as at least one CD4+ cell count and one viral load measurement. Factors associated with adequate monitoring were analysed using regression methods. The costs of the tests were estimated., Findings: The median follow-up time was 50.4 months; the proportion of 180-day periods with adequate CD4+ cell counts was 69% while the proportion with adequate monitoring was 62%. Adequate monitoring was more likely in participants who were older, who started ART more recently, whose first regimen included a non-nucleoside reverse transcriptase inhibitor or who had a CD4+ cell count less than 200 cells/µl at ART initiation. The cost of one CD4+ cell count ranged from 7.37 United States dollars (US$) in Argentina to US$ 64.09 in Chile; the cost of one viral load measurement ranged from US$ 20.34 in Brazil to US$ 186.28 in Haiti., Conclusion: In HIV-infected participants receiving ART in the WHO Region of the Americas, CD4+ cell count and viral load monitoring was often carried out less frequently than regional guidelines recommend. The laboratory costs of monitoring varied greatly.

Introduction: Long-term survival of HIV patients after initiating highly active antiretroviral therapy (ART) has not been sufficiently described in Latin America and the Caribbean, as compared to other regions. The aim of this study was to describe the incidence of mortality, loss to follow-up (LTFU) and associated risk factors for patients enrolled in the Caribbean, Central and South America Network (CCASAnet)., Methods: We assessed time from ART initiation (baseline) to death or LTFU between 2000 and 2014 among ART-naïve adults (≥18 years) from sites in seven countries included in CCASAnet: Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru. Kaplan-Meier techniques were used to estimate the probability of mortality over time. Risk factors for death were assessed using Cox regression models stratified by site and adjusted for sex, baseline age, nadir pre-ART CD4 count, calendar year of ART initiation, clinical AIDS at baseline and type of ART regimen., Results: A total of 16,996 ART initiators were followed for a median of 3.5 years (interquartile range (IQR): 1.6-6.2). The median age at ART initiation was 36 years (IQR: 30-44), subjects were predominantly male (63%), median CD4 count was 156 cells/µL (IQR: 60-251) and 26% of subjects had clinical AIDS prior to starting ART. Initial ART regimens were predominantly non-nucleoside reverse transcriptase inhibitor based (86%). The cumulative incidence of LTFU five years after ART initiation was 18.2% (95% confidence interval (CI) 17.5-18.8%). A total of 1582 (9.3%) subjects died; the estimated probability of death one, three and five years after ART initiation was 5.4, 8.3 and 10.3%, respectively. The estimated five-year mortality probability varied substantially across sites, from 3.5 to 14.0%. Risk factors for death were clinical AIDS at baseline (adjusted hazard ratio (HR)=1.65 (95% CI 1.47-1.87); p<0.001), lower baseline CD4 (HR=1.95 (95% CI 1.63-2.32) for 50 vs. 350 cells/µL; p<0.001) and older age (HR=1.47 (95% CI 1.29-1.69) for 50 vs. 30 years at ART initiation; p<0.001)., Conclusions: In this large, long-term study of mortality among HIV-positive adults initiating ART in Latin America and the Caribbean, overall estimates of mortality were heterogeneous, generally falling between those reported in high-income countries and sub-Saharan Africa.

HIV stigma as a barrier to retention in HIV care has not been well-studied outside the United States. We conducted a case-control study in Lima, Peru to examine this issue. Cases were out-of-care for ≥12 months (n = 66) and controls were recruited from patients in active care presenting for a clinic visit (n = 110). A previously validated HIV stigma scale with four domains was used. Associations between being out-of-care and each stigma domain were assessed using multivariable logistic regression. Stigma scores were highest for disclosure concerns. Modest associations were found for greater disclosure concerns (OR 1.16; 95 % CI 0.99, 1.36) and concerns with public attitudes (OR 1.20; 95 % CI 1.03, 1.40). Enacted stigma and negative self-image showed non-linear associations with being out-of-care that plateaued or declined, respectively, at higher levels of stigma. The threshold effect for enacted stigma warrants further exploration, while disclosure concerns may be especially amenable to intervention in this population.

Background: Access to highly active antiretroviral therapy (HAART) is expanding in Latin America. Many patients require second and third line therapy due to toxicity, tolerability, failure, or a combination of factors. The need for third line HAART, essential for program planning, is not known., Methods: Antiretroviral-naïve patients ≥18 years who started first HAART after January 1, 2000 in Caribbean, Central and South America Network (CCASAnet) sites in Argentina, Brazil, Honduras, Mexico, and Peru were included. Clinical trials participants were excluded. Third line HAART was defined as use of darunavir, tipranavir, etravirine, enfuvirtide, maraviroc or raltegravir. Need for third line HAART was defined as virologic failure while on second line HAART., Results: Of 5853 HAART initiators followed for a median of 3.5 years, 310 (5.3%) failed a second line regimen and 44 (0.8%) received a third line regimen. Cumulative incidence of failing a 2nd or starting a 3rd line regimen was 2.7% and 6.0% three and five years after HAART initiation, respectively. Predictors at HAART initiation for failing a second or starting a third line included female sex (hazard ratio [HR] = 1.54, 95% confidence interval [CI] 1.18-2.00, p = 0.001), younger age (HR = 2.76 for 20 vs. 40 years, 95% CI 1.86-4.10, p<0.001), and prior AIDS (HR = 2.17, 95% CI 1.62-2.90, p<0.001)., Conclusions: Third line regimens may be needed for at least 6% of patients in Latin America within 5 years of starting HAART, a substantial proportion given the large numbers of patients on HAART in the region. Improved accessibility to third line regimens is warranted.

Objectives: In developing nations, the use of operational parameters (OPs) in the prediction of clinical care represents a missed opportunity to enhance the care process. We modeled the impact of multiple measurements of antiretroviral treatment (ART) adherence on antiretroviral treatment outcomes in Peru., Design and Methods: Retrospective cohort study including ART naïve, non-pregnant, adults initiating therapy at Hospital Nacional Cayetano Heredia, Lima-Peru (2006-2010). Three OPs were defined: 1) Medication possession ratio (MPR): days with antiretrovirals dispensed/days on first-line therapy; 2) Laboratory monitory constancy (LMC): proportion of 6 months intervals with ≥1 viral load or CD4 reported; 3) Clinic visit constancy (CVC): proportion of 6 months intervals with ≥1 clinic visit. Three multi-variable Cox proportional hazard (PH) models (one per OP) were fit for (1) time of first-line ART persistence and (2) time to second-line virologic failure. All models were adjusted for socio-demographic, clinical and laboratory variables., Results: 856 patients were included in first-line persistence analyses, median age was 35.6 years [29.4-42.9] and most were male (624; 73%). In multivariable PH models, MPR (per 10% increase HR=0.66; 95%CI=0.61-0.71) and LMC (per 10% increase 0.83; 0.71-0.96) were associated with prolonged time on first-line therapies. Among 79 individuals included in time to second-line virologic failure analyses, MPR was the only OP independently associated with prolonged time to second-line virologic failure (per 10% increase 0.88; 0.77-0.99)., Conclusions: The capture and utilization of program level parameters such as MPR can provide valuable insight into patient-level treatment outcomes.

Raltegravir as initial HIV therapy was examined in a double-blind study; 160 patients were randomized to raltegravir (400 mg bid after dose-ranging), 38 to efavirenz, both with tenofovir/lamivudine. At week 240, HIV-RNA remained <50 copies per milliliter in 68.8% (raltegravir) versus 63.2% (efavirenz), and CD4 increases were 302 versus 276 cells per microliter, respectively. Early HIV-RNA decline predicted later CD4 increases in both groups. Raltegravir resistance was observed in 3 of 10 raltegravir recipients with virologic failure. Few drug-related adverse events were reported after week 48. Raltegravir had minimal effect on laboratory values, including lipids. Raltegravir with tenofovir/lamivudine showed durable efficacy and good tolerability over 5 years.

Background: Diagnosis of pulmonary tuberculosis (TB) among human immunodeficiency virus (HIV) patients remains complex and demands easy to perform and accurate tests. Xpert®MTB/RIF (MTB/RIF) is a molecular TB diagnostic test which is rapid and convenient; the test requires minimal human resources and reports results within two hours. The majority of performance studies of MTB/RIF have been performed in high HIV burden settings, thus TB diagnostic studies among HIV patients in low HIV prevalence settings such as Peru are still needed., Methodology/principal Findings: From April 2010 to May 2011, HIV-positive patients with high clinical suspicion of TB were enrolled from two tertiary hospitals in Lima, Peru. Detection of TB by MTB/RIF was compared to a composite reference standard Löwenstein-Jensen (LJ) and liquid culture. Detection of rifampicin resistance was compared to the LJ proportion method. We included 131 patients, the median CD4 cell count was 154.5 cells/mm(3) and 45 (34.4%) had TB. For TB detection among HIV patients, sensitivity of MTB/RIF was 97.8% (95% CI 88.4-99.6) (44/45); specificity was 97.7% (95% CI 91.9-99.4) (84/86); the positive predictive value was 95.7% (95% CI 85.5-98.8) (44/46); and the negative predictive value, 98.8% (95% CI 93.6-99.8) (84/85). MTB/RIF detected 13/14 smear-negative TB cases, outperforming smear microscopy [97.8% (44/45) vs. 68.9% (31/45); p = 0.0002]. For rifampicin resistance detection, sensitivity of MTB/RIF was 100% (95% CI 61.0-100.0) (6/6); specificity was 91.0% (95% CI 76.4-96.9) (30/33); the positive predictive value was 66.7% (95% CI 35.4-87.9) (6/9); and the negative predictive value was 100% (95% CI 88.7 -100.0) (30/30)., Conclusions/significance: In HIV patients in our population with a high clinical suspicion of TB, MTB/RIF performed well for TB diagnosis and outperformed smear microscopy.

Background: HIV-infected individuals have heightened cancer risk. With the advent of highly active antiretroviral therapy (HAART), the frequency of some AIDS-defining cancers (ADC) has decreased although certain non-AIDS-defining cancers (NADC) are becoming more frequent. Cancers among HIV-infected individuals in Latin American and the Caribbean have not yet been carefully studied., Methods: Cancer cases among the Caribbean, Central and South American network for HIV Research (CCASAnet) cohort were identified reviewing clinical records and pre-existing databases., Results: There were 406 cancers reported: 331 ADC (224 Kaposi sarcomas and 98 non Hodgkin lymphomas). Most frequent NADC (n = 75) were Hodgkin lymphoma and skin cancers. Seventy-three percent of NADC and 45% of ADC were diagnosed >1 year after HIV diagnosis. Fifty-six percent of ADC occurred before HAART start. Median time from HAART start until cancer diagnosis was 2.5 years for NADC and 0.5 years for ADC (P = <0.001). Within 3372 HAART starters, 158 were diagnosed with 165 cancers (82.4% ADC); 85 cases were previous to or concomitant with HAART initiation. Incidence of cancer after HAART initiation in 8080 person-years of follow-up was 7.2 per 1000 person-years (95% confidence interval = 5.5 to 9.3) for ADC and 2.7 (95% confidence interval = 1.8 to 4.1) for NADC; incidence was higher in the first 2 months, particularly for ADC (47.6). A pre-HAART ADC was a predictor of mortality after adjusting for age, sex, and CD4 at HAART initiation., Conclusions: ADC were the most frequent cancers in this region and were often diagnosed close to HIV diagnosis and HAART start. Incidence of cancer was highest around HAART initiation.

Regulatory T cells (Tregs) blunt uncontrolled immune responses. In advanced human immunodeficiency virus (HIV) infection, the total number of Tregs is decreased, but the proportion of T cells with a regulatory phenotype is highly variable. We studied CD4(+)CD25(+)FoxP3(+) T cells from patients successfully treated with combination antiretroviral therapy (ART). The proportion of CD4(+)CD25(+)FoxP3(+) cells transiently increased and then decreased from a median of 13% at baseline to 5.1% at 48 weeks, similar to values in normal subjects. These data suggest that with effective therapy, the regulatory cell numbers normalize, and that the inflammatory signals driving their production may also abate.

Background: There are few published reports of research training needs assessments and research training programs. In an effort to expand this nascent field of study and to bridge the gap between research and practice, we sought to systematically assess the research training needs of health care professionals working at Peruvian governmental institutions leading HIV and tuberculosis (TB) control and among senior stakeholders in the field., Methods: Six institutional workshops were conducted with the participation of 161 mid-level health professionals from agencies involved in national HIV and TB control. At each workshop informants completed a structured questionnaire and participated in small and large group discussions. Additional data and institutional commitment was obtained through in-depth interviews from 32 senior managers and researchers from the Ministry of Health, academia and NGOs., Results: Participants exhibited an overwhelming receptivity for additional research training, observing a gap between current levels of research training and their perceived importance. Specialized skills in obtaining funding, developing research protocols, particularly in operational, behavioral and prevention research were considered in greatest need. Beyond research training, participants identified broader social, economic and political factors as influential in infectious disease control., Conclusions: The needs assessment suggests that future training should focus on operational research techniques, rather than on clinical skill building or program implementation only. Strengthening health systems not only requires additional research training, but also adequate financial resources to implement research findings.

Background: HAART rollout in Latin America and the Caribbean has increased from approximately 210,000 in 2003 to 390,000 patients in 2007, covering 62% (51%-70%) of eligible patients, with considerable variation among countries. No multi-cohort study has examined rates of and reasons for change of initial HAART in this region., Methodology: Antiretroviral-naïve patients >or= 18 years who started HAART between 1996 and 2007 and had at least one follow-up visit from sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru were included. Time from HAART initiation to change (stopping or switching any antiretrovirals) was estimated using Kaplan-Meier techniques. Cox proportional hazards modeled the associations between change and demographics, initial regimen, baseline CD4 count, and clinical stage., Principal Findings: Of 5026 HIV-infected patients, 35% were female, median age at HAART initiation was 37 years (interquartile range [IQR], 31-44), and median CD4 count was 105 cells/uL (IQR, 38-200). Estimated probabilities of changing within 3 months and one year of HAART initiation were 16% (95% confidence interval (CI) 15-17%) and 28% (95% CI 27-29%), respectively. Efavirenz-based regimens and no clinical AIDS at HAART initiation were associated with lower risk of change (hazard ratio (HR) = 1.7 (95% CI 1.1-2.6) and 2.1 (95% CI 1.7-2.5) comparing neverapine-based regimens and other regimens to efavirenz, respectively; HR = 1.3 (95% CI 1.1-1.5) for clinical AIDS at HAART initiation). The primary reason for change among HAART initiators were adverse events (14%), death (5.7%) and failure (1.3%) with specific toxicities varying among sites. After change, most patients remained in first line regimens., Conclusions: Adverse events were the leading cause for changing initial HAART. Predictors for change due to any reason were AIDS at baseline and the use of a non-efavirenz containing regimen. Differences between participant sites were observed and require further investigation.

Background: Whereas access to antiretroviral therapy (ART) for HIV-infected individuals in the developing world is increasing, data on factors impacting initial regimen durability are lacking., Methods: Retrospective review patients starting initial ART at Instituto de Medicine Tropical (Lima, Peru) April 1, 2004 to December 30, 2007. Survival methods (Kaplan-Meier, Cox proportional hazard) assessed factors associated with regimen durability including an interaction term between nucleoside reverse transcriptase inhibitor backbone and time., Results: Decreased initial regimen durability was observed with weight <60 kg [hazards ratio (HR) = 1.77; 95% confidence interval (CI) = 1.25-2.51], CD4 <200 (HR = 1.73; 95% CI = 1.03-2.91), and zidovudine (AZT) use at <120 days (HR = 2.09; 95% CI = 1.22-3.57). In contrast, after 120 days, AZT use decreased risk of discontinuation (HR = 0.52; 95% CI = 0.28-0.95). Early (<120 days) toxicity-related discontinuation of AZT containing regimens was observed in 44% of patients <50 kg at baseline vs. 14% of those >70 kg. An increased risk of early toxicity-related discontinuation of AZT-containing regimens was observed for baseline weight <60 kg (HR = 2.52; 95% CI = 1.46-4.35)., Conclusions: Lower baseline weight and lower CD4 values at ART initiation were associated with decreased regimen durability. Compared with didanosine/stavudine, AZT use initially increased, then subsequently (>120 days) lowered hazards for regimen discontinuation. Weight <60 kg was associated with an increased risk of toxicity-related AZT discontinuation. As ART use expands globally, further study into maximally durable, least toxic regimens, and the role of weight-based AZT dosing is imperative.

Objectives: The purpose of this study was to evaluate the safety and efficacy of raltegravir vs efavirenz-based antiretroviral therapy after 96 weeks in treatment-naive patients with HIV-1 infection., Methods: Multicenter, double-blind, randomized study of raltegravir (100, 200, 400, or 600 mg twice a day) vs efavirenz (600 mg every day), both with tenofovir/lamivudine (TDF/3TC), for 48 weeks, after which raltegravir arms were combined and all dosed at 400 mg twice a day. Eligible patients had HIV-1 RNA > or =5000 copies per milliliter and CD4 T cells > or =100 cells per microliter., Results: One hundred ninety-eight patients were randomized and treated; 160 received raltegravir and 38 received efavirenz. At week 96, 84% of patients in both groups achieved HIV-1 RNA <400 copies per milliliter; 83% in the raltegravir group and 84% in the efavirenz group achieved <50 copies per milliliter (noncompleter = failure). Both groups showed similar increases in CD4 T cells (221 vs 232 cells/uL, respectively). An additional 2 patients (1 in each group) met the protocol definition of virologic failure between weeks 48 and 96; no known resistance mutations were observed in the raltegravir recipient; the efavirenz recipient had nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor resistance mutations. Investigator reported drug-related clinical adverse events (AEs) were less frequent with raltegravir (51%) than efavirenz (74%). Drug-related AEs occurring in >10% of patients in either group were nausea in both groups and dizziness and headache in the efavirenz group. Laboratory AEs remained infrequent. Raltegravir had no adverse effect on total or low-density lipoprotein cholesterol or on triglycerides. Neuropsychiatric AEs remained less frequent with raltegravir (34%) than efavirenz (58%). There were no drug-related serious AEs in patients receiving raltegravir., Conclusions: In antiretroviral therapy-naive patients, raltegravir with TDF/3TC had potent antiretroviral activity, which was similar to efavirenz/TDF/3TC and was sustained to week 96. Raltegravir was generally well tolerated; drug-related AEs were less frequent in patients treated with raltegravir compared with efavirenz.

Background: Although nearly 2 million people live with HIV in Latin America and the Caribbean, mortality rates after initiation of highly active antiretroviral therapy (HAART) have not been well described., Methods: Five thousand one hundred fifty-two HIV-infected, antiretroviral-naive adults from clinics in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru starting HAART during 1996-2007 were included. First-year mortality rates and their association with demographics, regimen, baseline CD4, and clinical stage were assessed., Results: Overall 1-year mortality rate was 8.3% [95% confidence interval (CI): 7.6% to 9.1%], although variable across sites: 2.6%, 3.7%, 6.0%, 13.0%, 10.8%, 3.5%, and 9.8% for clinics in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru, respectively. Eighty percent of deaths occurred within the first 6 months. Median baseline CD4 was 107 cells per milliliter, ranging from 79 (Peru) to 163 (Argentina). Mortality estimates adjusting for CD4 were similar across sites (1.1%-2.8% for CD4 = 200), except for Haiti, 7.5%, and Honduras, 7.0%. Death was associated with lower CD4 [adjusted hazard ratio for CD4 = 200 vs. CD4 = 50 was 0.58; 95% CI: 0.40 to 0.85] and clinical AIDS (hazard ratio = 3.1; 95% CI: 2.1 to 4.5)., Conclusions: Mortality rates were similar to those reported elsewhere for resource-limited settings. Disease stage at HAART initiation, treatment eligibility criteria, program age, and background mortality rates may explain some variability in prognosis between sites.

Background: In 2004, cases of HIV and syphilis were reported in an indigenous community in the Peruvian Amazon. This study sought to determine the prevalence of HIV and syphilis in four remote communities of the same indigenous ethnic group located further from an urban center than the original community, and to identify risk factors for HIV and syphilis transmission., Methods: Rapid and confirmatory tests for HIV and syphilis were performed. A questionnaire elicited demographic information, risk factors for sexually transmitted infections, and knowledge/beliefs about HIV/AIDS., Results: We collected 282 blood samples and conducted interviews with 281 (99.6%) participants. The confirmed syphilis prevalence rate was 3.2% (9/282; 3.7% (5/135) for men and 2.7% (4/147) for women). The confirmed HIV prevalence rate was 0.7% (2/282), with both infections in men who had sex with men (MSM). Self-reported MSM activity was 39.7%. There was poor knowledge about HIV infection, transmission, and prevention, and low acceptance of known prevention methods., Conclusions: HIV and syphilis are now prevalent in remote Amazonian communities of an indigenous group in Peru. Expansion of the HIV epidemic into the Amazon requires an urgent public health response.

Objectives: Our aim was to investigate CD4+ cell recovery and adverse outcome after highly active antiretroviral therapy (HAART) under the Peruvian National Program for HIV., Methods: A prospective, observational study was conducted between May 2004 and September 2005. Data were collected from records of patients receiving HAART at a public hospital under the Peruvian National Program for HIV. Predictors of CD4+ cell count recovery and adverse outcome were analyzed by multiple regression., Results: Three hundred and twenty-six patients were included in the study. The mean increase in CD4+ cell count at six months was 114 cells/microl (95% confidence interval: 103-126). Patients with a lower CD4+ cell count at baseline and those starting HAART with a didanosine-based regimen had a higher increase in CD4+ cell count at six months. Patients starting HAART with a stavudine-based regimen had a lower increase in CD4+ cell count at six months. World Health Organization clinical stage IV at diagnosis of HIV infection, a low body weight at baseline, and starting HAART with a stavudine-based regimen were independently associated with an adverse outcome., Conclusions: The CD4+ cell response to HAART under Peruvian National Program for HIV was comparable with reports from other countries. However, the fact that advanced clinical disease predicted adverse outcome emphasizes the need for earlier access to HAART.

Background: Raltegravir is an HIV-1 integrase strand-transfer inhibitor with potent in vitro activity. This study explored the antiretroviral activity and safety of raltegravir in treatment-naive patients with plasma HIV-1 RNA levels > or = 5000 copies/mL and CD4 T-cell counts > or = 100 cells/mm., Methods: Multicenter, double-blind, randomized, controlled study of raltegravir at doses of 100, 200, 400, and 600 mg twice daily versus efavirenz at a dose of 600 mg/d, all in combination with tenofovir at a dose of 300 mg/d and lamivudine at a dose of 300 mg/d (clinicaltrials.gov identifier: NCT00100048)., Results: In the 198 patients treated (160 on raltegravir and 38 on efavirenz), the mean HIV-1 RNA level ranged from 4.6 to 4.8 log10 copies/mL at baseline. At weeks 2, 4, and 8, the proportion of patients achieving an HIV-1 RNA level <50 copies/mL was greater in each of the raltegravir treatment groups than in the efavirenz group. By week 24, all treatment groups appeared similar, with plasma HIV-1 RNA levels <400 copies/mL in 85% to 98% of patients and <50 copies/mL in 85% to 95% of patients. These reductions were maintained through week 48 in 85% to 98% of patients and in 83% to 88% of patients, respectively. Five (3%) patients on raltegravir and 1 (3%) on efavirenz experienced virologic failure before week 48. Drug-related clinical adverse events were less common with raltegravir than with efavirenz. After 24 and 48 weeks of treatment, raltegravir did not result in increased serum levels of total cholesterol, low-density lipoprotein cholesterol, or triglycerides., Conclusions: Raltegravir at all doses studied was generally well tolerated in combination with tenofovir and lamivudine. Raltegravir exhibited potent and durable antiretroviral activity similar to that of efavirenz at 24 and 48 weeks but achieved HIV-1 RNA levels below detection at a more rapid rate.

Background: A total lymphocyte count (TLC) of 1200 cells/mL has been used as a surrogate for a CD4 count of 200 cells/microL in resource-limited settings with varying results. We developed a more effective method based on a decision tree algorithm to classify subjects., Methods: A decision tree was used to develop models with the variables TLC, hemoglobin, platelet count, gender, body mass index, and antiretroviral treatment status of subjects from the University of Alabama at Birmingham (UAB) observational database. Models were validated on data from the Birmingham Veterans Affairs Medical Center (BVAMC) and Zambia, with primary decision trees also generated from these data., Results: A total of 1189 patients from the UAB observational database were included. The UAB decision tree classified a CD4 count < or =200 cells/microL as better than a TLC cut-point of 1200 cells/mL, based on the area under the curve of the receiver-operator characteristic curve (P < 0.0001). When applied to data from the BVAMC and Zambia, the UAB-based decision tree performed better than the TLC cut-point of 1200 cells/mL (BVAMC: P < 0.0001; Zambia: P = 0.0009) but worse than a decision tree based on local data (BVAMC: P < or = 0.0001; Zambia: P < or = 0.0001)., Conclusion: A decision tree algorithm based on local data identifies low CD4 cell counts better than one developed from a different population or a TLC cut-point of 1200 cells/mL.

Little data are available on how HIV and other sexually transmitted infections (STIs) affect indigenous people in Latin America, including Peru. We conducted a sero-epidemiologic survey of HIV infection and syphilis in a native community, the Chayahuita, an indigenous population in the Amazon region of Peru. The seroprevalences of HIV and syphilis in adults were 7.5% (6 of 80) and 6.3% (5 of 80), respectively. None of the participants had ever used a condom. Male to male sexual behavior was common. At the current levels of HIV prevalence, there is the risk of a negative impact on the survival of the Chayahuita ethnic group as a whole. The outcomes of this study highlight the need for urgent medical and anthropologic approaches to stop HIV transmission in indigenous Amazonian communities.

We characterized regulatory T cells from antiretroviral-naive HIV patients by flow cytometry. The proportion of CD4 cells positive for CD25 and Foxp3 was increased, mainly in those with CD4 cell counts less than 200 cells/microl. The total number of Foxp3-positive cells correlated with the CD4 cell count. Further studies are needed on whether Foxp3-positive cell numbers or function explain the susceptibility to autoimmune and inflammatory diseases seen in some patients with advanced HIV.

Introduction: Diarrhea, a common complication and one of the most important causes of malabsorption and malnutrition in AIDS patients. Our objective was to determine the parasitic causes of diarrhea in patients with HIV-AIDS at the Cayetano Heredia National Hospital (Lima, Peru)., Methods: We included 217 HIV-AIDS patients who reported diarrhea between May 2002 and September 2005. We analyzed 1-3 stool samples per patient using six methods to detect oocysts, cysts, eggs and larvae of parasites., Results: The average patients age was 34.5 years (range 15-68); 75.12% were males. Patients with diarrhea during two weeks or more were 149/217 (68.66%). A total of 123 parasites were detected in 103/217 patients (47.5%) 18/217 (8.3%) had mixed parasitic infections. Cryptosporidium spp. was the most frequent parasite detected. It was more prevalent in the group of patients who had diarrhea for two or more weeks than those who had diarrhea for less than two weeks (22.82% vs. 10.29%, p=0.029). Other frequent parasitosis cases were isosporidiasis (10.6%), giardiasis (8.3%) and strongyloidiasis (6.9%)., Conclusion: Intestinal parasitosis is frequent in HIV-AIDS patients at the Cayetano Heredia National Hospital. The most common opportunistic pathogens were Criptosporidium spp. and Isospora belli and the most frequent non-opportunistic pathogens were Giardia lamblia and Strongyloidiasis stercoralis.

We report a case of acute, self-resolving leptospirosis presenting in a HIV-positive patient from the Peruvian Amazon. The patient presented with an undifferentiated acute febrile illness that resolved without treatment, diagnosed retrospectively as leptospirosis by serology and real-time polymerase chain reaction. Five months later, he was admitted because of a febrile illness with jaundice, hepatosplenomegaly, peripheral edema, and oral candidiasis. Because of the clinical suspicion of AIDS, stored sera of the previous admission were tested, and HIV seropositivity was confirmed, proving that the condition was present at the first admission. Acute leptospirosis in HIV coinfection is not inevitably severe, and there is probably a wide variation in clinical manifestations similar to what occurs in immuno-competent hosts.

Unlabelled: This study was done in patients with HIV infection and upper digestive symptoms as odinophagia, dysphagia and/or retrosternal pain who attended the Cayetano Heredia National Hospital in Lima, Perú. Those included in the study had an upper endoscopy and a CD4 count. Also previous opportunistic infections were determined. Samples were taken from the oropharyngeal cavity and sent for direct exam and culture. During endoscopy, photos were taken from the upper, middle, and lower third of the esophagus and the esophageal compromise was classified. Biopsies and brushings samples were obtained and sent for direct exam, histopathology and culture., Results: 751 patients with HIV infection attended the Cayetano Heredia National Hospital between May 1996 and June 1999, 83 were included due to esophageal symptoms. Male / Female ratio : 4/1, mean age : 30.95 +/- 9.87. Cultures positive for Candida: 84.30% of esophageal biopsies samples, 88% of esophageal brushings and 60.2% of oropharyngeal cavity. The C. albicans species was isolated in 95.7% of biopsies, 93% of brushings and 96% of oropharyngeal cavity. The most common endoscopic finding was white plaques (71%), endoscopic grade 3 (36.1%). The most frequent previous opportunistic infection was PCP pneumonia followed by TBC. The positive predictive value for white plaques in patients with dysphagia and odynophagia was 89.8%. CD4 count between 0 and 50 lymphocytes per mm(3) was seen in 70% of the cases. The mean of CD4 lymphocytes of these patients was lower (p< 0.01) when compared to the mean of patients in the control group with no symptoms., Conclusions: Candida albicans was the most common isolated pathogen in the esophagus in patients with HIV infection and with esophageal symptoms, a significant difference in CD4 count between these patients and the control group was determined. The positive predictive value for finding esophageal white plaques in patients dysphagia and odinophagia was high, and there was no difference between the average of CD4 count and the endoscopic grade of esophageal involvement.

Objective: Genotype determination and risk group analysis of HIV-1 infected individuals in selected regions of South America., Design: Cross-sectional convenience sampling of HIV-1-positive individuals in Peru, Ecuador, Uruguay and Paraguay from March, 1994 through September, 1998., Methods: HIV-1-positive subjects were identified through the national AIDS surveillance program in each country. A standardized questionnaire was used to obtain demographic, clinical and risk factor data on each study subject. Viral DNA was extracted from participants' peripheral blood mononuclear cells either directly or after co-cultivation. A nested PCR was used to obtain selected fragments of the envelope genes for genotyping by the heteroduplex mobility assay (HMA). A 600 bp sequence encompassing the V3 loop was sequenced from a selection of 23 of these samples for phylogenetic analysis and confirmation of HMA genotype., Results: Among the 257 successfully genotyped HIV-1-positive samples, genotype B was found in 98.3% (228/232) of those obtained from subjects in Peru, Ecuador, and Paraguay. In contrast, 56% (14/25) of the samples from Uruguay were genotype F, and the remainder were genotype B. Genotype F was detected for the first time in Peru (2/224) and Paraguay (1/4), and genotype A for the first time in Peru (1/224). Phylogenetic analysis confirmed the genotype identified by HMA in the 23 samples sequenced. There was no detectable genetic clustering of HIV-1 within the different high-risk groups or geographic locations., Conclusions: These findings verify and extend the presence of several different HIV-1 genotypes in South America.

Background and Objectives: A survey was conducted to determine the sexual behavior practices and prevalence of HIV-1, HTLV-I/II, and T. pallidum infections among unlicensed female sex workers (FSWs) in Lima, Peru., Goal of This Study: To assess the role of unlicensed FSWs as a potential source of retroviral and T. pallidum infection., Study Design: Female sex workers from 15 brothels were enrolled. Sera samples were obtained and tested for antibodies to HIV-1, HTLV-I, and Treponema pallidum., Results: Of 158 FSWs studied, all were negative for HIV-1, 6 were positive for HTLV-I, and 5 were positive for Treponema pallidum. Of their male clients, 75% used condoms, whereas only 3% reported condom use with their steady partners. When condoms were always used by clients, the history of a sexually transmitted disease was significantly reduced (p < 0.01), and the prevalence of HTLV-I (p < 0.05) and syphilis was lower among these workers., Conclusion: Data suggested that the low rate of sexually transmitted diseases among FSWs reflected the high rate of condom use by their male clients.

Objective: To determine the extent of the HIV-1 epidemic in Peru., Design: Part of a national serosurvey in Peru., Methods: Between January 1986 and December 1990, 140,976 serum samples were tested for HIV-1 antibody., Results: HIV-1 antibody was found in a high percentage of serum samples provided by 4300 homosexual men (26%), 2204 male sexually transmitted disease patients (10%), 145 drug users (13%), 269 hemophiliacs (10%), and 146 unlicensed female prostitutes (10%). In addition, the prevalence of HIV-1 infection increased substantially among these groups between the beginning and end of the survey period. A low but rising prevalence of HIV-1 antibody was found during this period among serum samples provided by 83,526 blood donors and 11,101 military personnel:total period prevalence, 0.25 and 0.32%, respectively., Conclusion: These data indicate that HIV-1 infection is epidemic in Peru among groups at high risk of sexually and parenterally transmitted diseases, and that the risk of infection appears to be low but possibly increasing among the general population.