Suchergebnisse

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

Abstract
Introduction
Guided by an intersectional approach, we assessed the association between social categories (individual and combined) on time to linkage to HIV care in Tennessee.

Methods
Tennessee residents diagnosed with HIV from 2012-2016 were included in the analysis (n=3750). Linkage was defined by the first CD4 or HIV RNA test date after HIV diagnosis. We used Cox proportional hazards models to assess the association of time to linkage with individual-level variables. We modeled interactions between race, age, gender, and HIV acquisition risk factor (RF), to understand how these variables jointly influence linkage to care.

Results
Age, race, and gender/RF weAima A. Ahonkhaire strong individual (p < 0.001 for each) and joint predictors of time to linkage to HIV care (p < 0.001 for interaction). Older individuals were more likely to link to care (aHR comparing 40 vs. 30 years, 1.20, 95%CI 1.11-1.29). Blacks were less likely to link to care than Whites (aHR= 0.73, 95% CI: 0.67-0.79). Men who have sex with men (MSM) (aHR = 1.18, 95%CI: 1.03-1.34) and heterosexually active females (females) (aHR = 1.32, 95%CI: 1.14-1.53) were more likely to link to care than heterosexually active males. The three-way interaction between age, race, and gender/RF showed that Black males overall and young, heterosexually active Black males in particular were least likely to establish care.

Conclusions
Racial disparities persist in establishing HIV care in Tennessee, but data highlighting the combined influence of age, race, gender, and sexual orientation suggest that heterosexually active Black males should be an important focus of targeted interventions for linkage to HIV care.

AbstractIntroductionReducing high‐risk behaviours (i.e. multiple partnership, condomless anal/vaginal sex, alcohol use before sex, illicit drug use) after HIV diagnosis is critical for curtailing HIV transmission. We designed an intervention to explore peer‐ counselling in reducing high‐risk behaviours among newly diagnosed HIV‐positive Chinese men who have sex with men (MSM).MethodsWe randomized 367 newly diagnosed HIV‐positive men to either standard‐of‐care (SOC; n = 183) or peer‐counselling intervention (n = 184), and followed them for 12 months (visit at 0‐, 3‐, 6‐, 9‐ and 12‐month). SOC participants received counselling on high‐risk behaviour reduction by clinic staff. Intervention participants received both SOC and peer counselling. A generalized estimating equation was used to compare pre‐post diagnosis high‐risk behaviour change; logistic regression was used to assess the likelihood of practicing high‐risk behaviours between intervention and SOC participants. Both intent‐to‐treat and per‐protocol (full‐dosage) approaches were used for the analyses.ResultsFor pre‐ and post‐diagnosis comparisons, multiple partnership fell from 50% to 16% (p < 0.001), alcohol use before sex from 23% to 9% (p = 0.001), illicit drug use from 33% to 6% (p < 0.001), condomless anal sex from 47% to 4% (insertive from 23% to 2%; receptive from 36% to 3%; p < 0.001). In the intent‐to‐treat analysis accounting for repeated measures, peer counselling was more likely to reduce insertive anal sex (AOR = 0.65; 95% CI: 0.45 to 0.94), condomless anal sex (AOR = 0.27; 95% CI: 0.10 to 0.64) and illicit drug use (AOR = 0.32; 95% CI: 0.16 to 0.64). In the per‐protocol analysis, peer counselling was associated with a lower likelihood of using illicit drug (OR = 0.23; 95% CI: 0.07 to 0.81) and having condomless vaginal sex with women (OR = 0.12; 95% CI: 0.07 to 0.98).ConclusionsWe observed a 14 to 43% decrease in the prevalence of selected high‐risk behaviours after HIV diagnosis. Peer counselling had a greater impact in reducing condomless anal sex with men, illicit drug use and condomless vaginal sex with women over time. Future studies with exclusive peer‐counselling arm are necessary to test its efficacy and effectiveness among Chinese MSM.Clinical Trial Number: NCT01904877

AbstractBackgroundHIV 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.MethodsWLWH (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.ResultsAmong 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.ConclusionHIV 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.

BackgroundA low body mass index (BMI) at antiretroviral therapy (ART) initiation is a strong predictor of mortality among HIV‐infected adults in resource‐constrained settings. The relationship between nutrition and inflammation‐related serum biomarkers and early treatment outcomes (e.g., less than 90 days) in this population is not well described.MethodsAn observational cohort of 142 HIV‐infected adults in Lusaka, Zambia, with BMI under 16 kg/m2or CD4+lymphocyte counts of less than 50 cells/mm3, or both, was followed prospectively during the first 12 weeks of ART. Baseline and serial post‐treatment phosphate, albumin, ferritin and highly sensitive C‐reactive protein (hsCRP) serum levels were measured. The primary outcome was mortality.ResultsLower baseline phosphate and albumin serum levels, and higher ferritin and hsCRP, were significantly associated with mortality prior to 12 weeks (p < 0.05 for all comparisons), independent of known risk factors for early ART‐associated mortality in sub‐Saharan Africa. The time‐dependent interval change in albumin was associated with mortality after adjusting for the baseline value (AHR 0.62 [0.43, 0.89] per 5 g/L increase), but changes in the other biomarkers were not.ConclusionsThe predictive value of serum biomarkers for early mortality in a cohort of adults with malnutrition and advanced HIV in a resource‐constrained setting was primarily driven by pre‐treatment values, rather than post‐ART changes. Interventions to promote earlier HIV diagnosis and treatment, address nutritional deficiencies, and identify the etiologies of increased systemic inflammation may improve ART outcomes in this vulnerable population.

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

IntroductionWe assessed trends in HIV Care Continuum outcomes associated with delayed disease progression and reduced transmission within a large Latin American cohort over a decade: clinical retention, combination antiretroviral therapy (cART) use and viral suppression (VS).MethodsAdults from Caribbean, Central and South America network for HIV epidemiology clinical cohorts in seven countries contributed data between 2003 and 2012. Retention was defined as two or more HIV care visits annually, >90 days apart. cART was defined as prescription of three or more antiretroviral agents annually. VS was defined as HIV‐1 RNA <200 copies/mL at last measurement annually. cART and VS denominators were subjects with at least one visit annually. Multivariable modified Poisson regression was used to assess temporal trends and examine associations between age, sex, HIV transmission mode, cohort, calendar year and time in care.ResultsAmong 18,799 individuals in retention analyses, 14,380 in cART analyses and 13,330 in VS analyses, differences existed between those meeting indicator definitions versus those not by most characteristics. Retention, cART and VS significantly improved from 2003 to 2012 (63 to 77%, 74 to 91% and 53 to 82%, respectively; p<0.05, each). Female sex (risk ratio (RR)=0.97 vs. males) and injection drug use as HIV transmission mode (RR=0.83 vs. male sexual contact with males (MSM)) were significantly associated with lower retention, but unrelated with cART or VS. MSM (RR=0.96) significantly decreased the probability of cART compared with heterosexual transmission.ConclusionsHIV Care Continuum outcomes improved over time in Latin America, though disparities for vulnerable groups remain. Efforts must be made to increase retention, cART and VS, while engaging in additional research to sustain progress in these settings.

IntroductionLong‐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).MethodsWe 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.ResultsA 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).ConclusionsIn 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.

AbstractIntroductionContraceptive implants containing etonogestrel and levonorgestrel have emerged as popular contraceptive options among women in areas of high HIV burden in sub‐Saharan Africa. However, recent pharmacokinetic data have shown drug–drug interactions between implants and efavirenz‐containing antiretroviral therapy (ART), reducing the effectiveness of the implants. Here, we evaluated pregnancy incidence in 6‐month intervals following implant initiation among women using efavirenz and contraceptive implants to assess whether the risk of breakthrough pregnancy is higher after specific periods of implant use.MethodsWe used data from a retrospective longitudinal analysis of women living with HIV ages 18–45 years in western Kenya who attended HIV‐care facilities between 2011 and 2015. We used Cox proportional hazard models to compute hazard ratios (HRs) for breakthrough pregnancy by implant type and ART regimen. Depending on the model, we adjusted for socio‐demographic and clinical factors, programme, site and interaction between calendar time and ART regimen. We utilized inverse probability weights (IPWs) to account for three sampling phases (electronic medical record [EMR], chart review and phone interview) and calculated overall parameter estimates.ResultsWomen contributed 14,768 woman‐years from the largest sampling phase (EMR). The median age was 31 years. Women used etonogestrel implants for 26–69% of the time and levonorgestrel implants for 7–31% of the time, depending on the sampling phase. Women used efavirenz, nevirapine or no ART for 27–33%, 40–46% and 15–26% of follow‐ups, respectively. When combining sampling phases, there was little evidence to suggest that the relative hazard of pregnancy among efavirenz‐containing ART users relative to nevirapine‐containing ART changed with length of time on implants: IPW‐adjusted HR of 3.1 (CI: [1.5; 6.4]) at 12 months, 3.4 (CI: [1.8; 6.3]) at 24 months, 3.8 (CI: [1.9; 7.7]) at 36 months and 4.2 (CI: [1.6; 11.1]) at 48 months (interaction p‐value = 0.88). Similarly, no significant change in HRs over time was found when comparing women not using ART to nevirapine‐containing ART users (interaction p‐value = 0.49).ConclusionsWe did not find evidence to suggest implants being more fallible from drug–drug interactions with efavirenz at later time intervals of implant use. Thus, we would not recommend shortening the duration of implant use or replacing implants sooner when concomitantly used with efavirenz.

AbstractIntroductionIdentification of persons living with human immunodeficiency virus (HIV)‐associated tuberculosis (TB) at increased risk for unfavourable TB outcomes would inform efforts to improve such outcomes. We sought to identify factors associated with a decreased risk of unfavourable TB treatment outcomes among people living with HIV‐infection (PLHIV) in low‐ and middle‐income countries (LMIC), with a specific focus on directly observed therapy (DOT) compared with self‐administered therapy (SAT) during the continuation phase of anti‐TB therapy.MethodsWe conducted a retrospective cohort study among adults diagnosed with HIV‐associated TB in Africa, Asia and the Americas from 2012 to 2013; data were collected from 2012 to 2016. Unfavourable TB treatment outcomes (death during TB treatment, and TB treatment failure or recurrence) were defined according to World Health Organization criteria. Receipt of DOT was obtained at the site level and defined as ≥5 days of DOT per week. The person administering DOT and treatment location varied by site. Lack of receipt of DOT was defined as SAT. Multivariable logistic regression estimated the adjusted odds of unfavourable TB treatment outcomes.ResultsAmong 1862 adults with HIV‐associated TB included, 252 (13.5%) had unfavourable TB outcomes (226 deaths, 26 recurrences/failures). Overall, 1825 (98%) received DOT in the intensive phase and 1617 (87%) received DOT in the continuation phase. DOT in the continuation phase was not significantly associated with unfavourable TB outcomes (aOR 1.43, 95% CI 0.86 to 2.38) compared to SAT. Body mass index (BMI) change during anti‐TB treatment (per 2 units increase, aOR 0.74, 95% CI 0.68 to 0.82) and CD4+ count at TB diagnosis (200 vs. 50 cells/µL, aOR 0.54, 95% CI 0.39 to 0.73) were both independently associated with decreased odds of unfavourable TB treatment outcomes.ConclusionsIn this large, international cohort of people living with HIV‐associated TB in LMIC who received intensive phase DOT, DOT during the continuation phase of anti‐TB therapy was not associated with a decreased odds of unfavourable TB treatment outcomes compared to SAT. Randomized trials evaluating the effect of continuation‐phase DOT on TB outcomes among PLHIV are needed.