The Population Impact of Late Presentation With Advanced HIV Disease and Delayed Antiretroviral Therapy in Adults Receiving HIV Care in Latin America.
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SUBMITTER: Belaunzaran-Zamudio PF
PROVIDER: S-EPMC7443201 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:INTRODUCTION:We evaluated HIV drug resistance in adults who received early vs. delayed antiretroviral therapy (ART) in a multinational trial [HIV Prevention Trials Network (HPTN) 052, enrollment 2005-2010]. In HPTN 052, 1763 index participants were randomized to start ART at a CD4 cell count of 350-550 cells/mm (early ART arm) or <250 cells/mm (delayed ART arm). In May 2011, interim study results showed benefit of early ART, and all participants were offered ART regardless of CD4 cell count; the study ended in 2015. METHODS:Virologic failure was defined as 2 consecutive viral loads >1000 copies/mL >24 weeks after ART initiation. Drug resistance testing was performed for pretreatment (baseline) and failure samples from participants with virologic failure. RESULTS:HIV genotyping results were obtained for 211/249 participants (128 early ART arm and 83 delayed ART arm) with virologic failure. Drug resistance was detected in 4.7% of participants at baseline; 35.5% had new resistance at failure. In univariate analysis, the frequency of new resistance at failure was lower among participants in the early ART arm (compared with delayed ART arm, P = 0.06; compared with delayed ART arm with ART initiation before May 2011, P = 0.032). In multivariate analysis, higher baseline viral load (P = 0.0008) and ART regimen (efavirenz/lamivudine/zidovudine compared with other regimens, P = 0.024) were independently associated with higher risk of new resistance at failure. CONCLUSIONS:In HPTN 052, the frequency of new drug resistance at virologic failure was lower in adults with early ART initiation. The main factor associated with reduced drug resistance with early ART was lower baseline viral load.
| S-EPMC5844834 | biostudies-literature
Project description:IntroductionKaposi's sarcoma (KS) remains the most frequent malignancy in persons living with HIV (PWH) in Latin America. We examined KS trends and outcomes from Latin American clinical sites in the era of increased access to antiretroviral therapy (ART).MethodsCohorts in Brazil, Peru, Mexico, Honduras, Argentina and Chile contributed clinical data of PWH ≥16 years old from 2000 to 2017, excluding patients with KS diagnosed before clinic enrolment. We compared KS incidence over time using multivariable incidence rate ratios. Predictors of KS before/at or after ART initiation and of mortality after KS were examined using Cox regression.ResultsOf 25 981 PWH, 481 had incident KS, including 200 ART-naïve and 281 ART-treated patients. From 2000 to 2017, the incidence of KS decreased from 55.1 to 3.0 per 1000 person-years. In models adjusting for CD4 and other factors, the relative risk for KS decreased from 2000 to 2008. Since 2010, the adjusted risk of KS increased in the periods before and ≤90 days after ART initiation but decreased >90 days after ART. In addition to low CD4 and male-to-male sex, KS risk after ART was associated with age and history of other AIDS-defining illnesses. Mortality after KS (approximately 25% after five years) was not associated with either year of KS diagnosis nor timing of diagnosis relative to ART initiation.ConclusionsKS incidence in Latin America has remained stable in recent years and risk is highest before and shortly after ART initiation. Early diagnosis of HIV and ART initiation remain critical priorities in the region.
| S-EPMC7787071 | biostudies-literature
Project description:BackgroundLittle is known about the long-term outcomes of children living with HIV in Latin America. Few studies have examined antiretroviral therapy (ART) regimen switches in the years after the introduction of ART in this population. This study aimed to assess clinical outcomes among children who started second-line ART in the Caribbean, Central and South America network for HIV epidemiology.MethodsChildren (<18 years old) with HIV who switched to second-line ART at sites within Caribbean, Central and South America network for HIV epidemiology were included. The cumulative incidence and relative hazards of virologic failure while on second-line ART, loss to follow-up, additional major ART regimen changes, and all-cause mortality were evaluated using competing risks methods and Cox models.ResultsA total of 672 children starting second-line ART were included. Three years after starting second-line ART, the cumulative incidence of death was 0.10 [95% confidence interval (CI) 0.08 to 0.13], loss to follow-up was 0.14 (95% CI: 0.11 to 0.17), and major regimen change was 0.19 (95% CI: 0.15 to 0.22). Of those changing regimens, 35% were due to failure and 11% due to toxicities/side effects. Among the 312 children with viral load data, the cumulative incidence of virologic failure at 3 years was 0.62 (95% CI: 0.56 to 0.68); time to virologic failure and regimen change were uncorrelated (rank correlation -0.001; 95% CI -0.18 to 0.17).ConclusionsPoor outcomes after starting second-line ART in Latin America were common. The high incidence of virologic failure and its poor correlation with changing regimens was particularly worrisome. Additional efforts are needed to ensure children receive optimal ART regimens.
| S-EPMC8192432 | biostudies-literature
Project description:BackgroundThere 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.MethodsWe 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.Findings30 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.InterpretationLife 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.FundingNational Institutes of Health.TranslationFor the Spanish translation of the abstract see Supplementary Materials section.
| S-EPMC8171816 | biostudies-literature
Project description:Accelerating antiretroviral therapy (ART) administration, improving retention, and achieving viral suppression in low- and middle-income countries must be prioritized. We evaluated trends and disparities in these milestones in a large Latin American cohort. Adults starting ART (ARTstart) from 2003 to 2014 at Caribbean, Central, and South America network for HIV epidemiology sites were assessed for care cascade outcomes: CD4 cell count >200?cells/mm3 at ARTstart; retention (?1 visit at one year after ARTstart); viral suppression (?1 HIV-1 RNA <200 copies/ml at one year after ARTstart). Modified Poisson regression provided adjusted prevalence ratios by age, gender, and HIV transmission risk, accounting for site and year of ARTstart. Proportions achieving ARTstart and suppression improved over time (p?<?0.05). Older age was associated with better retention and viral suppression, but not ARTstart at CD4 cell count >200?cells/mm3. Females and men who have sex with men (MSM) were more likely to have CD4 cell count >200?cells/mm3 at ARTstart. Injection drug users (IDUs) were less likely to be retained while MSM were more likely to achieve viral suppression (all p?<?0.05). Despite improvements in these outcomes over the course of a decade in this cohort, significant disparities existed, disadvantaging younger patients, men, and IDUs. These gaps indicate continued progress in providing early diagnosis and ARTstart remain critical.
| S-EPMC5826619 | biostudies-literature
Project description:IntroductionOptimal adherence to antiretroviral therapy is closely related with suppression of the HIV viral load in plasma, slowing disease progression and decreasing HIV transmission rates. Despite its importance, the estimated proportion of people living with HIV in Latin America and the Caribbean with optimal adherence has not yet been reported in a meta-analysis. Moreover, little is known of the factors leading to poor adherence which may be setting-specific. We present a pooled estimate of adherence to antiretroviral therapy (ART) of people living with HIV in Latin America and Caribbean, report the methods used to measure adherence and describe the factors associated with poor adherence among the selected studies.MethodsWe electronically searched published studies up to July 2016 on the PubMed, Web of Science and Virtual Health Library (Latin America and the Caribbean Regional Portal); considering the following databases: MEDLINE, LILACS, PAHO and IBECS. Two independent reviewers selected and extracted data on ART adherence and study characteristics. Pooled estimate of adherence was derived using a random-effects model. Risk of bias in individual studies was assessed independently by two investigators using the Risk of Bias Assessment tool for Non-randomized Studies (RoBANS).Results and discussionThe meta-analysis included 53 studies published between 2005 and 2016, which analysed 22,603 people living with HIV in 25 Latin America and Caribbean countries. Overall adherence in Latin America and Caribbean was 70% (95% CI: 63-76; I2 = 98%), similar to levels identified by studies conducted in high-income regions. Self-report was the most frequently used method to measure adherence. Subgroup analysis showed that adherence was higher for the shortest recall time frame used, as well as in countries with lower income level, Gross National Income (GNI) per capita and Human Development Index (HDI). Studies reported diverse adherence barriers, such as alcohol and substance misuse, depression, unemployment and pill burden.ConclusionsOur study suggests that adherence to ART in Latin America and Caribbean may be below the sufficient levels required for a successful long-term viral load suppression.
| S-EPMC5810329 | biostudies-literature
Project description:BackgroundSelection of an appropriate patient-reported outcome (PRO) instrument for a clinical trial requires knowledge of the instrument's responsiveness to detecting treatment effects. The purpose of this study was to examine the responsiveness of two health-related quality of life (HRQL) instruments used in clinical trials involving HIV-infected adults: the HIV-targeted Medical Outcomes Study HIV Health Survey (MOS-HIV), and a generic measure, the EuroQol-5D (EQ-5D).MethodsA systematic review identified clinical trials using the MOS-HIV or EQ-5D to assess outcomes for HIV-infected adults. Data abstracted from each study included study type, treatment regimen(s), PRO results, and effect size (either reported or calculated). Effect size was calculated as the difference between baseline and follow-up mean scores divided by the baseline standard deviation. Magnitude was categorized as small (d=0.20), medium (d=0.50), and large (d=0.80).ResultsBetween 2005 and 2010, the MOS-HIV was administered in 12 trials. Significant differences were observed between groups and over time in physical health summary (PHS) and mental health summary (MHS) scores (P<0.05) in subjects switching therapy after experiencing Grade-2 adverse events. Effect sizes were medium (0.55 and 0.49 for PHS and MHS, respectively) among treatment-naïve adults beginning therapy (two studies), but negligible among treatment-experienced adults (0.04 and 0.13 for PHS and MHS, respectively; three studies). The EQ-5D was used in five trials between 2001 and 2010. It was responsive to occurrences of adverse events and opportunistic infections, with small-to-medium effect sizes (range 0.30-0.50) in each of its five dimensions.ConclusionsA systematic review of PRO study results showed both the MOS-HIV and EQ-5D were responsive to changes between groups and/or over time in treatment-naïve HIV-infected patients. These instruments may be used either individually or together in clinical trials to measure changes in HRQL.
| S-EPMC3602001 | biostudies-literature
Project description:BackgroundA growing population of older adults with HIV will increase demands on HIV-related healthcare. Nearly a quarter of people receiving care for HIV in Latin America are currently 50 years or older, yet little is known about the frequency of comorbidities in this population. We estimated the prevalence and incidence of non-communicable diseases (NCDs) among people 50 years of age or older (?50yo) receiving HIV care during 2000-2015 in six centers affiliated with the Caribbean, Central and South American network for HIV epidemiology (CCASAnet).MethodsWe estimated the annual prevalence, and overall prevalence and incidence of cardiovascular diseases, diabetes, hypertension, dyslipidemia, psychiatric disorders, chronic liver and renal diseases, and non-AIDS-defining cancers, and multimorbidity (more than one NCD) of people ?50yo receiving care for HIV. Analyses were performed according to age at enrollment into HIV care (<50yo and ?50yo).ResultsWe included 3,415 patients ?50yo, of whom 1,487(43%) were enrolled at age ?50 years. The annual prevalence of NCDs increased from 32% to 68% and multimorbidity from 30% to 40% during 2000-2015. At the last registered visit, 53% of patients enrolled <50yo and 50% of those enrolled ?50yo had at least one NCD. Most common NCDs at the last visit in each age-group at enrollment were dyslipidemia (36% in <50yo and 28% in ?50yo), hypertension (17% and 18%), psychiatric disorders (15% and 10%), and diabetes (11% and 12%).ConclusionsThe prevalence of NCDs and multimorbidity in people ?50 years receiving care for HIV in CCASAnet centers in Latin America increased substantially in the last 15 years. Our results make evident the need of planning for provision of complex, primary care for aging adults living with HIV.
| S-EPMC7299309 | biostudies-literature
Project description:To evaluate antiretroviral (ARV) drug exposure and other factors during pregnancy that may increase the risk of neurologic conditions (NCs) in HIV-exposed/uninfected (HEU) infants. A prospective cohort study was conducted at 24 clinical sites in Latin America and the Caribbean. Data on maternal demographics, health, HIV disease status, and ARV use during pregnancy were collected. Infant data included measurement of head circumference after birth and reported medical diagnoses at birth, 6-12 weeks, and 6 months. Only infants with maternal exposure to combination ARV therapy (cART) (?3 drugs from ?2 drug classes) during pregnancy were included. Microcephaly, defined as head circumference for age z-score less than -2, and NC were evaluated for their association with covariates, including individual ARVs, using bivariable and logistic regression analyses. From 2002 to 2009, 1,400 HEU infants met study inclusion criteria. At least one NC was reported in 134 (9.6%; 95% confidence interval [CI]: 8.1-11.2), microcephaly in 105 (7.5%; 95% CI: 6.2-9.0), and specific neurologic diagnoses in 33 (2.4%; 95% CI: 1.6-3.3) HEU infants. Microcephaly and NC were not significantly associated with any specific ARV analyzed (p > 0.05). Covariates associated with increased odds of NC included male sex (odds ratio [OR] = 1.9; 95% CI: 1.3-2.8), birth weight <2.5 kg (OR = 3.1; 95% CI: 2.1-4.8), 1-min Apgar score <7 (OR = 2.5; 95% CI: 1.4-4.4), and infant infections (OR = 2.5; 95% CI: 1.5-4.1). No ARV investigated was associated with adverse neurologic outcomes. Continued investigation of such associations may be warranted as new ARVs are used during pregnancy and cART exposure during the first trimester becomes increasingly common.
| S-EPMC4817559 | biostudies-literature
Project description:BACKGROUND:Identifying characteristics of HIV-infected adults likely to have poor treatment outcomes can be useful for targeting interventions efficiently. Research in economics and psychology suggests that individuals' intertemporal time preferences, which indicate the extent to which they trade-off immediate vs. future cost and benefits, can influence various health behaviors. While there is empirical support for the association between time preferences and various non-HIV health behaviors and outcomes, the extent to which time preferences predict outcomes of those receiving antiretroviral therapy (ART) has not been examined previously. METHODS:HIV-infected adults initiating ART were enrolled at a health facility in Kenya. Participants' time preferences were measured at enrollment and used to classify them as having either a low or high discount rate for future benefits. At 48 weeks, we assessed mortality and ART adherence, as measured by Medication Event Monitoring System (MEMS). Logistic regression models adjusting for socio-economic characteristics and risk factors were used to determine the association between time preferences and mortality as well as MEMS adherence ?90%. RESULTS:Overall, 44% (96/220) of participants were classified as having high discount rates. Participants with high discount rates had significantly higher 48-week mortality than participants with low discount rates (9.3% vs. 3.1%; adjusted odds ratio 3.84; 95% CI 1.03, 14.50). MEMS adherence ?90% was similar for participants with high vs. low discount rates (42.3% vs. 49.6%, AOR 0.70; 95% CI 0.40, 1.25). CONCLUSION:High discount rates were associated with significantly higher risk of mortality among HIV-infected patients initiating ART. Greater use of time preference measures may improve identification of patients at risk of poor clinical outcomes. More research is needed to further identify mechanisms of action and also to build upon and test the generalizability of this finding.
| S-EPMC4684319 | biostudies-literature