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BackgroundThe etiology of dementias and cognitive decline remain largely unknown. It is widely accepted that inflammation in the central nervous system plays a critical role in the pathogenesis of dementia. However, less is known about the role of the peripheral immune system and interactions with cortisol, though evidence suggests that these, too, may play a role.MethodsUsing data from 1337 participants aged 60+ years from the Sacramento Area Latino Study of Aging (observational cohort) we investigated variation in trajectories of cognitive decline by pathogen IgG and cytokine levels. Linear mixed effects models were used to examine the association between baseline Interleukin (IL)-6, C-reactive protein, tumor necrosis factor (TNF)-α, and five persistent pathogens' IgG response and trajectories of cognition over 10 years, and to examine interactions between immune biomarkers and cortisol. Stratified cumulative incidence functions were used to assess the relation between biomarkers and incident dementia. Inverse probability weights accounted for loss-to-follow-up and confounding.ResultsIL-6, TNF-α, and CMV IgG were statistically significantly associated with a higher log of Modified Mini-Mental State Examination errors (IL-6, β=0.0935 (95%CI: 0.055, 0.13), TNF-alpha β= 0.0944 (95%CI: 0.032, 0.157), and CMV, β= 0.0409 (95%CI: 0.013, 0.069)). Furthermore, cortisol interacted with HSV-1 and IL-6, and CRP for both cross-sectional cognitive function and rate of decline. No statistically significant relationship was detected between biomarkers and incidence of dementia.ConclusionsThese findings support the theory that the peripheral immune system may play a role in cognitive decline but not incident dementia. Furthermore, they identify specific markers amenable for intervention for slowing decline.

Poverty alleviation programs can reduce HIV incidence but may have greater impacts when combined with other psychosocial interventions. We modeled the change in HIV incidence among South African adolescent girls and young women (AGYW) associated with combining a cash transfer (the South African Child Support Grant (CSG)) with other structural and behavioral interventions. We modeled observational data from the HPTN 068 study where 2328 HIV negative AGYW (13-20 years) were followed for 4 years. In a Monte Carlo simulation based on this cohort (N = 10,000), CSG receipt was not independently associated with HIV incidence. Providing the CSG combined with increasing caregiver care and reducing adolescent depression had the largest reduction in HIV incidence with the fewest number of combined interventions (RD - 3.0%; (95% CI - 5.1%, - 0.9%). Combining a monthly grant with interventions to increase caregiver care and reduce adolescent depression could substantially reduce HIV incidence above the provision of cash alone.

In an analysis of randomized trials, use of efavirenz for treatment of human immunodeficiency virus (HIV) infection was associated with increased suicidal thoughts/behaviors. However, analyses of observational data have found no evidence of increased risk. To assess whether population differences might explain this divergence, we transported the effect of efavirenz use from these trials to a specific target population. Using inverse odds weights and multiple imputation, we transported the effect of efavirenz on suicidal thoughts/behaviors in these randomized trials (participants were enrolled in 2001-2007) to a trials-eligible cohort of US adults initiating antiretroviral therapy while receiving HIV clinical care at medical centers between 1999 and 2015. Overall, 8,291 cohort participants and 3,949 trial participants were eligible. Prescription of antidepressants (19% vs. 13%) and injection drug history (16% vs. 10%) were more frequent in the cohort than in the trial participants. Compared with the effect in trials, the estimated hazard ratio for efavirenz on suicidal thoughts/behaviors was attenuated in our target population (trials: hazard ratio (HR) = 2.3 (95% confidence interval (CI): 1.2, 4.4); transported: HR = 1.8 (95% CI: 0.9, 4.4)), whereas the incidence rate difference was similar (trials: HR = 5.1 (95% CI: 1.6, 8.7); transported: HR = 5.4 (95% CI: -0.4, 11.4)). In our target population, there was greater than 20% attenuation of the hazard ratio estimate as compared with the trials-only estimate. Transporting results from trials to a target population is informative for addressing external validity.

BackgroundUnderstanding advances in the care and treatment of adults with HIV as well as remaining gaps requires comparing differences in mortality between persons entering care for HIV and the general population.ObjectiveTo assess the extent to which mortality among persons entering HIV care in the United States is elevated over mortality among matched persons in the general U.S. population and trends in this difference over time.DesignObservational cohort study.SettingThirteen sites from the U.S. North American AIDS Cohort Collaboration on Research and Design.Participants82 766 adults entering HIV clinical care between 1999 and 2017 and a subset of the U.S. population matched on calendar time, age, sex, race/ethnicity, and county using U.S. mortality and population data compiled by the National Center for Health Statistics.MeasurementsFive-year all-cause mortality, estimated using the Kaplan-Meier estimator of the survival function.ResultsOverall 5-year mortality among persons entering HIV care was 10.6%, and mortality among the matched U.S. population was 2.9%, for a difference of 7.7 (95% CI, 7.4 to 7.9) percentage points. This difference decreased over time, from 11.1 percentage points among those entering care between 1999 and 2004 to 2.7 percentage points among those entering care between 2011 and 2017.LimitationMatching on available covariates may have failed to account for differences in mortality that were due to sociodemographic factors rather than consequences of HIV infection and other modifiable factors.ConclusionMortality among persons entering HIV care decreased dramatically between 1999 and 2017, although those entering care remained at modestly higher risk for death in the years after starting care than comparable persons in the general U.S. population.Primary funding sourceNational Institutes of Health.

Despite improvements in access to antiretroviral treatment over the past decade, sub-optimal HIV care outcomes persist among youth with HIV (YWH) in rural South Africa. Psychosocial stressors could impede improved HIV treatment outcomes within this population. We linked self-reported psychosocial health and demographic data from a cross-sectional survey conducted among YWH aged 12-24 in rural South Africa to individual medical record data, including facility visit history and viral load measurements. Poisson regression with robust standard errors was used to estimate the associations between five psychosocial stressors- heightened depressive symptoms (Center for Epidemiological Studies-Depression scale scores ≥ 16), lower social support (Medical Outcomes Social Support Scale scores ≤ 38), lower resilience (Conner-Davidson Resilience Scale scores ≤ 73), lower self-esteem (Rosenberg Self-Esteem Scale scores ≤ 21), and higher perceived stress (Sheldon Cohen Perceived Stress Scale scores ≥ 10)- and viral non-suppression (viral load ≥ 400 copies/mL) and loss to care (no documented clinic visits within the 90 days prior to survey), separately. A total of 359 YWH were included in this analysis. The median age of study participants was 21 (interquartile range: 16-23), and most were female (70.2%), single (82.4%), and attending school (54.7%). Over a quarter of participants (28.1%) had heightened depressive symptoms. Just 16.2% of all participants (n = 58) were lost to care at the time of survey, while 32.4% (n = 73) of the 225 participants with viral load data were non-suppressed. The prevalence of non-suppression in individuals with lower self-esteem was 1.71 (95% confidence interval: 1.12, 2.61) times the prevalence of non-suppression in those with higher self-esteem after adjustment. No meaningful association was observed between heightened depressive symptoms, lower social support, lower resilience, and higher perceived stress and viral non-suppression or loss to care in adjusted analyses. Retention in care and viral suppression among YWH in rural South Africa are below global targets. Interventions aimed at improving viral suppression among YWH should incorporate modules to improve participant's self-esteem as low self-esteem is associated with viral non-suppression in this setting. Future studies should longitudinally explore the joint effects of co-occurring psychosocial stressors on HIV care outcomes in YWH and assess meaningful differences in these effects by age, gender, and route of transmission.

ObjectivesThe Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 and other cross-sectional metrics can lead to potentially counterintuitive conclusions when used to evaluate health systems' performance. This study demonstrates how time and population dynamics impact UNAIDS 90-90-90 metrics in comparison with a longitudinal analogue.DesignA simplified simulation representing a hypothetical population was used to estimate and compare inference from UNAIDS 90-90-90 metrics and longitudinal metrics based on Kaplan-Meier-estimated 2-year probability of transition between stages.MethodsWe simulated a large cohort over 15 years. Everyone started out at risk for HIV, and then transitioned through the HIV care continuum based on fixed daily probabilities of acquiring HIV, learning status, entering care, initiating antiretroviral therapy (ART), and becoming virally suppressed, or dying. We varied the probability of ART initiation over three five-year periods (low, high, and low). We repeated the simulation with an increased probability of death.ResultsThe cross-sectional probability of being on ART among persons who were diagnosed responded relatively slowly to changes in the rate of ART initiation. Increases in ART initiation rates caused apparent declines in the cross-sectional probability of being virally suppressed among persons who had initiated ART, despite no changes in the rate of viral suppression. In some cases, higher mortality resulted in the cross-sectional metrics implying improved healthcare system performance. The longitudinal continuum was robust to these issues.ConclusionThe UNAIDS 90-90-90 care continuum may lead to incorrect inference when used to evaluate health systems performance. We recommend that evaluation of HIV care delivery include longitudinal care continuum metrics wherever possible.

Background Frailty is a dynamic syndrome characterized by reduced physiological reserve to maintain homeostasis. Prospective studies have reported frailty worsening in women with breast cancer during chemotherapy, with improvements following treatment. We evaluated whether the Faurot frailty index, a validated claims-based frailty measure, could identify changes in frailty during chemotherapy treatment and identified predictors of trajectory patterns. Methods We included women (65+ years) with stage I-III breast cancer undergoing adjuvant chemotherapy in the SEER-Medicare database (2003-2019). We estimated the Faurot frailty index (range: 0-1; higher scores indicate greater frailty) at chemotherapy initiation, 4 months postinitiation, and 10 months postinitiation. Changes in frailty were compared to a matched noncancer comparator cohort. We identified patterns of frailty trajectories during the year following chemotherapy initiation using K-means clustering. Results Twenty-one thousand five hundred and ninety-nine women initiated adjuvant chemotherapy. Mean claims-based frailty increased from 0.037 at initiation to 0.055 4 months postchemotherapy initiation and fell to 0.049 10 months postinitiation. Noncancer comparators experienced a small increase in claims-based frailty over time (0.055-0.062). We identified 6 trajectory patterns: a robust group (78%), 2 resilient groups (16%), and 3 nonresilient groups (6%). Black women and women with claims for home hospital beds, wheelchairs, and Parkinson's disease were more likely to experience nonresilient trajectories. Conclusions We observed changes in a claims-based frailty index during chemotherapy that are consistent with prior studies using clinical measures of frailty and identified predictors of nonresilient frailty trajectories. Our study demonstrates the feasibility of using claims-based frailty indices to assess changes in frailty during cancer treatment. [ABSTRACT FROM AUTHOR]

Cause-specific mortality is an important outcome in studies of interventions to improve survival, yet causes of death can be misclassified. Here, we present an approach to performing sensitivity analyses for misclassification of cause of death in the parametric g-formula. The g-formula is a useful method to estimate effects of interventions in epidemiologic research because it appropriately accounts for time-varying confounding affected by prior treatment and can estimate risk under dynamic treatment plans. We illustrate our approach using an example comparing acquired immune deficiency syndrome (AIDS)-related mortality under immediate and delayed treatment strategies in a cohort of therapy-naive adults entering care for human immunodeficiency virus infection in the United States. In the standard g-formula approach, 10-year risk of AIDS-related mortality under delayed treatment was 1.73 (95% CI: 1.17, 2.54) times the risk under immediate treatment. In a sensitivity analysis assuming that AIDS-related death was measured with sensitivity of 95% and specificity of 90%, the 10-year risk ratio comparing AIDS-related mortality between treatment plans was 1.89 (95% CI: 1.13, 3.14). When sensitivity and specificity are unknown, this approach can be used to estimate the effects of dynamic treatment plans under a range of plausible values of sensitivity and specificity of the recorded event type.

BackgroundEfavirenz has been a mainstay of antiretroviral therapy (ART) for over 15 years in the US. Its association with neuropsychiatric side effects may influence clinical prescribing and management.MethodsWe included HIV-infected adults enrolled in care at seven sites across the US, who initiated combination ART between 1999 and 2015. We examined the proportion initiating and continuing on efavirenz, overall and by mental health status. Log binomial and Cox models were used to estimate associations between mental health, clinical and sociodemographic characteristics and initiating or switching from efavirenz as first-line ART.ResultsOf the 8,230 participants included, 3,710 (45%) initiated efavirenz. In multivariable analyses, prior mono- or dual-ART, ART initiation after 2006, being female, intravenous drug use, antidepressant prescription, previous mental health diagnosis and baseline CD4+ T-cell count >350 cells/mm3 were inversely associated with initiating efavirenz. Participants initiating efavirenz had a faster time to a regimen switch, compared with those initiating an efavirenz-free regimen (P-value

Heavy drinking is prevalent among people living with HIV. Studies use tools like patient-reported outcomes (PROs) to quantify alcohol use in a detailed, timely manner. However, if alcohol misuse influences PRO completion, selection bias may result. Our study included 14,145 adult HIV patients (133,036 visits) from CNICS who were eligible to complete PROs at an HIV primary care visit. We compared PRO completion proportions between patients with and without a clinical diagnosis of at-risk alcohol use in the prior year. We accounted for confounding by baseline and visit-specific covariates. PROs were completed at 20.8% of assessed visits. The adjusted difference in PRO completion proportions was -3.2% (95% CI -5.6 to -0.8%). The small association between receipt of an at-risk alcohol use diagnosis and decreased PRO completion suggests there could be modest selection bias in studies using the PRO alcohol measure.

ObjectiveTo explore the effectiveness of raltegravir-based antiretroviral therapy (ART) on treatment response among ART-naive patients seeking routine clinical care.DesignCohort study of adults enrolled in HIV care in the United States.MethodsWe compared virologic suppression and CD4 cell count recovery over a 2.5 year period after initiation of an ART regimen containing raltegravir or efavirenz using observational data from a US clinical cohort, generalized to the US population of people with diagnosed HIV. We accounted for nonrandom treatment assignment, informative censoring, and nonrandom selection from the US target population using inverse probability weights.ResultsOf the 2843 patients included in the study, 2476 initiated the efavirenz-containing regimen and 367 initiated the raltegravir-containing regimen. In the weighted intent-to-treat analysis, patients spent an average of 74 (95% confidence interval: 41, 106) additional days alive with a suppressed viral load on the raltegravir regimen than on the efavirenz regimen over the 2.5-year study period. CD4 cell count recovery was also superior under the raltegravir regimen.ConclusionPatients receiving raltegravir spent more time alive and suppressed than patients receiving efavirenz, but the probability of viral suppression by 2.5 years after treatment was similar between groups. Optimizing the amount of time spent in a state of viral suppression is important to improve survival among people living with HIV and to reduce onward transmission.

Marginal structural models for time-fixed treatments fit using inverse-probability weighted estimating equations are increasingly popular. Nonetheless, the resulting effect estimates are subject to finite-sample bias when data are sparse, as is typical for large-sample procedures. Here we propose a semi-Bayes estimation approach which penalizes or shrinks the estimated model parameters to improve finite-sample performance. This approach uses simple symmetric data-augmentation priors. Limited simulation experiments indicate that the proposed approach reduces finite-sample bias and improves confidence-interval coverage when the true values lie within the central "hill" of the prior distribution. We illustrate the approach with data from a nonexperimental study of HIV treatments.

BackgroundEvidence about the effect of initiating efavirenz-containing combination antiretroviral therapy (ART) as the first-line therapy on suicidal thoughts remains conflicting.MethodsUsing data from a cohort of HIV-infected adults enrolled in routine care across 5 sites in the United States, we included participants with a baseline patient-reported outcome measure and detectable viral load who initiated ART between 2011 and 2014. Participants were followed until the earliest of the following: first suicidal thoughts, discontinuation of initial ART regimen, death, loss to care (>12 months with no HIV appointments), or administrative censoring (2014-2015). Suicidal thoughts were measured using a Patient Health Questionnaire-9 item. We used weighted marginal structural Cox models to estimate the effect of initiating efavirenz-containing ART, versus efavirenz-free ART, on the hazard of active or passive suicidal thoughts after ART initiation, accounting for confounding by channeling bias.ResultsOverall, 597 participants were followed for a median of 19 months (13,132 total person-months); 147 (25%) initiated efavirenz-containing ART. At ART initiation, 38% of participants reported suicidal thoughts or depressive symptoms. Initiating efavirenz-based ART was associated with a hazard ratio (HR) for suicidal thoughts below the null in the crude analysis [HR, 0.88; 95% confidence interval (CI): 0.53 to 1.45] and above the null in the weighted analysis (HR, 1.21; 95% CI: 0.66 to 2.28). Among those with a prior mental health issue, the weighted HR was 1.76 (95% CI: 0.45 to 6.86).ConclusionsAfter accounting for measured channeling bias, we observed no strong evidence that initiating efavirenz-containing ART increased the hazard of suicidal thoughts.

Background: During the 2010 Deepwater Horizon (DWH) disaster, response and cleanup workers were potentially exposed to toxic volatile components of crude oil. However, to our knowledge, no study has examined exposure to individual oil spill-related chemicals in relation to cardiovascular outcomes among oil spill workers. Objectives: Our aim was to investigate the association of several spill-related chemicals [benzene, toluene, ethylbenzene, xylene, n-hexane (BTEX-H)] and total hydrocarbons (THC) with incident coronary heart disease (CHD) events among workers enrolled in a prospective cohort. Methods: Cumulative exposures to THC and BTEX-H across the cleanup period were estimated via a job-exposure matrix that linked air measurement data with self-reported DWH spill work histories. We ascertained CHD events following each worker's last day of cleanup work as the first self-reported physician-diagnosed myocardial infarction (MI) or a fatal CHD event. We estimated hazard ratios (HR) and 95% confidence intervals for the associations of exposure quintiles (Q) with risk of CHD. We applied inverse probability weights to account for bias due to confounding and loss to follow-up. We used quantile g-computation to assess the joint effect of the BTEX-H mixture. Results: Among 22,655 workers with no previous MI diagnoses, 509 experienced an incident CHD event through December 2019. Workers in higher quintiles of each exposure agent had increased CHD risks in comparison with the referent group (Q1) of that agent, with the strongest associations observed in Q5 (range of HR = 1.14-1.44). However, most associations were nonsignificant, and there was no evidence of exposure-response trends. We observed stronger associations among ever smokers, workers with Conclusions: Higher exposures to volatile components of crude oil were associated with modest increases in risk of CHD among oil spill workers, although we did not observe exposure-response trends. https://doi.org/10.1289/EHP11859, Introduction The 2010 Deepwater Horizon (DWH) disaster was the largest marine oil spill in U.S. history. (1) An estimated 4.9 million barrels of crude oil were discharged into the Gulf [...]

Background.The long-term effectiveness of human immunodeficiency virus (HIV) treatments containing integrase inhibitors is unknown.Methods.We use observational data from the Centers for AIDS Research Network of Integrated Clinical Systems and the Centers for Disease Control and Prevention to estimate 4-year risk of AIDS and all-cause mortality among 415 patients starting a raltegravir regimen compared to 2646 starting an efavirenz regimen (both regimens include emtricitabine and tenofovir disoproxil fumarate). We account for confounding and selection bias as well as generalizability by standardization for measured variables, and present both observational intent-to-treat and per-protocol estimates.Results.At treatment initiation, 12% of patients were female, 36% black, 13% Hispanic; median age was 37 years, CD4 count 321 cells/µL, and viral load 4.5 log10 copies/mL. Two hundred thirty-five patients incurred an AIDS-defining illness or died, and 741 patients left follow-up. After accounting for measured differences, the 4-year risk was similar among those starting both regimens (ie, intent-to treat hazard ratio [HR], 0.96 [95% confidence interval {CI}, .63-1.45]; risk difference, -0.9 [95% CI, -4.5 to 2.7]), as well as among those remaining on regimens (ie, per-protocol HR, 0.95 [95% CI, .59-1.54]; risk difference, -0.5 [95% CI, -3.8 to 2.9]).Conclusions.Raltegravir and efavirenz-based initial antiretroviral therapy have similar 4-year clinical effects. Vigilance regarding longer-term comparative effectiveness of HIV regimens using observational data is needed because large-scale experimental data are not forthcoming.

Prompt initiation of combination antiretroviral therapy (ART) is important to reduce comorbidity and mortality among people living with HIV, especially for those with a low CD4 cell count. However there is evidence that not everyone receives prompt initiation of ART after enrolling into HIV care. The current study investigated factors associated with failure to initiate ART within two years of entering into care among those with a CD4 count at or below 350 cells/mm3. The sample included 4,907 ART-naive patients with a CD4 count at or below 350 cells/mm3 enrolled between January 1, 2003 and December 31, 2012 at any of eight clinical sites in the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). The two-year risk of delayed ART initiation was estimated using a log-binomial regression model with stabilized inverse probability of censoring weights for those lost to follow-up. Adjusting for other factors, an earlier enrollment date was the sole demographic characteristic associated with an increased risk of delayed ART initiation. Higher CD4 count, lower viral load, and a prevalent AIDS diagnosis were clinical characteristics associated with delayed ART initiation. Gender, age, race/ethnicity and HIV risk factors such as reported male-to-male sexual contact and injection drug use were not associated with delayed ART initiation. This study identified characteristics of patients for whom treatment was strongly to moderately recommended but who did not initiate ART within two years of entering care. Despite the known benefits of early antiretroviral therapy initiation, a lower viral load measurement may continue to be an important clinical characteristic in the more recent era with current ART initiation guidelines. These findings provide a target for closer monitoring and intervention to reduce disparities in HIV care.

Introduction: Pregnant women living with HIV can achieve viral suppression and prevent HIV mother-to-child transmission (MTCT) with timely HIV testing and early ART initiation and maintenance. Although it is recommended that pregnant women undergo HIV testing early in antenatal care in Malawi, many women test positive during breastfeeding because they did not have their HIV status ascertained during pregnancy or they tested negative during pregnancy but seroconverted postpartum. We sought to estimate the association between the timing of last positive HIV test (during pregnancy vs. breastfeeding) and outcomes of maternal viral suppression and MTCT in Malawi's PMTCT programme. Methods: We conducted a two-stage cohort study among mother-infant pairs in 30 randomly selected high-volume health facilities across five nationally representative districts of Malawi between 1 July 2016 and 30 June 2017. Log-binomial regression was used to estimate prevalence ratios (PR) and risk ratios (RR) for associations between timing of last positive HIV test (i.e. breastfeeding vs. pregnancy) and maternal viral suppression and MTCT, controlling for confounding using inverse probability weighting. Results: Of 822 mother-infant pairs who had available information on the timing of the last positive HIV test, 102 mothers (12.4%) had their last positive test during breastfeeding. Women who lived one to two hours (PR = 2.15; 95% CI: 1.29 to 3.58) or >2 hours (PR = 2.36; 95% CI: 1.37 to 4.10) travel time to the nearest health facility were more likely to have had their last positive HIV test during breastfeeding compared to women living Conclusions: MTCT in Malawi occurred disproportionately among women with a last positive HIV test during breastfeeding. Testing delayed until the postpartum period may lead to higher MTCT. To optimize maternal and child health outcomes, PMTCT programmes should focus on early ART initiation and providing targeted testing, prevention, treatment and support to breastfeeding women. Keywords: antiretroviral therapy; mother-to-child transmission; HIV; Option B+; PMTCT; viral suppression, 1 | INTRODUCTION Antiretroviral therapy (ART) for HIV-positive pregnant and breastfeeding women (PBFW) has proved to be life-saving for both mother and infant. As a treatment for HIV, ART improves [...]

BackgroundThe goal of targeted antiretroviral therapy initiation is to minimize disease progression among patients with human immunodeficiency virus while minimizing the therapeutic burden on these patients. We examine whether the effect of delaying therapy initiation from 500 cells/mm(3) to 350 or 200 cells/mm(3) is modified by age at entry into care.MethodsWe used the parametric g-formula to compare 10-year mortality under 3 CD4 cell count thresholds for therapy initiation among 3532 patients who entered care at 1 of 8 sites in the United States between 1998 and 2013. Results are reported separately for patients 18 to 34, 35 to 44, and 45 to 65 years of age at study entry.ResultsIn the observed data, 10-year mortality was 13% (165 deaths). Mortality increased from 11% under therapy initiation at 500 cells/mm(3) to 12% at 350 cells/mm(3) (risk difference [RD]: 0.87; 95% confidence interval [CI]: .56, 2.17) and to 14% at 200 cells/mm(3) (RD: 2.71; 95% CI: 1.79, 5.38). The effect of delaying therapy became greater with age: RDs comparing the 350-cells/mm(3) threshold with the 500-cells/mm(3) threshold ranged from -0.03 (95% CI: -0.15, 1.76) for patients 18 to 34 years of age to 0.99 (95% CI: -.27, 1.98) for patients 35 to 44 and to 2.30 (95% CI: 1.29, 5.42) for patients 45 to 65.ConclusionsDelaying therapy increased 10-year mortality in the full cohort. Subgroup analysis highlights that patients entering care at older ages may be more vulnerable to the consequences of delayed ART initiation than younger patients.

BackgroundUsing a dynamic visual display, we examine the changes in human immunodeficiency virus type 1 (HIV-1) plasma viral load and CD4 cell count for 5 years after antiretroviral therapy initiation in a large cohort of patients with HIV.MethodsPatients at a Centers for AIDS Research Network of Integrated Clinical Systems site who initiated combination antiretroviral therapy between 1 January 2000 and 31 December 2012 were followed for 5 years for HIV-1 plasma viral load, CD4 cell count, and mortality. The joint distribution of CD4 cell count and viral load over time was depicted in an animated display using a bivariate kernel smoother.ResultsWithin days of therapy initiation, many patients had a suppressed viral load and their median CD4 cell count had increased. However, the median CD4 cell count remained below normal levels throughout follow-up period and the proportion of patients with high viral load occasionally increased, even years after therapy initiation.ConclusionsThe dramatic changes in viral load and CD4 cell count after therapy initiation highlight the overwhelming effectiveness of antiretroviral therapy in the modern era. However, this work also emphasizes the need for pharmaceutical or behavioral interventions to prevent virologic failure and to stimulate complete recovery of normal CD4 cell count.

BackgroundEnsuring equal access to antiretroviral therapy (henceforth therapy) should alleviate disparities in health outcomes among persons infected with human immunodeficiency virus (HIV). However, evidence supporting the persistence of disparities in survival following therapy initiation is mixed.MethodsPatients initiating therapy in eight academic medical centers in the Centers for AIDS Research Network of Integrated Clinical Systems between 1 January 1998 and 30 December 2011. Patients (n = 10 017) were followed from therapy initiation until death from any cause, administrative censoring at 10 years after therapy initiation or the end of follow-up on 31 December 2011. The 10-year risk of all-cause mortality was calculated from standardized Kaplan-Meier survival curves.ResultsPatients were followed for a median of 4.7 years (interquartile range: 2.2, 8.2). During 51 121 person-years of follow-up, 1224 of the 10 017 patients died. The overall 10-year mortality risk was 20.2% (95% confidence interval [CI], 19.2%, 21.3%). Black men and women experienced standardized 10-year all-cause mortality risks that were 7.2% (95% CI, 4.3%, 10.1%) and 7.9% (95% CI, 3.9%, 12.0%) larger (absolute difference) than white men. White women, Hispanic men, and Hispanic women all had lower 10-year mortality than white men.ConclusionsThese data serve as a call to action to identify modifiable mechanisms leading to these observed mortality disparities among HIV-infected black patients. Effective interventions are needed to ensure that the goal of the National HIV/AIDS Strategy to overcome health disparities becomes a reality.

Background In sub-Saharan Africa, 3 community-facility linkage (CFL) models-Expert Clients, Community Health Workers (CHWs), and Mentor Mothers-have been widely implemented to support pregnant and breastfeeding women (PBFW) living with HIV and their infants to access and sustain care for prevention of mother-to-child transmission of HIV (PMTCT), yet their comparative impact under real-world conditions is poorly understood. Methods and findings We sought to estimate the effects of CFL models on a primary outcome of maternal loss to follow-up (LTFU), and secondary outcomes of maternal longitudinal viral suppression and infant 'poor outcome' (encompassing documented HIV-positive test result, LTFU, or death), in Malawi's PMTCT/ART program. We sampled 30 of 42 high-volume health facilities ('sites') in 5 Malawi districts for study inclusion. At each site, we reviewed medical records for all newly HIV-diagnosed PBFW entering the PMTCT program between July 1, 2016 and June 30, 2017, and, for pregnancies resulting in live births, their HIV-exposed infants, yielding 2,589 potentially eligible mother-infant pairs. Of these, 2,049 (79.1%) had an available HIV treatment record and formed the study cohort. A randomly selected subset of 817 (40.0%) cohort members underwent a field survey, consisting of a questionnaire and HIV biomarker assessment. Survey responses and biomarker results were used to impute CFL model exposure, maternal viral load, and early infant diagnosis (EID) outcomes for those missing these measures to enrich data in the larger cohort. We applied sampling weights in all statistical analyses to account for the differing proportions of facilities sampled by district. Of the 2,049 mother-infant pairs analyzed, 62.2% enrolled in PMTCT at a primary health center, at which time 43.7% of PBFW were [less than or equal to]24 years old, and 778 (38.0%) received the Expert Client model, 640 (31.2%) the CHW model, 345 (16.8%) the Mentor Mother model, 192 (9.4%) [greater than or equal to]2 models, and 94 (4.6%) no model. Maternal LTFU varied by model, with LTFU being more likely among Mentor Mother model recipients (adjusted hazard ratio [aHR]: 1.45; 95% confidence interval [CI]: 1.14, 1.84; p = 0.003) than Expert Client recipients. Over 2 years from HIV diagnosis, PBFW supported by CHWs spent 14.3% (95% CI: 2.6%, 26.1%; p = 0.02) more days in an optimal state of antiretroviral therapy (ART) retention with viral suppression than women supported by Expert Clients. Infants receiving the Mentor Mother model (aHR: 1.24, 95% CI: 1.01, 1.52; p = 0.04) and [greater than or equal to]2 models (aHR: 1.44, 95% CI: 1.20, 1.74; p < 0.001) were more likely to undergo EID testing by age 6 months than infants supported by Expert Clients. Infants receiving the CHW and Mentor Mother models were 1.15 (95% CI: 0.80, 1.67; p = 0.44) and 0.84 (95% CI: 0.50, 1.42; p = 0.51) times as likely, respectively, to experience a poor outcome by 1 year than those supported by Expert Clients, but not significantly so. Study limitations include possible residual confounding, which may lead to inaccurate conclusions about the impacts of CFL models, uncertain generalizability of findings to other settings, and missing infant medical record data that limited the precision of infant outcome measurement. Conclusions In this descriptive study, we observed widespread reach of CFL models in Malawi, with favorable maternal outcomes in the CHW model and greater infant EID testing uptake in the Mentor Mother model. Our findings point to important differences in maternal and infant HIV outcomes by CFL model along the PMTCT continuum and suggest future opportunities to identify key features of CFL models driving these outcome differences., Author(s): Michael E. Herce 1,2,*, Maganizo B. Chagomerana 1,2, Lauren C. Zalla 3, Nicole B. Carbone 1, Benjamin H. Chi 4, Michael T. Eliya 5, Sam Phiri 2,6, Stephanie M. [...]

Introduction: Providing outreach HIV prevention services at venues (i.e. 'hotspots') where people meet new sex partners can decrease barriers to HIV testing services (HTS) for key populations (KP) in sub-Saharan Africa (SSA). We offered venue-based HTS as part of bio-behavioural surveys conducted in urban Malawi and Angola to generate regional insights into KP programming gaps and identify opportunities to achieve the 'first 90' for KP in SSA. Methods: From October 2016 to March 2017, we identified and verified 1054 venues in Luanda and Benguela, Angola and Zomba, Malawi and conducted bio-behavioural surveys at 166 using the PLACE method. PLACE interviews community informants to systematically identify public venues where KP can be reached and conducts bio-behavioural surveys at a stratified random sample of venues. We present survey results using summary statistics and multivariable modified Poisson regression modelling to examine associations between receipt of outreach worker-delivered HIV/AIDS education and HTS uptake. We applied sampling weights to estimate numbers of HIV-positive KP unaware of their status at venues. Results: We surveyed 959 female sex workers (FSW), 836 men who have sex with men (MSM), and 129 transgender women (TGW). An estimated 71% of HIV-positive KP surveyed were not previously aware of their HIV status, receiving a new HIV diagnosis through PLACE venue-based HTS. If venue-based HTS were implemented at all venues, 2022 HIV-positive KP (95% CI: 1649 to 2477) who do not know their status could be reached, including 1666 FSW (95% CI: 1397 to 1987), 274 MSM (95% CI: 160 to 374), and 82 TG (95% CI: 20 to 197). In multivariable analyses, FSW, MSM, and TGW who received outreach worker-delivered HIV/AIDS education were 3.15 (95% CI: 1.99 to 5.01), 3.12 (95% CI: 2.17 to 4.48), and 1.80 (95% CI: 0.67 to 4.87) times as likely, respectively, as those who did not to have undergone HTS within the last six months. Among verified venues, Conclusions: Availability of HTS and other HIV prevention services was limited at venues. HIV prevention can be delivered at venues, which can increase HTS uptake and HIV diagnosis among individuals not previously aware of their status. Delivering venue-based HTS may represent an effective strategy to reach the 'first 90' for KP in SSA. Keywords: Key and vulnerable populations; HIV testing; HIV prevention; venue-based outreach; hotspots; sub-Saharan Africa; Malawi; Angola Additional Supporting Information may be found online in the Supporting information tab for this article., 1 | INTRODUCTION Key populations (KP) face a disproportionate HIV burden in sub-Saharan Africa (SSA) [1]. Driven by stigma, discrimination, limited KP-friendly services, and other structural barriers, the HIV prevention, [...]