Mortality In People Living With HIV Research Articles

Diet Quality and Liver Health in People Living with HIV in the MASH Cohort: A Multi-Omic Analysis of the Fecal Microbiome and Metabolome.

The gut-liver axis has been recognized as a potential pathway in which dietary factors may contribute to liver disease in people living with HIV (PLWH). The objective of this study was to explore associations between dietary quality, the fecal microbiome, the metabolome, and liver health in PLWH from the Miami Adult Studies on HIV (MASH) cohort. We performed a cross-sectional analysis of 50 PLWH from the MASH cohort and utilized the USDA Healthy Eating Index (HEI)-2015 to measure diet quality. A Fibrosis-4 Index (FIB-4) score < 1.45 was used as a strong indication that advanced liver fibrosis was not present. Stool samples and fasting blood plasma samples were collected. Bacterial composition was characterized using 16S rRNA sequencing. Metabolomics in plasma were determined using gas and liquid chromatography/mass spectrometry. Statistical analyses included biomarker identification using linear discriminant analysis effect size. Compared to participants with FIB-4 ≥ 1.45, participants with FIB-4 < 1.45 had higher intake of dairy (p = 0.006). Fibrosis-4 Index score was inversely correlated with seafood and plant protein HEI component score (r = -0.320, p = 0.022). The relative abundances of butyrate-producing taxa Ruminococcaceae, Roseburia, and Lachnospiraceae were higher in participants with FIB-4 < 1.45. Participants with FIB-4 < 1.45 also had higher levels of caffeine (p = 0.045) and related metabolites such as trigonelline (p = 0.008) and 1-methylurate (p = 0.023). Dietary components appear to be associated with the fecal microbiome and metabolome, and liver health in PLWH. Future studies should investigate whether targeting specific dietary components may reduce liver-related morbidity and mortality in PLWH.

2360. Serum Cholesterol Variability and Mortality in PLWH On Lipid-Lowering Therapy

Abstract Background In people living with HIV (PLWH), consistent use of lipid lowering therapy (LLT) is associated with lower all-cause mortality and use of tenofovir disoproxil fumarate (TDF) with reduced serum cholesterol (C). In the general population, high cholesterol variability (CV) is independently associated with all-cause mortality. We explored the relationship between consistency of LLT/TDF exposure, cholesterol variability, and mortality in PLWH. Methods In a cohort of 15,860 PLWH who achieved undetectable viremia on ART between 2001 and 2011 we used multivariable Cox modeling, stratified by prevalent cardiovascular disease (CVD) to identify predictors of mortality and built multi-level marginal structural models for different LLT/TDF exposure levels based on percentage of days covered (PDC) over the past year, categorizing exposures into low (PDC &amp;lt; 50%), high (50–93%), and consistent (≥94%). The latter two were further subdivided into single and dual exposures for a composite LLT model where we explored effect sizes before and after inclusion of time-updated absolute C values and its 1-year coefficient of variation (CoV). We also examined the relationship between consistency of LLT/TDF use and C variability in a mixed linear model. Results During a median follow-up (f/u) of 4.3 years, there were 2,269 deaths. For 43% of f/u time patients were exposed to TDF, for 13% to non-statin LLT, and for 17% to statins. The hazard ratio (HR) of death for consistent use was 0.38, 95% confidence interval (CI) 0.32–0.45 for TDF, 0.40 (CI:0.28–0.58) for non-statin LLT, and 0.50 (CI:0.40–0.63) for statins (Fig 1). In the composite model, increasing LLT intensity was inversely associated with mortality risk but low C and high CV remained strong independent predictors of death. High HDL C values were protective (Table). The effect sizes for high LLT intensity and high HDL-CV moderately decreased when they were modeled jointly. Compared to unexposed patients, HDL CoV was significantly lower during consistent LLT exposures but higher for patients with low LLT exposure (Fig 2). Conclusion In PLWHA, intensity of LLT exposure is inversely related with all-cause mortality. The highest LLT intensity levels were associated with the lowest HDL-CV. This could serve as a partial explanation for the lower mortality. Disclosures Roger Bedimo, MD, Gilead Sciences: Advisor/Consultant|Janssen: Advisor/Consultant|Merck &amp; Co.: Advisor/Consultant|Merck &amp; Co.: Grant/Research Support|ViiV Healthcare: Advisor/Consultant.

The challenge of minimizing tuberculosis burden in people living with HIV in the Asia Pacific.

The challenge of minimizing tuberculosis burden in people living with HIV in the Asia Pacific.

Mortality predictive factors of people living with human immunodeficiency virus and bloodstream infection

IntroductionPortugal has one of the highest mortality rates for people living with HIV (PLWHIV) in Europe. After antiretroviral therapy introduction, HIV-associated mortality declined, included the one associated with bloodstream infection (BSI). However it is still high, and European data are scarce . Therefore, characterizing BSI and defining prognostic factors may improve our approach. MethodsThis was a 10-year retrospective study of predictive factors for 30-day and 3-year mortality in PLWHIV with BSI in a tertiary infectious diseases ward. ResultsOf 2134 PLWHIV admissions, 145 (6.8%) had a BSI, mostly respiratory and catheter-related bacteremia and globally community-acquired. Nosocomial infections occurred in 42 (36%) cases, mostly caused by Enterococcus spp, Staphylococcus aureus, and Candida spp. PLWHIV with a BSI had higher 30-day mortality (27%) compared to those without a BSI (14%). APACHE II score, corticotherapy, and current intravenous drug use (IDU) had a prognostic impact on 30-day mortality. Three-year survival was 54% in PLWHIV with a BSI; a CD4 <200 cells, vascular or chronic pulmonary disease, and lymphoma were prognostic factors. ConclusionsPatients with a BSI were more likely to present advanced HIV disease, have more comorbidities, a longer length of stay, and higher 30-day mortality. IDU and severity of infection determined the short-term prognosis. Three-year mortality was primarily influenced by lower CD4 cell counts, hematological tumor, and cardiopulmonary comorbidities. Systemic corticotherapy may influence nosocomial BSI and short-term prognosis.

Cost-effectiveness of newer technologies for the diagnosis of Mycobacterium tuberculosis infection in Brazilian people living with HIV

Tuberculosis is the leading cause of death among people living with HIV (PLH). Preventive tuberculosis therapy reduces mortality in PLH, especially in those with a positive tuberculin skin test (TST). New, more specific technologies for detecting latent tuberculosis infection (LTBI) are now commercially available. We sought to analyse the cost-effectiveness of four different strategies for the diagnosis of LTBI in PLH in Brazil, from the Brazilian public health care system perspective. We developed a Markov state-transition model comparing four strategies for the diagnosis of LTBI over 20 years. The strategies consisted of TST with the currently used protein purified derivative (PPD RT 23), two novel skin tests using recombinant allergens (Diaskintest [Generium Pharmaceutical, Moscow, Russia] and EC [Zhifei Longcom Biologic Pharmacy Co., Anhui, China]), and the QuantiFERON-TB-Gold-Plus (Qiagen, Hilden, Germany). The main outcome was cost (in 2020 US dollars) per quality-adjusted life years (QALY). For the base case scenario, the Diaskintest was dominant over all other examined strategies. The cost saving estimate per QALY was US $1375. In sensitivity analyses, the Diaskintest and other newer tests remained cost-saving compared to TST. For PLH, TST could be replaced by more specific tests in Brazil, considering the current national recommendations.

Community-Acquired Pneumonia and Risk of Cardiovascular Events in People Living With HIV.

BackgroundHospitalization with community‐acquired pneumonia (CAP) is associated with an increased risk of cardiovascular disease (CVD) events in patients uninfected with HIV. We evaluated whether people living with HIV (PLWH) have a higher risk of CVD or mortality than individuals uninfected with HIV following hospitalization with CAP.Methods and ResultsWe analyzed data from the Veterans Aging Cohort Study on US veterans admitted with their first episode of CAP from April 2003 through December 2014. We used Cox regression analyses to determine whether HIV status was associated with incident CVD events and mortality from date of admission through 30 days after discharge (30‐day mortality), adjusting for known CVD risk factors. We included 4384 patients (67% [n=2951] PLWH). PLWH admitted with CAP were younger, had less severe CAP, and had fewer CVD risk factors than patients with CAP who were uninfected with HIV. In multivariable‐adjusted analyses, CVD risk was similar in PLWH compared with HIV‐uninfected (hazard ratio [HR], 0.89; 95% CI, 0.70–1.12), but HIV infection was associated with higher mortality risk (HR, 1.49; 95% CI, 1.16–1.90). In models stratified by HIV status, CAP severity was significantly associated with incident CVD and 30‐day mortality in PLWH and patients uninfected with HIV.ConclusionsIn this study, the risk of CVD events during or after hospitalization for CAP was similar in PLWH and patients uninfected with HIV, after adjusting for known CVD risk factors and CAP severity. HIV infection, however, was associated with increased 30‐day mortality after CAP hospitalization in multivariable‐adjusted models. PLWH should be included in future studies evaluating mechanisms and prevention of CVD events after CAP.

Accuracy of the tuberculosis point-of-care Alere determine lipoarabinomannan antigen diagnostic test using α-mannosidase treated and untreated urine in a cohort of people living with HIV in Guatemala

BackgroundImproved point-of-care diagnostic tests for tuberculosis (TB) in severe immune suppressed people living with HIV (PLWH) are needed to decrease morbidity and mortality outcomes. The aim of the study is to evaluate the performance of the lipoarabinomannan antigen test (LAM-test) with and without α-mannosidase pre-treated urine in a cohort of PLWH in primary care clinics in Guatemala. We further determined TB incidence, and mortality rates and its risk factors in PLWH with TB symptoms.MethodsProspective longitudinal study of PLWH with TB symptoms. Urine samples were collected at 2 HIV sites to test the sensitivity of the LAM-test in urine with and without α-mannosidase pre-treatment. A composite reference standard of either a positive Mycobacterium tuberculosis complex culture and/or GeneXpert® MTB/RIF (Xpert, Cepheid, Sunnyvale, CA, USA) results was used in the LAM-test diagnostic accuracy studies. Cox proportional hazards regression was used to study mortality predictors.ResultsThe overall sensitivity of the LAM-test was of 56.1% with 95% CI of (43.3–68.3). There were no differences in the LAM-test sensitivity neither by hospital nor by CD4 T cell values. LAM-test sensitivity in PLWH with < 200 CD4 T cells/µl was of 62.2% (95% CI 46.5–76.2). There were no significant differences in sensitivity when comparing LAM-test results obtained from untreated vs. α-mannosidase treated urine [55.2% (95% CI 42.6–67.4) vs. 56.9% (95% CI 44–69.2), respectively]. TB incidence in our cohort was of 21.4/100 person years (PYs) (95% CI 16.6–27.6), and mortality rate was of 11.1/100 PYs (95% CI 8.2–15.0). Importantly, PLWH with a positive LAM-test result had an adjusted hazard ratio (aHR) of death of 1.98 (1.0–3.8) with a significant p value of 0.044 when compared to PLWH with a negative LAM-test result.ConclusionsIn this study, α-mannosidase treatment of urine did not significantly increase the LAM-test performance, however; this needs to be further evaluated in a large-scale study due to our study limitations. Importantly, high rates of TB incidence and mortality were found, and a positive LAM-test result predicted mortality in PLWH with TB clinical symptoms.

Gender difference in all-cause mortality of people living with HIV in Iran: findings from a 20-year cohort study.

Gender differences in the efficacy of treatment and the mortality of HIV-infected patients have not yet been fully elucidated. For the first time, we used data from a 20-year cohort of people living with HIV (PLWH) in four provinces (Fars, Bushehr, Bandar Abbas, and Kohgiluyeh and Boyer-Ahmad) in the southern part of Iran to assess the gender difference in all-cause mortality in PLWH in Iran. We analysed data for 1216 patients aged ≥ 15years who were diagnosed with HIV/AIDS between 1997 and 2017. Three hundred and fourteen (25.8%) were women. The death rate from all causes among women was 13.7% vs. 43.8% among men (P<0.001). All-cause mortality was significantly associated with gender [the adjusted hazard ratio (aHR) for men compared with women was 3.20], not being on antiretroviral therapy (ART) compared with being on ART at the last visit (aHR5.42), older age (aHR1.03), delayed HIV diagnosis compared with early diagnosis (aHR1.72), history of incarceration (aHR1.57), higher log CD4 count at diagnosis (aHR0.54), and prophylaxis for Pneumocystis pneumonia (aHR0.09). The results of this 20-year cohort study suggest that gender is an important predictor of survival among HIV-infected patients. Improving early HIV diagnosis and early ART initiation in men, as well as increased access to hepatitis C virus treatment are needed to increase the survival rate of HIV-infected patients in Iran.

Prevalence of Asymptomatic Cryptococcal Antigenemia and Association with Follow-up Risk of Cryptococcal Meningitis and Mortality among HIV Infected Patients in North West India: A Prospective Cohort Study.

Cryptococcal meningitis is an important cause of morbidity and mortality in HIV infected individuals. In the era of universal antiretroviral therapy, the incidence of immune reconstitution inflammatory syndrome (IRIS) related cryptococcal meningitis has increased. Detection of serum cryptococcal antigen in asymptomatic PLHIV (People Living With HIV) and preemptive treatment with fluconazole can decrease the burden of cryptococcal disease. We conducted this study to find the prevalence of asymptomatic cryptococcal antigenemia in India and its correlation with mortality in PLHIV. This was a prospective observational study. HIV infected ART naïve patients with age of ≥ 18 years who had CD4 counts ≤ 100 /μL were included and serum cryptococcal antigen test was done. These patients were followed for six months to look for the development of Cryptococcal meningitis and mortality. A total of 116 patients were analyzed. Asymptomatic cryptococcal antigenemia was detected in 5.17% of patients and is correlated with increased risk of cryptococcal meningitis and mortality on follow-up in PLHIV. Serum cryptococcal antigen positivity is correlated with an increased risk of Cryptococcal meningitis and mortality in PLHIV. We recommend the screening of asymptomatic PLHIV with CD4 ≤ 100/μL for serum cryptococcal antigen, so that pre-emptive treatment can be initiated to reduce morbidity and mortality.

Cardiometabolic Characterization Of People Living With HIV Seeking Treatment In The South Texas Region

PURPOSE: To characterize the cardiometabolic profile of people living with HIV (PLWH). We hypothesized that a majority of PLWH would have 3 or more cardiometabolic risk markers. METHODS: A large dataset from electronic medical records (EMR) of PLWH seeking care at several public health care institutions was used for this investigation. 200 PLWH from the South Texas Region were included. We identified cardiometabolic risk markers from the EMR system to characterize the cardiometabolic profile of PLWH in this region. The cardiometabolic variables considered were: cholesterol (≥ 200 mg/dL), triglycerides (TG) (≥ 150 mg/dL), glycated hemoglobin (HbA1C) (≥ 6.5%), body mass index (BMI) (≥ 30 kg/m2), and blood pressure (SBP ≥ 140 mmHg / DBP ≥ 90 mmHg). Demographic variables retrieved from the EMR were: height (in), weight (lbs), age (yrs), gender (M/F), race, viral load (copies/mL), and CD4+ T-cell percentage (%CD4). We identified the first encounter as representation of the initiation of care. Descriptive statistics such as percentages, means, standard deviations (SD) or ranges were calculated for all variables. RESULTS: The sample was comprised of 35% Hispanics and 65% Non-Hispanics, primarily Caucasians (75%) and Black (19%). Approximately 77% classified themselves as men. Age, weight, and height were 49.88 ± 12.2 yrs; 179.1 ± 44.3 lbs; 67.4 ± 3.8 in, respectively. %CD4 and viral load were 20.8 ± 10.5 % and 27,102 ± 102,813 copies/mL, respectively. On average, the values of the cardiometabolic risk markers were borderline high: HbA1C=6.17 ± 1.84% (range: 4-13); TG=190 ± 156.1 mg/dL (range: 37-1,099); cholesterol=177 ± 42.7 mg/dL (range: 80-362); SBP= 129.9 ± 17.2 mmHg (range: 92-187); DBP=78.2 ± 11.8 mmHg (range: 52-117); BMI=29.5 ± 7.4 kg/m2 (range: 21-53). However, after evaluating the range of values of the sample, close to 50% of PLWH had elevated values in at least 3 of the cardiometabolic risk markers. CONCLUSIONS: PLWH in the South Texas region exhibit an elevated cardiometabolic risk profile. Due to the greater morbidity and mortality in PLWH with cardiometabolic disease, early intervention is imperative. Exercise professionals should be included as part of the healthcare team at the initiation of care to improve the cardiometabolic profile of PLWH.

Cardiovascular disease among people living with HIV in Brazil.

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

Cryptococcal antigenemia is associated with meningitis or death in HIV-infected adults with CD4 100\u2013200 cells/mm3

BackgroundCryptococcal antigen (CrAg) screening with fluconazole prophylaxis has been shown to prevent cryptococcal meningitis and mortality for people living with HIV (PLWH) with CD4 < 100 cells/mm3. While cryptococcal meningitis occurs in individuals with CD4 100–200 cells/mm3, there is limited evidence that CrAg screening predicts cryptococcal meningitis or mortality among this group with moderate immunosuppression. Current IDSA and WHO clinical guidelines recommend restricting CrAg screening to PLWH with CD4 < 100 cells/mm3.MethodsWe conducted a prospective cohort study of PLWH 18+ years who had not initiated ART in South Africa. We followed participants for 14 months to determine onset of cryptococcal meningitis or all-cause mortality. At study completion, we retrospectively tested stored serum samples for CrAg using an enzyme immunoassay (EIA). We calculated CD4-stratified incidence rates of outcomes and used Cox proportional hazards to measure associations between CrAg positivity and outcomes.ResultsWe enrolled 2383 PLWH, and 1309 participants had serum samples tested by CrAg EIA. The median CD4 was 317 cells/mm3 (interquartile range: 173–491 cells/mm3). By CD4 count at baseline, there were 209 individuals with a CD4 count of 100–200 cells/mm3 and available CrAg test results. Of these, four (1.9%) tested positive. Two of four (IR: 58.8 per 100 person-years) CrAg+ participants and 11 of 205 (IR: 5.6 per 100 person-years) CrAg- participants developed cryptococcal meningitis or died for an overall rate of death or cryptococcal meningitis that was 10.0-times higher for those who were CrAg+ (95% confidence interval: 2.2–45.3). Among those with CD4 < 100 cell/mm3 and CrAg EIA test results (N = 179), ten (5.6%) participants tested CrAg+. Among this group, seven of ten (IR: 137.6 per 100 person-years) CrAg+ participants and 26 of 169 (IR: 17.8 per 100 person-years) CrAg- participants developed cryptococcal meningitis or died, for a rate of death or cryptococcal meningitis that was 6.3-times higher for those who were CrAg+ (95% confidence interval: 2.7–14.6).ConclusionsAlthough few PLWH with moderate immunosuppression screened CrAg positive, a positive CrAg test was predictive of increased risk of cryptococcal meningitis or death. Similar to those with a CD4 < 100 cell/mm3, systematic CrAg screening may reduce morbidity and mortality in PLWH with CD4 100–200 cells/mm3.

Characteristics of Immune Checkpoint Inhibitors Trials Associated With Inclusion of Patients With HIV

Since antiretroviral therapy became widely available in the late 1990s, there has been a dramatic reduction in AIDS-related deaths due to opportunistic infections.1 The life expectancy of people living with HIV (PLWH) receiving antiretroviral therapy now approaches that of the general population, particularly for those with a CD4+ T-cell count within the normal range.2 Conversely, cancer has become a leading cause of morbidity and mortality in PLWH. From 1995 to 2009, cancer resulted in nearly two-fold as many deaths per 100 000 person-years in PLWH than in the general population (327 deaths per 100 000 person-years vs 186 deaths per 100 000 person-years).3 Non–AIDS-defining cancers represent 70% of these deaths and will increase with aging of the PLWH population.3 During the past decade, clinical trials of immune checkpoint inhibitors (ICIs) have changed the treatment landscape of many cancers. Historically, PLWH have been excluded from participation in oncology trials, which may affect generalizability of findings. In this systematic review and meta-analysis, we investigated characteristics of ICI trials associated with inclusion of PLWH.

2548. Provider Adherence to Cervical Cancer Screening in HIV Patient Populations

BackgroundAntiretroviral therapy has nearly normalized the life expectancy of people living with HIV (PLWH). However, malignancies still remain a major cause of morbidity and mortality in PLWH, and thus an important part of the clinical visit is age appropriate screening and referral to care, from Lancet 2019 for the poster. Most cases of cervical cancer occur in women who were either never screened or were screened inadequately. Over-screening for cervical cancer, on the other hand, leads to unnecessary stress and procedures, adding increased costs to the patient and to the healthcare system. The central aim of this project is to evaluate provider adherence at the Immunology Center (IC) to cervical cancer screening guidelines and to identify factors associated with over and underscreening.MethodsA retrospective chart review from January 1, 2015, to December 31, 2017 was performed. Study included HIV-seropositive women seen at the IC between April 2014 and June 2018. Exclusion criteria includes prior hysterectomy, abnormal cytology, cervical excision procedures, or other causes of immunosuppression.ResultsOf the 803 HIV-positive women identified, n = 262 met criteria for inclusion in the study. Overall adherence was 48%, with statistical significance found in cervical cancer screening between MDs and NPs, with an OR = 2.51 (P < 0.01). In regard to gender of provider, statistical significance in over screening was found between male and female providers, with an OR = 4.3 (P < 0.01), and in under screening between male and female providers, with an OR = 0.43 (P < 0.05). Over screening led to 44 excess pap smears over a 2-year period, yielding an excess cost of $6461. HPV co-testing was underutilized, with only one-third of encounters having HPV testing performed.ConclusionThis project gives us the opportunity to reeducate and retrain the clinical staff and practitioners providing cervical cancer screening at the Immunology Center. This is an ongoing quality improvement project, where adherence will be reassessed on a continuous basis at one-year intervals to ensure compliance with guidelines-based cervical cancer screening among female HIV seropositive patients at the Immunology Center. Disclosures All authors: No reported disclosures.

Markers of chronic obstructive pulmonary disease are associated with mortality in people living with HIV.

Aging people living with HIV (PLWH) face an increased burden of comorbidities, including chronic obstructive pulmonary disease (COPD). The impact of COPD on mortality in HIV remains unclear. We examined associations between markers of COPD and mortality among PLWH and uninfected study participants. Longitudinal analysis of the Examinations of HIV-Associated Lung Emphysema (EXHALE) cohort study. EXHALE includes 196 PLWH and 165 uninfected smoking-matched study participants who underwent pulmonary function testing and computed tomography (CT) to define COPD and were followed. We determined associations between markers of COPD with mortality using multivariable Cox regression models, adjusted for smoking and the Veterans Aging Cohort Study (VACS) Index, a validated predictor of mortality in HIV. Median follow-up time was 6.9 years; the mortality rate was 2.7/100 person-years among PLWH and 1.7/100 person-years among uninfected study participants (P = 0.11). The VACS Index was associated with mortality in both PLWH and uninfected study participants. In multivariable models, pulmonary function and CT characteristics defining COPD were associated with mortality in PLWH: those with airflow obstruction (forced expiratory volume in 1 s/ forced vital capacity <0.7) had 3.1 times the risk of death [hazard ratio 3.1 (95% confidence interval 1.4-7.1)], compared with those without; those with emphysema (>10% burden) had 2.4 times the risk of death [hazard ratio 2.4 (95% confidence interval 1.1-5.5)] compared with those with ≤ 10% emphysema. In uninfected subjects, pulmonary variables were not significantly associated with mortality, which may reflect fewer deaths limiting power. Markers of COPD were associated with greater mortality in PWLH, independent of the VACS Index. COPD is likely an important contributor to mortality in contemporary PLWH.

Prediction of long-term outcomes of HIV-infected patients developing non-AIDS events using a multistate approach.

ObjetivesOutcomes of people living with HIV (PLWH) developing non-AIDS events (NAEs) remain poorly defined. We aimed to classify NAEs according to severity, and to describe clinical outcomes and prognostic factors after NAE occurrence using data from CoRIS, a large Spanish HIV cohort from 2004 to 2013.DesignProspective multicenter cohort study.MethodsUsing a multistate approach we estimated 3 transition probabilities: from alive and NAE-free to alive and NAE-experienced (“NAE development”); from alive and NAE-experienced to death (“Death after NAE”); and from alive and NAE-free to death (“Death without NAE”). We analyzed the effect of different covariates, including demographic, immunologic and virologic data, on death or NAE development, based on estimates of hazard ratios (HR). We focused on the transition “Death after NAE”.Results8,789 PLWH were followed-up until death, cohort censoring or loss to follow-up. 792 first incident NAEs occurred in 9.01% PLWH (incidence rate 28.76; 95% confidence interval [CI], 26.80–30.84, per 1000 patient-years). 112 (14.14%) NAE-experienced PLWH and 240 (2.73%) NAE-free PLWH died. Adjusted HR for the transition “Death after NAE” was 12.1 (95%CI, 4.90–29.89). There was a graded increase in the adjusted HRs for mortality according to NAE severity category: HR (95%CI), 4.02 (2.45–6.57) for intermediate-severity; and 9.85 (5.45–17.81) for serious NAEs compared to low-severity NAEs. Male sex (HR 2.04; 95% CI, 1.11–3.84), age>50 years (1.78, 1.08–2.94), hepatitis C-coinfection (2.52, 1.38–4.61), lower CD4 cell count at cohort entry (HR 2.49; 95%CI 1.20–5.14 for CD4 cell count below 200 and HR 2.16; 95%CI 1.01–4.66 for CD4 cell count between 200–350, both compared to CD4 cell count higher than 500) and concomitant CD4<200 cells/mL (2.22, 1.42–3.44) were associated with death after NAE. CD4 count and HIV-1 RNA at engagement, previous AIDS and hepatitis C-coinfection predicted mortality in NAE-free persons.ConclusionNAEs, including low-severity events, increase prominently the risk for mortality in PLWH. Prognostic factors differ between NAE-experienced and NAE-free persons. These findings should be taken into account in the clinical management of PLWH developing NAEs and may permit more targeted prevention efforts.

Empirical treatment for TB in HIV: lessons from a cohort study of people living with HIV treated in Recife, Brazil

BackgroundTuberculosis (TB) is the leading cause of death related to HIV worldwide. This study analyzes the survival of People Living with HIV (PLHIV) reporting cough without bacteriological confirmation of TB and identify factors associated with death.MethodsProspective cohort with a consecutive sample of PLHIV, aged ≥ 18 years. Patient inclusion criteria were complaint of current cough of any duration at the time of the first study interview or during their subsequent routine visits to health services and for whom AFB sputum smear was either negative or not performed during the whole follow-up period. Kaplan-Meier method was used to calculate the probability of survival. We estimated the Hazard Ratio (HR) in bivariate and multivariate Cox regression analyses.ResultsMortality was 4.6 per 100 py; 73% were receiving HAART at recruitment. Average time from the first recorded date of cough until empirical treatment for tuberculosis was six months. Mortality was higher when the CD4 count was low (HR = 5.3; CI 95%: 3.2-9.0; p = 0.000), in those with anemia (HR = 3.0; CI 95%: 1.6-5.6; p = 0.001) and with abnormal chest X-rays (HR = 2.4; CI 95%: 1.4-4.0; p = 0.001). Mortality was higher in those receiving empirical TB treatment (HR = 2.4; CI 95%: 1.4-4.0; p = 0.002), but only in those with normal X-rays, no history of tuberculosis and no bacteriology requests. Empirical treatment for TB was more frequent in PLHIV with low CD4 counts, anemia, history of opportunistic infections, weight loss, previous tuberculosis, negative bacteriology test (as opposed to not having a test) and abnormal chest X-ray.ConclusionsHigher mortality in PLHIV reporting a current cough without bacteriological confirmation of tuberculosis was identified for those with a CD4 cell count <200, abnormal chest X-ray, anemia and empirical treatment for tuberculosis. Mortality was not significantly higher in those empirically treated for TB, who had three characteristics suggestive of the disease (abnormal chest X-ray, history of TB treatment, AFB sputum smear or M.tb culture testing). Routine cohorts are not an adequate setting to evaluate the impact of empirical treatment for TB on the mortality of PLHIV.

The Effect of Tuberculosis on Mortality in HIV Positive People: A Meta-Analysis

BackgroundTuberculosis is a leading cause of death in people living with HIV (PLWH). We conducted a meta analysis to assess the effect of tuberculosis on mortality in people living with HIV.MethodsMeta-analysis of cohort studies assessing the effect of tuberculosis on mortality in PLWH. To identify eligible studies we systematically searched electronic databases (until December 2008), performed manual searches of citations from relevant articles, and reviewed conference proceedings. Multivariate hazard ratios (HR) of mortality in PLWH with and without tuberculosis, estimated in individual cohort studies, were pooled using random effect weighting according to “Der Simonian Laird method” if the p-value of the heterogeneity test was <0.05.ResultsFifteen cohort studies were systematically retrieved. Pooled overall analysis of these 15 studies estimating the effect of tuberculosis on mortality in PLWH showed a Hazard Ratio (HR) of 1.8 (95% confidence interval (CI): 1.4–2.3). Subanalysis of 8 studies in which the cohort was not exposed to highly active antiretroviral therapy (HAART) showed an HR of 2.6 (95% CI: 1.8–3.6). Subanalysis of 6 studies showed that tuberculosis did not show an effect on mortality in PLWH exposed to HAART: HR 1.1 (95% CI: 0.9–1.3).ConclusionThese results provide an indication of the magnitude of benefit to an individual that could have been expected if tuberculosis had been prevented. It emphasizes the need for additional studies assessing the effect of preventing tuberculosis or early diagnosis and treatment of tuberculosis in PLWH on reducing mortality. Furthermore, the results of the subgroup analyses in cohorts largely exposed to HAART provide additional support to WHO's revised guidelines, which include promoting the initiation of HAART for PLWH co-infected with tuberculosis. The causal effect of tuberculosis on mortality in PLWH exposed to HAART needs to be further evaluated once the results of more cohort studies become available.