Baseline CD4 T-cell Count Research Articles

Effect of high-dose multivitamin supplements on alanine aminotransferase elevations among adults living with HIV on antiretroviral therapy in Tanzania.

HIV infection can cause malabsorption and rapid utilization of nutrients. A randomized trial of multivitamin supplementation among people living with HIV/AIDS (PLWHA) initiating antiretroviral therapy (ART) in Tanzania was stopped early due to increased alanine aminotransferase (ALT) concentrations in the multiple recommended dietary allowances (RDA) multivitamin group. We conducted detailed analysis to assess the effect of multivitamins on ALT elevations and evaluate whether subgroups of PLWHA have greater hepatotoxicity risks associated with the use of high-dose multivitamins. We utilized data from a randomized, double-blind trial conducted in 2006-2009 that assessed the effect of high-dose multivitamins that contained vitamin B complex, vitamin C, and vitamin E at multiple RDA as compared to standard-dose multivitamins containing single RDAs among adults initiating ART in Tanzania. We evaluated the effect of high-dose multivitamins on incident mild/moderate ALT elevations > 40 IU/L, persistent ALT elevations > 40 IU/L (2 + clinic visits), and severe ALT elevations > 200IU/L using Cox proportional hazard models. We then evaluated effect modification by patient characteristics to determine if subgroups of PLWHA experienced different magnitudes of risk for ALT elevations associated with high-dose multivitamins. High-dose multivitamins increased the risk of incident mild/moderate ALT elevations > 40 IU/mL as compared to standard-dose multivitamins (hazard ratio (HR): 1.41; 95%CI: 1.26,1.58) as well as incident sustained mild/moderate ALT elevations (HR: 1.19; 95%CI: 1.04,1.36), but there was no overall effect on severe ALT elevations (HR: 1.44; 95% CI: 0.91,2.28). There was no evidence that the effect of high-dose multivitamins on any or sustained mild/moderate ALT elevations was modified by any patient characteristic. However, CD4 T-cell count was found to modify the effect of high-dose multivitamins on severe ALT elevations (p-value for interaction:0.01). Among participants with a baseline CD4 T-cell count ≤ 100 cells/µL, individuals receiving high-dose multivitamins had 3.74 times (95%CI: 1.52-9.17) the risk of incident severe ALT elevations compared to standard-dose multivitamins, while participants with CD4 T-cell counts > 100 cells/µL, appeared to have no effect of high-dose multivitamins on severe ALT elevations (HR:0.92; 95% CI: 0.50,1.67). High-dose RDA multivitamin supplementation increased the incidence of any mild to moderate ALT elevations among adults starting ART in Tanzania and the magnitude of the risk does not appear to differ by patient characteristics. However, immunocompromised PLWHA with CD4 T-cell counts < 100 cells/µL may experience greater risk of severe ALT elevations associated with the use of high-dose multivitamins. Although the study findings offer significant insights, it is essential to take into account limitations imposed by newer cART regimes.

Trajectories of CD4 T-cell count, CD8 T-cell count, and CD4/CD8 ratio in patients with HIV and long-term virological suppression based on Yunnan HIV cohort.

Our objective was to evaluate the trajectory of immunology in patients with HIV with different baseline CD4 T-cell count strata after antiretroviral therapy (ART) under long-term viral suppression. This was a sub-analysis focused on patients with virological suppression for at least 5 years after ART. Data were obtained from the Yunnan HIV cohort in China. Patients were categorized according to prespecified baseline CD4 T-cell counts. The trajectories of CD4 T-cell count, CD8 T-cell count, and CD4/CD8 ratio changing over time were fitted using a B-spline regression model. The Cox proportional hazards regression model was used to assess the association of baseline CD4 T-cell count with the risk of both immunological responder (IR) and CD4/CD8 ratio normalization. A total of 2618 patients with a median follow-up of 7.25 years (interquartile range [IQR] 5.92-8.75) were included. Over a period of 12 years, the mean CD4 T-cell count remained above 500 cells/μL in all groups. The mean CD4/CD8 ratio was solely normalized in patients whose baseline CD4 T-cell counts were above 350 cells/μL. Patients with higher baseline CD4 T-cell counts showed higher risks of both IR and CD4/CD8 ratio normalization than those with the lowest (all p trend <0.001). A higher baseline CD4 T-cell count predicted a shorter time for both IR and CD4/CD8 ratio normalization. Long-term, sustained viral suppression may not be able to fully normalize immunological functions in patients with HIV. A high baseline CD4 T-cell count benefits IR and CD4/CD8 ratio normalization.

Prevalence of high-risk human papillomavirus genotypes in outpatient Malian women living with HIV: a pilot study.

Long-term exposure to high-risk human papillomavirus (Hr-HPV) is a well-known necessary condition for development of cervical cancer. The aim of this study is to screen for Hr-HPV using vaginal self-sampling, which is a more effective approach to improve women's adherence and increase screening rates. This pilot study included a total of 100 Women living with HIV (WLWHIV), recruited from the Center for Listening, Care, Animation, and Counseling of People Living with HIV in Bamako. Hr-HPV genotyping was performed on Self-collected samples using the Cepheid GeneXpert instrument. The median age of WLWHIV was 44 (interquartile range [IQR], 37-50) years. Approximately 92% of the study participants preferred self-sampling at the clinic, and 90% opted to receive result notifications via mobile phone contact. The overall prevalence of Hr-HPV among study participants was 42.6%, and the most frequent Hr-HPV sub-types observed were HPV18/45 (19.1%), HPV31/35/33/52/58 (13.8%), and HPV39/68/56/66 (12.8%), followed by HPV16 (5.3%), and HPV51/59 (5.3%). WLWHIV under 35 years of age had a higher frequency of Hr-HPV compared to their older counterparts, with rates of 30% versus 11.1% (p = 0.03). The duration of antiretroviral treatment showed an inverse association with Hr-HPV negativity, with patients on treatment for 15 (IQR, 10-18) years versus 12 (IQR = 7-14) years for Hr-HPV positive patients (95% CI [1.2-5.8], t = 3.04, p = 0.003). WLWHIV with baseline CD4 T-Cell counts below 200 exhibited a higher frequency of Hr-HPV compared to those with baseline CD4 T-Cell counts above 200 (17.9% versus 1.9%, p = 0.009). However, other demographics and clinical factors, such as marital status, age of sexual debut, parity, education, history of abortion, history of preeclampsia, and cesarean delivery, did not influence the distribution of Hr-HPV genotypes. Our findings indicate that WLWHIV under the age of 35 years old exhibited the highest prevalence of Hr-HPV infection, with HPV18/45 being the most prevalent subtype. Additionally, WLWHIV with baseline CD4 T-Cell counts below 200 showed the highest infection rates.

Clinical outcomes and risk factors for immune recovery and all-cause mortality in Latin Americans living with HIV with virological success: a retrospective cohort study.

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

A Systematic Review and Meta-Analysis on the Impact of Statin Treatment in HIV Patients on Antiretroviral Therapy

The rate of new human immunodeficiency virus (HIV) infections globally is alarming. Although antiretroviral therapy (ART) improves the quality of life among this group of patients, ARTs are associated with risk of cardiovascular diseases (CVD). Moreover, virally suppressed patients still experience immune activation associated with HIV migration from reservoir sites. Statins are widely recommended as therapeutic agents to control ART-related CVD; however, their impacts on the cluster of differentiation (CD)4 count and viral load are inconsistent. To assess the effect of statins on markers of HIV infections, immune activation and cholesterol, we thoroughly reviewed evidence from randomised controlled trials. We found 20 relevant trials from three databases with 1802 people living with HIV (PLHIV) on statin-placebo treatment. Our evidence showed no significant effect on CD4 T-cell count standardised mean difference (SMD): (-0.59, 95% confidence intervals (CI): (-1.38, 0.19), p = 0.14) following statin intervention in PLHIV on ART. We also found no significant difference in baseline CD4 T-cell count (SD: (-0.01, 95%CI: (-0.25, 0.23), p = 0.95). Our findings revealed no significant association between statins and risk of viral rebound in PLHIV with undetectable viral load risk ratio (RR): (1.01, 95% CI: (0.98, 1.04), p = 0.65). Additionally, we found a significant increase in CD8+CD38+HLA-DR+ T-cells (SMD (1.10, 95% CI: (0.93, 1.28), p < 0.00001) and CD4+CD38+HLA-DR+ T-cells (SMD (0.92, 95% CI: (0.32, 1.52), p = 0.003). Finally, compared to placebo, statins significantly reduced total cholesterol (SMD: (-2.87, 95% CI: (-4.08, -1.65), p < 0.0001)). Our results suggest that the statin lipid-lowering effect in PLHIV on ART may elevate immune activation without influencing the viral load and CD4 count. However, due to the limited evidence synthesised in this meta-analysis, we recommend that future powered trials with sufficient sample sizes evaluate statins' effect on CD4 count and viral load, especially in virally suppressed patients.

Predictors of low-level HIV viraemia and virological failure in the era of integrase inhibitors: A Spanish nationwide cohort.

To pinpoint factors associated with low-level viraemia (LLV) and virological failure (VF) in people living with HIV in the era of high-efficacy antiretroviral treatment (ART) and widespread use of integrase strand transfer inhibitor (INSTIs)-based ART. We included adults aged >18years starting their first ART between 2015 and 2018 in the Spanish HIV/AIDS Research Network National Cohort (CoRIS). Low-level viraemia was defined as plasma viral load (pVL) of 50-199 copies/mL at weeks 48 and 72 and VF was defined as pVL ≥50 copies/mL at week 48 and pVL ≥200 copies/mL at week 72. Multivariable logistic regression models assessed the impact on LLV and VF of baseline CD4 T-cell count, CD4/CD8 T-cell ratio and pVL, initial ART classes, age at ART initiation, time between HIV diagnosis and ART initiation, gender and transmission route. Out of 4186 participants, 3120 (76.0%) started INSTIs, 455 (11.1%) started boosted protease inhibitors (bPIs) and 443 (10.8%) started nonnucleoside reverse transcriptase inhibitors (NNRTIs), either of them with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs). Low-level viraemia was met in 2.5% of participants and VF in 4.3%. There were no significant differences throughout the years for both virological outcomes. Baseline HIV-1 RNA >5log10 copies/mL was the only consistent predictor of higher risk of LLV [adjusted odds ratio (aOR) = 9.8, 95% confidence interval (CI): 2.0-48.3] and VF (aOR = 5.4, 95%CI: 1.9-15.1), even in participants treated with INSTIs. The rates of LLV and VF were low but remained steady throughout the years. Baseline HIV-1 RNA >5log10 copies/mL showed a persistent association with LLV and VF even in participants receiving INSTIs.

Treatment outcomes in HIV infected patients older than 50 years attending an HIV clinic in Harare, Zimbabwe: A cohort study.

There is a growing number of older people living with HIV (OPLHIV). While a significant proportion of this population are adults growing into old age with HIV, there are also new infections among OPLHIV. There is a lack of data describing the outcomes of OPLHIV who commenced antiretroviral therapy (ART) after the age of 50 years in sub-Saharan Africa. We conducted a cohort study of patients who enrolled in care at Newlands Clinic in Harare, Zimbabwe, at ages ≥50 years between February 2004 and March 2020. We examined demographic characteristics, attrition, viral suppression, immunological and clinical outcomes. Specifically, we described prevalent and incident HIV-related communicable and non-communicable comorbidities. We calculated frequencies, medians, interquartile ranges (IQR), and proportions; and used Cox proportional hazards models to identify risk factors associated with death. We included 420 (57% female) who commenced ART and were followed up for a median of 5.6 years (IQR 2.4-9.9). Most of the men were married (n = 152/179, 85%) whereas women were mostly widowed (n = 125/241, 51.9%). Forty per cent (n = 167) had WHO stage 3 or 4 conditions at ART baseline. Hypertension prevalence was 15% (n = 61) at baseline, and a further 27% (n = 112) had incident hypertension during follow-up. During follow-up, 300 (71%) were retained in care, 88 (21%) died, 17 (4%) were lost to follow-up, and 15 (4%) were transferred out. Of those in care, 283 (94%) had viral loads <50 copies/ml, and 10 had viral loads >1000 copies/ml. Seven patients (1.7%) were switched to second line ART during follow-up and none were switched to third-line. Higher baseline CD4 T-cell counts were protective against mortality (p = 0.001) while male sex (aHR: 2.29, 95%CI: 1.21-4.33), being unmarried (aHR: 2.06, 95%CI: 1.13-3.78), and being unemployed (aHR: 2.01, 95%CI: 1.2-3.37) were independent independent risk factors of mortality. There was high retention in care and virologic suppression in this cohort of OPLHIV. Hypertension was a common comorbidity. Being unmarried or unemployed were significant predictors of mortality highlighting the importance of sociologic factors among OPLHIV, while better immune competence at ART commencement was protective against mortality.

Incidence of Hepatotoxicity and Factors Associated During Highly Active Antiretroviral Therapy in People Living with HIV in Ethiopia: A Prospective Cohort Study.

IntroductionHepatotoxicity is one of the risk factors associated with treatment non-adherence, which is the main risk factor for drug resistance. Therefore, this study aimed to determine the incidence and risk factors of hepatotoxicity during highly active antiretroviral therapy (HAART) among people living with HIV in Ethiopia.MethodsA prospective cohort study was conducted between April 2007 and January 2011 at Saint Peter Specialized Hospital, Akaki and Kality Health Centers, Addis Ababa, Ethiopia. A total of 316 HIV-infected adult individuals (70 participants were HIV and TB co-infected and 246 were infected with HIV alone) were included in this study. The study participants were followed for a total of 18 months with or without HAART. Socio-demographic data were collected using a structured questionnaire, and venous blood samples were collected for laboratory tests. Logistic regression and Poisson regression were used to determine the independent effect of each variable on hepatotoxicity at baseline and end of follow-up.ResultsOf 316 HIV-infected people, 72 (22.8%) participants had an elevated ALT/AST which was 100% mild-to moderate hepatotoxicity at baseline. Baseline CD4 T-cell count (p = 0.027) and HIV co-infection with TB (p < 0.001) were independently associated with hepatotoxicity at baseline. The overall incidence rate of hepatotoxicity in participants on HAART (21.8 per 100 person-years) was lower than participants who were HAART naïve (33.3 per 100 person-years) (p = 0.009).ConclusionHigh incidence of mild-to-moderate hepatotoxicity and low severe hepatotoxicity were observed in HIV-infected individuals who were on HAART or were HAART naïve. HAART may minimize the occurrence of hepatotoxicity. Although HAART could minimize hepatotoxicity among HIV-infected people, to manage mild and moderate hepatotoxicity liver function test monitoring is required.

Immunological and Psychological Efficacy of Meditation/Yoga Intervention Among People Living With HIV (PLWH): A Systematic Review and Meta-analyses of 19 Randomized Controlled Trials.

An expanding number of mind-body therapies are being used to reduce the psychological burden of peoples living with human immunodeficiency virus (HIV). However, the effects on the immune system and mental health varied among studies. This meta-analysis was conducted to summarize the randomized controlled trials to draw comprehensive conclusions regarding the psycho-immunological efficacy. Random-effects models were used to assess the outcome of interest. Egger's tests were used to identify publication bias. Subgroup and meta-regression were used to explore potential moderators. This review was registered on the PROSPERO database (CRD42019148118). Nineteen randomized controlled trials with a total sample size of 1,300 were included in this meta-analysis. Regarding immune system outcome, mind-body therapy significantly improved CD4 T-cell counts (Cohen's d = 0.214, p = .027) and maintained (0.427, p = .049). In addition, baseline CD4 T-cell counts and years since HIV diagnosis significantly moderated the efficacy of mind-body practices on CD4 improvement (all ps < .001). Regarding mental health outcome, mind-body therapy significantly reduced stress, depression, and anxiety symptoms (0.422, p < .001; 0.506, p < .001, and 0.709, p < .001, respectively) while improving quality of life (0.67, p < .001). Meditation/yoga intervention could result in potential benefits with regard to improved CD4 T-cell counts immediately after the intervention and at long-term follow-up, while also improving their mental health. The cost-effective meditation/yoga intervention should be integrated into routine care for people living with HIV, especially for those with lower CD4 baseline and fewer years since diagnosis.

Assessment of Tp-e interval and Tp-e/QT ratio in patients with human immunodeficiency virus

ObjectiveSudden cardiac death (SCD) plays an important part in all-cause mortality in patients infected with human immunodeficiency virus (HIV). The T-peak to T-end (Tp-e) interval, corrected Tp-e (Tp-ec) interval, and Tp-e/QT ratio on the ECG are parameters used to stratify risk for SCD. The objective of this study was to investigate the differences between HIV-infected patients and healthy individuals in terms of Tp-e interval, Tp-ec interval, and Tp-e/QT ratio, as well as other influencing factors. MethodsNinety-eight HIV-infected patients and 62 healthy controls were included in this prospective case-control study. Tp-e interval, Tp-ec interval, and Tp-e/QT ratio were measured in all participants. Echocardiographic examination and routine laboratory analysis were performed. In addition, CD4 T-cell count and HIV RNA levels were assessed in HIV-infected patients. ResultsAll baseline characteristics were comparable in both groups. The median survival of those living with HIV was 20.63 months; 53% of them had controlled viral load, and 74% were receiving antiretroviral therapy. Mean baseline CD4 T-cell count was 409. In HIV-infected patients, the Tp-e interval and Tp-ec interval were prolonged, and the Tp-e/QT ratio was higher (p<0.001, p<0.001 and p=0.021, respectively). In bivariate and partial correlation analyses, there was a negative correlation between CD4 T-cell level and Tp-e interval, Tp-ec interval, and Tp-e/QT ratio. ConclusionTp-e interval, Tp-ec interval, and Tp-e/QT ratio were greater in HIV-infected patients compared with healthy individuals. HIV-infected patients, particularly those with low baseline CD4 T-cell counts, should be closely monitored due to risk of SCD.

HIV-1 genotype is independently associated with immunodeficiency progression among Chinese men who have sex with men: an observational cohort study.

HIV-1 genetic diversity is increasing among men who have sex with men (MSM) in China, but the association of HIV-1 genotype with disease progression remains to be elucidated. We collected data in an observational longitudinal cohort study of 860 HIV-1-infected MSM in Guangzhou, China between January 2008 and March 2017. Kaplan-Meier analysis and Cox proportional hazard model were used to predict the time from HIV-1 diagnosis to immunodeficiency progression (CD4 cell count < 200 cells/μl) as well as adjusted hazard ratio (aHR). CRF01_AE and HIV-1 subtype B infection were associated with higher percentage of patients progressed to immunodeficiency and higher incidence of immunodeficiency than infection with CRF07_BC or CRF55_01B. Compared with CRF07_BC, the time from HIV-1 diagnosis to immunodeficiency were different among the major HIV-1 genotypes, which ranked as follows, in descending order: CRF07_BC (7.03 years) > CRF55_01B (5.71 years, P = 0.014; aHR 3.752, P = 0.0923) > CRF01_AE (5.18 years, P < 0.001; aHR 4.733, P = 0.0152). HIV-1 genotype, viral load and baseline CD4 T-cell count were three independent variables associated with disease progression. Our results confirm differential rates of immunodeficiency progression as a function of HIV-1 genotype. The impact of HIV-1 genotype on HIV epidemics, patient management and prevention should be further investigated.

321. Low Volumetric Bone Density at Proximal Femur in HIV-Infected Men and Its Risk Factors: Comparison with Community-Dwelling Non-Infected Men

BackgroundIndividuals with HIV infection is at increased risk of low area bone mineral density (BMD) and fracture. However, data regarding volumetric BMD (vBMD) of central bone determined by quantitative computed tomography (QCT) which can distinguish the cortical and trabecular bone component are limited.MethodsFrom November 2017 to October 2018, we measured spine and hip vBMD in HIV-infected men aged 30 years or older at the tertiary center. QCT data were compared with 1:2 matched control by age- and body mass index (BMI) sampled from a community-based healthy individual cohort. HIV-specific risk factors for low total hip vBMD as a primary outcome were identified using multivariate linear regression models.ResultsA total of 83 HIV-infected men and 166 control were analyzed (mean age 47.4 vs. 47.0 year; BMI 23.3 vs. 23.7 kg/m2; P > 0.05). In HIV-infected men, vBMD of trochanter, intertrochanter and total hip was significantly lower than that of non-infected men. (198 ± 31 vs. 213 ± 32; 339 ± 50 vs. 356 ± 47; 280 ± 41 vs. 296 ± 41 mg/cc; all P < 0.05) Association between HIV infection and lower total hip vBMD remained robust (Adjusted β -14.4; P = 0.013) after adjustment for age, diabetes, smoking, and vitamin D status. In HIV cohort, low CD4 T-cell count at initial diagnosis (< 200 vs. ≥200 cells/μL; Adjusted β = −6.7, P = 0.015) and use of protease inhibitor (vs. integrase inhibitor; Adjusted β = −29.9, P = 0.029) were negatively associated with total hip vBMD, after adjustment for age, BMI, and duration of HIV infection, whereas tenofovir disoproxil fumarate use was not. (Adjusted β −12.1, P = 0.280) In HIV-infected men with low tertile total hip vBMD, the levels of β-crosslaps (0.42 ± 0.23 vs. 0.30 ± 0.16 ng/mL; P = 0.012) and osteocalcin (22.10 ± 8.65 vs. 16.57 ± 6.04 ng/mL; P = 0.001) were higher than those with middle-upper tertile total hip vBMD.ConclusionHIV-infected men had lower hip vBMD compared with age- and BMI-matched non-infected men. Low baseline CD4 T-cell count and protease inhibitor use were independent risk factors for lower total hip vBMD. High born turnover was attributable to the negative effect on born health of HIV-infected men.Disclosures All authors: No reported disclosures.

Associated factors for progression to AIDS among HIV-infected people who use drugs: a retrospective cohort study in Dongguan, China

ObjectivesInjection drug use is the most important risk factor for the spread of HIV in China over the past two decades. People who use drugs (PWUD) who were diagnosed at...

Associations between baseline biomarkers and lung function in HIV-positive individuals.

The aim of this study was to analyse the association of baseline biomarker data with cross-sectional lung function and subsequent decline in lung function in HIV-positive persons. Lung function was modelled in all START pulmonary substudy participants who had baseline biomarker data and good-quality spirometry. In longitudinal analyses, we restricted to those participants with at least one good-quality follow-up spirometry test. We performed linear regression of baseline forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC and their longitudinal slopes on log2-transformed baseline biomarkers with adjustment for age, sex, race, region, smoking status, baseline CD4+ T-cell counts and baseline HIV-RNA. Biomarkers included D-dimer, high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, IL-27, serum amyloid A, soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cell adhesion molecule (sVCAM)-1, albumin and total bilirubin. Among 903 included participants, baseline median age was 36 years, CD4+ cell count was 647 cells/μl, and 28.5% were current smokers. In adjusted analyses, elevated markers of systemic inflammation (hsCRP, IL-6 and serum amyloid A) were associated with lower baseline FEV1 and FVC. Elevated D-dimer and IL-6 were associated with worse airflow obstruction (lower FEV1/FVC). Despite these cross-sectional associations at baseline, no associations were found between baseline biomarkers and subsequent longitudinal lung function decline over a median follow-up time of 3.9 years (3293 spirometry-years of follow-up). Commonly available biomarkers, in particular markers of systemic inflammation, are associated with worse cross-sectional lung function, but do not associate with subsequent lung function decline among HIV-positive persons with early HIV infection and baseline CD4 T-cell counts more than 500 cells/μl.

Brief Report: Gut Structural Damage: an Ongoing Process in Chronically Untreated HIV Infection.

To investigate the longitudinal changes of gut structural damage in chronically untreated HIV infection. This is a 96-week prospective, single-site, cohort study of antiretroviral therapy-naive HIV-infected participants. Intestinal fatty acid-binding proteins (I-FABP) were used as a surrogate marker of gut structural damage. We assessed changes in I-FABP over 96 weeks and examined the associations between I-FABP, HIV variables, and inflammation. Spearman's correlations and linear mixed-effect models were used to study relationships among variables. A total of 63 HIV-infected, antiretroviral therapy-naive patients were included in this analysis. At baseline, 76% were male; 62% were African American, with median age and body mass index of 40 years and 27 kg/m, respectively. Median HIV-RNA and CD4 T-cell counts were 5520 copies per milliliter and 588 cells per mm, respectively. I-FABP significantly increased from baseline to week 96 (mean change +333.9 pg/mL; P = 0.03), and this increase was associated with viral replication (rho = +0.4; P = 0.03). I-FABP levels were found to be associated with markers of inflammation: sTNFR-II (rho = 0.4, P = 0.02) and sVCAM-1 (rho = 0.04; P < 0.01) at all study time points. Lower baseline CD4 T-cell counts was found to be independently associated with I-FABP progression after adjusting for baseline characteristic variables (P = 0.02). Gut structural damage is an ongoing process in the chronic phase of untreated HIV infection and is largely dependent on viral replication. I-FABP was found to be associated with worse immune function, increased inflammation, and viremia in chronically untreated HIV infection, supporting its role as a biomarker of intestinal barrier dysfunction.

Enrichment of gut-derived Fusobacterium is associated with suboptimal immune recovery in HIV-infected individuals

We explored the gut microbiota profile among HIV-infected individuals with diverse immune recovery profiles following long-term suppressive ART and investigated the relationship between the altered bacteria with markers of immune dysfunction. The microbiota profile of rectal swabs from 26 HIV-infected individuals and 20 HIV-uninfected controls were examined. Patients were classified as suboptimal responders, sIR (n = 10, CD4 T-cell <350 cells/ul) and optimal responders, oIR (n = 16, CD4 T-cell >500 cells/ul) after a minimum of 2 years on suppressive ART. Canonical correlation analysis(CCA) and multiple regression modelling were used to explore the association between fecal bacterial taxa abundance and immunological profiles in optimal and suboptimal responders. We found Fusobacterium was significantly enriched among the HIV-infected and the sIR group. CCA results showed that Fusobacterium abundance was negatively correlated with CD4 T-cell counts, but positively correlated with CD4 T-cell activation and CD4 Tregs. Multiple linear regression analysis adjusted for age, baseline CD4 T-cell count, antibiotic exposure and MSM status indicated that higher Fusobacterium relative abundance was independently associated with poorer CD4 T-cell recovery following ART. Enrichment of Fusobacterium was associated with reduced immune recovery and persistent immune dysfunction following ART. Modulating the abundance of this bacterial taxa in the gut may be a viable intervention to improve immune reconstitution in our setting.

Biomarkers of Progression after HIV Acute/Early Infection: Nothing Compares to CD4⁺ T-cell Count?

Progression of HIV infection is variable among individuals, and definition disease progression biomarkers is still needed. Here, we aimed to categorize the predictive potential of several variables using feature selection methods and decision trees. A total of seventy-five treatment-naïve subjects were enrolled during acute/early HIV infection. CD4+ T-cell counts (CD4TC) and viral load (VL) levels were determined at enrollment and for one year. Immune activation, HIV-specific immune response, Human Leukocyte Antigen (HLA) and C-C chemokine receptor type 5 (CCR5) genotypes, and plasma levels of 39 cytokines were determined. Data were analyzed by machine learning and non-parametric methods. Variable hierarchization was performed by Weka correlation-based feature selection and J48 decision tree. Plasma interleukin (IL)-10, interferon gamma-induced protein (IP)-10, soluble IL-2 receptor alpha (sIL-2Rα) and tumor necrosis factor alpha (TNF-α) levels correlated directly with baseline VL, whereas IL-2, TNF-α, fibroblast growth factor (FGF)-2 and macrophage inflammatory protein (MIP)-1β correlated directly with CD4+ T-cell activation (p < 0.05). However, none of these cytokines had good predictive values to distinguish “progressors” from “non-progressors”. Similarly, immune activation, HIV-specific immune responses and HLA/CCR5 genotypes had low discrimination power. Baseline CD4TC was the most potent discerning variable with a cut-off of 438 cells/μL (accuracy = 0.93, κ-Cohen = 0.85). Limited discerning power of the other factors might be related to frequency, variability and/or sampling time. Future studies based on decision trees to identify biomarkers of post-treatment control are warrantied.

High Treatment Success Rates Among HIV-Infected Multidrug-Resistant Tuberculosis Patients After Expansion of Antiretroviral Therapy in Botswana, 2006-2013.

Few studies have examined multidrug-resistant (MDR) tuberculosis (TB) treatment outcomes among HIV-infected persons after widespread expansion of antiretroviral therapy (ART). We describe MDR-TB treatment outcomes among HIV-infected and HIV-uninfected patients in Botswana after ART expansion. We retrospectively reviewed data from patients who started MDR-TB therapy in Botswana during 2006-2013. Multivariable regression models were used to compare treatment outcomes between HIV-infected and HIV-uninfected patients. We included 588 MDR-TB patients in the analysis, of whom, 47 (8.0%) and 9 (1.5%) were diagnosed with pre-extensively drug-resistant (XDR)-TB and XDR-TB, respectively. Of the 408 (69.4%) HIV-infected patients, 352 (86.0%) were on ART or started ART during treatment, and median baseline CD4 T-cell count was 234 cells/mm. Treatment success rates were 79.4% and 73.0% among HIV-uninfected and HIV-infected patients, respectively (P = 0.121). HIV-infected patients with CD4 T-cell count <100 cells/mm were more likely to die during treatment compared with HIV-uninfected patients (adjusted risk ratio = 1.890; 95% CI: 1.098 to 3.254). High rates of treatment success were achieved with programmatic management of MDR-TB and HIV in Botswana after widespread expansion of ART. However, a 2-fold increase in mortality was observed among HIV-infected persons with baseline CD4 <100 cells/mm compared with HIV-uninfected persons.

Long-term body composition changes in antiretroviral-treated HIV-infected individuals.

Body composition impacts physical function and mortality. We compared long-term body composition changes after antiretroviral therapy (ART) initiation in HIV-infected individuals to that in HIV-uninfected controls. Prospective observational study. We performed dual-energy x-ray absorptiometry (DXA) approximately 7.5 years after initial DXA in available HIV-infected individuals who received DXAs during the randomized treatment trial AIDS Clinical Trials Group A5202. For controls, we used DXA results from HIV-uninfected participants in the Boston Area Community Health/Bone and Women's Interagency HIV Study cohorts. Repeated measures analyses compared adjusted body composition changes between HIV-infected and HIV-uninfected individuals. Multivariable analyses evaluated factors associated with body composition change in HIV-infected individuals. We obtained DXA results in 97 HIV-infected and 614 HIV-uninfected participants. Compared with controls, HIV-infected individuals had greater adjusted lean mass and total, trunk, and limb fat gain during the first 96 weeks of ART. Subsequently, HIV-infected individuals lost lean mass compared with controls. Total, trunk, and limb fat gains after 96 weeks of ART slowed in HIV-infected individuals but remained greater than in controls. Lower CD4 T-cell count was associated with lean mass and fat gain during the initial 96 weeks of ART, but subsequently no HIV-related characteristic was associated with body composition change. Consistent with a 'return to health effect', HIV-infected individuals, especially those with lower baseline CD4 T-cell counts, gained more lean mass and fat during the first 96 weeks of ART than HIV-uninfected individuals. Continued fat gain and lean mass loss after 96 weeks may predispose HIV-infected individuals to obesity-related diseases and physical function impairment.

Prevention of Early Mortality by Presumptive Tuberculosis Therapy Study: An Open Label, Randomized Controlled Trial.

Early mortality after initiation of antiretroviral therapy (ART) occurs in 9-39% of patients in sub-Saharan Africa. A significant proportion of deaths are attributable to tuberculosis (TB). Low baseline CD4 T-cell count and low body mass index (BMI) are strongly associated with early mortality. We hypothesized that initiation of ART concurrent with presumptive anti-TB chemotherapy in high-risk patients would reduce mortality within the first 6 months by treating unrecognized TB. From October 2011 to December 2012, ART-naive, smear-negative participants with a CD4 T-cell count < 50 cells/μL and BMI < 18 kg/m2 were randomly assigned to undergo either empiric four-drug anti-TB treatment followed 2 weeks later by efavirenz-based ART (N = 23) (ART + TB) or ART only (N = 20). This open-label, 1:1 randomized, controlled trial took place in Uganda, Mozambique, and Gabon and was stopped prematurely by the sponsor for slow recruitment. Overall, the 43 participants had a median CD4 of 22 (interquartile range [IQR]: 9-35) cells/μL and a median BMI of 17.5 (IQR: 16.6-18.0) kg/m2 The mortality was 14% (95% confidence interval [CI]: 5.3-27.9); two (10.0%) participants (ART-only group), and four (17.4%; ART + TB group). The associated hazard ratio (HR) for all-cause mortality was 1.6 (95% CI: 0.30-8.90). Despite limited enrollment, the study did not suggest that empiric TB treatment in severely immunosuppressed patients with low BMI decreased mortality and, had an HR in the opposite direction than expected. Notably, two participants in the ART + TB group died with autopsy-confirmed drug-induced hepatotoxicity. Improved TB diagnostics sensitive in immunosuppressed patients presenting late to care are urgently needed for more targeted interventions.