HIV Disease Progression Research Articles

Material Security Scale as a Measurement of Poverty among Key Populations At-Risk for HIV/AIDS in Malaysia: An Implication for People Who Use Drugs and Transgender People during the COVID-19 Pandemic.

The HIV epidemic is fueled by poverty; yet, methods to measure poverty remain scarce among populations at risk for HIV infection and disease progression to AIDS in Malaysia. Between August and November 2020, using data from a cross-sectional study of people who use drugs, (PWUD), transgender people, sex workers and men who have sex with men, this study examined the reliability and validity of a material security scale as a measurement of poverty. Additionally, we assessed factors associated with material security scores. We performed confirmatory factor analysis (CFA) for 268 study participants included in the analysis. A revised nine-item three-factor structure of the material security scale demonstrated an excellent fit in CFA. The revised material security score displayed good reliability, with Cronbach’s alpha of 0.843, 0.826 and 0.818 for housing, economic resources and basic needs factors, respectively. In a subsequent analysis, PWUD and transgender people were less likely to present good material security scores during the pandemic, compared to their counterparts. The revised nine-item scale is a useful tool to assess poverty among key populations at-risk for HIV/AIDS with the potential to be extrapolated in similar income settings.

Gut-dependent inflammation and alterations of the intestinal microbiota in individuals with perinatal HIV exposure and different HIV serostatus.

HIV-exposed infected (HEI) and uninfected (HEU) children represent the two possible outcomes of maternal HIV infection. Modifications of the intestinal microbiome have been linked to clinical vulnerability in both settings, yet whether HEI and HEU differ in terms of gut impairment and peripheral inflammation/activation is unknown. We performed a cross-sectional, pilot study on fecal and plasma microbiome as well as plasma markers of gut damage, microbial translocation, inflammation and immune activation in HIV-infected and uninfected children born from an HIV-infected mother. Fecal and plasma microbiome were determined by means of 16S rDNA amplification with subsequent qPCR quantification. Plasma markers were quantified via ELISA. Forty-seven HEI and 33 HEU children were consecutively enrolled. The two groups displayed differences in fecal beta-diversity and relative abundance, yet similar microbiome profiles in plasma as well as comparable gut damage and microbial translocation. In contrast, monocyte activation (sCD14) and systemic inflammation (IL-6) were significantly higher in HEI than HEU. In the setting of perinatal HIV infection, enduring immune activation and inflammation do not appear to be linked to alterations within the gut. Given that markers of activation and inflammation are independent predictors of HIV disease progression, future studies are needed to understand the underlying mechanisms of such processes and elaborate adjuvant therapies to reduce the clinical risk in individuals with perinatal HIV infection.

HLA-B∗46 associates with rapid HIV disease progression in Asian cohorts and prominent differences in NK cell phenotype

Human leukocyte antigen (HLA) alleles have been linked to HIV disease progression and attributed to differences in cytotoxic T lymphocyte (CTL) epitope representation. These findings are largely based on treatment-naive individuals of European and African ancestry. We assessed HLA associations with HIV-1 outcomes in 1,318 individuals from Thailand and found HLA-B∗46:01 (B∗46) associated with accelerated disease in three independent cohorts. B∗46 had no detectable effect on HIV-specific Tcell responses, but this allele is unusual in containing an HLA-C epitope that binds inhibitory receptors on natural killer (NK) cells. Unbiased transcriptomic screens showed increased NK cell activation in people with HIV, without B∗46, and simultaneous single-cell profiling of surface proteins and transcriptomes revealed a NK cell subset primed for increased responses in the absence of B∗46. These findings support a role for NK cells in HIV pathogenesis, revealed by the unique properties of the B∗46 allele common only in Asia.

Improving functioning in HIV+ patients with chronic pain and comorbid depression: Protocol for a randomized clinical trial testing a collaborative behavioral health intervention based on behavioral activation

ObjectivePersons living with HIV (PWH) experience a disproportionate level of comorbid chronic pain and depression compared to individuals who do not have a diagnosis of HIV. Many PWH report pain that impairs daily function, is severe, and requires medical management. Depression alone is associated with HIV disease progression, medication non-adherence, and increased mortality. Given that numerous studies show that PWHs have chronic pain and depression despite pharmacologic treatment, there is a clear need for additional treatment modalities to address these conditions. DesignIn this paper, we describe our protocol for a multisite, randomized controlled trial of the effectiveness of a collaborative behavioral intervention, called HIV-Pain and Sadness Support (HIVPASS), designed for PWH who endorse chronic pain and depressive symptoms, as compared to an attention matched Health Education (HE) condition. The HIVPASS intervention is based on Behavioral Activation and designed to target both pain and depression using an integrated model that promotes collaboration between HIV medical and psychological providers. Setting and methodsWe plan to (1) recruit PWH who endorse chronic pain and depression in three sites located in New England and the Midwestern United States and (2) compare our HIVPASS intervention to a full attention matched HE intervention with the primary outcome of pain interference, and secondary outcomes of depression, physical activity, HIV medication adherence, and health-related quality of life. Follow-up assessments will occur monthly for three months during the intervention phase and then during the post-intervention phase at months four, six, nine and twelve. ConclusionsWe provide descriptions of our protocol and interventions of our randomized controlled trial for comorbid chronic pain and depression in PWH.Trial Registration: http://ClinicalTrials.govNCT02766751https://clinicaltrials.gov/ct2/show/NCT02766751?term=stein%2C+michael&draw=2&rank=5

Relationship Between Anemia and Systemic Inflammation in People Living With HIV and Tuberculosis: A Sub-Analysis of the CADIRIS Clinical Trial.

People with HIV (PWH) are at increased risk of developing active tuberculosis (TB), and anemia is a common complication in both conditions. Anemia in TB patients has been linked to immune activation, levels of inflammatory biomarkers in blood, and risk for HIV disease progression and death. In this study we show that anemia was associated with a more pronounced inflammatory profile in HIV-TB coinfected persons in a cohort of 159 individuals with advanced HIV disease (CD4 count < 100 cells/µL) recruited as part of a randomized clinical trial (NCT00988780). A panel of plasma biomarkers was assessed on plasma obtained prior to combination antiretroviral therapy (cART) initiation. We performed a series of multidimensional analyses including clinical variables and concentrations of inflammatory biomarkers to profile systemic inflammation of PWH with and without anemia. We observed that TB participants presented with moderately lower levels of hemoglobin than non-TB participants. These participants also presented a higher Degree of Inflammatory Perturbation (DIP) score, related to increased levels of IFN-γ and TNF. The DIP was associated with TB coinfection and anemia before cART initiation. Future mechanistic studies are warranted to assess the determinants of such associations and the implications on treatment outcomes.

Soluble Insulin Receptor Levels in Plasma, Exosomes, and Urine and Its Association With HIV-Associated Neurocognitive Disorders.

BackgroundHIV-associated neurocognitive disorders (HAND) are one of the HIV-associated comorbidities affecting 20–50% of the people with HIV (PWH) infection. We found that the soluble insulin receptor (sIR) levels in plasma and cerebrospinal fluid (CSF) were significantly higher in HIV-infected women. The mechanism of sIR release into the plasma remains unknown, but the detection of the sIR in exosomes may uncover novel mechanisms of sIR secretion from HIV-infected cells and its contribution to HIV disease progression and HAND development. Quantification of sIR in urine may represent a less invasive and more accessible diagnostic tool. Our objective was to quantify sIR levels in plasma, plasma-derived exosomes, and urine, and evaluate their association with HAND and renal function.MethodsWe measured full-length sIR in the plasma and urine of 38 controls and 76 HIV-infected women by ELISA, and sIR, HIV-1 Tat, and reactive oxygen species (ROS) in exosomes by flow cytometry.ResultsPlasma and exosomes with sIR were significantly higher in HIV-infected women when compared with controls and HAND. Exosomal sIR positively correlated with exosomal ROS and exosomal HIV-1 Tat in HIV-infected women. Exosomal ROS was significantly higher in HIV-infected women with more symptomatic cognitive impairment. Plasma-derived exosomes exhibited significantly higher levels of astrocyte (GFAP) and neuronal (L1CAM) markers in HIV-infected women, confirming the presence of circulating CNS-derived exosomes in the blood of HIV-infected women. Urine sIR positively correlated with eGFR in controls, but not in HIV-infected women, regardless there was no significant difference in renal function as determined by the estimated glomerular filtration rate (eGFR, p = 0.762). In HIV-infected women, higher plasma sIR correlated with lower urine sIR that could suggest sIR retention in blood or decreased renal filtration.DiscussionHigher plasma sIR levels and their correlation with ROS in plasma-derived exosomes with HAND suggest a combined role of metabolic disturbances, oxidative stress, exosome release, and cognitive decline. Communication between CNS and periphery is compromised in PWH, thus plasma-derived exosomes may shed light on disrupted cellular mechanisms in the brain of PWH. High plasma and low urine sIR levels could suggest sIR retention in blood or decreased renal filtration.

Cannabis Use and Body Composition in People Living with HIV (PLWH) From the Miami Adult Studies on HIV (MASH) Cohort

ObjectivesCannabis is the most prevalently used substance in the United States and among people living with HIV (PLWH). Underserved minorities living with HIV suffer from high rates of obesity. Yet, little is known about the implications of cannabis use on body composition in PLWH. Thus, we sought to determine the association between cannabis use and body composition PLWH.MethodsIn this cross-sectional study, participants were selected from the ongoing Miami Adult Studies on HIV (MASH) cohort. Cannabis use was self-reported and confirmed with urinalysis for cannabis along with other illicit drugs (American Bio Medica Corp, Kinderhook, NY). Participants were selected if they did not use any illicit drugs and excluded if they used illicit drugs other can cannabis. Informed consent, demographics, and anthropometrics were collected by trained personnel. HIV viral load (VL, copies/mL), and CD4+ cells (cells/mL) were abstracted from medical records. Descriptive statistics were used to analyze demographics, cannabis use, overweight (BMI ≥ 25 kg/m2) and VL (suppressed VL < 50 copies/mL). SPSS 26 was used to analyze the linear association between cannabis use and BMI. Logistic regression calculated the odds ratio (OR) of cannabis use and overweight status. Independent sample t-test compared CD4+ cell count and VL between the cannabis-using and non-using groups.ResultsParticipants’ mean age was 53.6 ± 8.3 years (n = 346), 42.5% were female, 57.5% were Black, and 73.1% had a BMI ≥ 25 kg/m2 (overweight). Cannabis users accounted for 34.1% of the sample. The frequency of participants with a suppressed VL was 80.3%. No significant differences in CD4+ count or VL between the cannabis users and non-users (p > .05). Cannabis use was associated with a lower BMI adjusted for age, sex, race and ethnicity, CD4+ count, and VL (b = −1.8 SE = 0.83, p = .03). Also, cannabis use was associated with reduced odds of being overweight after adjusting for age, sex, race and ethnicity, CD4+ count, and VL (OR: 0.44, 95% CI: 0.23–0.83; p = 0.01).ConclusionsThe use of cannabis was associated with lower BMI and decreased odds of being overweight or obese. Cannabis use did not significantly affect crucial markers of HIV disease progression (CD4+ count and VL) negatively. Longitudinal research is needed to further assess these associations and determine its medicinal efficacy in weight management.Funding SourcesNIDA.

Multi-method global sensitivity analysis of mathematical models

Increasingly-sophisticated parameter-sensitivity analysis techniques continue to be developed, and each technique comes with its own set of advantages and disadvantages. Selecting which parameter-sensitivity method to use for a particular model, however, is not a straightforward task. In this work, we present a multi-method framework that incorporates three global sensitivity analysis methods: two variance-based methods and one derivative-based method. The two variance-based methods are Sobol’s method and MeFAST. The derivative-based method is known as DGSM (Derivative-based Global Sensitivity Measures). MeFAST (Multi test eFAST) is a new parameter sensitivity analysis implementation we built upon the eFAST (Extended Fourier Amplitude Sensitivity Test) algorithm. The improvements incorporated into MeFAST address some important aspects of prior eFAST implementations. We present an intuitive description of each implemented algorithm along with MATLAB codes and a guide to tuning algorithm hyper-parameters for better efficiency. We demonstrate the full methodology and workflow using two example mathematical models of different complexity: the first is a model of HIV disease progression and the second is a model of tumor growth. The computational framework we provide generates graphics for visualizing and comparing the results of all three sensitivity analysis algorithms (DGSM, Sobol, and MeFAST). This algorithm output comparison tool allows one to make a more informed decision when assessing which parameters most importantly influence model outcomes.

Inversed Ratio of CD39/CD73 Expression on γδ T Cells in HIV Versus Healthy Controls Correlates With Immune Activation and Disease Progression

Backgroundγδ T cells are unconventional T cells that have been demonstrated to be crucial for the pathogenesis and potentially for the cure of HIV-1 infection. The ectonucleotidase CD39 is part of the purinergic pathway that regulates immune responses by degradation of pro-inflammatory ATP in concert with CD73. Few studies on the expression of the ectoenzymes CD73 and CD39 on human γδ T cells in HIV have been performed to date.MethodsPBMC of n=86 HIV-1-infected patients were compared to PBMC of n=26 healthy individuals using 16-color flow cytometry determining the surface expression of CD39 and CD73 on Vδ1 and Vδ2 T cells in association with differentiation (CD45RA, CD28, CD27), activation and exhaustion (TIGIT, PD-1, CD38, and HLA-DR), and assessing the intracellular production of pro- and anti-inflammatory cytokines (IL-2, TGF-ß, TNF-α, Granzyme B, IL-10, IFN-γ) after in vitro stimulation with PMA/ionomycin.ResultsCD39 and CD73 expression on γδ T cells were inversed in HIV infection which correlated with HIV disease progression and immune activation. CD39, but not CD73 expression on γδ T cells of ART-treated patients returned to levels comparable with those of healthy individuals. Only a small subset (<1%) of γδ T cells co-expressed CD39 and CD73 in healthy or HIV-infected individuals. There were significantly more exhausted and terminally differentiated CD39+ Vδ1 T cells regardless of the disease status. Functionally, IL-10 was only detectable in CD39+ γδ T cells after in vitro stimulation in all groups studied. Viremic HIV-infected patients showed the highest levels of IL-10 production. The highest percentage of IL-10+ cells was found in the small CD39/CD73 co-expressing γδ T-cell population, both in healthy and HIV-infected individuals. Also, CD39+ Vδ2 T cells produced IL-10 more frequently than their CD39+ Vδ1 counterparts in all individuals regardless of the HIV status.ConclusionsOur results point towards a potential immunomodulatory role of CD39+ and CD73+ γδ T cells in the pathogenesis of chronic HIV infection that needs further investigation.

Two years after lockdown: reviewing the effects of COVID-19 on health services and support for adolescents living with HIV in South Africa.

IntroductionSouth Africa's progress towards the 95‐95‐95 goals has been significantly slower among adolescents living with HIV (ALHIV), among whom antiretroviral therapy (ART) adherence, retention in care and viral suppression remain a concern. After 2 years of living with COVID‐19, it is important to examine the direct and indirect effects of the pandemic on healthcare resources, access to HIV services and availability of support structures, to assess their impact on HIV care for ALHIV.DiscussionThe COVID‐19 response in South Africa has shifted healthcare resources towards combatting COVID‐19, affecting the quality and availability of HIV services—especially for vulnerable populations, such as ALHIV. The healthcare system's response to COVID‐19 has threatened to diminish fragile gains in engaging ALHIV with HIV services, especially as this group relies on overburdened public health facilities for their HIV care. Reallocation of limited health resources utilized by ALHIV disrupted healthcare workers’ capacity to form and maintain therapeutic relationships with ALHIV and monitor ALHIV for ART‐related side effects, treatment difficulties and mental health conditions, affecting their ability to retain ALHIV in HIV care. Prevailing declines in HIV surveillance meant missed opportunities to identify and manage opportunistic infections and HIV disease progression in adolescents. “Lockdown” restrictions have limited access to healthcare facilities and healthcare workers for ALHIV by reducing clinic appointments and limiting individual movement. ALHIV have had restricted access to social, psychological and educational support structures, including national feeding schemes. This limited access, coupled with reduced opportunities for routine maternal and sexual and reproductive health services, may place adolescent girls at greater risk of transactional sex, child marriages, unintended pregnancy and mother‐to‐child HIV transmission.ConclusionsAdolescent HIV care in South Africa is often overlooked; however, ART adherence among ALHIV in South Africa is particularly susceptible to the consequences of a world transformed by COVID‐19. The current structures in place to support HIV testing, ART initiation and adherence have been reshaped by disruptions to health structures, new barriers to access health services and the limited available education and psychosocial support systems. Reflecting on these limitations can drive considerations for minimizing these barriers and retaining ALHIV in HIV care.

Increased HBV Coinfection and Decreased IFN-γ-Producing HBV-Specific CD8+ T Cell Numbers During HIV Disease Progression.

ObjectiveTo investigate the characteristics and mechanism of the dynamics of HBV infection with the progression of HIV disease and to explore the different responses of T lymphocytes to HBV in HIV patients in different stages of disease.MethodsWe compared the rates and characteristics of HBV coinfection between 372 early HIV-infected and 306 chronically HIV-infected men who have sex with men (MSM) in the Beijing Youan Hospital from October 2006 to November 2014. We further analysed IFN-γ-producing HBV-specific CD8+ T cells in 15 early HIV-infected individuals and 20 chronic HIV-infected individuals with HBV coinfection.ResultsTwenty-three HBsAg-positive cases were detected among the 372 early HIV-infected patients of this cohort, and the coinfection rate was 6.18%, while 35 HBsAg-positive cases were detected among the 306 chronically HIV-infected patients, with a coinfection rate of 11.44%. The coinfection rate of the chronically HIV-infected patients was significantly higher than that of the early-infected patients (p=0.0005). The median CD4+ T cell count in the early HIV infection patients was 445 cells/μL (196-1,030 cells/μL), which was higher than that in the chronic HIV infection patients [358 cells/μL (17-783 cells/μL)] (p<0.001). The proportion of IFN-γ-producing CD8+ T cells in early HIV-infected patients was significantly higher than that in chronically HIV-infected patients.ConclusionThe coinfection rate of HBV in HIV patients increases with HIV disease progression, which might be related to the decreased IFN-γ-producing HBV-specific CD8+ T cell numbers. The closely monitored HBV serum markers from the early stage of HIV infection are warranted.

The relationship of hair glucocorticoid levels to immunological and virological outcomes in a large cohort of combination antiretroviral therapy treated people living with HIV

BackgroundExisting literature mostly investigated the relationship of acute or short-term glucocorticoid exposure to HIV disease progression using cortisol levels in serum, saliva, or urine. Data are limited on the relationship of long-term glucocorticoid exposure to HIV disease progression. This study examined whether hair glucocorticoid levels, novel retrospective indicators of long-term glucocorticoid exposure, are associated with two common indicators of HIV disease progression (CD4 count and HIV viral load) among a large cohort of combination antiretroviral therapy treated Chinese people living with HIV (PLHIV).MethodsA total of 1198 treated PLHIV provided hair samples for glucocorticoid (cortisol and cortisone) assay and completed a survey assessing sociodemographic, lifestyle, and HIV-related characteristics. Meanwhile, CD4 count and HIV viral load were retrieved from their medical records. Spearman correlation was used to examine the associations of hair cortisol and cortisone levels to continuous CD4 count and HIV viral load. Multivariate logistic regression was used to predict CD4 count < 500 cells/mm3.ResultsBoth hair cortisol and cortisone levels were negatively associated with CD4 count but not with HIV viral load. The odds ratio for CD4 count < 500 cells/mm3 was 1.41 [95% CI 0.99–2.00] and 2.15 [95% CI 1.51–3.05] for those with hair cortisol and cortisone levels in the highest quartile compared to the lowest when controlling for sociodemographic, lifestyle, HIV-related covariates, and HIV viral load.ConclusionHair glucocorticoid levels were associated with CD4 count but not viral load in treated Chinese PLHIV. Our data furtherly supported the hypothesis that elevated glucocorticoid levels are associated with the lower CD4 count.

Longitudinal analysis of the prevalence and correlates of heavy episodic drinking and self-reported opioid use among a national cohort of patients with HIV.

Heavy episodic drinking (HED) is a risk factor for opioid-related overdose and negatively impacts HIV disease progression. Among a national cohort of patients with HIV (PWH), we examined sociodemographic and clinical correlates of concomitant HED and self-reported opioid use. We used data collected from 2002 through 2018 from the Veterans Aging Cohort Study, a prospective cohort including PWH in care at eight US Veterans Health Administration sites. HED was defined as consuming six or more drinks at least once in the year prior to survey collection. We examined the relationship between HED and self-reported opioid use and created a 4-level composite variable of HED and opioid use. We used multinomial logistic regression to estimate odds of reporting concomitant HED and self-reported opioid use. Among 3702 PWH, 1458 (39.4%) reported HED during the study period and 350 (9.5%) reported opioid use. In the multinomial model, compared to reporting neither HED nor opioid use, lifetime housing instability (adjusted odds ratio [aOR] 1.54, 95% confidence interval [CI] 1.01 to 2.35), Veterans Aging Cohort Study Index 2.0 (a measure of disease severity; aOR 1.14, 95% CI 1.02 to 1.28), depressive symptoms (aOR 2.27, 95% CI 1.42 to 3.62), past-year cigarette smoking (aOR 3.06, 95% CI 1.53 to 6.14), cannabis use (aOR 1.69, 95% CI 1.09 to 2.62), and cocaine/stimulant use (aOR 11.54, 95% CI 7.40 to 17.99) were independently associated with greater odds of concomitant HED and self-reported opioid use. Compared to having attended no college, having some college or more (aOR 0.39, 95% CI 0.26 to 0.59) was associated with lower odds of concomitant HED and self-reported opioid use. Among PWH, concomitant HED and self-reported opioid use are more common among individuals with depressive symptoms and substance use, structural vulnerabilities, and greater illness severity. Efforts to minimize opioid-related risk should address high-risk drinking as a modifiable risk factor for harm among these groups.

Detection of HIV Virologic Failure and Switch to Second-Line Therapy: A Systematic Review and Meta-analysis of Data From Sub-Saharan Africa.

BackgroundThe late recognition of virologic failure (VF) places persons with HIV in Sub-Saharan Africa at risk for HIV transmission, disease progression, and death. We conducted a systematic review and meta-analysis to determine if the recognition and response to VF in the region has improved.MethodsWe searched for studies reporting CD4 count at confirmed VF or at switch to second-line antiretroviral therapy (ART). Using a random-effects metaregression model, we analyzed temporal trends in CD4 count at VF—or at second-line ART switch—over time. We also explored temporal trends in delay between VF and switch to second-line ART.ResultsWe identified 26 studies enrolling patients with VF and 10 enrolling patients at second-line ART switch. For studies that enrolled patients at VF, pooled mean CD4 cell count at failure was 187 cells/mm3 (95% CI, 111 to 263). There was no significant change in CD4 count at confirmed failure over time (+4 cells/year; 95% CI, –7 to 15). Among studies that enrolled patients at second-line switch, the pooled mean CD4 count was 108 cells/mm3 (95% CI, 63 to 154). CD4 count at switch increased slightly over time (+10 CD4 cells/year; 95% CI, 2 to 19). During the same period, the mean delay between confirmation of VF and switch was 530 days, with no significant decline over time (–14 days/year; 95% CI, –58 to 52).ConclusionsVF in Africa remains an event recognized late in HIV infection, a problem compounded by ongoing delays between VF and second-line switch.

CRF07_BC is associated with slow HIV disease progression in Chinese patients

HIV subtypes convey important epidemiological information and possibly influence the rate of disease progression. In this study, HIV disease progression in patients infected with CRF01_AE, CRF07_BC, and subtype B was compared in the largest HIV molecular epidemiology study ever done in China. A national data set of HIV pol sequences was assembled by pooling sequences from public databases and the Beijing HIV laboratory network. Logistic regression was used to assess factors associated with the risk of AIDS at diagnosis ([AIDSAD], defined as a CD4 count < 200 cells/µL) in patients with HIV subtype B, CRF01_AE, and CRF07_BC. Of the 20,663 sequences, 9,156 (44.3%) were CRF01_AE. CRF07_BC was responsible for 28.3% of infections, followed by B (13.9%). In multivariable analysis, the risk of AIDSAD differed significantly according to HIV subtype (OR for CRF07_BC vs. B: 0.46, 95% CI 0.39─0.53), age (OR for ≥ 65 years vs. < 18 years: 4.3 95% CI 1.81─11.8), and transmission risk groups (OR for men who have sex with men vs. heterosexuals: 0.67 95% CI 0.6─0.75). These findings suggest that HIV diversity in China is constantly evolving and gaining in complexity. CRF07_BC is less pathogenic than subtype B, while CRF01_AE is as pathogenic as B.

Cognitively Based Compassion Training for HIV Immune Nonresponders-An Attention-Placebo Randomized Controlled Trial.

Chronic inflammation is associated with increased morbidity and mortality for people with HIV (PWH). Psychological stress is an important contributor to this chronic inflammation. We hypothesized that a cognitively based compassion training (CBCT) approach could reduce inflammation and psychological stress in immune nonresponder PWH. An attention-placebo randomized controlled trial design to evaluate the acceptability of CBCT among PWH and its effects on key aspects of stress and immune function compared with an active-attention control group (NCT02395289). This study was conducted at an HIV clinic in Atlanta, Georgia. Eligible individuals determined by (1) adherence to antiretroviral therapy for at least a year, (2) virologic suppression; and (3) stable CD4+ T-cell counts <350 cells/μL were randomized in a 2:1 ratio to either CBCT or control in 2 study periods: April-May, 2016, and September-December, 2016. Psychological measures and inflammatory biomarkers associated with HIV disease progression (IL-1β, TNF-α, sCD14, IL-6, and IL-10) were obtained for all study participants at baseline and at the time of study completion. We found a significant association between CBCT practice time engagement and fold reduction in IL-6 and TNF-α levels. There was no association between CBCT practice time and other biomarkers markers assessed (IL-1β, sCD14, and IL-10). These changes were coincident with significant increases in self-reported psychological well-being and HIV disease acceptance and in benefits for CBCT participants. We also observed fewer instances of virologic failure for those in the CBCT arm compared with controls. CBCT is a novel and feasible nonmedication-based intervention that could reduce inflammation and psychological stress in PWH.

Evaluating the cost-effectiveness of a pre-exposure prophylaxis program for HIV prevention for men who have sex with men in Japan

Men who have sex with men (MSM) have been disproportionally affected by the HIV epidemic in many countries, including Japan. Although pre-exposure prophylaxis (PrEP) is a strong prevention tool, it is not yet approved in Japan. A Markov model was developed to describe HIV infection and disease progression in an MSM cohort (N = 1000) in Japan receiving a PrEP program. The model was used to evaluate the cost-effectiveness of a PrEP program. HIV/AIDS treatment, screening, hospitalization due to AIDS, and PrEP were considered as costs and quality-adjusted life-years (QALYs) gained as utilities. Cost-effectiveness was assessed by comparing the incremental cost-effectiveness ratio (ICER) over a 30-year period against the willingness to pay (WTP) threshold. One-way sensitivity and probabilistic sensitivity analyses were performed. With 50% PrEP coverage, the PrEP program became dominant against the program without PrEP, using a threshold of 5.0 million JPY/QALY (45,455 USD). The probabilistic sensitivity analysis revealed that the PrEP program was dominant or at least cost-effective in most cases of 10,000 simulations. Therefore, preparing cheaper PrEP pills, which results in PrEP being dominant or ICER being lower than the WTP threshold, is important to make the program cost-effective. Introduction of PrEP to an MSM cohort in Japan would be cost-effective over a 30-year time horizon.

Iron supplementation and paediatric HIV disease progression: a cohort study among children receiving routine HIV care in Dar es Salaam, Tanzania.

Anaemia is common among HIV-infected children and iron supplementation is prescribed routinely for the prevention and management of anaemia among children. Limited evidence suggests iron supplementation may have adverse effects among HIV-infected populations. We aimed to estimate the effect of iron supplement use on mortality, disease progression and haematological outcomes among HIV-infected children in Dar es Salaam, Tanzania. A prospective cohort study was conducted among HIV-infected children (aged 0-14 years) receiving antiretroviral treatment or supportive care between October 2004 and September 2014. Clinical data were recorded on morbidity and vital status, haematological status and prescriptions at each clinical visit. Cox proportional hazards models adjusted for time-varying covariates were used to estimate the association of time-varying iron supplementation on the hazard rate of mortality, HIV disease stage progression, tuberculosis incidence and anaemia and microcytosis persistence. In all, 4229 children were observed during 149 260 clinic visits for a mean follow-up of 2.9 years. After adjustment for time-varying clinical covariates, time-varying iron supplementation was associated with a 2.87 times higher hazard rate of mortality (95% CI: 1.70, 4.87) and a 1.48 times higher hazard rate of HIV disease stage progression (95% CI: 1.10, 1.98). Iron supplementation was also associated with a lower rate of anaemia persistence (HR = 0.47; 95% CI: 0.37, 0.61). No differences in the association between iron supplementation and clinical outcomes were observed by antiretroviral therapy or anaemia status. Iron supplementation may increase the risk of HIV disease stage progression and mortality among HIV-infected children, while reducing the risk of anaemia.

Pre-infection plasma cytokines and chemokines as predictors of HIV disease progression

Previous studies have highlighted the role of pre-infection systemic inflammation on HIV acquisition risk, but the extent to which it predicts disease progression outcomes is less studied. Here we examined the relationship between pre-infection plasma cytokine expression and the rate of HIV disease progression in South African women who seroconverted during the CAPRISA 004 tenofovir gel trial. Bio-Plex 200 system was used to measure the expression of 47 cytokines/chemokines in 69 seroconvertors from the CAPRISA 004 trial. Cox proportional hazards regression analyses were used to measure associations between cytokine expression and CD4 decline prior to antiretroviral therapy initiation. Linear regression models were used to assess whether pre-infection cytokine expression were predictors of disease progression outcomes including peak and set-point viral load and CD4:CD8 ratio at less and greater than180 days post infection. Several cytokines were associated with increased peak HIV viral load (including IL-16, SCGFβ, MCP-3, IL-12p40, SCF, IFNα2 and IL-2). The strongest association with peak viral load was observed for SCGFβ, which was also inversely associated with lowest CD4:CD8 ratio < 180 days post infection and faster CD4 decline below 500 cells/µl (adjusted HR 4.537, 95% CI 1.475–13.954; p = 0.008) in multivariable analysis adjusting for age, study site, contraception, baseline HSV-2 status and trial arm allocation. Our results show that pre-infection systemic immune responses could play a role in HIV disease progression, especially in the early stages of infection.

Th17 CD4+ T-Cell as a Preferential Target for HIV Reservoirs.

Among CD4+ T-cells, T helper 17 (Th17) cells play a sentinel role in the defense against bacterial/fungal pathogens at mucosal barriers. However, Th17 cells are also highly susceptible to HIV-1 infection and are rapidly depleted from gut mucosal sites, causing an imbalance of the Th17/Treg ratio and impairing cytokines production. Consequently, damage to the gut mucosal barrier leads to an enhanced microbial translocation and systemic inflammation, a hallmark of HIV-1 disease progression. Th17 cells’ expression of mucosal homing receptors (CCR6 and α4β7), as well as HIV receptors and co-receptors (CD4, α4β7, CCR5, and CXCR4), contributes to susceptibility to HIV infection. The up-regulation of numerous intracellular factors facilitating HIV production, alongside the downregulation of factors inhibiting HIV, helps to explain the frequency of HIV DNA within Th17 cells. Th17 cells harbor long-lived viral reservoirs in people living with HIV (PLWH) receiving antiretroviral therapy (ART). Moreover, cell longevity and the proliferation of a fraction of Th17 CD4 T cells allow HIV reservoirs to be maintained in ART patients.