Pulmonary Function in Brazilians Living with HIV: A Comparative Cross-Sectional Study

Immunogenicity and Safety of Inactivated SARS-CoV-2 Vaccine in People Living with HIV: A Cross-Sectional Study

Discovering metabolic pathways associated with immune activation in people living with HIV following ChAdOx1 nCoV-19 vaccination using mass spectrometry.

We aimed to analyze the efficacy and safety of an inactivated SARS‐CoV‐2 vaccine in people living with HIV (PLWH). A total of 143 PLWH and 50 healthy individuals were included in this study. A commercially available magnetic chemiluminescence enzyme immunoassay kit was used to detect serum IgG and IgM antibodies against SARS‐CoV‐2. Serum levels of SARS‐CoV‐2‐specific IgG were significantly higher in the control group than in the PLWH group (p = 0.001). Overall, 76% of individuals in the control group were detected with seropositivity IgG against SARS‐CoV‐2 compared to 58% in the PLWH group (p = 0.024). In PLWH with IgG seropositivity, CD4+ T‐cell counts before antiretroviral therapy (ART) was higher (p = 0.015). Multivariable analysis indicated that CD4+ T cells at IgG detection (odds ratio [OR] = 1.004, p = 0.006) and time after vaccination (OR = 0.977, p = 0.014) were independently associated with seropositivity IgG against SARS‐CoV‐2 in PLWH. Neutralizing antibody (nAb) titers in PLWH against wild‐type SARS‐CoV‐2 were similar to those in the control group (p = 0.160). The proportion of seropositive nAbs against wild‐type SARS‐CoV‐2 was also similar (95% in the control group vs. 97% in the PLWH group, p = 0.665). Similar results were obtained when nAb was detected against the delta variants with similar titers (p = 0.355) and a similar proportion of seropositive nAbs were observed (p = 0.588). All the side effects observed in our study were mild and self‐limiting. The inactivated COVID‐19 vaccine appears to be safe with good immunogenicity in Chinese PLWH.

What Might Surviving Coronavirus Disease 2019 Look Like for People Living with HIV?

The impact of cryptococcosis on cerebral structure and MRI characteristics in people living with HIV (PWH) who have cryptococcal meningoencephalitis remains underexplored. Existing evidence mainly comes from small-scale studies.This study aimed to clarify the effects of cryptococcal meningoencephalitis on brain structural changes and MRI features in PWH. A total of 190 patients with intracranial cryptococcosis were enrolled and categorized, based on HIV serostatus, into the PWH group (n = 127) and the people linving without HIV(PWOH) group (n = 63). Laboratory parameters, brain volumes, and MRI findings were compared between the two groups. In the two groups, continuous variables were compared using the independent samples t-test, while categorical data were analyzed using the χ² test. The PWH with cryptococcosis group was significantly younger than the PWOH group (51 ± 13 years vs. 60 ± 14 years, P < 0.05). Additionally, this group showed lower peripheral blood leukocyte, platelet, hemoglobin, and lymphocyte counts (all P < 0.05).Cerebrospinal fluid (CSF) analysis in PWH showed lower protein levels (0.97 ± 0.9 vs. 1.31 ± 1.11), decreased cell counts—predominantly polymorphonuclear cells—and increased glucose levels (2.18 ± 1.03 vs. 1.64 ± 1.29) compared with the PWOH. Brain volumetric analysis revealed that the PWH with cryptococcosis group had a reduction in total brain tissue volume (70.1 ± 3.9 vs. 72.0 ± 4.3), a decreased proportion of white matter (33.3 ± 2.9 vs. 35.3 ± 3.3), and an increased proportion of CSF space (29.9 ± 3.9 vs. 28.0 ± 4.3) (all P < 0.05). Additionally, the relative volume proportions of the hippocampus (0.68 ± 0.27 vs. 0.52 ± 0.25) and basal ganglia (1.71 ± 0.41 vs. 1.48 ± 0.34) were significantly larger in the PWH (P < 0.05). On MRI, leptomeningeal enhancement was more frequently observed in the PWOH group, whereas the PWH with cryptococcosis group demonstrated a higher incidence of lacunar infarcts. PWH with intracranial cryptococcosis show cerebral white matter atrophy, accompanied by compensatory expansion of cerebrospinal fluid (CSF) volume and a relative enlargement of deep gray matter nuclei, particularly affecting the hippocampus and basal ganglia. These structural changes are associated with inflammatory alterations in CSF and an elevated risk of vascular complications, such as lacunar infarction.

Advances in antiretroviral therapy (ART) have normalized the life expectancy of people living with HIV (PLWH) but have been linked to a premature presentation of age-related comorbidities, including cancer. Telomere length (TL) is a marker of cellular aging and was investigated in blood leukocytes from 78 PLWH on ART, compared with 163 HIV-uninfected controls. The PLWH group was stratified into three subgroups: HIV-only (&lt;em&gt;n&lt;/em&gt; = 57), HIV with AIDS-defining cancer (ADC, &lt;em&gt;n&lt;/em&gt; = 9), and HIV with NADC (&lt;em&gt;n&lt;/em&gt; = 12). Quantitative polymerase chain reaction (qPCR) was used to measure the Relative Telomere Length (RTL), expressed as a T/S ratio. The mean RTL was significantly longer in PLWH (&lt;em&gt;p&lt;/em&gt; = 0.0002) and in the HIV/Cancer group (&lt;em&gt;p&lt;/em&gt; = 0.0125) than in the control group (&lt;em&gt;n&lt;/em&gt; = 163). In addition, the mean RTL was significantly longer in the PLWH group with non-AIDS-defining cancers (NADCs) compared to the control group (&lt;em&gt;p&lt;/em&gt; = 0.03). However, no statistical difference between the HIV-only versus the HIV/cancer groups concerning RTL was observed. PLWH with a longer time since diagnosis of HIV infection (&gt;13 years) had a trend towards longer RTL, showing a borderline statistical significance (&lt;em&gt;p&lt;/em&gt; = 0.06). Analysis by cancer type showed ADCs were mainly Kaposi’s sarcoma (44.5%) and cervical cancer (33.3%), while NADCs were most commonly anal cancer (25%) and breast cancer (16.7%). These findings support the thesis that long-term ART may be associated with telomere elongation in PLWH, challenging the general perception of telomere shortening in this population. The significantly longer RTL in the NADC group suggests that telomere elongation confers greater cellular replicative potential, which might contribute to the elevated cancer risk in PLWH.

BackgroundAntiretroviral therapy has significantly improved prognosis in treatment against HIV infection, however, prolonged exposure is associated to cardiovascular diseases, lipodystrophy, type 2 diabetes, insulin resistance, metabolic alteration, as obesity which includes the accumulation of oxidative stress in adipose tissue. FGF21 is a peptide hormone that is known to regulate glucose and lipid metabolism. FGF21 is expressed and secreted primarily in the liver and adipose tissue, promoting oxidation of glucose/fatty acids and insulin sensitivity. Alterations in FGF21 may be associated with the development of insulin resistance, metabolic syndrome and cardiovascular disease. We hypothesized that FGF21 protein levels are associated with metabolic abnormalities, placing special attention to the alterations in relation to the concurrence of overweight/obesity in people living with HIV (PLWH).DesignSerum FGF21 was analyzed in 241 subjects, 160 PLWH and 81 unrelated HIV-uninfected subjects as a control group. Clinical records were consulted to obtain CD4+ cell counting and number of viral RNA copies. Serum FGF21 levels were tested for correlation with anthropometric and metabolic parameters; glucose, cholesterol, HDL, LDL, VLDL, triglycerides, insulin and indexes of atherogenesis and insulin resistance (HOMA).ResultsThe participants were classified into four groups: (i) PLWH with normal weight, (ii) PLWH with overweight/obesity, (iii) HIV-uninfected with normal weight, and (iv) HIV-uninfected with overweight/obesity.Insulin levels were higher in normal-weight PLWH than in the HIV-uninfected group but not statistically significant, however, for the overweight/obesity PLWH group, insulin levels were significantly higher in comparison with the other three groups (p<0.0001). For FGF21, serum levels were slightly higher in the overweight/obesity groups in both patients and controls.In HIV-infected subjects, FGF21 levels showed a strong positive correlation with triglycerides, insulin levels and insulin resistance with a p-value <0.0001. In the seronegative group, FGF21 was only correlated with weight and waist circumference, showing an important association of FGF21 levels with the degree of obesity of the individuals.ConclusionInsulin resistance and FGF21 elevations were observed in overweight-obese PLWH. FGF21 elevation could be viewed as a compensation mechanism as, in the control group, FGF21 correlations appeared to be confined to weight and waist circumference. This can be explained based on the action of FGF21 promoting the uptake of glucose in adipose tissue. In PLWH, FGF21 was low, possibly as a result of a change in adiposity leading to a metabolic disruption.

To explore the mechanism of action of San Ren Decoction (SRD) in people living with HIV (PLWH) treatment using network pharmacology, molecular docking technology, and cellular experiments. The active ingredients and potential targets of the Chinese traditional herb in SRD were determined from traditional Chinese Medicine Systems Pharmacology and Bioinformatics Analysis Tool for Molecular Mechanism of traditional Chinese medicine. The therapeutic targets of SRD in AIDS were identified using GeneCards, OMIM, DisGeNET, and DrugBank. The overlap between disease and component targets was determined to identify the potential targets of SRD in AIDS. The network of "Chinese herbs-active ingredients-targets" for SRD was accessed using Cytoscape. A protein-protein interaction network was prepared using STRING. The Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to perform enrichment analysis of signaling pathways. Molecular docking experiments and visualization of results were performed using Auto Dock Vina and PyMOL. Based on the results of network pharmacology, a drug-containing serum was prepared through cellular experiments. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples of PLWH and divided into three groups: the PLWH group, the PLWH + PI3K/Akt inhibitor group, and the PLWH + SRD drug-containing serum group (represented by PLWH, ZSTK474, and SRD, respectively). Healthy human PBMCs were used in the control group. After grouped culturing, quantitative polymerase chain reaction and enzyme-linked immunosorbent assay were performed to detect and confirm gene and protein expression in each group. Quercetin, luteolin, myristic acid, honokiol, arachidonic acid, and other core components were the active ingredients in SRD. The core targets of SRD in AIDS included CAV1, SRC, HSP90AA1, AKT1, PI3K, STAT1, and RAF1. Gene ontology functional enrichment analysis revealed the positive regulation of gene expression, the response to foreign stimuli, and other observations. KEGG pathway enrichment analysis showed the involvement of the PI3K/Akt, TLR, and other pathways. Molecular docking results indicated that the primary active ingredients of SRD exhibited stable binding with the core proteins. In vitro and invivo experiments showed that the mRNA and protein levels of AKT1, Caspase8, mTOR, PI3K, STAT1, and Bcl-2 were higher in PLWH. SRD may help regulate PLWH by inhibiting the PI3K/Akt signaling pathway. The results of this study indicated that SRD may play a role in PLWH treatment through multiple components and multiple targets to regulate the PI3K/Akt signaling pathway.

IntroductionMost existing vaccines require higher or additional doses or adjuvants to provide similar protection for people living with HIV (PLWH) compared with HIV-uninfected individuals. Additional research is necessary to inform...

Data on the burden of hypertension among people living with HIV (PLWH) in Africa are limited, especially after new expert consensus hypertension guidelines were published in 2017. The authors sought to assess the prevalence and factors associated with hypertension among PLWH. This is a cross-sectional study involving PLWH on combination antiretroviral therapy (cART) (n=250) compared with sex-matched cART-naïve PLWH (n=201) in Ghana. Hypertension was defined as blood pressure≥140/90mmHg or use of antihypertensive drugs. The authors also assessed the prevalence and predictors associated with hypertension using the recent guideline recommended cutoff BP≥130/80mmHg. Multivariate logistic regression models were fitted to identify factors associated with hypertension among PLWH. The mean age of PLWH on cART was 45.7±8.6years, and 42.9±8.8years among PLWH cART-naive with 81% of study participants being women. The prevalence of hypertension among PLWH on cART and PLWH cART-naïve was 36.9% and 23.4%, P=0.002 at BP≥140/90mmHg and 57.2% and 42.3%, respectively, P=0.0009, at BP≥130/80mmHg. Factors associated with hypertension at BP≥140/90mmHg in the PLWH group with adjusted odds ratio (95% CI) were increasing age, 2.08 (1.60-2.71) per 10years, and body mass index, 1.53 (1.24-1.88) per 5kg/m2 rise. At BP≥130/80mmHg, cART exposure, aOR of 1.77 (95% CI: 1.20-2.63), family history of hypertension, aOR of 1.43 (1.12-1.83), and hypertriglyceridemia, aOR of 0.54 (0.31-0.93), were associated with hypertension. Among PLWH, cART exposure was associated with higher prevalence of hypertension per the new guideline definition, a finding which warrants further investigation and possible mitigation.

In recent years, Uganda has experienced rapid growth in networked groups of people living with HIV (PLHIV) who provide support, engage in advocacy, treatment and care and raise the profile of HIV in the public domain. This qualitative study focused the benefits of joining a networked group, relationships between groups, impact of networked groups on the community and shaping private and public experience living with HIV. Data were collected from two Ugandan districts, using semi-structured interviews, focus group discussions (FGDs), observation and reviews of group records and archives. Respondents (n=46) were adults living with HIV, and members of rural and urban PLHIV groups. Narratives from PLHIV (n=27) were gathered, and records from PLHIV group service-registers (n=20) reviewed. Key Informants (n=15) were purposively selected for interview, based on participation in PLHIV groups, utilisation of network services and their positions as key stakeholders. FGDs were held with network support agents (NSAs), members of PLHIV groups, and their leaders. Following qualitative analysis, findings suggest that for respondents, PLHIV networks enhance the impact and effectiveness of individual groups: the whole is greater than the sum of the parts. For groups, being part of a wider network allows for diversity of service delivery, and well-defined roles for individuals to participate in community support and sensitisation, with a reduction in the experience of stigma. We conclude that networking PLHIV groups is an effective strategy for improving the quality and reach of community-based HIV services. Governments should be encouraged to support networks and include them in policy-making at the national level. Local and regional groups should explore further ways to collaborate and expand support to PLHIV in Uganda.

Optimal management of cardiovascular disease should start with the identification of subjects at subclinical stages. However, available tools are not always accurate or affordable. We assess the usefulness of ultrasound-guided measurement of abdominal fat layers as a surrogate marker of cardiovascular risk. We performed a cross-sectional, case-control, exploratory, pilot study in 10 people living with HIV (PLWH) and 10 HIV-uninfected subjects (control group) matched for age, sex, and body mass index. All participants were men 45-60 years of age, with no active disease or previous abdominal surgery; the PLWH group had been virologically suppressed for ≥2 years under stable antiretroviral therapy. The thickness of abdominal superficial and deep subcutaneous fat, preperitoneal fat, omental (periaortic) fat, and retroperitoneal (perirenal) fat was compared between both groups. Correlations between fat layers and traditional markers of cardiovascular risk were assessed. The thickness of most layers was always higher among PLWH. The differences were statistically significant for the preperitoneal fat layer (p = .04). The presence of atherosclerotic plaque was correlated with the preperitoneal fat layer in the PLWH group (odds ratio = 1.49, p = .02), and metabolic syndrome was correlated with superficial subcutaneous fat, although this was low (odds ratio = 0.54, p = .02). In the control group, several associations were found between carotid intima media thickness and abdominal fat layers. All abdominal fat layers were thicker in the PLWH group, especially preperitoneal fat, and several associations were found between specific fat layers and traditional cardiovascular risk markers. Our results suggest that the thickness of abdominal fat layers, assessed by ultrasound, could be a marker of cardiovascular risk. However, further studies with larger populations are required to confirm these findings.

There is limited information about COVID-19 vaccines in people living with HIV (PLWH). We aimed to compare the immunogenicity and effectiveness of the Sinopharm BIBP COVID-19 inactivated vaccine between PLWH and non-HIV individuals in the Omicron era. We evaluated the production of receptor-binding domain (RBD), spike, SARS-CoV-2 IgG, and neutralizing antibodies in both PLWH (case) and individuals without HIV (control) groups three months after they received the second dose of the vaccine. All participants were also followed during three months after the second dose for the COVID-19 infection and its outcomes (hospital admission, need to intensive care unit, and mortality). A total of 250 individuals comprising 150 PLWH and 100 people without HIV were recruited. The mean age was 42.2 years. The infection rate was significantly higher in non-HIV individuals than in PLWH (63% vs. 21.3%, p &lt; 0.001). The hospitalization rate in the PLWH group was significantly hig1her than that in the non-HIV group (5.3% vs. 1%, p = 0.009). There were no significant differences in the mean levels of Spike antibody (84.4 ± 34.4 vs. 95 ± 109.5 RU/mL), RBD antibody (65.6 ± 42 vs. 69 ± 42.3 RU/mL), and SARS-CoV-2 IgG (2.9 ± 2.5 vs. 3 ± 2.3 Index) between the groups. The mean value of neutralizing antibodies was significantly higher in non-HIV individuals (34 ± 23.3 vs. 26.2 ± 20 µg/mL, p = 0.005). The Sinopharm BIBP COVID-19 inactivated vaccine can be as immunogenic in PLWH as in non-HIV individuals. This vaccine is likely more effective in preventing Omicron-associated hospitalization in non-HIV individuals.

The relationship between mental disorders other than depression or anxiety, and low adherence to both antiretroviral treatment (ART) and linkage to HIV care are unclear. The aim of our study was to compare the prevalence of mental disorders in people living with HIV (PLHIV) in Spain who present low versus high adherence to ART. We performed a cross-sectional study comparing two groups of PLHIV: 20 PLHIV with low adherence and 80 PLHIV with high adherence to ART. PLHIV who met at least one of the following criteria were included in the low-adherence group: virological failure (HIV-VL > 50 copies/mL in two consecutive blood samples); low attendance to scheduled clinical visits (≥2 missed visits in last year); irregular administration of ART (≥10 forgotten doses in the last month); and interruption of ART for more than 1 week. Inclusion criteria for high adherence were: PLHIV who had been on stable ART for more than 1 year with an HIV-VL below 50 copies/mL and without missed visits over the previous 12 months. The Millon Clinical Multiaxial Inventory was administered to participants. PLHIV with low adherence showed higher scores for all mental disorders compared with those with high adherence. And, in the multivariate binary logistic regression analysis, drug dependence and post-traumatic stress disorder were independently associated with low adherence (Nagelkerke R2 = 0.0686). In conclusion, PLHIV with poorly controlled HIV infection presented important psychological vulnerabilities. Mental health should be checked at the beginning of ART and during follow-up, especially in PLHIV with low adherence or low linkage to the health care system.

The safety and immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with HIV (PLWH) in real-world studies remain controversial. Thus, we conducted a comprehensive systematic review and meta-analysis to address this issue. Data search were conducted from PubMed, Web of Science and EMBASE. Adverse events following vaccination, the risk ratio (RR) of SARS-CoV-2–specific IgG seroconversion and the level of anti–SARS-CoV-2 neutralizing antibodies were compared between the PLWH group and a healthy control group. A total of 10,582 PLWH from 22 studies were included. In our analysis, the incidence of local or systemic adverse events after the first SARS-CoV-2 vaccine dose was not statistically different between PLWH and healthy controls. However, there was a statistical difference after the second dose (RR, 0.83; 95% CI, 0.71–0.98). The seroconversion rate of SARS-CoV-2 IgG antibodies in PLWH was significantly lower than that in the healthy control group (RR, 0.94; 95% CI, 0.89–0.98; I 2 = 80%, P &lt; 0.01). The anti–SARS-CoV-2 neutralizing antibody titers in PLWH after full immunization were also significantly lower than those in the healthy control group (RR, 0.91; 95% CI, 0.85–0.98; I 2 = 81%, P &lt; 0.01). The safety and tolerance of COVID-19 vaccines in PLWH are acceptable. However, their immunogenicity may be impaired to a certain extent, characterized by a lower IgG seroconversion rate and neutralizing antibody titers compared with healthy individuals. These findings should provide guidance for optimizing future COVID-19 vaccination strategies among PLWH.