Plasma Levels of Secreted Cytokines in Virologically Controlled HIV-Infected Aging Adult Individuals on Long-Term Antiretroviral Therapy.

HIV-infected (HIV+) aging adult individuals who have achieved undetectable viral load and improved CD4 T cell counts due to long-term antiretroviral therapy (ART) may continue to experience inflammation and immunosenescence. Therefore, we evaluated the plasma levels of proinflammatory and anti-inflammatory cytokines in 173 HIV+ aging adult individuals with age ranging from 22 to 81 years on long-term ART with viral load mostly <20 HIV RNA copies/mL and compared with 92 HIV-uninfected (HIV- or healthy controls) aging individuals. We found that the median levels of TNF-α, IFN-γ, IL-1ß, IL-6, and IL-10 were higher (p < 0.001 to <0.0001) and IL-17 trended lower in HIV+ individuals than healthy controls. Increasing CD4 T cell counts in the HIV+ cohort did not significantly change the circulating cytokine levels, although levels of IL-1ß increased. However, IL-17 levels significantly decreased with increasing CD4 counts in the healthy controls and yet unchanged in the HIV+ cohort. Of note, the levels of circulating IL-17 were significantly reduced comparatively in the healthy controls where the CD4 count was below 500, yet once above 500 the levels of CD4, IL-17 levels were comparable with the HIV+ cohort. With increasing CD8 T cell counts, the levels of these cytokines were not significantly altered, although levels of TNF-α, IFN-γ, and IL-6 declined, whereas IL-1ß and IL-17 were slightly elevated. Furthermore, increasing age of the HIV+ cohort did not significantly impact the cytokine levels although a slight increase in TNF-α, IL-6, IL-10, and IL-17 was observed. Similarly, these cytokines were not significantly modulated with increasing levels of undetectable viral loads, whereas some of the HIV+ individuals had higher levels of TNF-α, IFN-γ, and IL-1ß. In summary, our findings show that HIV+ aging adult individuals with undetectable viral load and restored CD4 T cell counts due to long-term ART still produce higher levels of both proinflammatory and anti-inflammatory cytokines compared with healthy controls, suggesting some level of inflammation.

Knowledge, Attitude, and Practice Towards Mpox and Associated Factors Among HIV-Infected Individuals - Beijing Municipality, China, 2023.

What is already known about this topic?: Approximately 50% of patients with mpox are human immunodeficiency virus (HIV)-infected globally. Studies have shown that individuals with advanced HIV infection tend to have more severe clinical manifestations and higher mortality rates after mpox infection. What is added by this report?: The study revealed that individuals living with HIV have a low level of Knowledge, Attitude, and Practice (KAP) towards mpox. Several factors, including age, registered residence, sexual orientation, education level, viral load, and co-occurrence of other sexually transmitted diseases, were found to influence the KAP towards mpox. What are the implications for public health practice?: This study is the first to investigate the KAP of mpox among individuals living with HIV. The findings suggest that mpox health education should prioritize individuals with co-existing sexually transmitted diseases (STDs) and a high viral load.

TLR3 polymorphisms in HIV infected individuals naïve to ART.

BACKGROUND: TLR3 polymorphisms affect the risk of HIV infection and modify the disease course. Consequently, we analyzed the association of TLR3 polymorphism (rs5743312, rs3775296, and rs3775291) with susceptilbity to HIV-1 acquisition and disease progression. METHOD: This is a cross-sectional study. Genotyping of TLR3 polymorphisms were completed by the utilization of the PCR-RFLP technique in 153 HIV naive subjects and 158 healthy controls. RESULT: A haplotype is a physical grouping of genomic variants that tend to be inherited together. The TCC haplotype was increased in HIV infected individuals compared with healthy controls (0.05% versus 0.03%). TLR3 rs3775291CT genotype was associated to the early stage of HIV infection (OR=2.19, P=0.04), with a higher occurrence in advance stage of HIV infection when contrasted with healthy controls (41.2% versus 32.3%). TLR3 rs3775296 CA genotype was likely to be associated with intermediate stage of HIV infection (19.5% versus 31.6%, OR=0.42, P=0.06). TLR3 rs5743312TT genotype was used to be greater prevalence in advanced stage of HIV infection compared with healthy controls (2.9% versus 1.9%). TLR3 rs3775296CA genotype was less prevalent in HIV subjects devouring tobacco when contrasted with non-users (9.1% versus 34.9%, OR=0.25, P=0.09). TLR3 rs3775296AA and rs3775291CT and TT genotypes have been overrepresented in HIV subjects using alcohol when contrasted with non-users (5.6% versus 1.1%, OR=1.83, P=0.67; 50.0% versus 42.2%, OR=1.84, P=0.31; 5.6% versus 3.3%, OR=2.70, P=0.50). In multivariate examination, rs5743312TT genotype showed a greater risk for HIV infection (OR=1.86, P=0.50). CONCLUSION: TLR3 rs3775291 C/T polymorphism may assist the risk of disease progression in alcohol consumers. TLR3 rs3775291 CT genotype may enhance the disease progression whereas the TLR3 rs3775296 CA genotype may protect for disease progression.

First Report on HHV-6 Infection Among HIV-Infected Individuals Residing in Surabaya, Indonesia.

BACKGROUND: Morbidity and mortality from acquired immunodeficiency syndrome (AIDS) are often associated with the reactivation of a herpes virus infection. Human herpesvirus-6 (HHV-6) is usually common in childhood infections that remain latent and can act as opportunists during immunosuppression to reactivate and cause disease. In human immunodeficiency virus (HIV)-infected patients, the impact of HHV-6 infection can be an up-regulator of HIV replication and accelerate progress towards AIDS. However, studies on HHV-6 infection have never been done in Surabaya, Indonesia. PURPOSE: To determine the presence of HHV-6 infection among HIV-infected individuals residing in Surabaya, Indonesia. PATIENTS AND METHODS: Plasma and peripheral blood mononuclear cells (PBMCs) were collected from 85 HIV-infected individuals in Universitas Airlangga Hospital, Surabaya, as well as 85 healthy controls. DNA extracted from PBMCs was subjected to PCR to determine HHV-6 infection, while plasma of HIV-infected individuals was used for viral RNA quantification using real-time PCR. RESULTS: HHV-6 infection was detected in 17.6% (15/85) of HIV-infected individuals, and in 3.53% (3/85) of healthy controls. Thus, HHV-6 infection was more likely to be found in HIV-infected individuals than in healthy controls (odds ratio 5.85; 95% confidence interval, 1.6-21). The HHV-6B was the most common subtype identified in both HIV-infected individuals (12/15) and healthy controls (3/3). The HHV-6A and co-infection between HHV-6A and HHV-6B were only found in HIV-infected individuals (2/15 and 1/15, respectively). Viral RNA load of HIV-infected individuals was not correlated to HHV-6 infection. CONCLUSION: Our results indicate the emergence of HHV-6 infection among HIV-infected individuals residing in Surabaya, Indonesia, and the risk of HHV-6 infection was higher in HIV-infected individuals than in healthy controls.

A Pilot Intervention Trial to Promote Sexual Health and Stress Management Among HIV-Infected Men Who Have Sex with Men.

Men who have sex with men (MSM) experience HIV disparities. This study pilot-tested a two session, group-delivered intervention to promote sexual health and stress management skills for HIV-infected MSM. Participants (N = 80) were randomized to an immediate or delayed intervention condition. Analyses of covariance examined intervention efficacy. Compared to the delayed condition, intervention condition participants reported: greater HIV transmission knowledge (p < .001), higher HIV disclosure self-efficacy (p = .004), stronger intentions to refuse unprotected sex (p = .05), decreased frequency of unprotected anal or oral sex (p = .03), decreased perceived stress levels (p = .03), and higher coping self-efficacy (p = .003). Differences in the number of unprotected anal sex episodes, condom attitudes, and level of social support did not differ between conditions. Findings provide evidence of intervention acceptability and suggest the brief intervention may enhance stress management skills and modify sexual risk behavior antecedents for HIV-infected MSM.

Impact of etravirine on hospitalization rate between 2005 and 2011 among heavily treated HIV-1-infected individuals on failing regimens.

BACKGROUND: Etravirine (ETR), a non-nucleoside reverse transcriptase inhibitor (NNRTI) available in France since 2006, is indicated for antiretroviral-experienced HIV-infected adults, in combination with a ritonavir-boosted protease inhibitor (PI). To assess its clinical impact in routine care, we compared hospitalization rates according to ETR + PI prescription or not, among heavily treated HIV-1 infected individuals on failing regimens between 2005 and 2011. METHODS: From the French Hospital Database on HIV (ANRS CO4), we selected heavily treated individuals (prior exposure to at least 2 nucleoside reverse transcriptase inhibitor (NRTI), 2PI and 1 NNRTI) with viral load (VL) > 50 copies/mL who started a new antiretroviral (ARV) regimen between 2005 and 2011. Using an intention-to-continue-treatment approach, hospitalization rates were calculated for the individuals who received ETR + PI, during the months after initiating ETR + PI (ETR + PI) or for the individuals who received ETR + PI, in the months before ETR + PI initiation and for the individuals who never received ETR + PI (no ETR + PI). hospitalization from an AIDS-defining cause and hospitalization from a non-AIDS defining cause rates were also calculated. Poisson regression models were used to compare the incidences between the two groups, with adjustment for potential confounders. RESULTS: Of 3884 patients who met the inclusion criteria, 838 (21.6%) received ETR + PI. During 13,986 person-years (P-Y) of follow-up, there were 2484 hospitalizations in 956 individuals. The hospitalization rates per 1000 P-Y were 169.0 among individuals exposed to ETR + PI and 179.3 among those not exposed to ETR + PI. After adjustment, the respective hospitalization rates were 148.8 and 186.7 per 1000 P-Y, with an estimated relative risk of 0.80 (95%CI: 0.71-0.90), AIDS hospitalization rates were 11.5 and 22.7 per 1000 P-Y, with an estimated relative risk of 0.51(95%CI: 0.39-0.66) and non-AIDS hospitalization rates were 139.5 and 152.2 per 1000 P-Y, with an estimated relative risk of 0.92 (95%CI: 0.80-1.05). CONCLUSIONS: Between 2005 and 2011, access to ETR + PI was associated with a 20% reduction in the hospitalization rate among heavily treated HIV-1-infected individuals. This reduction was mainly due to a reduction in the AIDS hospitalization rate.

Association Between Gut Microbiota and CD4 Recovery in HIV-1 Infected Patients.

Composition of the gut microbiota has been linked with human immunedeficiency virus (HIV)-infected patients on antiretroviral therapy (ART). Evidence suggests that ART-treated patients with poor CD4+ T-cell recovery have higher levels of microbial translocation and immune activation. However, the association of the gut microbiota and immune recovery remains unclear. We performed a cross-sectional study on 30 healthy controls (HC) and 61 HIV-infected individuals, including 15 immunological ART responders (IRs), 20 immunological ART non-responders (INRs) and 26 untreated individuals (VU). IR and INR groups were classified by CD4+ T-cell counts of ≥350 cells/mm3 and <350 cells/mm3 after 2 years of ART, respectively. Each subject's gut microbiota composition was analyzed by metagenomics sequencing. Levels of CD4+ T cells, CD8+HLA-DR+ T cells and CD8+CD38+ T cells were measured by flow cytometry. We identified more Prevotella and fewer Bacteroides in HIV-infected individuals than in HC. Patients in INR group were enriched with Faecalibacterium prausnitzii, unclassified Subdoligranulum sp. and Coprococcus comes when compared with those in IR group. F. prausnitzii and unclassified Subdoligranulum sp. were overrepresented in individuals in VU group with CD4+ T-cell counts <350 cells/mm3. Moreover, we found that the relative abundance of unclassified Subdoligranulum sp. and C. comes were positively correlated with CD8+HLA-DR+ T-cell count and CD8+HLA-DR+/CD8+ percentage. Our study has shown that gut microbiota changes were associated with CD4+ T-cell counts and immune activation in HIV-infected subjects. Interventions to reverse gut dysbiosis and inhibit immune activation could be a new strategy for improving immune reconstitution of HIV-1-infected individuals.

Effect of matrix metalloproteinase-21 (572C/T) polymorphism on HIV-associated neurocognitive disorder.

Remodeling of extracellular matrix (ECM) by matrix metalloproteinases (MMPs) is a presumed reason for the development of HIV-associated neurocognitive disorders (HAND). The coding region polymorphism in MMP-21 572C/T gene may have a potential functional effect on ECM remodeling. Hence, we aimed to examine the association of MMP-21 polymorphism with the modulation of HAND severity and its prevalence in HIV-infected and healthy individuals. Genotyping of MMP-21 572C/T polymorphism was performed by PCR-RFLP in total 150 HIV-infected individuals, 50 with HAND, 100 without HAND and 150 healthy controls. MMP-21 572TT genotype was predominantly higher in HAND patients compared with no HAND (OR = 1.63, p = 0.57). MMP-21 572T allele was associated with reduce risk for HAND severity (OR = 0.50, p = 0.04). Similarly, MMP-21 572TT genotype underrepresented in HIV-infected individuals compared to healthy controls (3.0% vs 6.7%, OR = 0.27, p = 0.08). MMP-21 572CT genotype and early HIV disease stage showed a higher risk for the advancement of HIV disease with marginal significance (OR = 1.89, p = 0.07). MMP-21 572CT genotype increased the risk for the modulation of HAND severity in tobacco users (OR = 1.98, p = 0.43). MMP-21 572CT genotype among tobacco and alcohol users showed elevated risk for the development of HAND in HIV-infected individuals (OR = 2.30, p = 0.15; OR = 1.86, p = 0.23). Similarly, MMP-21 572TT genotype enhanced the risk for the development of HAND in tobacco users (OR = 3.48, p = 0.40). In conclusion, the presence of coding region 572T allele may have protection for HAND severity. MMP-21 572C/T polymorphism and tobacco and alcohol usage may facilitate the development of HAND.

Research on expression of NKG2 C/NKG2 A receptors on T cells in HIV infected individuals and relationship with disease progression / 中国免疫学杂志

Objective:To study the changes of NKG2C/NKG2A expressed on T cells in HIV chronically infected individuals and HAART-treatment AIDS patients and the relationship with disease progression of HIV. Methods: We collected peripheral blood from HIV chronically infected individuals,HAART-treatment AIDS patients and healthy human and used the flow cytometry by staining fluorescent antibody to detect the NKG2C/NKG2A receptors expressed on T cells. Results:NKG2C+,NKG2A+ and NKG2C+NKG2A-expressed on T cells in HIV chronically infected individuals were significantly higher than the healthy control group ( P=0. 025,P=0. 032,P=0. 029),while in HAART-treatment AIDS patients were significantly lower than that in HIV chronically infected individuals (P=0. 033,P=0. 037,P=0. 018),returned to the normal levels with no significant difference compared with the healthy control group. The absolute number of peripheral blood CD4+ T lymphocytes in HIV chronically infected individuals was negative correlation with T cells which expressing NKG2A+,NKG2C+NKG2A+ and NKG2C-NKG2A+( r=-0. 697,P<0. 000 1;r=-0. 463,P=0. 015;r=-0. 693,P<0. 000 1). What was more,the absolute number of peripheral blood CD4+ T lymphocytes had positive correlation with the ratio of NKG2C and NKG2A expressed on T cells receptor in HIV chronically infected individuals(r=0. 476,P=0. 012). Conclusion:Studying the expression of NKG2C and NKG2A receptors on T cell has great significance in HIV infected individuals, which may provide a scientific basis for clinical prognosis of HIV infection.

Enteric pathogens in HIV infected and HIV uninfected individuals with diarrhea in Pune.

BACKGROUND: Diarrhea in HIV infected individuals is a common complication seen in about 90% of patients in developing countries. The objective of this study was to identify enteric pathogens in HIV infected and HIV uninfected individuals in Pune. METHOD: This study was conducted from January 2009 to May 2010 on 331 consecutive patients presenting with diarrhea admitted at Naidu Municipal Corporation Hospital, Pune and processed using conventional methods. RESULTS: Intestinal parasitic pathogens were detected in 60% (39/65) of HIV infected and 14.3 (38/266) of HIV uninfected individuals. Bacterial pathogens were detected in 34% (22/65) of HIV infected individuals and 28.2% (75/266) of the HIV uninfected individuals. The common enteric pathogens detected in HIV infected individuals were Cystoisospora belli (28%, 18/65) followed by Cryprotosporidium parvum (12%, 8/65). In HIV uninfected individuals Entamoeba histolytica (7.1%, 19/266) followed by Shigella flexnari (4.9%, 13/266) were the most common pathogens. The difference in detection of enteric parasites in HIV infected individuals and HIV uninfected individuals was found to be significant (p < 0.01). CONCLUSIONS: Intestinal parasitic pathogens are more common in HIV infected antiretroviral therapy naïve patients. Early detection of enteric pathogens by routine examination of stool samples will help in the management and to improve the quality of life for HIV infected individuals.

Study on the mortality and risk factors among HIV-infected individuals during 1989-2011 in Dehong prefecture, Yunnan province / 中华流行病学杂志

Objective To examine the mortality and risk factors among HIV-infected patients during 1989-2011 in Dehong prefecture,Yunnan province.Methods All HIV-infected patients reported during 1989-2011 in Dehong prefecture who held local residency were included in the study.Mortality rates and cumulative survival rates were calculated.Multiple regression analysis under Cox proportional hazard model was conducted to examine the risk factors for deaths.Results A total of 13 006 HIV-infected patients were included in this study including 73.2％ males,79.1％ peasants and 48.7％ married at the time of reporting.64.5％ of the patients were ethnic minorities,and 68.7％ were illiterate or having received only primary school education.All the patients were followed-up for a total of 55 962.30 person-years with 4648 patients died,with overall mortality rate as 8.31/100person-years.The mortality rate had been increasing from 1990 to 2004 but decreasing since 2005.The average survival time since the identification of HIV infection was 9.48 years overall,and was 16.65 years for those having received antiretroviral treatment (ART) and 7.67 years for those without ART.Data from multiple regression analysis indicated that ART and socio-demographic characteristics such as age,gender,ethnicity,occupation,marital status,education background etc.were significantly associated with death among HIV-infected patients.Conclusion The comprehensive AIDS campaigns including ART had significantly reduced the deaths among HIV-infected patients in Dehong prefecture.More efforts on the scaling up program of ART as well as the enhanced management and follow-up program tailored for HIV-infected patients with different sociodemographic characteristics were needed to further reduce the deaths in the area.