Microbiomes detected by cerebrospinal fluid metagenomic next-generation sequencing among patients with and without HIV with suspected central nervous system infection.

BACKGROUND: Opportunistic infections in the central nervous system (CNS) can be a serious threat to people living with HIV. Early aetiological diagnosis and targeted treatment are crucial but difficult. Metagenomic next-generation sequencing (mNGS) has significant advantages over traditional detection methods. However, differences in the cerebrospinal fluid (CSF) microbiome profiles of patients living with and without HIV with suspected CNS infections using mNGS and conventional testing methods have not yet been adequately evaluated. METHODS: We conducted a retrospective cohort study in the first hospital of Changsha between January 2019 and June 2022 to investigate the microbiomes detected using mNGS of the CSF of patients living with and without HIV with suspected CNS infections. The pathogens causing CNS infections were concurrently identified using both mNGS and traditional detection methods. The spectrum of pathogens identified was compared between the two groups. RESULTS: Overall, 173 patients (140 with and 33 without HIV) with suspected CNS infection were enrolled in our study. In total, 106 (75.7%) patients with and 16 (48.5%) patients without HIV tested positive with mNGS (p = 0.002). Among the enrolled patients, 71 (50.7%) with HIV and five (15.2%) without HIV tested positive for two or more pathogens (p < 0.001). Patients with HIV had significantly higher proportions of fungus (20.7% vs. 3.0%, p = 0.016) and DNA virus (59.3% vs. 21.2%, p < 0.001) than those without HIV. Epstein-Barr virus (33.6%) was the most commonly identified potential pathogen in the CSF of patients living with HIV using mNGS, followed by cytomegalovirus (20.7%) and torque teno virus (13.8%). The top three causative pathogens identified in patients without HIV were Streptococcus (18.2%), Epstein-Barr virus (12.1%), and Mycobacterium tuberculosis (9.1%). In total, 113 patients living with HIV were diagnosed as having CNS infections. The rate of pathogen detection in people living with HIV with a CNS infection was significantly higher with mNGS than with conventional methods (93.8% vs. 15.0%, p < 0.001). CONCLUSION: CSF microbiome profiles differ between patients living with and without HIV with suspected CNS infection. mNGS is a powerful tool for the diagnosis of CNS infection among people living with HIV, especially in those with mixed infections.

Are people living with HIV have a low vulnerability to omicron variant infection: results from a cross-sectional study in China.

BACKGROUND: A surge of more than 80 million Omicron variant infected cases was reported in China less than a month after the "zero COVID" strategy ended on December 7, 2022. In this circumstance, whether people living with HIV (PLWH) in China experience a similar risk is not clear. METHODS: A cross-sectional study was conducted in the Wuchang District of Wuhan between December 20, 2022, and January 18, 2023 through a self-administered online survey. PLWH and HIV-negative people aged ≥ 18 years old who volunteered for this survey were eligible. The prevalence of Omicron variant infection between PLWH and HIV-negative people was compared, and the factors associated with the Omicron variant infection among PLWH and HIV-negative people were further evaluated, respectively. RESULTS: In total, 890 PLWH and 1,364 HIV-negative adults from Wuchang District were enrolled. Among these participants, 690 PLWH (77.5%) and 1163 HIV-negative people (85.3%) reported SARS-CoV-2 infection. Gender, chronic disease conditions, and COVID-19 vaccination status significantly differed between the two groups. After adjusting gender, age, comorbidities, and COVID-19 vaccination status, the risk of SARS-CoV-2 infection among PLWH was significantly lower than among HIV-negative people (aOR 0.56, 95%CI 0.42-0.76). Multivariable logistic regression analysis showed that PLWH with older age and detectable HIV-viral load (HIV-VL) had decreased risk of SARS-CoV-2 infection (aOR 0.98, 95%CI 0.96-0.99; aOR 0.59, 95%CI 0.36-0.97). Compared with PLWH receiving one/two doses of COVID-19 vaccines, no significant differences in the risk of SARS-CoV-2 infection were observed among PLWH receiving three doses of inactivated vaccines and four doses of vaccines (three doses of inactivated vaccines plus one dose of inhaled recombinant adenovirus type 5 (AD5)-vectored vaccine). Among HIV-negative people, those receiving four doses of COVID-19 vaccines had a lower risk of SARS-CoV-2 infection than those receiving one/two doses (aOR 0.14, 95%CI 0.08-0.25). CONCLUSIONS: Our study proves that PLWH have a lower risk of Omicron variant infection than HIV-negative people. However, even PLWH with younger age and virological suppression should strengthen the prevention against SARS-CoV-2 infection. Three doses of inactivated vaccines plus one dose of inhaled recombinant AD5-vectored COVID-19 vaccine may provide better protection for HIV-negative people.

Characterization of peripheral cytokine-secreting cells responses in HIV/TB co-infection.

Background: Currently the responses of peripheral cytokine-secreting cells in the natural course of human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection haven't been fully elucidated. Methods: The function of peripheral proinflammatory, regulatory and cytotoxic cytokine-secreting cells were investigated by direct intracellular cytokine staining (ICS) and flow cytometry, additionally, the absolute numbers of different cytokine-secreting cells were measured among patients with HIV/TB co-infection (HT group), and compared them with the healthy controls (HC group), patients with TB (TB group) and patients with HIV infection (HIV group). After one week's anti-TB treatment, the changes of the percentages of cytokine-secreting cells were further evaluated in TB and HT groups. Results: Totally 26 individuals in the HC group, 51 in the TB group, 26 in the HIV group and 29 in the HT group were enrolled. The HT. HT group exhibited significantly lower absolute numbers of IFN-γ+CD4+, IFN-γ+CD8+, TNF-α+CD4+, IL17A+CD4+ T cells and TNF-α+CD14+ monocytes than the TB and HIV groups. Compared with the TB group, the percentages of CD8+ T cells secreting IFN-γ and perforin (p=0.010; p=0.043) were significantly lower among the HT group. Compared with the HIV group, the percentages of CD4+, CD8+ T cells and CD14+ monocytes secreting TNF-α (p=0.013; p=0.001; p<0.001) were significantly decreased, and the percentage of CD8+ T cells secreting IL-17A (p=0.015) was significantly increased among the HT group. Both the percentages of CD4+ T cells secreting TGF-ß (p<0.001; p=0.001), and CD4+ and CD8+ T cells secreting granzyme A (all p<0.001), were significantly higher among the HT group than among the TB group and HIV group. After one week's anti-TB treatment, an increased percentage of CD4+ T cells secreting TNF-α (p=0.003) was found in the TB group, and an increased percentage of CD8+ T cells secreting TNF-α (p=0.029) was found in the HT group. Conclusion: Significantly different functional profiles of peripheral proinflammatory, regulatory, and cytotoxic cytokine-secreting cells were observed in the natural course of HIV/TB co-infection compared to TB and HIV infection alone, even though the absolute numbers of those cells were significantly lower in HIV/TB co-infection. TNF-α-secreting CD8+ T cells may be a more sensitive marker for early evaluation of anti-TB treatment efficacy in patients with HIV/TB co-infection.

Microbiomes Detected by Bronchoalveolar Lavage Fluid Metagenomic Next-Generation Sequencing among HIV-Infected and Uninfected Patients with Pulmonary Infection.

Comparison of lung microbiomes between HIV-infected and uninfected patients with pulmonary infection by metagenomic next-generation sequencing (mNGS) has not been described in China. The lung microbiomes detected in bronchoalveolar fluid (BALF) by mNGS among HIV-infected and uninfected patients with pulmonary infection were reviewed in the First Hospital of Changsha between January 2019 and June 2022. In total, 476 HIV-infected and 280 uninfected patients with pulmonary infection were enrolled. Compared with HIV-uninfected patients, the proportions of Mycobacterium (P = 0.011), fungi (P < 0.001), and viruses (P < 0.001) were significantly higher in HIV-infected patients. The higher positive rate of Mycobacterium tuberculosis (MTB; P = 0.018), higher positive rates of Pneumocystis jirovecii and Talaromyces marneffei (all P < 0.001), and higher positive rate of cytomegalovirus (P < 0.001) contributed to the increased proportions of Mycobacterium, fungi, and viruses among HIV-infected patients, respectively. The constituent ratios of Streptococcus pneumoniae (P = 0.007) and Tropheryma whipplei (P = 0.002) in the bacteria spectrum were significantly higher, while the constituent ratio of Klebsiella pneumoniae (P = 0.005) was significantly lower in HIV-infected patients than in HIV-uninfected patients. Compared with HIV-uninfected patients, the constituent ratios of P. jirovecii and T. marneffei (all P < 0.001) in the fungal spectrum were significantly higher, while the constituent ratios of Candida and Aspergillus (all P < 0.001) were significantly lower in HIV-infected patients. In comparison to HIV-infected patients without antiretroviral therapy (ART), the proportions of T. whipplei (P = 0.001), MTB (P = 0.024), P. jirovecii (P < 0.001), T. marneffei (P < 0.001), and cytomegalovirus (P = 0.008) were significantly lower in HIV-infected patients on ART. Significant differences in lung microbiomes exist between HIV-infected and uninfected patients with pulmonary infection, and ART influences the lung microbiomes among HIV-infected patients with pulmonary infection. IMPORTANCE A better understanding of lung microorganisms is conducive to early diagnosis and treatment and will improve the prognosis of HIV-infected patients with pulmonary infection. Currently, few studies have systematically described the spectrum of pulmonary infection among HIV-infected patients. This study is the first to provide comprehensive information on the lung microbiomes of HIV-infected patients with pulmonary infection (as assessed by more sensitive metagenomic next-generation sequencing of bronchoalveolar fluid) compared with those from HIV-uninfected patients, which could provide a reference for the etiology of pulmonary infection among HIV-infected patients.

A tale of two conditions: when people living with HIV meet three doses of inactivated COVID-19 vaccines.

Background: Currently, data on long-term immune responses to a homogenous booster dose of the inactivated COVID-19 vaccine are still limited among people living with HIV (PLWH). Methods: A prospective cohort study with a 13-month follow-up was conducted in China between March 2021 and August 2022 to evaluate the dynamics of SARS-CoV-2 specific humoral and cellular immunity against three doses of the inactivated COVID-19 vaccine from before the first dose until 6 months after the booster dose vaccination among PLWH in comparison to healthy controls (HC). Results: 43 PLWH on antiretroviral therapy (ART) and 23 HC were enrolled. Compared with HC, the neutralizing antibodies (nAbs) levels among PLWH were significantly lower on days 14, 30, 60, 90, and 120 after the booster dose vaccination. Among PLWH, the nAbs titers on days 14, 30, and 60 after the booster dose were significantly higher than the peak of the second dose. However, on day 180 after the booster dose, the nAbs titers were similar to the peak of the second dose vaccination. Compared with HC, the frequencies of IFN-γ-secreting and TNF-α-secreting CD4+ and CD8+ T cells among PLWH were lower on days 14 and 180 after the booster dose vaccination. Among PLWH, increased T cell immunity was induced by the booster dose of the vaccine and kept stable on day 180 after the booster dose vaccination. Conclusion: Although a homogenous booster dose following two doses of the inactivated COVID-19 vaccine among PLWH could elicit higher nAb titers, reduce antibody decay, and maintain T cell responses even 6 months after vaccination, the overall immunogenicity of the booster dose was found to be lower among PLWH than among healthy controls. Further strategies are needed to improve immunogenicity to the inactivated COVID-19 vaccine among PLWH.

Adverse pregnancy outcomes associated with antiretroviral therapy initiated before pregnancy and during pregnancy: a retrospective study in Hubei province, China.

Background: Antiretroviral therapy (ART) initiation before pregnancy was reported to have an increased risk of adverse pregnancy outcomes (APOs) than ART initiation during pregnancy. However, the risks of APOs associated with different ART regimens initiated before or during pregnancy remain unknown. Methods: Pregnant women living with HIV (PWLHIV) from Hubei Province, China, were retrospectively enrolled between January 1, 2004, and December 31, 2021. The trends of ART initiation time and application of different ART regimens were evaluated over time, separately. Using no ART exposure before and during pregnancy as control, the risks of APOs associated with protease inhibitor (PI) based regimens and non-nucleoside reverse transcriptase inhibitors (NNRTIs) based regimens initiated before pregnancy were analyzed; and the risks of APOs associated with PI-based regimens, NNRTIs based regimens and zidovudine (AZT) monotherapy initiated during pregnancy were analyzed. APOs, including low birthweight (LBW), stillbirth, preterm birth (PTB) and early miscarriage, were reviewed. Results: Among 781 PWLHIV including 1,010 pregnancies, 522 pregnancies (51.7%) were exposed to ART before or during pregnancy. Of them, the proportion of ART initiation before pregnancy per year increased from around 20% in the early period to more than 60% after 2019. Efavirenz (EFV)-nucleoside reverse transcriptase inhibitors (NRTIs) (32.2%), LPV/r-NRTIs (31.2%), and nevirapine (NVP)-NRTIs (27.4%) were the most commonly used regimens, and the proportion of LPV/r-NRTIs used per year has increased to around 50.0% in recent years. LPV/r-NRTIs was associated with higher risks of LBW whether initiated before pregnancy [adjusted OR (aOR) = 2.59, 95%CI 1.04-6.45, p = 0.041] or during pregnancy (aOR = 2.19, 95%CI 1.03-4.67, p = 0.041), compared with no exposure to ART before and during pregnancy. However, no matter initiated before or during pregnancy, LPV/r-NRTIs had no significantly increased risks of stillbirth, PTB and early miscarriage, and EFV /NVP-NRTIs and AZT monotherapy had no significantly increased risks of LBW, stillbirth, PTB and early miscarriage when compared with no exposure to ART before and during pregnancy. Conclusion: Our data suggests that LPV/r-NRTIs has been widely used among PWLHIV in recent years. However, the potential risk of LBW should be continuously monitored among PWLHIV whether LPV/r-NRTIs is initiated before or during pregnancy.

Willingness to receive the COVID-19 vaccine among HIV positive men who have sex with men in China: a cross-sectional study.

BACKGROUND: People living with HIV(PLWH) are deemed more vulnerable to the SARS-CoV-2 infection than the uninfected population. Vaccination is an effective measure for COVID-19 control, yet, little knowledge exists about the willingness of men who have sex with men (MSM) living with HIV in China to be vaccinated. METHODS: This cross-sectional study evaluated the willingness of MSM living with HIV to receive COVID-19 vaccination in six cities of Guangdong, China, from July to September 2020. Factors associated with willingness to receive COVID-19 vaccination using multivariable logistic regression. RESULTS: In total, we recruited 944 HIV-positive MSM with a mean age of 29.2 ± 7.7 years. Of all participants, 92.4% of them were willing to receive the COVID-19 vaccine. Participants who were separated, divorced, or widowed (adjusted OR: 5.29, 95%CI: 1.02-27.48), had an annual income higher than 9,000 USD (adjusted OR: 1.70, 95%CI: 1.01-2.86), had ever taken an HIV self-test (adjusted OR: 1.78, 95%CI: 1.07-2.95), had ever disclosed sexual orientation to a doctor/nurse (adjusted OR: 3.16, 95%CI: 1.33-7.50), had ever disclosed sexual orientation to others besides their male partners (adjusted OR: 2.18, 95%CI: 1.29-3.69) were more willing to receive the vaccine. Sex with a female partner in the past six months decreased the likelihood of willingness to receive the vaccine (adjusted OR: 0.40, 95%CI: 0.17-0.95). Economic burden, worry that my health condition could not bear the risk of receiving COVID-19 vaccines, and concern that the vaccination would affect the immune status and antiretroviral therapy were the main reasons for unwillingness to receive vaccination. CONCLUSION: Our study showed that HIV-positive MSM had a high willingness to receive the COVID-19 vaccination. Targeted interventions such as health education should be conducted among MSM with HIV infection to enhance COVID-19 vaccine uptake.

Humoral immune response to inactivated COVID-19 vaccination at the 3rd month among people living with HIV.

BACKGROUND: Research on the immune response to inactivated COVID-19 vaccination among people living with HIV (PLWH) is limited, especially among those with low CD4+ T lymphocyte (CD4 cell) count. This prospective cohort study aimed to assess the humoral immune response to inactivated COVID-19 vaccination among PLWH compared to HIV negative controls (HNCs) and to determine the impact of CD4 cell count on vaccine response among PLWH. METHODS: The neutralizing antibodies (nAbs) and the specific IgM and IgG-binding antibody responses to the inactivated COVID-19 vaccine at the third month after the second dose of inactivated COVID-19 vaccination were measured among 138 PLWH and 35 HNCs. Multivariable logistic regression and multiple linear regression models were conducted to identify factors associated with the seroconversion rate of antibodies and the magnitude of anti-SARS-CoV-2 antibody titers, respectively. RESULTS: At the end of the third month after two doses of vaccination, the seroconversion rates of IgG were comparable between PLWH (44.9%; 95% CI 36.5-53.3%) and HNCs (60.0%; 95% CI 42.9-77.1%), respectively. The median titers and seroconversion rate of nAbs among PLWH were 0.57 (IQR: 0.30-1.11) log10 BAU/mL and 29.0% (95% CI 21.3-36.8%), respectively, both lower than those in HNCs (P < 0.05). After adjusting for age, sex, comorbidities, and CD4 cell count, the titers and seroconversion rate of nAbs were comparable between PLWH and HNCs (P > 0.05). Multivariable regression analyses showed that CD4 cell count < 200/µL was independently associated with lower titers and seroconversion rate of nAbs among PLWH (P < 0.05). A positive correlation was observed between the CD4 cell count and nAbs titers in PLWH (Spearman's ρ = 0.25, P = 0.0034). CONCLUSION: Our study concluded that the immune response to inactivated COVID-19 vaccination among PLWH was independently associated with CD4 cell count, PLWH with lower CD4 cell count showed a weaker humoral immune response, especially those with CD4 cell count < 200/µL. This finding suggests that expanding COVID-19 vaccination coverage among PLWH is impendency. In addition, aggressive ART should be carried out for PLWH, especially for those with low CD4 cell count, to improve the immune response to vaccines.

Adverse pregnancy outcomes among pregnant women living with HIV in Hubei province, China: prevalence and risk factors.

Mother-to-child transmission of Human Immunodeficiency Virus (HIV) has been greatly reduced with the advance of intervention technology. However, adverse pregnancy outcomes (APOs) are still common, and little is known about the driving forces of APOs among pregnant women living with HIV in China. Between January 2004 and December 2020, a total of 638 pregnancies among pregnant women living with HIV were enrolled in this study, 84 (13.2%) pregnancies with 87 APOs were reported. Preterm birth (3.8%), ectopic pregnancy (3.4%), spontaneous abortion (2.0%), and embryo arrest (1.7%) were the most common APOs in pregnant women living with HIV. Exposure to antiretroviral drugs (ARVs) during the first trimester (RR = 4.077, 95% CI: 0.521, 1.484, P<0.001) and the first CD4+ T lymphocyte count (CD4 count)≤ 350/µl (RR = 2.227, 95% CI: 0.063, 0.991, P = 0.026) were risk factors of APOs. The age≤ 30 years (RR = -2.513, 95% CI: -1.067, -0.132, P = 0.012) was associated with the decreasing of APOs. Encouraging people to initiate combination antiretroviral therapy and reach a high CD4 count level before pregnancy would be helpful to prevent APOs. Pregnant women exposed to ARVs in the first trimester needed more attention for APOs.

Six-month humoral immune response to inactivated COVID-19 vaccine among people living with HIV.

Longitudinal humoral immune response to inactivated COVID-19 vaccines among people living with HIV (PLWH) have not yet been systematically investigated. We conducted a 6-month longitudinal study among vaccinated PLWH and HIV-Negative Controls (HNC) to determine whether the humoral immune response effects of the inactivated COVID-19 vaccine are different between the two groups of people. Totally, 46 PLWH and 38 HNC who received the inactivated COVID-19 vaccine on days 0 and 28 were enrolled. The SARS-CoV-2 neutralizing antibodies (nAbs) and total specific IgM and IgG antibodies were examined on Day 0-Day190. The level and positive seroconversion rate of nAbs peaked on Day 42 in HNC while peaked on Day 70 in PLWH, then decreased gradually with the extension of the vaccination period after the peaks. The peak level of nAbs in PLWH on Day 70, (GMC 8.07 BAU/mL, 95% CI 5.67-11.48) was significantly lower than in HNC on Day 42 (GMC 18.28 BAU/mL, 95% CI 10.33-32.33, P =0.03). The decrease in the geometric mean concentrations (GMCs) of nAbs was observed as 42.9% in PLWH after peak level, which decreased from 8.07 BAU/mL [95% CI: 5.67-11.48] on Day 70 to 4.61 BAU/mL [95% CI: 3.35-6.34] on Day 190 (p = 0.02). On Day 190, only seven (18%, [95% CI: 6-40]) HNC and five (11%, [95% CI: 4-25]) PLWH maintained positive nAbs response respectively. The geometric mean ELISA units (GMEUs) and positive seroconversion rate of IgG in PLWH dropped significantly from Day 70 (GMEUs, 0.20 EU/mL, [95% CI: 0.13-0.34]; seroconversion, 52%, [95% CI: 34-69]) to Day 190 (GMEUs, 0.05 EU/mL, [95% CI: 0.03-0.08], P<0.001; seroconversion, 18%, [95% CI: 8-33], P<0.001). There was no significant difference in levels and seroconversion rates of nAbs and IgG between the two groups on Day 190. The peak immunogenicity of the inactivated COVID-19 vaccine was delayed and inferior in PLWH compared to HNC, while no significant difference was found in six-month immunogenicity between the two groups.

Frequency and functional profile of circulating TCRαß+ double negative T cells in HIV/TB co-infection.

BACKGROUND: Increased frequency of circulating double negative T (DNT, CD4-CD8-CD3+) cells with protective immune function has been observed in human immunodeficiency virus (HIV) infection and tuberculosis (TB). Here the role of circulating TCRαß+ DNT cells was further investigated in HIV/TB co-infection. METHODS: A cross-sectional study was conducted to investigate the frequency and functional profiles of peripheral TCRαß+ DNT cells including apoptosis, chemokine and cytokine expression among healthy individuals and patients with TB, HIV infection and HIV/TB co-infection by cell surface staining and intracellular cytokine staining combined with flow cytometry. RESULTS: Significantly increased frequency of TCRαß+ DNT cells was observed in HIV/TB co-infection than that in TB (p < 0.001), HIV infection (p = 0.039) and healthy controls (p < 0.001). Compared with TB, HIV/TB co-infection had higher frequency of Fas expression (p = 0.007) and lower frequency of Annexin V expression on TCRαß+ DNT cells (p = 0.049), and the frequency of Annexin V expression on Fas+TCRαß+ DNT cells had no significant difference. TCRαß+ DNT cells expressed less CCR5 in HIV/TB co-infection than that in TB (p = 0.014), and more CXCR4 in HIV/TB co-infection than that in HIV infection (p = 0.043). Compared with healthy controls, TB and HIV/TB co-infection had higher frequency of TCRαß+ DNT cells secreting Granzyme A (p = 0.046; p = 0.005). In TB and HIV/TB co-infection, TCRαß+ DNT cells secreted more granzyme A (p = 0.002; p = 0.002) and perforin (p < 0.001; p = 0.017) than CD4+ T cells but similar to CD8+ T cells. CONCLUSIONS: Reduced apoptosis may take part in the mechanism of increased frequency of peripheral TCRαß+ DNT cells in HIV/TB co-infection. TCRαß+ DNT cells may play a cytotoxic T cells-like function in HIV/TB co-infection.

Isolation, characterization and anti-UVB irradiation activity of an extracellular polysaccharide produced by Lacticaseibacillus rhamnosus VHPriobi O17.

The purpose of this study was to isolate exopolysaccharides (EPS) from lactic acid bacteria (LAB) and evaluate EPS anti-UVB viability. Lacticaseibacillus rhamnosus VHPriobi O17 with high EPS production was screened from 34 strains of LAB. The EPS (OP-2) produced by L. rhamnosus VHPriobi O17 was purified by alcohol precipitation and DEAE-µSphere anion exchange chromatography. By ion chromatography, FT-IR spectrum and gel column chromatography, EPS (OP-2) was a novel Man-like polysaccharide with the weight-averaged molecular of 84.2 kDa. The EPS (OP-2) can effectively alleviate HaCaT cells apoptosis and overproduction of reactive oxygen species (ROS) induced by UVB. The results also showed that it inhibited the release of pro-inflammatory cytokines (IL-1α, IL-6 and IL-8); and suppressed the phosphorylation cascade of JNK and p38 MAPK to reduce the expression level of active-caspase3, ultimately prevented cell apoptosis. Thus, the EPS produced by L. rhamnosus VHPriobi O17 have the potential to be used for human anti-UVB irradiation.

Complete Genome Sequence of Limosilactobacillus reuteri Strain VHProbi M07, Isolated from Breast Milk.

The probiotic strain of Limosilactobacillus reuteri VHProbi M07 was isolated from fresh breast milk. Here, we report the whole-genome sequence of this strain. The whole genome comprised 2,041,530 bp with a GC content of 38.89%.

Co-creation using crowdsourcing to promote PrEP adherence in China: study protocol for a stepped-wedge randomized controlled trial.

BACKGROUND: Adherent pre-exposure prophylaxis (PrEP) uptake can prevent HIV infections. Despite the high HIV incidence, Chinese key populations have low PrEP uptake and adherence. New interventions are needed to increase PrEP adherence among key populations in China. Co-creation methods are helpful to solicit ideas from the community to solve public health problems. The study protocol aims to describe the design of a stepped-wedge trial and to evaluate the efficacy of co-created interventions to facilitate PrEP adherence among key populations in China. METHODS: The study will develop intervention packages to facilitate PrEP adherence among Chinese key populations using co-creation methods. The study will then evaluate the efficacy of the co-created intervention packages using a stepped-wedge randomized controlled trial. This four-phased closed cohort stepped-wedge design will have four clusters. Each cluster will start intervention at three-month intervals. Seven hundred participants who initiated PrEP will be recruited. Participants will be randomized to the clusters using block randomization. The intervention condition includes receiving co-created interventions in addition to standard of care. The control condition is the standard of care that includes routine clinical assessment every 3 months. All participants will also receive an online follow-up survey every 3 months to record medication adherence and will be encouraged to use a WeChat mini-app for sexual and mental health education throughout the study. The primary outcomes are PrEP adherence and retention in PrEP care throughout the study period. We will examine a hypothesis that a co-created intervention can facilitate PrEP adherence. Generalized linear mixed models will be used for the primary outcome analysis. DISCUSSION: Developing PrEP adherence interventions in China faces barriers including suboptimal PrEP uptake among key populations, the lack of effective PrEP service delivery models, and insufficient community engagement in PrEP initiatives. Our study design addresses these obstacles by using co-creation to generate social media-based intervention materials and embedding the study design in the local healthcare system. The study outcomes may have implications for policy and intervention practices among CBOs and the medical system to facilitate PrEP adherence among key populations. TRIAL REGISTRATION: The study is registered in Clinical Trial databases in China (ChiCTR2100048981, July 19, 2021) and the US (NCT04754139, February 11, 2021).

Humoral Immune Response to Inactivated COVID-19 Vaccination at the 3rd Month among People Living with HIV.

Background: Research on the immune response to inactivated COVID-19 vaccination among people living with HIV (PLWH) is limited, especially among those with low CD4+ T lymphocyte (CD4 cell) count. This cross-sectional study aimed to assess the humoral immune response to inactivated COVID-19 vaccination among PLWH compared to HIV negative controls (HNC) and to determine the impact of CD4 cell count on vaccine response among PLWH. Methods: The neutralizing antibodies (nAbs) and the specific IgM and IgG-binding antibody responses to the inactivated COVID-19 vaccine at the third month after the second dose of inactivated COVID-19 vaccination were measured among 138 PLWH and 35 HNC. Multivariable logistic regression and multiple linear regression models were conducted to identify factors associated with the seroconversion rate of antibodies and the magnitude of anti-SARS-CoV-2 antibody titers, respectively. Results: At the end of the third month after two doses of vaccination, the seroconversion rates of IgG were comparable between PLWH (8.7%; 95%CI, 3.9-13.5%) and HNC (11.4%; 95%CI, 0.3-22.5%), respectively. The median titers and seroconversion rate of nAbs among PLWH were 0.57 (IQR: 0.30-1.11) log 10 BAU/mL and 29.0% (95%CI: 21.3-36.8%), respectively, both lower than those in HNC ( P ＜0.05). After adjusting for age, sex, comorbidities, and CD4 cell count, the titers and seroconversion rate of nAbs were comparable between PLWH and HNC (P＞0.05). Multivariable regression analyses showed that CD4 cell count＜200 /µL was independently associated with lower titers and seroconversion rate of nAbs among PLWH ( P ＜0.05). A positive correlation was observed between the CD4 cell count and nAbs titers in PLWH (Spearman'sρ=0.25, P =0.034). Conclusion: Our study concluded that the immune response to inactivated COVID-19 vaccination among PLWH was independently associated with CD4 cell count, PLWH with lower CD4 cell count showed a weaker humoral immune response, especially those with CD4 cell count＜200 /µL. This finding suggests that expanding COVID-19 vaccination coverage among PLWH is impendency. In addition, aggressive ART should be carried out for PLWH, especially for those with low CD4 cell count, to improve the immune response to vaccines.

Immune response and safety to inactivated COVID-19 vaccine: a comparison between people living with HIV and HIV-naive individuals.

BACKGROUND: Multi-types COVID-19 vaccines have shown safety and efficacy against COVID-19 in adults. Although current guidelines encourage people living with HIV (PLWH) to take COVID-19 vaccines, whether their immune response to COVID-19 vaccines is distinct from HIV-free individuals is still unclear. METHODS: Between March to June 2021, 48 PLWH and 40 HNC, aged 18 to 59 years, were enrolled in the study in Wuchang district of Wuhan city. All of them received inactivated COVID-19 vaccine (Sinopharm, WIBP-CorV, Wuhan Institute of Biological Products Co. Ltd) at day 0 and the second dose at day 28. The primary safety outcome was the combined adverse reactions within 7 days after each injection. The primary immunogenicity outcomes were SARS-CoV-2 neutralizing antibodies (nAbs) responses by chemiluminescence and total specific IgM and IgG antibodies responses by ELISA and colloidal gold at baseline (day 0), day 14, day 28, day 42, and day 70. RESULTS: In total, the study included 46 PLWH and 38 HNC who finished 70 days' follow-up. The frequency of adverse reactions to the first and second dose was not different between PLWH (30% and 11%) vs. HNC (32% and 24%). NAbs responses among PLWH peaked at day 70, while among HNC peaked at day 42. At day 42, the geometric mean concentration (GMC) and seroconversion rate of nAbs among PLWH were 4.46 binding antibody units (BAU)/mL (95% CI 3.18-5.87) and 26% (95% CI 14-41), which were lower than that among HNC [GMC (18.28 BAU/mL, 95% CI 10.33-32.33), seroconversion rate (63%, 95% CI 44-79)]. IgG responses among both PLWH and HNC peaked at day 70. At day 70, the geometric mean ELISA units (GMEU) and seroconversion rate of IgG among PLWH were 0.193 ELISA units (EU)/mL (95% CI 0.119-0.313) and 51% (95% CI 34-69), which was lower than that among HNC [GMEU (0.379 EU/mL, 95% CI 0.224-0.653), seroconversion rate (86%, 95% CI 64-97)]. There were no serious adverse events. CONCLUSIONS: Early humoral immune response to the inactivated COVID-19 vaccine was weaker and delayed among the PLWH population than that among HNC. This observation remained consistent regardless of a high CD4 count with effective antiretroviral therapy.

The Role of CD4+CD8+ T Cells in HIV Infection With Tuberculosis.

Background: Tuberculosis (TB) is an important opportunistic infection in acquired immunodeficiency diseases (AIDS). Although the frequency of CD4+CD8+ double-positive (DP) T cells has been observed to increase in pathological conditions, their role (phenotypic and functional) is poorly described, especially in human immunodeficiency virus (HIV) infection with TB (HIV/TB (HT) coinfection). Methods: The percentage and phenotypic and functional properties of peripheral blood DP T cells in patients with HT coinfection in comparison to uninfected controls and to patients with HIV or TB mono-infection were analyzed by direct intracellular cytokine staining (ICS). Results: Total and CD4lowCD8high DP T cells were significantly increased in patients with both HIV and TB mono-infection, especially in patients with HT coinfection. Compared with healthy controls (HCs), the percentage of DP T cells expressing chemokine receptor 5 (CCR5) in patients with HT coinfection was significantly higher. Compared with HCs and patients with TB, a lower percentage of tumor necrosis factor α (TNF-α) secreting DP T cells and a higher percentage of granzyme A-secreting DP T cells were observed in patients with HIV mono-infection and HT coinfection, respectively. In addition, DP T cells expressed more cytolytic markers (granzyme A and perforin) than CD4+ T cells, but similarly to CD8+ T cells in patients with HT coinfection. Conclusions: Our data suggested that HT coinfection resulted in a marked increase in DP T cells, especially the CD4lowCD8high subpopulation. DP T cells may be susceptible to HT coinfection, and have the same cytotoxic function as CD8+ T cells.

Risk of SARS-CoV-2 Infection Among People Living With HIV in Wuhan, China.

Background: In the era of the COVID-19 pandemic, people living with HIV (PLWH) face more challenges. However, it is unclear if PLWH is more susceptible to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than HIV-negative individuals. This study aimed to explore the prevalence of the SARS-CoV-2 infection and the associated risk factors among PLWH. Methods: From 1 to 30 May 2020, we conducted a cross-sectional survey that enrolled 857 PLWH and 1,048 HIV-negative individuals from the Wuchang district in Wuhan, China. Our data analysis compared the rate of the SARS-CoV-2 infection among PLWH and HIV-negative participants, and the proportions of symptomatic patients and asymptomatic infectors between the two groups. We also assessed the risk factors associated with the SARS-CoV-2 infection among PLWH. Results: Overall, 14/857 (1.6%) PLWH and 68/1,048 (6.5%) HIV-negative participants were infected with SARS-CoV-2. Among the SARS-CoV-2-infected PLWH participants, 6/14 (42.8%) were symptomatic patients, 4/14 (28.6%) were SARS-CoV-2 nucleic acid-positive asymptomatic infectors, and 4/14 (28.6%) were serology-positive asymptomatic infectors. Among the infected HIV-negative participants, 5/68 (7.4%) patients were symptomatic and 63/68 (92.6%) were serology-positive asymptomatic infectors. The rate of the SARS-CoV-2 infection was lower among the PLWH than in the HIV-negative group (1.96% vs. 5.74%, p = 0.001) and the rate of morbidity among the symptomatic patients was similar between the two groups (p = 0.107). However, there were more serology-positive asymptomatic infectors among the infected HIV-negative participants than among the infected PLWH (0.54% vs. 5.46%, p = 0.001). Furthermore, being 50 years or older (aOR = 4.50, 95% CI: 1.34-15.13, p = 0.015) and having opportunistic infections (aOR = 9.59, 95% CI: 1.54-59.92, p = 0.016) were associated with an increased risk of SARS-CoV-2 infection among PLWH. Conclusions: PLWH has more varied forms of the SARS-CoV-2 infection than the HIV-negative population and should, therefore, undertake routine screening to avoid late diagnosis. Also, older age (≥50 years) and having opportunistic infections increase the risks of SARS-CoV-2 infection among PLWH.

COVID-19 Vaccination Willingness Among People Living With HIV in Wuhan, China.

Vaccination is essential to controlling the pandemic of coronavirus disease 2019 (COVID-19). People living with HIV (PLWH) were considered more vulnerable to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection compared with the general population. Therefore, it is urgent to protect PLWH from SARS-CoV-2 infection. For PLWH, vaccine hesitancy could be more common and may compromise vaccine coverage. Our study aimed to investigate the willingness to receive the COVID-19 vaccination among PLWH and associated factors. A cross-sectional online survey was performed among PLWH and the general population from 4 April to 18 April 2021 in Wuhan, China. The multivariable logistic regression was used to analyze associated factors for COVID-19 vaccination willingness among PLWH. A total of 556 PLWH and 570 individuals from the general population were enrolled. The COVID-19 vaccine willingness among PLWH was 60.8%, which was relatively lower than that in the general population (80.9%) (P < 0.001). The results of multivariable analysis indicated that PLWH with comorbidities (OR = 2.07, 95% CI: 1.25-3.45), those who had idea about PLWH would be more serious if they were infected with SARS-CoV-2 (OR = 1.67, 95% CI: 1.11-2.51) and those who thought their antiretroviral therapy (ART) would be affected by COVID-19 epidemic (OR = 2.04, 95% CI: 1.22-3.42) had higher willingness to receive COVID-19 vaccination. PLWH who had a monthly income over 5,000 RMB (OR = 0.64, 95% CI: 0.45-0.92) and had a sex orientation as non-homosexual (OR = 0.67, 95% CI: 0.47-0.96) were associated with lower willingness for COVID-19 vaccination. Our findings showed that the PLWH had a lower willingness for COVID-19 vaccination compared with the general population in Wuhan. Targeted interventions such as health education should be conducted to increase the willingness for COVID-19 vaccination among PLWH, thus enhancing COVID-19 vaccine uptake among PLWH.