HIV-1 RNA Levels Research Articles

İnsan immün yetmezlik virüsü ile enfekte hastalarda sifiliz ko-enfeksiyonunun değerlendirilmesi ve rapid plasma reagin (RRP) titresinin sifiliz evresine göre takibi

Aim: Syphilis co-infection in HIV-infected patients is associated by a delayed serological response. The aim of this study is to obtain current data on the frequency of HIV/syphilis co-infection, the monitoring of rapid plasma reagin (RPR) titer after treatment, and factors affecting the serologic response. Methods: Serological tests for syphilis of HIV patients followed between January 2015 and March 2023 were evaluated retrospectively. Demografic data (age, sex), level of HIV RNA, RPR, Treponema pallidum haemagglutination test (TPHA), and syphilis stage were obtained from hospital electronic database. Serological response was defined according to Centers for Disease Control and Prevention (CDC) criteria. Results: Syphilis co-infection was detected in 36.2% of the patients, all of them were male. Distribution of syphilis stage was primary 2.9%, secondary 9.7%, latent 80.6%, and neurosyphilis 6.8%, respectively. All patients with primary, secondary, and neurosyphilis had ≥4-fold decrease in RPR titer within 12 months after treatment, while two patients with latent syphilis didn’t have a decrease in titer within 12-24 months. Overall serologic response was 95.8%. Comparing the time to a 4-fold decrease in the RPR titer in terms of syphilis stage, there was no statistically significant difference. Patients with initial RPR titer >1: 32 achieved faster serologic response than those with initial RPR titer ≤1: 32. Conclusion: HIV/syphilis coinfection rate was notably high. It is promising that most patients had a serologic response within the time-frame defined by the CDC. It should be considered that treatment response may take longer in patients with an initial RPR titer ≤32. Further prospective studies are needed to understand the factors associated with serologic response in HIV/syphilis co-infected patients.

On a path toward a broad-spectrum anti-viral: inhibition of HIV-1 and coronavirus replication by SR kinase inhibitor harmine.

This study highlights the crucial role RNA processing plays in regulating viral gene expression and replication. By targeting SR kinases, we identified harmine as a potent inhibitor of HIV-1 as well as coronavirus (HCoV-229E and multiple SARS-CoV-2 variants) replication. Harmine inhibits HIV-1 protein expression and reduces accumulation of HIV-1 RNAs in both cell lines and primary CD4+ T cells. Harmine also suppresses coronavirus replication post-viral entry by preferentially reducing coronavirus sub-genomic RNA accumulation. By focusing on host factors rather than viral targets, our study offers a novel approach to combating viral infections that is effective against a range of unrelated viruses. Moreover, at doses required to inhibit virus replication, harmine had limited toxicity and minimal effect on the host transcriptome. These findings support the viability of targeting host cellular processes as a means of developing broad-spectrum anti-virals.

Virological and immunological correlates of HIV post-treatment control after temporal antiretroviral therapy during acute HIV infection.

People with HIV rarely control viral replication after cessation of antiretroviral therapy (ART). We present a person with HIV with extraordinary post-treatment control (PTC) for over 23 years after temporary ART during acute HIV infection (AHI) leading to a new insight in factors contributing to PTC. Viral reservoir was determined by HIV qPCR, Intact Proviral DNA Assay and quantitative viral outgrowth assay. Viral replication kinetics were determined in autologous and donor PBMC. IgG levels directed against HIV envelope and neutralizing antibodies were measured. Immune phenotyping of T-cells and HIV-specific T-cell responses were analyzed by flow cytometry. The case presented with AHI and a plasma viral load of 2.7 million copies/mL. ART was initiated 2 weeks after diagnosis and interrupted after 26 months. Replicating virus was isolated shortly after start ART. At 18 years after treatment interruption HIV-DNA in CD4+ T-cells and low levels of HIV-RNA in plasma (<5 copies/ml) were detectable. Stable HIV envelope glycoprotein-directed IgG was present during follow-up, but lacked neutralizing activity. Strong antiviral CD8+ T-cell responses, in particular targeting HIV-gag, were detected during 25 years follow-up. Moreover, we found a P255A mutation in an HLA-B∗44:02 restricted gag-epitope, which was associated with decreased replication. We describe an exceptional case of post-treatment control, which is likely associated with sustained potent gag-specific CD8+ T-cell responses in combination with a replication attenuating escape mutation in gag. Understanding the initiation and preservation of the HIV-specific T-cell responses could guide the development of strategies to induce HIV control.

CSF Inflammation Markers Associated with Asymptomatic Viral Escape in Cerebrospinal Fluid of HIV-Positive Individuals on Antiretroviral Therapy.

HIV establishes a viral reservoir in the CNS despite viral suppression in the blood on antiretroviral therapy (ART). In a minority of people with HIV (PWH), HIV RNA is detectable in CSF when HIV RNA in plasma is undetectable or HIV RNA levels are higher in CSF compared with plasma, an event termed CSF viral escape that can occur with or without neurological symptoms. Asymptomatic CSF viral escape occurs in 3-20% of PWH on ART, yet associated biomarkers are unclear. To identify biomarkers associated with asymptomatic CSF viral escape, we performed a matched group study of PWH on ART with vs. without CSF viral escape (n = 10 and n = 60, respectively, matched for age, duration of HIV infection, nadir CD4 count, and ART regimen) and 50 HIV-negative controls. PWH were on 3 or more ART drugs for >1 year, and the group with no CSF viral escape was suppressed below 50 copies/mL in plasma and CSF. Biomarkers of inflammation (IFN-γ, IL-1β, IL-6, IL-8, IL-15, IP-10, MCP-1, VEGF), cell adhesion (ICAM-1, VCAM-1), CNS injury (NFL), and glial activation (GFAP, YKL-40) were measured in paired plasma and CSF using the Meso Scale Discovery platform. PWH with vs. without CSF viral escape had more individuals (40%) with a plasma viral load (VL) > 50 copies/mL, higher CSF VL (median 156 vs. 40 copies/mL; p < 0.0001), lower CD4 count (318 vs. 512; p = 0.045), and higher CSF WBC (median [IQR] 4 [0-22] vs. 2 [0-4] cells/µL; p = 0.15) but similar proportions with HIV-associated neurocognitive disorders (HAND) (50% vs. 47%). CSF viral escape was associated with increased IL-1β, IFN-γ, IP-10, ICAM-1, and VCAM-1 in CSF but not plasma; IP-10 had the strongest association (p = 0.0008). CSF VL and WBC correlated with IFN-γ, IP-10, ICAM-1, and VCAM-1 (p < 0.05). Although markers of CNS injury showed no significant association with asymptomatic CSF viral escape, CSF YKL-40 correlated positively with CSF IL-1β (p = 0.003), IFN-γ (p = 0.0008), IP-10 (p < 0.0001), and NFL (p = 0.06) and negatively with neurocognitive T scores (p = 0.02). These findings identify CSF inflammation and glial activation markers that may serve as surrogate measures of HIV persistence in the CNS for future studies on therapeutics targeting the CNS reservoir.

Long-term persistence of transcriptionally-active "defective" HIV-1 proviruses: Implications for persistent immune activation during antiretroviral therapy.

People with HIV-1 (PWH) on effective antiretroviral therapy (ART) continue to exhibit chronic systemic inflammation, immune activation, and persistent elevations in markers of HIV-1 infection (including HIV-DNA, cell-associated (CA) HIV-RNA, and antibodies to HIV-1 proteins) despite prolonged suppression of plasma HIV-RNA levels <50 copies/mL. Here, we investigated the hypothesis that non-replicating but transcriptionally- and translationally-competent "defective" HIV-1 proviruses may be one of drivers of these phenomena. A combined cohort of 23 viremic and virologically suppressed individuals on ART were studied. HIV-DNA, CA HIV-RNA, western blot (WB) score (measure of anti-HIV-1 antibodies as a surrogate for viral protein expression in vivo), and key biomarkers of inflammation and coagulation (IL-6, hsCRP, TNF-alpha, tissue factor, and D-dimer) were measured in peripheral blood and analyzed using a combined cross-sectional and longitudinal approaches. Sequences of HIV-DNA and CA HIV-RNA obtained via 5'LTR-to-3'LTR PCR and single-genome sequencing were also analyzed. We observed similar long-term persistence of multiple, unique, transcriptionally-active "defective" HIV-1 provirus clones (average: 11 yrs., range: 4-20 yrs.) and antibody responses against HIV-1 viral proteins among all ART-treated participants evaluated. A direct correlation was observed between the magnitude of HIV-1 WB score and the levels of transcription of "defective" HIV-1 proviruses (r = 0.73, p < 0.01). Additional correlations were noted between total CD8+ T cell counts and HIV-DNA (r = 0.52, p = 0.01) or CA HIV-RNA (r = 0.65, p < 0.01). These findings suggest a novel interplay between transcription and translation of "defective" HIV-1 proviruses and the persistent immune activation seen in the setting of treated chronic HIV-1 infection.

HIV RNA and HCV RNA Levels, and Mortality: The Japan Cohort Study of HIV Patients Infected through Blood Products

Background: Most hemophiliacs living with HIV are co-infected with HCV. In their clinical practice, the long-term effects of anti-HIV and anti-HCV therapies have not been sufficiently investigated. Objective: This study aimed to evaluate changes in HIV RNA and HCV RNA levels and the prognosis in hemophiliacs living with HIV over 24 years in Japan. Methods: We used cohort study data of 578 hemophiliacs living with HIV. We analyzed trends in HIV RNA levels between the fiscal years 1997 and 2008 (first follow-up), and trends in HIV RNA and HCV RNA levels between the fiscal years 2009 and 2020 (second follow-up). Mortality rates by HIV RNA and HCV RNA levels were calculated from 11,207 observed person-years and 194 deaths. Results: The percentage of HIV RNA levels &lt;400 copies/mL rose in the first period of follow-up, and the percentage of HCV RNA-negative rose in the second period of follow-up. The participants with HIV RNA levels &lt;400 copies/mL had a significantly lower mortality rate than the others, with a ratio of 0.46 in the first period. HCV antibody-positive participants who were HCV RNA-negative had a significantly lower mortality rate than those who were HCV RNA-positive, with a ratio of 0.47 in the second period. Conclusion: After the introduction of combination anti-HIV therapy over 24 years in hemophiliacs living with HIV, HIV RNA levels decreased in the first half of this period, resulting in decreased mortality. Additionally, HCV RNA levels decreased in the second half of this study period, resulting in even further decreased mortality.

Fatty Acids Composition and HIV Infection: Altered Levels of n-6 Polyunsaturated Fatty Acids Are Associated with Disease Progression.

Fatty acids (FAs) are important regulators of immune responses and innate defense mechanisms. We hypothesized that disturbed FA metabolism could contribute to the progression of HIV infection. Plasma levels of 45 FAs were analyzed with gas chromatography in healthy controls and HIV-infected patients with regard to Mycobacterium avium complex (MAC) infection. In vitro, we assessed MAC-PPD-induced release of inflammatory cytokines in peripheral and bone marrow mononuclear cells (PBMC and BMMC) according to levels of n-6 polyunsaturated fatty acids (PUFAs). While plasma saturated FAs were higher in HIV infection, PUFAs, and in particular the n-6 PUFA arachidonic acid (AA), were lower in patients with advanced disease. The ratio between AA and precursor dihomo-γ-linolenic acid, reflecting Δ5-desaturase activity, was markedly lower and inversely correlated with plasma HIV RNA levels in these patients. Depletion of AA was observed prior to MAC infection, and MAC-PPD-induced release of TNF and IL-6 in PBMC and BMMC was lower in patients with low plasma AA. Our findings suggest that dysregulated metabolism of n-6 PUFAs may play a role in the progression of HIV infection. While high AA may contribute to chronic inflammation in asymptomatic HIV-infected patients, low AA seems to increase the susceptibility to MAC infection in patients with advanced disease.

Investigation of the Frequency of Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis and Mycoplasma genitalium in Men Living with HIV in Terms of Sociodemographic Characteristics and Behavioral Risk Factors

The aim of this study was to investigate the frequency of Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis and Mycoplasma genitalium in men living with HIV in terms of sociodemographic characteristics and behavioral risk factors. In this cross-sectional, single center study, all HIV-infected male patients, aged ≥ 18 years, including those being followed-up (n= 142) and the new admissions (n= 16) at Hacettepe University, Department of Infectious Diseases between March 1st, 2017 and May 1st, 2018 were included. After obtaining the informed consent form; age, follow-up days in STI-clinic, marital status, education, employment status; STI-related sign and symptoms, prior STI diagnosis, multiple sexual partners during the last year, exchanging sex for money, sexual orientation, drug use, condom use with regular and casual partner and also risk factors regarding partners were inquired as behavioural risk factors. A sample of first-voided urine of each participant was tested for the presence of Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis and Mycoplasma genitalium by using nucleic acid amplification test (NAAT) (BD-MAX system, BD Diagnostics, USA) and BD MAX Mycoplasma-Ureaplasma-OSR for BioGX, (BD Diagnostics, The Netherlands). All participants living with HIV, men who have sex with men (MSM) and heterosexual men were grouped as STI-positive and STI-negative and compared. For all statistical analysis, SPSS 24 software was used. During the period of 14 months; the data was determined as follows: median follow-up time was 1138 (IQR= 159.5- 1494.5) days, median age was 35 (IQR= 28-42) years, 73.3% were single, 68.3% were at least college graduates or had higher educational attainment, 78.1% were currently employed. Of the participants, 26.9% reported STI-related sign and symptoms, 50.0% at least one STI episode in the past. Nine (5.6%) M.genitalium, five (3.1%) N.gonorrhoeae, and four (2.5%) C.trachomatis were detected in the urine samples of 17 (10.7%) individuals. N.gonorrhoeae and C.trachomatis were detected simultaneously in only one patient's urine sample. STI-positive patients (n= 17) were determined to be younger compared to STI-negative group [(p= 0.02; 27 years (IQR= 24-37) vs 35 years (IQR= 28-42)], had prominent STI-related signs and symptoms (p< 0.001) and had more multiple sexual partners (p= 0.03). The median CD4+ T lymphocyte count were relatively lower (p= 0.03) in STI-positive patients and plasma HIV RNA level was higher compared to the STI-negative participants (p= 0.05). STI-positive MSM group were younger [p= 0.01; 26 years (IQR= 23.5-29) vs 33 years, (IQR= 28-40)], STI-related signs and symptoms were more prominent (p= 0.02), the frequency of exchanging sex for money/drugs among their partners (p= 0.03) was higher compared to their STI-negative counterparts. Among STI-positive heterosexual patients, the presence of STI-related signs and symptoms (p= 0.04), drug use among their partners (p= 0.04) and plasma HIV RNA level (p<0.01) were significantly higher. STI was identified as an important health problem in this series of men living with HIV, 63.0% of whom had MSM and had a relatively high education level and socioeconomic status. Young age, having multiple partners, drug use, exchanging sex for money/drugs were prominent among the participants and their partners. Public health studies should focus on preventing STIs in young people living with HIV who have behavioral risk factors.

HIV-1 RNA levels in semen of people on 'short-cycle' antiretroviral therapy.

Journal Article HIV-1 RNA levels in semen of people on ‘short-cycle’ antiretroviral therapy Get access Massimiliano Lanzafame, Massimiliano Lanzafame Unit of Infectious Diseases, Ospedale Santa Chiara, via Largo Medaglie d'oro 9 ,CAP 38122, Trento, Italy Corresponding author. E-mail: massimiliano.lanzafame@apss.tn.it Search for other works by this author on: Oxford Academic PubMed Google Scholar Andrea Delama, Andrea Delama Unit of Infectious Diseases, Ospedale Santa Chiara, via Largo Medaglie d'oro 9 ,CAP 38122, Trento, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Daniela Fait, Daniela Fait Unit of Infectious Diseases, Ospedale Santa Chiara, via Largo Medaglie d'oro 9 ,CAP 38122, Trento, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Lucia Collini, Lucia Collini Unit of Microbiology, Ospedale Santa Chiara,via Largo Medaglie d'oro 9,CAP 38122, Trento, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Sandro Vento Sandro Vento Faculty of Medicine, University of Puthisastra, Phnom Penh, Cambodia Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Antimicrobial Chemotherapy, dkad197, https://doi.org/10.1093/jac/dkad197 Published: 21 June 2023

Early on-treatment plasma interleukin-18 as a promising indicator for long-term virological response in patients with HIV-1 infection.

It is necessary to identify simple biomarkers that can efficiently predict the efficacy of long-term antiretroviral therapy (ART) against human immunodeficiency virus (HIV), especially in underdeveloped countries. We characterized the dynamic changes in plasma interleukin-18 (IL-18) and assessed its performance as a predictor of long-term virological response. This was a retrospective cohort study of HIV-1-infected patients enrolled in a randomized controlled trial with a follow-up of 144 weeks of ART. Enzyme-linked immunosorbent assay was performed to evaluate plasma IL-18. Long-term virological response was defined as HIV-1 RNA <20 copies/mL at week 144. Among the 173 enrolled patients, the long-term virological response rate was 93.1%. Patients with a long-term virological response had significantly lower levels of week 24 IL-18 than non-responders. We defined 64 pg./mL, with a maximum sum of sensitivity and specificity, as the optimal cutoff value of week 24 IL-18 level to predict long-term virological response. After adjusting for age, gender, baseline CD4+ T-cell count, baseline CD4/CD8 ratio, baseline HIV-1 RNA level, HIV-1 genotype and treatment strategy, we found that lower week 24 IL-18 level (≤64 vs. >64 pg./mL, a OR 19.10, 95% CI: 2.36-154.80) was the only independent predictor of long-term virological response. Early on-treatment plasma IL-18 could act as a promising indicator for long-term virological response in patients with HIV-1 infection. Chronic immune activation and inflammation may represent a potential mechanism; further validation is necessary.

Cerebrospinal fluid levels of 5-HIAA and dopamine in people with HIV and depression.

Depression is a common illness in people with HIV (PWH) and is associated with substantial morbidity and mortality. The mechanisms that underpin depression in PWH remain incompletely elucidated, and more research is therefore needed to develop effective treatments. One hypothesis is that neurotransmitter levels may be altered. These levels could be influenced by the chronic inflammation and viral persistence that occurs in PWH. We examined a panel of cerebrospinal fluid (CSF) neurotransmitters in PWH on suppressive antiretroviral therapy (ART), many of whom had a current depression diagnosis. CSF monoamine neurotransmitters and their metabolites were measured from participants in studies at the Emory Center for AIDS Research (CFAR). Only participants on stable ART with suppressed HIV RNA from both plasma and CSF were analyzed. Neurotransmitter levels were measured with high-performance liquid chromatography (HPLC). Neurotransmitters and their metabolites included dopamine (DA), homovanillic acid (HVA, a major metabolite of dopamine), serotonin (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA, a major metabolite of serotonin), and 4-hydroxy-3-methoxyphenylglycol (MHPG, a major metabolite of norepinephrine). Multivariable logistic regression was used to evaluate factors associated with depression. There were 79 PWH with plasma and CSF HIV RNA levels < 200 copies/mL at the time of the visit, and 25 (31.6%) carried a current diagnosis of depression. Participants with depression were significantly older (median age 53years versus 47years, P = 0.014) and were significantly less likely to be African American (48.0% versus 77.8%, P = 0.008). Participants with depression had significantly lower dopamine levels (median 0.49ng/mL versus 0.62ng/mL, P = 0.03) and significantly lower 5-HIAA levels (median 12.57ng/mL versus 15.41ng/mL, P = 0.015). Dopamine and 5-HIAA were highly correlated. In the multivariable logistic regression models, lower 5-HIAA was significantly associated with the depression diagnosis when accounting for other significant demographic factors. The associations between lower 5-HIAA, lower dopamine, and depression in PWH suggest that altered neurotransmission may contribute to these comorbid conditions. However, the effects of antidepressants on neurotransmitters cannot be ruled out as a factor in the 5-HIAA results.

HIV RNA/DNA Levels at Diagnosis Can Predict Immune Reconstitution: A Longitudinal Analysis.

HIV DNA mirrors the number of infected cells and the size of the HIV viral reservoir. The aim of this study was to evaluate the effect of pre-cART HIV DNA levels as a predictive marker of immune reconstitution and on the post-cART CD4 counts trends. HIV DNA was isolated from PBMCs and quantified by real-time PCR. Immune reconstitution was assessed up to four years. Piecewise-linear mixed models were used to describe CD4 count changes. 148 people living with HIV (PLWH) were included. The highest rate of immune reconstitution was observed during the first trimester. There was a trend showing that high HIV RNA level resulted in greater increase in CD4 count, especially during the first trimester of cART (difference above vs. below median 15.1 cells/μL/month; 95% CI -1.4-31.5; p = 0.073). Likewise, higher HIV DNA level would predict greater CD4 increases, especially after the first trimester (difference above vs. below median 1.2 cells/μL/month; 95% CI -0.1-2.6; p = 0.071). Higher DNA and RNA levels combined were significantly associated with greater CD4 increase past the first trimester (difference high/high vs. low/low 2.1 cells/μL/month; 95% CI 0.3-4.0; p = 0.024). In multivariable analysis, lower baseline CD4 counts predicted a greater CD4 rise. In successfully treated PLWH, pre-cART HIV DNA and HIV RNA levels are predictors of immune reconstitution.

Microbiological assessment reveals that Salmonella, Shigella and Campylobacter infections are widespread in HIV infected and uninfected patients with diarrhea in Mozambique.

Diarrhea is an important cause of hospitalizations in Mozambique. However, little attention has been paid to the impact HIV infection on the prevalence or clinical manifestations of enteric bacterial infections. This study aimed to determine the prevalence of Salmonella spp., Shigella spp. and Campylobacter spp. in HIV-infected and HIV-uninfected patients with diarrhea, identify risk factors for infection, and explore the association between HIV status, viral load, and bacterial prevalence. We conducted a case-control study at the Centro de Saúde de Mavalane and Centro de Saúde 1° de Maio in Maputo, Mozambique, from November 2021 to May 2022. We recruited 300 patients, including 150 HIV-infected (cases) and 150 HIV-uninfected patients (controls), aged between 0-88 years, presenting with diarrhea. Stool samples were collected for bacterial isolation through culture, and for each HIV-infected patient, 4 ml of venous blood were obtained for viral load detection through PCR. A total of 129 patients (43.0%) had at least one bacterial infection. The prevalence of Salmonella spp., Shigella spp. and Campylobacter spp. was 33.0% (n = 99), 15.0% (n = 45) and 4.3% (n = 13), respectively. The prevalence of any bacterial infection did not differ significantly between HIV-infected (45.3%, n = 68) and HIV-uninfected patients (40.7%, = 61) (p = 0.414). Overall, having 2-3 symptoms of enteric disease (p = 0.008) and a basic education (p = 0.030) were factors associated with bacterial infection. Of the 148 patients for whom HIV-1 RNA levels were available, 115 had copy numbers ≤ 75. Another 13 had levels between 76 and 1,000 and the remaining 20 had an average of 327,218.45 copies/ml. Bivariate logistic regression found that Shigella spp. were associated with HIV (p = 0.038), although no association was found in the multivariate analysis. Enteric infections are common in both HIV-infected and -uninfected patients. Low schooling influences the occurrence of enteric infections, which highlights the need to raise awareness about their prevention.

Does COVID-19 Vaccination with BNT162b2 Influence HIV-Related Immunological and Virological Markers? Data from 235 Persons Living with HIV at Cotugno Hospital, Naples, Italy: Immune Response After Second and Third Doses, and Influence on Immunovirological Markers.

Few data are available on the impact of COVID-19 vaccination on CD4 counts and HIV-RNA in persons living with HIV (PLWH). We present the data of 235 PLWH who were vaccinated with BNT162b2 in March 2021-February 2022 at the "Cotugno" hospital in Naples. PLWH treated at the "Cotugno" hospital, who were vaccinated at the hospital vaccination center, without prior COVID-19 and for whom immunological/virological data were available in the last 12 months and in the 6 months after vaccination were included. Antispike Ab were available for 187 and 64 PLWH after the second and third doses: PLWH with antispikes >33 binding antibodies units (BAU)/mL increased from 91% to 98%. Antinucleocapsid Ab performed in 147 and 56 patients identified 19 (13%) asymptomatic/paucisymptomatic COVID-19 infections after the second dose and an additional 15 (27%) after the third dose. Immunological/virological data were collected before vaccination (T0), after the second dose (T1), and after the third dose (T2). The absolute number of CD4 increased after the third dose (median 663, 657, and 707 at T0, T1, and T2; p < 0.000 T0 vs. T2). The proportion of patients with HIV-RNA <50 copies/mL increases significantly after the second dose (73%; 85.7%; 87.7%; p < 0.000 T0 vs. T2). The presence of COVID-19 asymptomatic/paucisymptomatic infections (demonstrated by the presence of antinucleocapsid Ab) significantly increases SARS-CoV-2 antispike Ab after second dose, but not after third dose. Asymptomatic/paucisymptomatic COVID-19 infections do not have influence on CD4 cell number and HIV-RNA level. Similarly, the presence of not-controlled HIV-RNA (HIV-RNA >50 copies/mL) does not influence antispike Ab response. According to our data, the response to SARS-CoV2 vaccination is effective in people living with HIV. Vaccination against COVID-19 appears to positively affect immunological and virological levels in people living with HIV.

Comparison of Immunological and Virological Recovery with Rapid, Early, and Late Start of Antiretroviral Treatment in Naive Plwh: Real-World Data.

Rapid initiation of antiretroviral therapy (ART) reduces the transmission of HIV infection in the community. This study aimed to determine whether rapid ART initiation is effective compared to standard ART treatment in our country. Patients were grouped based on time to treatment initiation. HIV RNA levels, CD+4 T cell count, CD4/CD8 ratio, and ART regimens were recorded at baseline and follow-up visits for 12 months. There were 368-ART naive adults (treatment initiated at the time of HIV diagnosis; 143 on the first day, 48 on the second-seventh day, and 177 after the seventh day). Although virological suppression rates at 12th months were higher in all groups, over 90% on average, there were no statistically significant differences in HIV-1 RNA suppression rates, CD+4 T cell count, and CD4/CD8 ratio normalization in the studied months but in multivariate logistic regression analysis; showed a significant correlation between both virological and immunological response and those with CD4+ T <350 cells/mL at 12th month in total patients. Our findings support the broader application of recommendations for rapid ART initiation in HIV patients.

Efficacy and safety of ainuovirine versus efavirenz combination therapies with lamivudine/tenofovir disoproxil fumarate for medication of treatment-naïve HIV-1-positive adults: week 48 results of a randomized controlled phase 3 clinical trial followed by an open-label setting until week 96

Ainuovirine (ANV) is a new non-nucleoside reverse transcriptase inhibitor (NNRTI), which was initially synthesized in Korea and later further developed in both Korea and China. A randomized, double-blind, double-dummy, positive parallel group, non-inferiority, phase 3 trial was conducted in 7 sites across China. Eligible HIV-1-positive antiretroviral therapy (ART)-naïve adults aged 18-65 years were randomly assigned in a 1:1 ratio to receive tenofovir disoproxil fumarate and lamivudine (TDF+3TC) in combination with either ANV (ANV group) or efavirenz (EFV group) for up to 48 weeks. Subsequently, participants in both groups received one of the two drug combinations according to their choice until week 96 in an observational study under an open-label setting. The primary endpoint was the proportion of participants achieving HIV RNA <50 copies/mL at week 48, with non-inferiority pre-specified at a margin of 10%. The secondary efficacy endpoints were logarithmic changes in HIV RNA, percentage of participants with HIV RNA levels ≤400 copies/mL and changes in the CD4 T-cell count after 48 and 96 weeks of treatment, as well as the percentage of participants with HIV RNA levels <50 copies/mL at 96 weeks of treatment. Safety endpoints were the incidence of adverse events and laboratory abnormalities evaluated according to the Division of AIDS criteria. This study was registered with the Chinese Clinical Trial Registry (Registration number: ChiCTR1800019041). Between November 27, 2018 and March 11, 2021, a total of 826 participants were screened, and 630 were finally enrolled and randomly assigned (1:1) to either ANV (n=315) or EFV (n=315) groups. The mean age was 30.6±9.4 years and most participants were male (94.6%). At week 48, 274 (87.0%) of 315 participants in the ANV group and 288 (91.7%) of 314 in the EFV group achieved HIV-1 RNA <50 copies/mL and non-inferiority was established (difference:-4.7%, 95% CI:-9.6 to 0.1%). In the period, 293 participants continued to take the ANV regimen and 287 switched from the EFV to the ANV regimen. During the open-label period, 92.5% (271/293) of participants in the continued ANV group and 95.1% (273/287) in the ANV to EFV transfer group remained virologically suppressed (HIV-1 RNA <50 copies/mL) at week 96 (p=0.189). The incidence of NNRTI treatment-related adverse events (TEAEs) at week 48 was 67.6% in 315 participants in the ANV group, which was significantly lower than in 91.4% of 314 participants in the EFV group (p<0.001). The most common TEAEs (weeks 0-48) were dizziness (10.5%) and dyslipidemia (22.2%) in the ANV group vs. 51.0% and 34.4% in the EFV group, respectively, followed by transaminase elevation (9.2% vs. 29.0%), γ-glutamyl transferase elevation (8.3% vs. 19.1%), and rash (7.9% vs. 18.8%) (all p<0.001). After switching from EFV to ANV, TEAEs in the former EFV participants were significantly reduced in the following observational period of 48-96 weeks. The week 48 results indicated that the efficacy of ANV was non-inferior to EFV when combined with two NRTIs. The per-protocol risk difference at week 48 for the primary endpoint also supported non-inferiority. TEAEs in ANV treated participants were less frequent with regard to liver toxicity, dyslipidemia, neuropsychiatric symptoms and rash compared to the EFV group during the first 48 weeks of therapy. The effects were maintained during the 48-96 weeks of therapy. Jiangsu Aidea Pharmaceutical Co., Ltd.

Treatment with Antiviral Drugs Will Significantly Inhibit the HIV-1 RNA POL Gene Expression and Viral Load in AIDS Patients.

This study is to investigate the difference in HIV-1 RNA pol gene expression in AIDS patients before and after antiviral treatment and its effect on the expression level of CD4+/CD8+ T cells in peripheral blood. The participants included 200 AIDS patients who had undergone antiviral medication, and the quantity of HIV-1 RNA pol gene was determined using nested polymerase chain reaction (nPCR). The levels of CD3+, CD4+, and CD8+ T lymphocytes in peripheral blood were measured by flow cytometry before and after therapy. The receiver operating characteristics (ROC) curve was used to assess the impact of HIV-1 RNA pol gene expression and the CD4+/CD8+ ratio on the prognosis of AIDS patients. After three months of therapy, the levels of HIV-1 RNA and viral load in the patients showed a drastic decline, while the levels of CD4+/CD8+ were markedly elevated (P < 0.05). Logistic analysis revealed that patients' viral loads were positively correlated with HIV-1 RNA and negatively correlated with CD4+/CD8+ (P < 0.05). The alanine aminotransferase (ALT), white blood cell (WBC) count, Serum creatinine (Cr), total cholesterol (TC), triglyceride (TG), and platelet (PLT) levels significantly increased following a 24-month therapy, while no significant changes were observed in the level of aspartate aminotransferase (AST), red blood cell (RBC), and neutrophil (NEU) (%). (P > 0.05). Antiviral drugs significantly inhibit the HIV-1 RNA POL gene expression and viral load in AIDS patients but upregulate the expression level of CD4+/CD8+ T cells in peripheral blood.

Plasma Human Immunodeficiency Virus 1 RNA and CD4+ T-Cell Counts Are Determinants of Virological Nonsuppression Outcomes With Initial Integrase Inhibitor-Based Regimens: A Prospective RESPOND Cohort Study.

There are conflicting data regarding baseline determinants of virological nonsuppression outcomes in persons with human immunodeficiency virus (HIV) starting antiretroviral treatment (ART). We evaluated the impact of different baseline variables in the RESPOND cohort. We included treatment-naive participants aged ≥18 who initiated 3-drug ART, in 2014-2020. We assessed the odds of virological suppression (VS) at weeks 48 and 96 using logistic regression. Viral blips, low-level viremia (LLV), residual viremia (RV), and virological failure (VF) rates were assessed using Cox regression. Of 4310 eligible participants, 72% started integrase strand transfer inhibitor (INSTI)-based regimens. At 48 and 96 weeks, 91.0% and 93.3% achieved VS, respectively. At 48 weeks, Kaplan-Meier estimates of rates were 9.6% for viral blips, 2.1% for LLV, 22.2% for RV, and 2.1% for VF. Baseline HIV-1 RNA levels >100 000 copies/mL and CD4+ T-cell counts ≤200/µL were negatively associated with VS at weeks 48 (adjusted odds ratio, 0.51 [95% confidence interval, .39-.68] and .40 [.27-.58], respectively) and 96 and with significantly higher rates of blips, LLV, and RV. CD4+ T-cell counts ≤200/µL were associated with higher risk of VF (adjusted hazard ratio, 3.12 [95% confidence interval, 2.02-4.83]). Results were consistent in those starting INSTIs versus other regimens and those starting dolutegravir versus other INSTIs. Initial high HIV-1 RNA and low CD4+ T-cell counts are associated with lower rates of VS at 48 and 96 weeks and higher rates of viral blips, LLV, and RV. Low baseline CD4+ T-cell counts are associated with higher VF rates. These associations remain with INSTI-based and specifically with dolutegravir-based regimens. These findings suggest that the impact of these baseline determinants is independent of the ART regimen initiated.

Immunological Responses to Helminths and HIV-1 CoInfections

Aim: Helminth infections result from poor sanitation. We evaluated the effect of helminth infections on HIV disease progression through the monitoring of 2 outcomes: (1) plasma HIV-1 RNA Viral load (V/L) and (2) Cluster of Differentiation (CD4+) T-lymphocyte count amongst helminth-HIV-1 co-infected persons. We hypothesized that (1) concurrent helminth infections compromise immune control, resulting in rising VL and reduced CD4+ T-lymphocyte count (2) and that, subject to successful treatment, a decrease in plasma VL could slow down disease progression. Methods: We reviewed 2032 citations, evaluated 432 abstracts, and included 10 articles according to the PRISMA diagram. The methodologies were appraised using a Mixed Method Appraisal Tool (MMAT). Results: At enrolment, plasma VL was significantly higher in individuals with helminths (5.01 log10 vs. 3.41 log10, p &lt; 0.001). The effective range was 5.28 log10 copies/mL at baseline and 4.67 log10 copies/mL, (p &lt; 0.05) after treatment and a trend for 0.61 log10 lower VL. Significant interactions were seen in the successfully treated groups (p &lt; 0.001). CD4+ T-lymphocyte count values were not significantly different in the co-infection groups relative to those with HIV infection alone.&#x0D; Conclusion: Helminths and HIV-1 co-infections are associated with an increase in HIV-1 RNA levels that accelerate the progression of the sub-clinical disease to symptomatic AIDS.

Targeted plasma proteomics identifies MICA and IL1R1 proteins associated with HIV-1 reservoir size

HIV-1 reservoir shows high variability in size and activity among virally suppressed individuals. Differences in the size of the viral reservoir may relate to differences in plasma protein concentrations. We tested whether plasma protein expression levels are associated with levels of cell-associated (CA) HIV-1 DNA and RNA in 211 virally suppressed people living with HIV (PLHIV). Plasma concentrations of FOLR1, IL1R1, MICA, and FETUB showed a positive association with CA HIV-1 RNA and DNA. Moreover, SNPs in close proximity to IL1R1 and MICA genes were found to influence the levels of CA HIV-1 RNA and DNA. We found a difference in mRNA expression of the MICA gene in homozygotes carrying the rs9348866-A allele compared to the ones carrying the G allele (p<0.005). Overall, our findings pinpoint plasma proteins that could serve as potential targets for therapeutic interventions to lower or even eradicate cells containing CA HIV-1 RNA and DNA in PLHIV.