Plasma HIV Viral Load Research Articles

T-Follicular-Like CD8+ T Cell Responses in Chronic HIV Infection Are Associated With Virus Control and Antibody Isotype Switching to IgG.

T cell responses are considered critical for the in vivo control of HIV, but the contribution of different T cell subsets to this control remains unclear. Using a boosted flow cytometric approach that is able to differentiate CD4+ and CD8+ T cell Th1/Tc1, Th2/Tc2, Th17/Tc17, Treg and Tfh/Tfc-like HIV-specific T cell populations, we identified CD8+ Tfc responses that were related to HIV plasma viral loads and associated with rate of antibody isotype class switching to IgG. This favorable balance towards IgG responses positively correlated with increased virus neutralization, higher avidity of neutralizing antibodies and more potent antibody-dependent cell cytotoxicity (ADCC) in PBMCs from HIV controllers compared to non-controllers. Our results identified the CD8+ Tfc-like T-cell response as a component of effective virus control which could possibly be exploited therapeutically.

Risk of Immune Reconstitution Inflammatory Syndrome With Integrase Inhibitors Versus Other Classes of Antiretrovirals: A Systematic Review and Meta-analysis of Randomized Trials.

BackgroundIntegrase strand transfer inhibitors (InSTIs) decrease HIV plasma viral load faster than other antiretroviral classes. More rapid viral load decline has been associated with higher risk of immune reconstitution inflammatory syndrome (IRIS). There are conflicting reports on the association between InSTI and IRIS. We performed a systematic review and meta-analysis to compare the risk of IRIS among treatment-naïve HIV-positive patients starting InSTI versus non-InSTI regimens.MethodsWe searched PubMed, Scopus, Web of Science, Africa-Wide, and Cochrane databases from earliest available date to 26 November 2021, for randomised controlled trials (RCTs) having intervention arms with InSTI versus control arms without InSTI in patients initiating first-line antiretroviral therapy. The primary outcome was relative risk (RR) of IRIS, while the secondary outcome was RR of paradoxical tuberculosis-associated IRIS (TB-IRIS). Data were combined by random-effects meta-analysis according to the Mantel-Haenszel method. The protocol for this study is registered with PROSPERO, CRD42020213976.ResultsWe included 14 RCTs comprising 8696 participants from six continents for the primary outcome of IRIS, and a subset of 674 participants (from three RCTs) for the secondary outcome of paradoxical TB-IRIS. Risk of IRIS was similar between InSTI and non-InSTI regimens (RR, 0.93, 95% confidence interval [CI], 0.75 – 1.14). There was a trend towards a lower risk of paradoxical TB-IRIS with InSTI versus efavirenz regimens that was not statistically significant (RR, 0.64, 95% CI, 0.34 – 1.19).ConclusionsIn this meta-analysis among treatment-naïve patients commencing first-line antiretroviral therapy, InSTI regimens were not associated with higher risk of IRIS.

Enigma of the high prevalence of anti-SARS-CoV-2 antibodies in HIV-positive people with no symptoms of COVID-19 in Burkina Faso.

The severe acute respiratory syndrome due to the new coronavirus (SARS-CoV-2), responsible for coronavirus disease (COVID-19), has severely tested the global health response capacity, with predictions of a fatality for developing countries. To evaluate the prevalence of anti-SARS-CoV- 2 antibodies in People Living with HIV (PLHIV) with no COVID-19 symptoms in Burkina Faso. Seroprevalence was estimated by performing a qualitative screening test for SARS-CoV-2-specific immunoglobulins. The STANDARDTM Q COVID-19 IgM/IgG Combo Test kit from SD BIOSENSOR was used. Parameters like HIV plasma viral load, CD4 T cell count and C-Reactive Protein (CRP) expression were estimated. This study enrolled a total of 200 PLHIV aged 4-87 years who are asymptomatic for COVID-19. There were 36 (18%) positive for SARS-CoV-2 IgM and/or IgG of which three (1.50%) were positive for SARS-CoV-2 IgM and 33 (16.50%) for IgG. Among participants diagnosed as IgM positive, 66.67% (2/3) had the highest HIV viral loads with the lowest CD4 T cell counts (p<0.0001). The expression of CRP was relatively higher in COVID-19 IgG positive individuals (7.95±12.5 mg/L) than negative individuals (6.26±6.92 mg/L; p=0.37). The rate of IgG and IgM SARS-CoV-2 immunoglobulin carriage (18%), accompanied by a relatively high CRP levels, was revealed in this study among PLHIV. This serologic evidence and mild inflammation suggest that Burkina Faso escaped the worst, not necessarily because there were not many SARS-CoV-2 infections in its population, but because factors including genetic and environmental, might have resulted in many asymptomatic carriers.

HSV-2 increases replication of HIV in human T cells

Abstract Herpes simplex virus 2 (HSV-2) infection is a major factor driving the global HIV epidemic, leading to increased HIV plasma viral loads (PVLs) and transmission. Previous studies which focused on mucosal responses cannot explain the observed effects of HSV-2 on HIV PVLs. We sought to determine mechanisms by which HSV-2 increases HIV PVLs. CD4 T cells are recruited to sites of HSV-2 lesions and HSV-2 can infect these cells. Phenotyping of CD4 cells infected with HSV-2 in vitro suggested a preference for T follicular helper cells, an HIV latent reservoir. HSV infection of latently infected Jurkat-2D10 cells resulted in a 10-fold increase in HIV ltr expression. After exposing CD4 cells from HIV+ donors to HSV-2, HIV p24 was detected only in cells expressing HSV-2 glycoprotein B (gB), a marker of productive HSV-2 infection. Bulk and single cell RNAseq on FACS-purified, HSV-infected and uninfected CD4 cells demonstrated reduced expression of HIV restriction factors in HSV+ cells; HSV exposed but uninfected cells exhibited higher expression of interferon response genes, potentially explaining their resistance to HIV reactivation. HSV+ cells exhibited increased expression of the lncRNA MALAT1, which may promote HIV reactivation through epigenetic modification, and HSV infection of 2D10 and CD4 cells led to decreased histone deacetylase activity. Transfection of 2D10 cells with HSV protein VP16 resulted in significantly increased HIV ltr and MALAT1 gene expression, and reduced epigenetic silencing marks. HIV proteins were also increased by proteomic analyses. These findings identify several mechanisms by which HSV-2 directly triggers HIV reactivation, such as the up-regulation of the lncRNA MALAT1. Supported by grants from the NIH (R01 AI134367, T32 AI007501, T32 GM007288)

People with HIV have a higher risk of COVID‐19 diagnosis but similar outcomes to the general population

BackgroundWe investigated the effect of HIV on COVID‐19 outcomes with attention to selection bias due to differential testing and comorbidity burden.MethodsThis was a retrospective cohort analysis using four hierarchical outcomes: positive SARS‐CoV‐2 test, COVID‐19 hospitalization, intensive care unit (ICU) admission and hospital mortality. The effect of HIV status was assessed using traditional covariate‐adjusted, inverse probability‐weighted (IPW) analysis based on covariate distributions for testing bias (testing IPWs), HIV infection status (HIV‐IPWs) and combined models. Among people living with HIV (PWH), we evaluated whether CD4 count and HIV plasma viral load (pVL) discriminated between those who did and those who did not develop study outcomes using receiver operating characteristic analysis.ResultsBetween March and November 2020, 63 319 people were receiving primary care services at the University of California San Diego (UCSD), of whom 4017 were PWH. The PWH had 2.1 times the odds of a positive SARS‐CoV‐2 test compared with those without HIV after weighting for potential testing bias, comorbidity burden and HIV‐IPW [95% confidence interval (CI): 1.6–2.8]. Relative to people without HIV, PWH did not have an increased rate of COVID‐19 hospitalization after controlling for comorbidities and testing bias [adjusted incidence rate ratio (aIRR) = 0.5, 95% CI: 0.1–1.4]. PWH did not have a different rate of ICU admission (aIRR = 1.08, 95% CI: 0.31–3.80) or of in‐hospital death (aIRR = 0.92, 95% CI: 0.08–10.94) in any examined model. Neither CD4 count nor pVL predicted any of the hierarchical outcomes among PWH.ConclusionsPeople living with HIV have a higher risk of COVID‐19 diagnosis than those without HIV but the outcomes are similar in both groups.

Prospective multicentre head-to-head validation of host blood transcriptomic biomarkers for pulmonary tuberculosis by real-time PCR

BackgroundSensitive point-of-care screening tests are urgently needed to identify individuals at highest risk of tuberculosis. We prospectively tested performance of host-blood transcriptomic tuberculosis signatures.MethodsAdults without suspicion of tuberculosis were recruited from five endemic South African communities. Eight parsimonious host-blood transcriptomic tuberculosis signatures were measured by microfluidic RT-qPCR at enrolment. Upper respiratory swab specimens were tested with a multiplex bacterial-viral RT-qPCR panel in a subset of participants. Diagnostic and prognostic performance for microbiologically confirmed prevalent and incident pulmonary tuberculosis was tested in all participants at baseline and during active surveillance through 15 months follow-up, respectively.ResultsAmong 20,207 HIV-uninfected and 963 HIV-infected adults screened; 2923 and 861 were enroled. There were 61 HIV-uninfected (weighted prevalence 1.1%) and 10 HIV-infected (prevalence 1.2%) tuberculosis cases at baseline. Parsimonious signature diagnostic performance was superior among symptomatic (AUCs 0.85–0.98) as compared to asymptomatic (AUCs 0.61–0.78) HIV-uninfected participants. Thereafter, 24 HIV-uninfected and 9 HIV-infected participants progressed to incident tuberculosis (1.1 and 1.0 per 100 person-years, respectively). Among HIV-uninfected individuals, prognostic performance for incident tuberculosis occurring within 6–12 months was higher relative to 15 months. 1000 HIV-uninfected participants were tested for respiratory microorganisms and 413 HIV-infected for HIV plasma viral load; 7/8 signature scores were higher (p < 0.05) in participants with viral respiratory infections or detectable HIV viraemia than those without.ConclusionsSeveral parsimonious tuberculosis transcriptomic signatures met triage test targets among symptomatic participants, and incipient test targets within 6 months. However, the signatures were upregulated with viral infection and offered poor specificity for diagnosing sub-clinical tuberculosis.

Evaluation of Sociodemographic Factors and Prevalence of Oral Lesions in People Living with HIV from Cacoal, Rondônia, Amazon Region of Brazil.

Background: It is necessary to evaluate and understand the prevalence and risk factors of oral lesions (OL) in people living with HIV (PLWH) who were never studied before. The present study aimed to describe the prevalence of OL and its correlation with CD4+ T lymphocytes counts and HIV plasma viral load in PLWH treated in Rondônia. Methods: A cross-sectional study was carried out at Cacoal city, Rondônia state, Northern Brazil. Sociodemographic, epidemiological, immunologic and virological information of 113 PLWH were collected from medical records and dental examination was conducted to diagnose and classify OL in PLWH. Statistical analysis was performed using relative frequency distribution, ANOVA, Kruskal–Wallis, T-student and Mann-Whitney tests. Results: The overall prevalence of oral lesions was 28.3% (32/113), with candidiasis (7/32; 21.8%) and aphthous ulcer (7/32; 21.8%) being the most prevalent. There was a predominance of females, most patients being married, with a low level of education, a family income of 1 to 3 minimum wages and a single partner. An association was observed between the presence of oral lesions and a high viral load, as well as a lower occurrence of oral lesions in individuals with a higher count of CD4+ T cells. Conclusions: This study reveals a low prevalence of OL among PLWH, as well as the absence of relationship between HIV viral load, CD4+ T cells count and OL high prevalence.

Abnormal Shift in B Memory Cell Profile Is Associated With the Expansion of Circulating T Follicular Helper Cells via ICOS Signaling During Acute HIV-1 Infection.

Interactions between T follicular helper (Tfh) cells and germinal center B cells are essential for the differentiation of B cells and specific antibody responses against HIV-1 infection. However, the extent to which HIV-1 infection affects the dynamic interplay between these two cell populations in the bloodstream remains unclear. In this study, the dynamics of circulating Tfh (cTfh) and B cells and their relationship in individuals with acute and chronic HIV-1 infection were investigated. Twenty-five study subjects were enrolled from the Beijing PRIMO clinical cohort, a prospective cohort of HIV-1-negative men who have sex with men (MSM) for the identification of cases of acute HIV-1 infection (AHI) at Beijing Youan Hospital, Capital Medical University. Individuals with AHI were selected at random. Matched samples were also collected and analyzed from the same patients with chronic HIV-1 infection. None of the study subjects received antiretroviral therapy during acute or chronic infection. Multicolor flow cytometry was used for the immunophenotypic and functional characterization of cTfh cell and B cell subsets. AHI resulted in increased proportions in bulk cTfh, ICOS+cTfh or IL-21+ICOS+cTfh cells. In both acute and chronic infections, activated memory (AM), tissue-like memory (TLM), and plasmablast (PB) B cell levels were increased whilst resting memory (RM) and naïve mature (NM) B cell levels were decreased. Classical memory (CM) B cells were unaffected during infection. Association analyses showed that the levels of ICOS+cTfh and IL-21+ICOS+cTfh cells were negatively correlated with those of AM, CM, RM cells, and positively correlated with those of NM cells in AHI but not chronic HIV-1 infection stage (CHI). Moreover, the frequency of IL-21+ICOS+cTfh cells was also positively correlated with plasma HIV-1 viral load, and had an opposite association trend with CD4+T cell count in AHI. Our data suggests that HIV-1 infection drives the expansion of cTfh cells, which in turn leads to perturbations of B cell differentiation through ICOS signaling during acute infection stage. These findings provide insight on the role of ICOS in the regulation of cTfh/B cell interaction during AHI and may potentially guide the design of effective strategies for restoring anti-HIV-1 immunity in the infected patients.

Immunosuppressive Features of the Microenvironment in Lymph Nodes Granulomas from Tuberculosis and HIV–Co-Infected Patients

Tuberculosis (TB) and HIV co-infection claims many lives every year. This study assessed immune responses in Mycobacterium tuberculosis–infected lymph node tissues from HIV-negative and HIV-positive patients compared with the peripheral circulation with a focus on myeloid cells and the cell-signaling enzymes, inducible nitric oxide synthase, and arginase (Arg)-1. Methods included immunohistochemistry or confocal microscopy and computerized image analyses, quantitative real-time PCR, multiplex Luminex, and flow cytometry. These findings indicate enhanced chronic inflammation and immune activation in TB/HIV co-infection but also enhanced immunosuppressive responses. Poorly formed necrotic TB granulomas with a high expression of M. tuberculosis antigens were elevated in TB/HIV–co-infected lymph nodes, and inducible nitric oxide synthase and Arg-1 expression was significantly higher in TB/HIV–co-infected compared with HIV-negative TB or control tissues. High Arg-1 expression was found in myeloid cells with a phenotype characteristic of myeloid-derived suppressor cells (MDCS) that were particularly abundant in TB/HIV–co-infected tissues. Accordingly, Lin−/HLA-DRlow/int/CD33+/CD11b+/CD15+ granulocytic myeloid-derived suppressor cells were significantly elevated in blood samples from TB/HIV–co-infected patients. CD15+ myeloid-derived suppressor cells correlated with plasma HIV viral load and M. tuberculosis antigen load in tissue but were inversely associated with peripheral CD4 T-cells counts. Enhanced chronic inflammation driven by M. tuberculosis and HIV co-infection may promote Arg-1–expressing MDSCs at the site of infection thereby advancing TB disease progression.

Simultaneous monitoring of HIV viral load and screening of SARS-CoV-2 employing a low-cost RT-qPCR test workflow.

The COVID-19 pandemic interrupted routine care for individuals living with HIV, putting them at risk of virologic failure and HIV-associated illness. Often this population is at high risk for exposure to SARS-CoV-2 infection, and once infected, for severe disease. Therefore, close monitoring of HIV plasma viral load (VL) and screening for SARS-CoV-2 infection are needed. We developed a non-proprietary method to isolate RNA from plasma, nasal secretions (NS), or both. The extracted RNA is then submitted to RT-qPCR to estimate the VL and classify HIV/SARS-CoV-2 status (i.e., HIV virologic failure or suppressed; SARS-CoV-2 as positive, presumptive positive, negative, or indeterminate). In contrived samples, the in-house RNA extraction workflow achieved a detection limit of 200-copies per mL for HIV RNA in plasma and 100-copies per mL for SARS-CoV-2 RNA in NS. Similar detection limits were observed for HIV and SARS-CoV-2 in pooled plasma/NS contrived samples. When comparing in-house with standard extraction methods, we found high agreement (>0.91) between input and measured RNA copies for HIV LTR in contrived plasma; SARS-CoV-2 N1/N2 in contrived NS; and LTR, N1, and N2 in pooled plasma/NS samples. We further evaluated this workflow on 133 clinical specimens: 40 plasma specimens (30 HIV-positive), 67 NS specimens (31 SARS-CoV-2-positive), and 26 combined plasma/NS specimens (26 HIV-positive with 10 SARS-CoV-2-positive), and compared the results obtained using the in-house RNA extraction to those using a commercial kit (standard extraction method). The in-house extraction and standard extraction of clinical specimens were positively correlated: plasma HIV VL (R2 of 0.81) and NS SARS-CoV-2 VL (R2 of 0.95 and 0.99 for N1 and N2 genes, respectively); and pooled plasma/NS HIV VL (R2 of 0.71) and SARS-CoV-2 VL (R2 of 1 both for N1 and N2 genes). Our low-cost molecular test workflow ($1.85 per pooled sample extraction) for HIV RNA and SARS-CoV-2 RNA could serve as an alternative to current standard assays ($12 per pooled sample extraction) for laboratories in low-resource settings.

Anti-spike antibodies and neutralising antibody activity in people living with HIV vaccinated with COVID-19 mRNA-1273 vaccine: a prospective single-centre cohort study.

SummaryBackgroundVaccines against COVID-19 are a powerful tool to control the current SARS-CoV-2 pandemic. A thorough description of their immunogenicity among people living with HIV (PLWHIV) is necessary. We aimed to assess the immunogenicity of the mRNA-1273 vaccine among PLWHIV.MethodsIn this prospective cohort, adult PLWHIV outpatients were enrolled during the Italian vaccination campaign. Enrolment was allowed irrespective of ongoing combination antiretroviral therapy (ART), plasma HIV viral load and CD4+ T cell count. A two-dose regimen of mRNA-1273, with administrations performed 28 days apart, was employed. The primary outcomes were anti-spike (anti-S) antibody titres and neutralising antibody activity, assessed 28 days after completing the vaccination schedule. A convenient sample of individuals not affected by HIV was also collected to serve as control (referred as healthy-donors, HDs).FindingsWe enrolled 71 PLWHIV, mostly male (84·5%), with a mean age of 47 years, a median CD4+ T cell count of 747·0 cells per µL and a median HIV viral load <50 copies/mL. COVID-19-experienced PLWHIV displayed higher anti-S antibody titres (p=0·0007) and neutralising antibody activity in sera (p=0·0007) than COVID-19-naïve PLWHIV. When stratified according to CD4+ T cell count (<350 cells/μL, 350-500 cells/μL, >500 cells/μL), anti-S antibody titres (6/71, median 2173 U/mL [IQR 987-4109]; 7/71, 5763 IU/mL [IQR 4801->12500]; 58/71, 2449 U/mL [IQR 1524-5704]) were not lower to those observed among HDs (10, median 1425 U/mL [IQR 599-6131]). In addition, neutralising antibody activity, stratified according to the CD4+ T cell count (6/71, median 1314 [IQR 606-2477]; 7/71, 3329 IU/mL [IQR 1905-10508]; 58/71, 1227 U/mL [IQR 761-3032]), was like those displayed by HDs (10, median 2112 U/mL [IQR 719-8889]).InterpretationIn our cohort of PLWHIV with well-controlled ART, stable viral suppression and robust CD4+ T cell count, inoculation with mRNA-1273 vaccine given 4 weeks apart produced detectable humoral immune response, similar to individuals without HIV infection, supporting vaccination in PLWHIV.FundingThis study was partially supported by Italian Ministry of Health Ricerca Corrente 2021, by Intesa San Paolo COVID-19 emergency 2020 funds, and by Fondazione Cariplo Grant (INNATE-CoV).

Complex Interactions Between Human Immunodeficiency Virus Type-1, Sex, and Osteopontin Influence Viral Replication and Leukocyte Proportions in Tissues

Evidence suggesting that HIV pathogenesis differs by sex, a variable known to influence the extent and breadth of immune responses in health and disease continues to accumulate. Host factors that promote or inhibit HIV replication may do so in a way that varies by sex. Prior studies using cultured human macrophages demonstrated that osteopontin (OPN)/secreted phosphoprotein-1 (SPP1) stimulates HIV replication. To test whether OPN has the same positive impact on virus replication at the level of tissues, we used a humanized mice model of low-level chronic HIV infection and in which OPN RNA and protein expression was inhibited with targeted aptamers. Interestingly, 4 months after infection when there were no significant differences in HIV viral load in plasma between groups however in contrast, in the spleen, lung, and liver the tissue burden of HIV RNA, as well as the proportion of leukocytes in female and male mice differed depending on whether OPN was expressed or not. The findings collectively demonstrate the potential for complex interactions between host factors like OPN and sex to influence different facets of HIV tissue-level pathogenesis.

Brief Report: Vaginal Viral Shedding With Undetectable Plasma HIV Viral Load in Pregnant Women Receiving 2 Different Antiretroviral Regimens: A Randomized Clinical Trial.

Pregnant women using antiretrovirals (ARVs) may have persistent vaginal viral shedding, which could be associated with sexual and perinatal HIV transmission. However, there are scant data on vaginal viral load (VVL) in pregnant women with undetectable plasma viral load (PVL). This study was a post hoc analysis of an open-label randomized trial to evaluate the virologic response of 2 ART regimens. The participants were ART-naive women living with HIV initiating ART regimens between 20 and 36 weeks of pregnancy recruited at 19 clinical sites in 6 countries. Participants were randomized to receive 400 mg of raltegravir 2 times a day or 600 mg of efavirenz 4 times a day in addition to 150 mg of lamivudine and 300 mg of zidovudine 2 times a day. VVL and PVL tests were performed at every study visit. The primary outcome measures were HIV-1 PVL and VVL at maternal study week 4 and rates of perinatal HIV transmission. A total of 408 were enrolled, of whom 323 had VVL samples 4 weeks after enrollment and were included in this analysis. Among women with undetectable/nonquantifiable PVL during ART, the overall rate of quantifiable VVL at week 4 was 2.54% (7/275). Of the 275 with nonquantifiable PVL, 99.1% (115/116) and 96.2% (153/159) had nonquantifiable VVL in the efavirenz and raltegravir arms, respectively. None of the 7 women with quantifiable VVL at the week 4 study visit transmitted HIV to their infants. Detectable VVL in pregnant women with undetectable/nonquantifiable PVL while receiving ART was rare and not associated with perinatal HIV transmission.

Prevalence of oral human papillomavirus infection among Indian HIV-positive men who have sex with men: a cross-sectional study

BackgroundOral human papillomavirus (HPV) infection has been causally linked to a subset of oropharyngeal cancers in Western populations, and both oropharyngeal cancer and oral HPV infection are increased among HIV-positive individuals. India has high incidences of oral and oropharyngeal cancers, and Indian HIV-positive men who have sex with men (MSM) may be at increased risk of developing oropharyngeal cancers. However, there is little information available on the prevalence of oral HPV in this population.MethodsWe tested 302 HIV-positive Indian MSM for oral HPV infection using L1 HPV DNA PCR with probes specific for 29 types and a mixture of 10 additional types. CD4+ level and plasma HIV viral load (VL) were measured. Participants completed an interviewer-administered questionnaire including a sexual history.ResultsThe prevalence of oral HPV was 23.7% (95% CI: 19–29%) and 2.4% of participants had oncogenic HPV types. No participants had oral HPV type 16 (HPV-16) and the prevalence of other anogenital HPV types was low. Participants with higher CD4+ levels had reduced odds of having any oral HPV infection (OR: 3.1 [1.4–6.9]) in multivariable analyses.ConclusionsThis is the first report of oral HPV among Indian HIV-positive MSM. Our results show a high prevalence of oral HPV infection consistent with studies from Western populations. However, oncogenic anogenital HPV types were relatively uncommon in our study population. It is unknown what the impact of this distribution of oral HPV will be on oropharyngeal cancers. HIV-positive MSM in India should be monitored closely for oral and oropharyngeal pre-cancer and cancer.

Impact of the COVID-19 pandemic situation on HIV care in Liège, Belgium

Background Background: The COVID-19 pandemic and associated containment measures dramatically affected the health care systems including the screening of human immunodeficiency virus and the management people living with HIV around the world by making the access to preventive care services and specific medical monitoring more difficult. Objective Objective: To study the impact of the COVID-19 pandemic on the holistic care of people living with HIV in Liège (Belgium). Methods Methods: In this retrospective observational study conducted in Liège University Hospital, we compared the out-patient follow-up of HIV-infected individuals as well as the number of new HIV diagnoses between 2019 and 2020 and between the different waves of the COVID-19 pandemic in 2020. Results Results: In 2020, when compared to 2019, we observed a significant decrease in the number of new HIV diagnoses, especially during the first wave of the pandemic, and in the number of consultations undertaken by sexual health services, psychologists and specialists in infectious diseases at our HIV clinic. We also observed a decrease in the number of viral load assays and blood CD4 + T-cells count analyses performed, although we found less patients with HIV plasma viral load above 400 copies per mL in 2020. Finally, we noted a significant reduction in terms of screening of our HIV-infected patients for hepatitis C, syphilis, colorectal and anal cancers and hypercholesterolemia. Conclusions Conclusions: Our experience exhibits the deleterious impact of the COVID-19 pandemic on the HIV care and the need to implement new strategies to guarantee its continuum.

THE CHALLENGING DIAGNOSIS OF SERONEGATIVE ORAL SYPHILIS IN AN HIV-INFECTED PATIENT

<h3>Background</h3> In people living with HIV/syphilis-coinfection, overlapping of clinical stages and misleading anti-treponemal serologic tests have been described. This is the report of serological (false-negative) non-reactive, polymerase chain reaction (PCR)-confirmed syphilis in an HIV-infected patient. <h3>Case Description</h3> An HIV-infected male patient, 28-years-old, receiving antiretrovirals (TDF/FTC/DTG) with therapeutic success (CD4: 667 cells/mm³, undetectable HIV-plasma viral load), was referred to our Oral Pathology & Medicine Service in Mexico City. A 3-month asymptomatic ulcerated lesion on the right side of the soft palate and anterior pillar, with granular appearance, irregular borders, and measuring 2 to 3 cm in diameter, was observed. A painless, right cervical lymph node was present. A quantitative serum Venereal Disease Research Laboratory (VDRL) assay was nonreactive (serum was diluted 6-fold to rule out a prozone phenomenon and remained negative). Histopathologic analysis revealed an intense mixed inflammatory infiltrate; differential diagnosis included secondary syphilis, lymphoproliferative disorder, and deep mycotic infection. The immunohistochemistry (IHC) for <i>T. pallidum</i> was negative. DNA extraction was performed, and the <i>T. pallidum</i> gene polA was amplified by PCR; as a consequence, the patient received benzathine-penicillin G (2.4 million units) single dose. VDRL and treponemal FTA-abs were done twice, with negative results. A new biopsy revealed positive IHC<i>-T. pallidum</i>. Two months later, a mucous patch appeared on the tonsillar pillar, with histopathologic features of secondary syphilis and positivity for IHC-<i>T. pallidum</i>. VDRL and FTA-abs assays remained non-reactive. Oral lesions resolved after 3 doses of benzathine-penicillin G. <h3>Conclusions</h3> In absence of serological evidence, the diagnosis of oral syphilis is a challenge. PCR and IHC may represent supplementary helpful diagnostic tools.

Predictive factors of viral load high-risk events for virological failure in HIV/AIDS patients receiving long-term antiviral therapy

BackgroundIn the era of anti-retroviral therapy (ART), the plasma HIV viral load (VL) is an important primary indicator for monitoring the HIV treatment response. To optimize the clinical management of HIV/AIDS patients, we investigated VL high-risk events related to virological failure (VF) and further explored the preventive factors of VL high-risk events.MethodsThe data were derived from China’s HIV/AIDS Comprehensive Response Information Management System. HIV infected patients who initiated or received ART in Guangxi between 2003 and 2019 were included. The contributions of VL after 6 months of ART to VF and AIDS-related death were analysed by Kaplan-Meier curves, log-rank tests and Cox regression analyses. Both descriptive analyses and bivariate logistic regression were employed to further explore the preventive factors related to VL high-risk events of VF.ResultsThe cumulative rates of VF in the high low-level viremia group (high LLV) (χ2 = 18.45; P < 0.001) and non-suppressed group (χ2 = 82.99; P < 0.001) were significantly higher than those in the viral suppression (VS) group. Therefore, the VL high-risk events of VF was defined as highest VL > 200 copies/ml after 6 months of ART. Compared with the VS group, the adjusted hazard risk was 7.221 (95% CI: 2.668; 19.547) in the high LLV group and 8.351 (95% CI: 4.253; 16.398) in the non-suppressed group. Compared with single patients, married or cohabiting (AOR = 0.591; 95% CI: 0.408, 0.856) and divorced or separated (AOR = 0.425, 95% CI: 0.207, 0.873) patients were negatively associated with VL high-risk events. So were patients acquired HIV homosexually (AOR = 0.572; 95% CI: 0.335, 0.978). However, patients who had ART modification were 1.728 times (95% CI: 1.093, 2.732) more likely to have VL high-risk events, and patients who used cotrimoxazole during ART were 1.843 times (95% CI: 1.271, 2.672) more likely to have VL high-risk events.ConclusionsA VL greater than 200 copies/ml is a VL high-risk event for VF. Intervention measurements should be adopted to optimize the surveillance of ART in patients who are single or widowed, who have ART modification, and who use cotrimoxazole during ART.

Antiretroviral Therapy for HIV-Associated Cutaneous Kaposi's Sarcoma: Clinical, HIV-Related, and Sociodemographic Predictors of Outcome.

Kaposi's sarcoma (KS) is an AIDS-defining malignancy that can improve or worsen with antiretroviral therapy (ART). We aimed at identifying clinical, HIV-related, and sociodemographic factors associated with either progression or nonprogression (regression or stable disease) of ART-treated HIV-associated KS in patients with limited cutaneous disease. We conducted a prospective cohort study of ART-treated HIV-associated KS cases. Clinical, HIV-related, and sociodemographic variables were collected at baseline, and patients were followed up to determine treatment outcomes. Cox regression, linear mixed effects model, and Spearman's rank correlation were used for analysis. Half (50%) of the study participants had KS regression or stable disease, whereas the other half (50%) had disease progression during the treatment and follow-up period. Among the data analyzed, presence of KS nodules at baseline (hazard ratio = 5.47; 95% confidence interval = 1.32–22.65; p = .02) was an independent predictor of poor treatment outcome. Progressors and nonprogressors were indistinguishable in the changes they experienced in the HIV plasma viral load and CD4 counts as a result of ART. Even when cutaneous presentation is limited, the presence of nodular morphotype KS lesions should be considered an indicator for combined ART plus chemotherapy. Temporal trends in CD4 counts and HIV viral loads did not correlate with treatment outcome in ART-treated HIV-associated KS.

Prospective evaluation of accuracy of HIV viral load monitoring using the Aptima HIV Quant Dx assay with fingerstick and venous dried blood spots prepared under field conditions in Kenya.

Quantification of HIV-1 RNA is essential for clinical management of HIV patients. The limited throughput and significant hands-on time required by most HIV Viral load (VL) tests makes it challenging for laboratories with high test volume, to turn around patient results quickly. The Hologic Aptima HIV-1 Quant Dx Assay (Aptima), has the potential to alleviate this burden as it is high throughput and fully automated. This assay is validated for both plasma and dried blood spots (DBS), which are commonly used in resource limited settings. The objective of this study was to compare the performance of Aptima to Abbott RealTime HIV-1 Assay (Abbott RT), which was used as reference. This was a cross-sectional prospective study where HIV VL in finger stick (FS) DBS, venous blood (VB) DBS and plasma, collected from 258 consenting adults visiting 5 medical facilities in Kenya, Africa were tested in Aptima. The results were compared to plasma VL in Abbott RT at the medical decision point (MDP) of 1000 copies/mL and across Aptima assay range. The total agreement at MDP between plasma HIV VL in Abbott RT and plasma, FS and VB DBS tested in Aptima were 97.7%, 92.2% and 95.3% respectively with kappa statistic of 0.95, 0.84 and 0.90. The positive and negative agreement for all 3 sample types were >92%. Regression analysis between VL in Abbott RT plasma and various sample types tested in Aptima had a Pearson’s correlation coefficient ≥0.91 with systematic bias of < 0.20 log copies/mL on Bland-Altman analysis. The high level of agreement in Aptima HIV VL results for all 3 sample types with Abbott RT plasma VL along with the high throughput, complete automation, and ease of use of the Panther platform makes Aptima a good option for HIV VL monitoring for busy laboratories with high volume of testing.

Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide as Maintenance Treatment in HIV/HBV-Coinfected Patients.

The efficacy and safety of switching from tenofovir disoproxil fumarate-based antiretroviral therapy to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (E/C/F/TAF) has not been widely investigated in HIV/hepatitis B virus (HBV)-coinfected Asian population. Between February and October 2018, HIV/HBV-coinfected patients who had achieved HIV viral suppression with tenofovir disoproxil fumarate-containing regimens were switched to E/C/F/TAF. Assessments of plasma HBV and HIV viral load, HBV serology, renal function, lipid profiles, and bone mineral density (BMD) were performed at weeks 24 and 48 after switch. A total of 274 HIV/HBV-coinfected participants were enrolled, with 12.8% testing HBeAg-positive and 94.2% having plasma HBV DNA <20 IU/mL at baseline. At weeks 24 and 48, 92.7% and 89.8% achieved plasma HBV DNA <20 IU/mL; 4.7% and 5.1% had HBV DNA ≥20 IU/mL; and 2.6% and 5.1% had no data, respectively. At weeks 24 and 48, 95.6% and 94.2% of participants maintained HIV RNA <50 copies/mL, respectively. Compared with baseline, the median urine β2-microglobulin-to-creatinine ratio at week 48 decreased significantly from 165 to 90 μg/g (P < 0.001). The mean BMD of the spine and hip improved at week 48 (+1.77% and +1.33%, respectively). Significantly higher lipid profiles were observed after switch to E/C/F/TAF. Thirteen (4.7%) patients withdrew from the study before week 48, with 7 (2.6%) patients because of adverse effects. Switch to E/C/F/TAF maintained HBV and HIV viral suppression and resulted in the improvement of proteinuria and BMD of the spine and hip but increased lipid levels in HIV/HBV-coinfected patients at week 48.