Plasma HIV Viral Load Research Articles

Efficacy and safety of DTG plus 3TC for prophylaxis of perinatal transmission of HIV infection in pregnant women who have detectable viral load after 14 weeks of gestation: A pilot study (PREGNANCY)

Abstract Background The prevention of perinatal HIV transmission depends on the safe and effective use of antiretroviral therapy (ART). Simplifying treatment reduces drug exposure for both mother and child. We evaluated the safety and efficacy of DTG/3TC for antiretroviral-naïve pregnant women living with HIV (PWLHIV). Methods This proof-of-concept trial enrolled ART-naïve pregnant women over 15 years old with HIV infection and a gestational age between 14 and 28 weeks. Participants received a fixed-dose combination of DTG/3TC. Baseline HIV genotyping was performed. Participants were monitored at baseline, every 4 weeks, and at delivery. Infants were assessed at birth, 4 weeks, and 6 weeks of age. Outcomes included the proportion of women achieving an undetectable HIV-1 plasma viral load (<50 copies/mL) at delivery, therapy modification frequency, perinatal HIV transmission rate, and adverse events. Results Between January 2019 and March 2021, 20 women were enrolled. At baseline, the median CD4 cell count was 401.6 ± 113.6 cells/μL, increasing to 690.2 ± 266 cells/μL at delivery. Median viral load was 9,514 copies/mL. All women achieved an undetectable viral load after an average of 40 days. No cases of perinatal HIV transmission were detected. No therapy modifications were necessary during the study, and no adverse events were related to the ART. Conclusion In this pilot trial, DTG/3TC demonstrated safety and efficacy, with all participants achieving viral suppression before delivery. There were no cases of perinatal HIV transmission and no drug-related adverse events. DTG/3TC can be an option for initial treatment of drug-naïve PWLHIV.

Emergent resistance-associated mutations at first- or second-line HIV-1 virologic failure with second-generation InSTIs in two- and three-drug regimens: the Virostar-1 study.

Second-generation integrase strand transfer inhibitors (InSTIs) have a high barrier to resistance and potent antiretroviral activity. They are recommended as first- or second-line (FL and SL) options in two- and three-drug regimens (2DR and 3DR) in international treatment guidelines. However, there are limited real-world data on emerging resistance at the time of virological failure (VF) with these regimens. The Virostar-1 study objective is to analyse the emergence of resistance-associated mutations (RAMs) over 3 years with DTG-based 2DRs and DTG- or bictegravir (BIC)-based 3DRs in people living with HIV (PLWH) experiencing a VF (FL or SL). Retrospective analysis of genotypic resistance detected at the time of a FL or SL VF with BIC/FTC/TAF, DTG/ABC/3TC, DTG/3TC and DTG/RPV between 2019 and 2022 was conducted from a French multicentre database. VF was defined as two consecutive HIV-1 plasma viral loads > 50 c/mL. Sanger assays were performed at VF within standard clinical care. Resistance mutations were reported using the ANRS algorithm. Selection biases prevent group comparisons. During the period, N = 5986 PLWH were followed either in FL or SL. The VF rate was overall low: BIC/FTC/TAF, 6.8%; DTG/ABC/3TC, 7.5%; DTG/3TC, 5.1%; and DTG/RPV, 2.1%. Some emergent InSTI or NRTI RAMs were detected with BIC/FTC/TAF 4%, DTG/ABC/3TC 8.5%, DTG/3TC 18% and 39% emergent NNRTI RAMs with DTG/RPV. However, a complete absence of dual resistance against NRTIs and InSTIs was observed. We detected rare emergent InSTI RAMs and few emergent NRTI RAMs in PLWH failing DTG- or BIC-based regimens in FL or SL. The observed rates of emergent RAMs at VF were 4% with BIC/FTC/TAF, 8.5% with DTG/ABC/3TC, 18% with DTG/3TC and 39% with DTG/RPV.

Clinical-Laboratory Outcome of Cryptococcus sp. Multifocal Choroiditis in Acquired Immunodeficiency Syndrome Patients

ABSTRACT Purpose This study aims to describe the clinical and laboratory outcomes of patients with Acquired Immunodeficiency Syndrome (AIDS) presenting multifocal choroiditis secondary to Cryptococcus sp. infection. Methods We reviewed the clinical records of AIDS patients diagnosed with cryptococcal multifocal choroiditis at the Laboratory of Infectious Disease in Ophthalmology, Oswaldo Cruz Foundation, from January 2022 to March 2024. Patients meeting the criteria of typical fundus appearance associated with disseminated cryptococcosis laboratory diagnosis were included. Data collected included age, gender, symptoms, plasma HIV viral load, serum T-CD4+ cell count (cells/mm3), initial visual acuity (VA), laboratory methods for cryptococcosis diagnosis, treatment, and final VA. All patients underwent multimodal evaluation including spectral domain optical coherence tomography, fluorescein angiography (FA), and indocyanine green angiography (ICG). Results Six patients were evaluated, comprising five males (83%) and one female (17%), with a mean age of 36.5 years (standard deviation, SD: 10,46). Five patients (83%) presented with meningeal syndrome. Mean HIV plasma viral load was 262.959 copies/mm3 (SD: 209.469), and the mean serum T-CD4 count was 13.33 cells/mL (SD: 14,63). All patients tested positive for serum cryptococcal antigen (CRAG). Four patients (67%) had positive cerebrospinal fluid (CSF) culture and CRAG. Treatment included intravenous Amphotericin B and oral Fluconazole. Among twelve eyes (100%), four (33%) achieved visual recovery, while eight (67%) maintained initial VA. Lesions were more numerous and distinct on ICG compared to fundus examination and FA. Conclusion This study underscores the importance of clinical, laboratory, and multimodal evaluations in AIDS patients presenting with cryptococcal multifocal choroiditis.

The impact of analytical treatment interruptions and trial interventions on time to viral re-suppression in people living with HIV restarting ART in cure-related clinical studies: a systematic review and meta-analysis.

To assess the effectiveness of novel HIV curative strategies, "cure" trials require periods of closely monitored antiretroviral therapy (ART) analytical treatment interruptions (ATIs). We performed a systematic review and meta-analysis to identify the impact of ATI with or without novel therapeutics in cure-related studies on the time to viral re-suppression following ART restart. Medline, Embase and Web of Science databases were searched for human studies involving ATIs from 1 January 2015 till 22 April 2024. The primary outcome was time to first viral re-suppression (plasma HIV viral load [VL] <50 copies/ml) stratified by receipt of interventional drug with ATI (IA) or ATI-only groups. Random-effects proportional meta-analysis and multivariable Cox proportional hazards analysis were performed using R. Of 1073 studies screened, 13 were included that met the inclusion criteria with VL data available after restarting ART (n = 213 participants). There was no difference between time to viral suppression in IA or ATI-only cohorts (p = 0.22). For 87% of participants, viral suppression within 12 weeks of ART restart was achieved, and all eventually had at least one VL <50 copies/ml during follow-up. After adjusting for covariables, while participants in the IA cohort were associated with less rapid suppression (adjusted hazard ratio [aHR] 0.61, 95% CI 0.40-0.94, p = 0.026), other factors include greater log VL at ART restart (aHR 0.56, 95% CI 0.46-0.68, p<0.001), duration since HIV diagnosis (aHR 0.93, 95% CI 0.89-0.96) and longer intervals between HIV VL monitoring (aHR 0.66, 95% CI 0.59-0.74, p<0.001). However, the use of integrase inhibitors was associated with more rapid viral suppression (aHR 1.74, 95% CI 1.16-2.59). When designing studies involving ATIs, information on time to viral re-suppression after restarting ART is important to share with participants, and should be regularly monitored and reported, to assess the impact and safety of specific trial interventions in ATI studies. The majority of participants achieved viral suppression after restarting ART in ATI studies. ART regimens containing integrase inhibitors and frequent VL monitoring should be offered for people restarting ART after ATI studies to ensure rapid re-suppression.

Long-term impact of an integrated HIV/non-communicable disease care intervention on patient retention in care and clinical outcomes in East Africa.

To describe rates of retention in care and control of hypertension, diabetes and HIV among participants receiving integrated care services for a period of up to 24 months in East Africa. Between 5 October 2018 and 23 June 2019 participants enrolled into a prospective cohort study evaluating the feasibility of integrated care delivery for HIV, diabetes and hypertension from a single point of care in Tanzania and Uganda (MOCCA study). Integrated care clinics were established in 10 primary healthcare facilities and care was provided routinely according to national guidelines. Initial follow-up was 12 months. Outcomes were rates of retention in care, proportions of participants with controlled hypertension (blood pressure <140/90 mmHg), diabetes (fasting blood glucose <7.0 mmol/L) and HIV (plasma viral load <1000 copies/ml). The study coincided with the COVID-19 pandemic response. Afterwards, all participants were approached for extended follow-up by a further 12 months in the same clinics. We evaluated outcomes of the cohort at the end of long-term follow-up. The MOCCA study enrolled 2273 participants of whom 1911 (84.5%) were retained in care after a median follow-up of 8 months (Interquartile range: 6.8-10.7). Among these, 1283/1911 (67.1%) enrolled for a further year of follow-up, 458 (24.0%) were unreachable, 71 (3.7%) reverted to vertical clinics (clinics providing services dedicated to study conditions), 31 (1.6%) died and 68 (3.6%) refused participation. Among participants who enrolled for longer follow-up, mean age was 51.4 ± 11.7 years, 930 (72.5%) were female and 509 (39.7%) had multiple chronic conditions. Overall, 1236 (96.3%) [95% confidence interval 95.2%-97.3%] participants were retained in care, representing 1236/2273 (54.3%) [52.3%-56.4%] of participants ever enrolled in the study. Controlled hypertension, diabetes and HIV at the end of follow-up was, 331/618 (53.6%) [49.5%-57.5%], 112/354 (31.6%) [26.8%-36.8%] and 332/343 (96.7%) [94.3%-98.4%] respectively. Integrated care can achieve high rates of retention in care long term, but control of blood pressure and blood sugar remains low.

Depression: an individual-level early warning indicator of virologic failure in HIV patients in South Africa.

To identify individual-level early warning indicators of virologic failure in HIV patients receiving antiretroviral therapy (ART) in South Africa. A matched case-control study of individuals with and without virologic failure (VF) (>5 months on ART and HIV-1 plasma viral load >1,000 copies/mL) was conducted between June 2014 and June 2018. Of the 1,000 participants enrolled in the parent cohort, 96 experienced VF, and 199 additional controls were identified from the parent cohort and matched 1:2 (some matched 1:3) for sex, age, ART duration, and site. Participants were interviewed while clinical, pharmacy refill, laboratory, and objective pharmacological data were obtained. Multivariate conditional logistic regression models were constructed using model selection to identify factors associated with VF. Significant determinants of VF were identified using an alpha level of 0.05. In a full conditional model, higher cumulative ART adherence, quantified using tenofovir-diphosphate concentrations in dried blood spots (OR 0.26) and medication possession ratio (OR 0.98) were protective against VF, whereas an increase in total depression score (OR 1.20) was predictive of VF. This analysis demonstrates the importance of depression as a key individual-level early warning indicator of VF. Efforts to address mental health concerns among patients with people living with HIV could improve virologic suppression.

The prevalence of HIV resistance mutations and their influence on the shedding of HIV-1 into peritoneal dialysis effluent.

HIV drug resistance mutations (HIVDRMs) are important determinants of therapeutic effects and outcomes even in end-stage kidney failure (ESKF) people living with HIV (PLWHIV). This study evaluated the prevalence of HIVDRMs and their effect on the shedding of HIV-1 into peritoneal dialysis (PD) effluents. This cross-sectional study of PLWHIV and having ESKF and managed with antiretroviral therapy (ART) and PD,collected enrolled patients' demographic information, clinical and laboratory data, and sequenced HIV-1 RNA in unsuppressed plasma and PD effluent samples. HIV viral load and HIVDRMs were determined using qualitative polymerase chain reaction (qPCR) and Stanford University HIVDRM Database, respectively. There were 60 participants recruited with a median age of 43.0 (interquartilerange [IQR], 38.0-47) years and were predominantly on abacavir (88.3%), lamivudine (98.3%), and efavirenz (70%) for a median duration of 8 (IQR, 5-11) years. Among participants with detectable HIV-1 in PD effluents, the prevalence of HIVDRMs was 62.5% (5/8) compared to 7.7% (4/52) among those with undetectable HIV-1 (p = 0.001) with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations predominating. On Spearman's correlation analysis, high plasma HIV levels(ρ = 0.649, p < 0.001), T-cell CD4 count (ρ = -0370, p < 0.004), serum creatinine (ρ = -0.396, p < 0.002), and white blood cell count (ρ = -0.294, p < 0.023) levels were significant factors correlated with the detection of HIV-1 in PD effluents. Moreover, HIVDRMs presence (ρ = 0.504, p < 0.001) particularly NNRTI resistance (ρ = 0.504, p < 0.001)were also significantly correlated with detection of HIV-1 in PD effluents. The presence of HIVDRMs, high plasma HIV viral load, and T-cell CD4 count were correlated with HIV-1 shedding into PD effluents.

Pharmaco-virological outcomes and genotypic resistance profiles among children and adolescents receiving a DTG-based regimen in Togo.

Few data are available on the real-world efficacy of receiving tenofovir-lamivudine-dolutegravir (DTG) as HIV treatment, particularly among young people in West Africa. Here, we evaluated pharmaco-virological outcomes and resistance profiles among Togolese children and adolescents. A cross-sectional study was conducted in Lomé, Togo, enrolling antiretroviral-treated people with HIV aged from 18 months to 24 years. Plasma HIV-1 viral load and antiretroviral concentrations were measured. Next-Generation Sequencing (NGS) of protease, Reverse Transcriptase (RT) and integrase was performed on all samples with viral load >200 c/mL. Drug resistance mutations (DRMs) were identified and interpreted using the ANRS-MIE algorithm. 264 participants were enrolled (median age=17 years), 226 received a DTG-based regimen for a median of 20.5 months. Among them, virological suppression at the 200 c/mL threshold in 80.0% of the participants. Plasma DTG concentrations were adequate (i.e., >640 ng/mL), suboptimal and below the limit of quantification in 74.1%, 6.7% and 19.2% of participants receiving DTG, respectively. Overall, viruses resistant to any of Nucleoside RT Inhibitors, Non-NRTIs, and protease inhibitors were found in 52%, 66% and 1.6% of participants, respectively. A major integrase inhibitor DRM was observed in 9.4% (n=3/32, R263K, E138A-G140A-Q148R, and N155H) of participants with a viral load >200 c/mL. These first findings in such a large series of adolescents in a low-income country, showed a good virological response of 80% and the presence of an integrase DRM in 9.4% of the virological failures, supporting the need to monitor DTG drug resistance to reduce the risk of resistance acquisition.

Effect of dolutegravir on ferritin, iron, and C-reactive protein among people living with HIV and co-infections.

Dolutegravir-based antiretroviral therapy (ART) is currently recommended as the preferred first-line ART in many resource-limited settings. However, little is known about the clinical experience of dolutegravir within a context of prevalent co-infections. To assess virological outcomes, and iron, ferritin and C-reactive protein (CRP) levels among people living with HIV (PLWH) and co-infections after initiating or re-initiating dolutegravir-based ART. This prospective study was conducted between August 2022 and August 2023. Study participants were recruited from an HIV opportunistic infection clinic. Screening for co-infections (syphilis, hepatitis B virus, cytomegalovirus and herpes simplex virus) was performed at baseline, prior to ART initiation. Plasma HIV viral load (VL), CRP, ferritin and iron levels were measured at baseline and at the 6-month follow-up period. A total of 100 participants (51 women and 49 men) were enrolled in this study. The median age of the participants was 39 years. The prevalence of co-infections was 30%. Prior to ART initiation, participants with co-infections had higher VL, CRP and ferritin, and lower iron levels, compared to those without co-infections (P < 0.001). Following 6 months of ART, CRP and ferritin levels decreased while iron levels increased, regardless of co-infection status. However, CRP and ferritin remained significantly higher in those with co-infections despite similar and high rates of virologic suppression in both groups. The presence of co-infections in PLWH is associated with higher VL and with chronic inflammation. Ferritin and CRP decreased on dolutegravir-based ART but remained higher in people with co-infections despite similar rates of virologic suppression.

Outcomes of severely ill patients with AIDS treated with efavirenz or dolutegravir: a multicenter, observational study.

Currently, integrase inhibitors (INIs)-based ART regimens are the preferred initial therapy for AIDS patients. There is scarce information on the use of dolutegravir (DTG) among late-presenter people living with HIV (PLHIV). To compare the effect of DTG- or efavirenz (EFV)-based regimens on the outcomes of patients with advanced AIDS. We compared two cohorts of consecutive symptomatic AIDS patients (WHO stage 4, CD4 count<50 cells/mL) starting therapy with DTG-based (2018-2021, prospective cohort) or EFV-based regimens (2013-2016, retrospective cohort) from five Brazilian cities. The main endpoints were early (all-cause) mortality, viral suppression at 24 and 48 weeks, changes in CD4 count, and changes in initial therapy (for any reason). We included all eligible patients in a consecutive way (in both groups) until we reached 92 individuals per arm. The median baseline CD4 count (20 vs. 21 cells/mL) and the median HIV plasma viral load (5.5 copies/mL log10) were identical across the groups. Viral suppression rates were higher in the DTG group than in the EFV group at 24 (67.4% vs. 42.4%,) and 48 weeks (65.2% vs. 45.7%, p < 0.001 for both comparisons). More patients in the DTG group presented with CD4 > 200 cells/mL compared to the EFV group at 48 weeks (45% vs. 29%, p = 0.03). Treatment changes (ITT, M = F) were significantly more frequent in the EFV group (1% vs. 17%, p < 0.0001). The relative mortality rate was 25% lower in the DTG group, but without statistical significance. We detected a higher rate of virological suppression and greater treatment durability in patients with advanced AIDS treated with DTG than in those treated with EFV.

Revolutionizing HIV-1 Viral Load Monitoring in India: The Potential of Dried Blood Spot Analysis for Expanding Access and Improving Care.

India continues to grapple with a significant burden of HIV infections. Despite notable progress in prevention and treatment efforts, multiple challenges, such as high-risk populations, inadequate testing facilities, and limited access to healthcare in remote areas, persist. Though the Government of India offers HIV-1 plasma viral load testing at various medical centers, aiding treatment decisions and monitoring antiretroviral therapy effectiveness, enhancing care for individuals living with HIV under the National AIDS Control Program (NACP), the nation's large population and diverse demographics further complicate its outreach and response. Hence, strategic interventions and alternative methods of testing remain crucial to curbing HIV transmission and improving the quality of life for those affected. Dried blood spot (DBS) sampling has emerged as a convenient and cost-effective alternative for HIV-1 viral load testing, revolutionizing the landscape of diagnostic and monitoring strategies for HIV infection. Though the plasma-based viral load remains the gold standard for monitoring HIV-1, DBS-based HIV-1 viral load testing holds immense promise for improving access to care, particularly in resource-limited settings where traditional plasma-based methods may be logistically challenging. DBS entails the collection of a small volume of blood onto filter paper, followed by drying and storage. This approach offers numerous advantages, including simplified sample collection, transportation, and storage, reducing the need for cold-chain logistics. Recent studies have demonstrated the feasibility and accuracy of DBS-based HIV-1 viral load testing, revealing a strong correlation between DBS and plasma measurements. Its implementation can enhance the early detection of treatment failure, guide therapeutic decisions, and ultimately contribute to better clinical outcomes for HIV-infected individuals. Hence, this review explores the principles, advancements, feasibility, and implications of DBS-based HIV-1 viral load testing.

Paradoxical and Unmasking HIV Immune Reconstitution Inflammation Syndrome in Antiretroviral-Naïve Pregnant Women: A Prospective Cohort Study.

Following antiretroviral therapy (ART) initiation, HIV-associated immune reconstitution inflammatory syndrome (IRIS), indicated by an array of opportunistic infections, may occur, presenting as either paradoxical, a worsening of a previously treated infection, or unmasking, a flare-up of an underlying, previously undiagnosed infection. The impact of ART as the backbone of HIV treatment and prevention has prolonged the survival of people living with HIV. In pregnancy, benefits have been shown by slowing HIV progression and preventing perinatal transmission; however, there have been risks of adverse reactions with ART, including immune responses to both the fetus and mother. This study sought to estimate the incidence of HIV-IRIS cumulatively and by type either paradoxical or unmasking IRIS, determine the baseline maternal and HIV clinical markers as predictors of, and analyze the log-rank test for survival time to IRIS outcome assessed by relying on an increase in CD4 count and/or a rapid decrease in viral load. An active records study was conducted between June 2019 and March 2020 among ART-naïvepregnant women attending the antenatal care units (ANCu) at the Kenyatta National and MbagathiHospitals, Nairobi, Kenya. Participants were aged between 20 and 49 years and had a confirmed HIV-positive test. To ascertain a true case of IRIS, the diagnosis was adjudicated for accuracy and consistency by an independent review committee. Plasma HIV viral load, CD4 counts, and routine laboratory evaluations (hemoglobin, white blood cell count (WBC)) were performed by each hospital's clinical laboratory. The IRIS incidence was assessed using the International Network for Studies Against HIV-Associated IRIS (INSHI) during the first three months after ART initiation. Multivariate Cox regression with IRIS as the outcome, using the SPSSSurvival package, examined the relationship between baseline maternal characteristics and HIV clinical markers before ART initiation and IRIS, and finally, decision-tree analysis for predicting IRIS was performed. From a pool of 532 ART-naïvepregnant women, 133 (25%) developed IRIS, and 97 (72.9%) were in the unmasking category. The accumulated risk of experiencing IRIS symptoms increased from week two (hazard ratio (HR)=0.0287) to week 12 (HR=3.6158). Participants with a maternal BMI (MBMI) of 25-29.9 kg/m2 at baseline were at a higher risk of unmasking IRIS (HR=2.478; P=0.010). The WHO-HIV clinical stages 1 and 2 skewed towards paradoxical IRIS (regression coefficients =-0.111 and -0.276 (P<0.05)), while stage 4 skewed towards unmasking IRIS (regression coefficient=0.047, HR=1.048, P=0.941). A CD4 count > 500 cells/mm^3 skewed towards unmasking IRIS (regression coefficient=0.192, HR=1.211, P=0.416), while RNA-HIV viral loads >50 copies/ml towards paradoxical IRIS (regression coefficient=-0.199, HR=0.820, P=0.360. On decision tree analysis, 85% (P=0.001) of ART-naïve pregnant women with a baseline CD4 count below 500 copies/mm^3 presented with unmasking IRIS. For ART-naïvepregnant women, unmasking IRIS is the most common type, and an MBMI of 25-29.9 kg/m2, advanced HIV infection, a CD4 count <500 cells/mm^3, and a higher parity at baseline may be clinically useful predictors. The higher proportion of ART-naïvepregnant women experiencing unmasking as compared to paradoxical IRIS supports the need for earlier assessment based on potential predictors.

FERROPTOSIS IN CD4+ AND CD8+ T-CELLS IN THE SETTINGS OF HIV INFECTION

Introduction: Elevation of intracellular iron concentration triggers ferroptosis. Understanding the regulation and pathophysiological mechanisms of this process in HIV infection may contribute to antiretroviral therapy (cART) monitoring. Aim: To perform a correlation analysis of the intracellular labile-bound iron pool (LIP) in CD4+ and CD8+ T cells in association with CD4+, CD8+ T cells absolute count (AC) and CD4/CD8 index in HIV+ individuals on continuous cART with sustained viral suppression. Material and methods: Peripheral blood samples (Li heparin, n=34) were collected in the course of the routine immune monitoring of HIV+ individuals at four time points during 24 months. Plasma HIV viral load (VL) was determined with the Abbott Real-Time HIV-1 test (sensitivity 40 copies/ml). AC and percentage of CD4+ and CD8+ T cells were determined by direct flow cytometry (Multitest, BD Trucount, FACS Canto II). The intracellular content of LIP in CD4 and CD8 T cells (LIP CD4, LIP CD8) was measured at the beginning of the study, using acetoxymethyl ester and subsequent incubation with a chelator (Deferiprone). LIP was quantified according to the mean fluorescence intensity (MFI) (FACSCanto II, Diva 6.1.2). Results: In the settings of a higher LIP CD4 , high LIP CD8 correlated with increased CD8AC (Rho=0.70, p&lt;0.05) up to 11 (min. 6, max. 15) months after LIP measurement., and decreased CD4/CD8 ratio correlated inversely with LIP CD8 in all consecutive measurements (Rho= -0.71, p&lt;0.01 for all), Importantly, high LIP CD8 correlated with a lower CD4AC (Rho=-0.65, p&lt;0.05) up to five (min.1, max.8) months after LIP measurement. Conclusion: The increased concentration of intracellular LIP in CD8 cells in HIV+cART individuals could indicate viral activity in the settings of undetectable HIV VL, directly associated with ongoing cell ferroptosis.

Detection of cytokines in cervicovaginal lavage in HIV-infected women and its association with high-risk human papillomavirus.

Women living with HIV/AIDS (WLHA) have an increased prevalence of high-risk HPV infection (HR-HPV) and cervical intraepithelial neoplasia (CIN) and a greater risk of cervical cancer despite access to a new generation of antiretroviral therapy. The aim of this study is to evaluate the concentrations of different cytokines involved in the local immune response in WLHA, which is fundamental for understanding the pathogenesis of HPV-related cancer in this population. IL-1β, IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, IP-10, GM-CSF, and MIP-1α were investigated in the cervicovaginal lavage (CVL) of 106 WLHA attending at Hospital Universitario Professor Edgard Santos in Salvador, Bahia, Brazil, during the period December 2019 to April 2023 by Luminex®. All participants were also tested for Chlamydia trachomatis and Neisseria gonorrhoeae and underwent colposcopy, Pap smear, and Nugent score. HIV plasma viral load (VL) and CD4 cell count were performed for all WLHA. In this study, 22.6% (24/106) of WLHA were infected with HR-HPV. A higher proportion of patients with HR-HPV (66.7%) had detectable levels of IL-10 than those negative ones (40.2%, p = 0.02). More premenopausal women had either IL-6 (51.4%) or IP-10 (58.3%) than those in menopausal status (26.5% for IL-6 and 32.4% for IP-10, p = 0.013 and p = 0.011, respectively). Vaginosis was negatively associated with detection of IP-10 (24.2% vs. 61.4%, p < 0.001) and INF-γ (39.4% vs. 68.6%, p = 0.005). A positive association was detected for IL-1β (66.7 vs. 37.1%, p = 0.005) and IL-10 (63.6% vs. 37.1%, p = 0.01). VL and CD4 were not associated with the studied cytokines. We demonstrated a positive association between IL-10 and HPV infection in CVL, suggesting the predominance of the Th2 response in HIV/HPV co-infected patients. However, further studies with longer follow-up will be needed to evaluate the association of IL-10 with HPV infection, CIN, and cervical cancer in WLHA.

Honduras HIV cohort: HLA class I and CCR5-Δ32 profiles and their associations with HIV disease outcome.

We identify both canonical and novel human leukocyte antigen (HLA)-HIV associations, providing a first step toward improved understanding of HIV immune control among the understudied Honduras Mestizo population. Our results are relevant to understanding the protective or detrimental effects of HLA subtypes in Latin America because their unique HLA diversity poses challenges for designing vaccines against HIV and interpreting results from such vaccine trials. Likewise, the description of the HLA profile in an understudied population that shows a unique HLA immunogenetic background is not only relevant for HIV immunology but also relevant in population genetics, molecular anthropology, susceptibility to other infections, autoimmune diseases, and allograft transplantation.

Abstract 12041: Coronary Artery Calcium and All-Cause Mortality in the Multicenter Aids Cohort Study: MACS

Introduction: People living with HIV (PLWH) have more subclinical cardiovascular disease than people without HIV (PWOH), but few studies have evaluated risk for mortality based on coronary artery calcium (CAC) among this population. Purpose: This study aimed to determine the association between CAC and all-cause mortality among male PLWH and PWOH and to identify a potential interaction with HIV serostatus. Methods: The study population was derived from the MACS, a US prospective observational cohort study including male PLWH and PWOH. Participants underwent cardiac non-contrast computed tomography from July 2004 to November 2013. Men with atrial fibrillation, coronary heart disease, or coronary revascularization were excluded. Cox proportional hazards model was used to calculate adjusted hazard ratios [aHR] for all-cause mortality among men with vs. without baseline CAC (Agatston score&gt;0) and per standard deviation (SD) increment in continuous Agatston score [log (CAC+1)], controlling for demographic and cardiac risk factors. CAC differences by HIV serostatus were evaluated using multiplicative CACхHIV interaction terms. Results: Among 1344 males (mean age 50 years, CAC prevalence 46%, 823 (61%) PLWH), we observed 110 deaths (13%) among PLWH and 41 deaths (8%) among PWOH during the follow-up period (median: 13.4 years). Among PLWH, 62% had an undetectable plasma HIV viral load, the median CD4 cell nadir was 284 cells/μL, and 17% had a history of clinical AIDS. The age-adjusted mortality rate was 13.5 (95% CI: 11.0-16.5) among PLWH and 7.8 (5.4-10.9) among PWOH per 1000 person-years. CAC presence was associated with all-cause mortality among all participants (aHR=1.47, 95% CI: 1.02-2.11, p=0.04), and among PLWH (aHR=1.61, 1.04-2.47, p=0.03). In PWOH, we found no significant association (aHR=1.27, 0.63-2.59, p=0.50), although the interaction was not significant (p= 0.49). Higher log (CAC+1) was also associated with all-cause mortality among all participants (aHR=1.37 per SD, 1.15-1.63, p&lt;0.001) and among strata (PLWH, aHR=1.40, 1.13-1.73, p=0.002; and PWOH aHR=1.38, 1.00-1.91, p=0.049). Conclusion: CAC predicts all-cause mortality in a large cohort of PLWH and PWOH, with no significant difference in this association by HIV serostatus.

HIV viral load measurement: knowledge, attitudes and practices of health workers, Burkina Faso

Approximately a quarter of people living with HIV (PLHIV) had their plasma viral load (PVL) measured in 2020 in Burkina Faso. The purpose of this study was to assess the knowledge, attitudes, and practices (KAP) of health workers regarding HIV PVL measurement. A cross-sectional study was conducted among health workers involved in the care of PLHIV in the 13 regions of Burkina Faso in 2021. Scores were constructed to assess their KAP on PVL measurement. Factors associated with knowledge and practices were identified by logistic regression. A total of 255 health workers were surveyed. The majority had good knowledge (73%) and favorable attitudes (93%). However, 40% had inadequate practices. Taking into account the availability of a laboratory to carry out PVL tests within the health center, having a coordinating role increased the likelihood of having good knowledge, while not having a medical qualification reduced this likelihood. Good practices were more common among health workers working at the second level of the health pyramid. Interventions to increase the demand for a measurement of PVL are essential to improve the care of PLHIV. For example, future investigations could explore the role of mediators in increasing the demand for PVL among PLHIV and their caregivers.

P16 expression and recurrent cervical intraepithelial neoplasia after cryotherapy among women living with HIV.

The expression of p16 protein, a surrogate marker for high-risk human papillomavirus (hrHPV), is associated with cervical dysplasia. We evaluated correlates of p16 expression at treatment for high-grade cervical lesions and its utility in predicting the recurrence of cervical intraepithelial lesions grade 2 or higher (CIN2+) following cryotherapy among women with HIV. This is a subgroup analysis of women with HIV in Kenya with baseline cervical biopsy-confirmed CIN2+ who were randomized to receive cryotherapy and followed every six-months for two-years for biopsy-confirmed recurrence of CIN2+. P16 immunohistochemistry was performed on the baseline cervical biopsy with a positive result defined as strong abnormal nuclear expression in a continuous block segment of cells (at least 10-20 cells). Among the 200 women with CIN2+ randomized to cryotherapy, 160 (80%) had a baseline cervical biopsy specimen available, of whom 94 (59%) were p16-positive. p16 expression at baseline was associated with presence of any one of 14 hrHPV genotypes [Odds Ratio (OR) = 3.2; 95% Confidence Interval (CI), 1.03-9.78], multiple lifetime sexual partners (OR = 1.6; 95% CI, 1.03-2.54) and detectable plasma HIV viral load (>1,000 copies/mL; OR = 1.43; 95% CI, 1.01-2.03). Longer antiretroviral therapy duration (≥2 years) at baseline had lower odds of p16 expression (OR = 0.46; 95% CI, 0.24-0.87) than <2 years of antiretroviral therapy. Fifty-one women had CIN2+ recurrence over 2-years, of whom 33 (65%) were p16-positive at baseline. p16 was not associated with CIN2+ recurrence (Hazard Ratio = 1.35; 95% CI, 0.76-2.40). In this population of women with HIV and CIN2+, 41% of lesions were p16 negative and baseline p16 expression did not predict recurrence of cervical neoplasia during two-year follow up.

Soluble biomarkers of HIV-1-related systemic immune activation are associated with high plasma levels of growth factors implicated in the pathogenesis of Kaposi sarcoma in adults.

Human Herpesvirus-8 (HHV-8) is the etiologic agent of Kaposi's sarcoma (KS), a multicentric angio-proliferative cancer commonly associated with Human Immunodeficiency Virus (HIV) infection. KS pathogenesis is a multifactorial condition hinged on immune dysfunction yet the mechanisms underlying the risk of developing KS in HHV-8 seropositive adults remains unclear. Here we explored whether soluble markers of HIV-1-related systemic immune activation (SIA) and angiogenesis (VEGF and FGF acidic) are involved in the pathogenesis of KS in adults with HHV8. Blood samples from 99 HIV-1 infected and 60 HIV-1 uninfected adults were collected in Yaoundé, Cameroon. CD3+/CD4+ T cell counts and HIV-1 plasma viral load were determined using the Pima Analyzer and the RT-PCR technique, respectively. Plasma levels of SIA biomarkers (sCD163, sCD25/IL-2Rα, and sCD40/TNFRSF5) and biomarkers of progression to KS (VEGF and FGF acidic) were measured using the Luminex assay. Seropositivity (IgG) for HHV-8 was determined using the ELISA method. Overall, 20.2% (20/99) of HIV-1 infected and 20% (12/60) of HIV-1 uninfected participants were seropositive for HHV8. Levels of sCD163, sCD25/IL-2Rα, sCD40/TNFRSF5, and FGF acidic were higher in the HIV-1 and HHV8 co-infection groups compared to the HIV-1 and HHV8 uninfected groups (all P <0.05). In addition, Higher plasma levels of VEGF correlated with sCD163 (rs = 0.58, P =0.0067) and sCD40/TNFRSF5 (rs = 0.59, P = 0.0064), while FGF acidic levels correlated with sCD40/TNFRSF5 (rs = 0.51, P = 0.022) in co-infected. In HIV-1 mono-infected donors, VEGF and FGF acidic levels correlated with sCD163 (rs =0.25, P = 0.03 and rs = 0.30, P = 0.006 respectively), sCD25/IL-2Rα (rs = 0.5, P <0.0001 and rs = 0.55, P <0.0001 respectively) and sCD40/TNFRSF5 (rs = 0.7, P <0.0001 and rs = 0.59, P <0.0001 respectively) and even in patients that were virally suppressed sCD25/IL-2Rα (rs = 0.39, P = 0.012 and rs = 0.53, P = 0.0004 respectively) and sCD40/TNFRSF5 (rs = 0.81, P <0.0001 and rs = 0.44, P = 0.0045 respectively). Our findings suggest that although the development of KS in PLWH is multifactorial, HIV-associated SIA might be among the key drivers in coinfections with HHV8 and is independent of the patients' viremic status.

Human papillomavirus positivity and cervical lesions in relation to HIV infection: a comparative assessment in the Cameroonian female population.

Cervical lesions, induced by high-risk oncogenic human papillomavirus (HR-HPV), in the context of HIV remains a global health challenge. We determined the effect of HR-HPV on the development of cervical lesions in women with and without HIV infection. A cross-sectional analytical study was conducted among 257 women living in Cameroon. HIV serology, HR-HPV genotyping and cervico-vaginal smear (CVS) were performed for all participants; among those declared HIV positive, plasma HIV viral load and CD4 count were measured. Statistical analyses were performed using Graph Pad version 6.0; P#x003C;0.05 was considered statistically significant. The mean age of the participants in our study was 37±6.5 years. According to HIV serology, 184 (71.59%) were HIV-positive vs. 73 (28.40%) HIV-negative. Among the HIV-positive women, the median CD4 count was 438 [IQR: 317-597] cells/mm3 and the median viremia was #x003C;40 [IQR: #x003C;40-2318] copies/ml. After successful genotyping, the prevalence of HR-HPV was 36.32% (73/201), with a significantly higher proportion in HIV-infected individuals (41.98% (55/131) vs. 25.71% (18/70); P=0.02; OR=2.1). The overall rate of cervical lesions was 23.34% (60/257), with a non-significantly higher proportion in HIV-infected participants (25.00% (46/184) vs. 19.17% (14/73); P=0.31). Relevantly, the presence of HR-HPV was significantly associated with cervical lesions (P#x003C;0.0001; OR=5.07), with a higher odds of cervical lesion in HIV-positive individuals (P#x003C;0.0001 and OR=5.67) compared to HIV-negative individuals (P=0.03 and OR=3.83). Although oncogenic HPV appears to be an independent factor in the development of cervical lesions, this study reveals higher odds of cervical lesions among HIV/HPV co-infection than in HPV infection alone.