Change In CD4 Count Research Articles

Effect of interleukin 1b inhibition with canakinumab on inflammation and viral persistence in people with human immunodeficiency virus

Abstract Introduction Effectively treated people with HIV (PWH) have elevated risk of cardiovascular disease (CVD). Inflammatory markers are predictive of CVD and mortality among PWH. The role of the myeloid system in driving inflammation and atherosclerosis has been recently recognized. Canakinumab (a monoclonal antibody to IL-1β) reduces inflammation and CVD events among people with elevated hsCRP after myocardial infarction without HIV. We evaluated the impact of IL-1β inhibition using canakinumab on HIV parameters, inflammation, HIV persistence markers, arterial inflammation, and hematopoietic activity in PWH. Methods PWH on effective ART who had CVD or were at risk for CVD were randomized 2:1 to receive 150 mg of canakinumab subcutaneously or matched placebo at weeks 0 and 12. Arterial inflammation and bone marrow metabolic activity were assessed using F18 FDG PET/CT at baseline and week 18. T cell and monocyte activation were evaluated using multiparameter spectral cytometry. The viral reservoir was quantified using Tat/rev Induced Limiting Dilution Assay (TILDA), HIV DNA and cell-associated RNA. The primary endpoints were change in CD4 and CD8 count. We assessed group effects over time using linear mixed effects models. Results 33 individuals were randomized (median age of 60 years old (IQR 57.5, 64.5) and 94% male); 25 received canakinumab and 8 received placebo. There were no significant differences at baseline. As expected, IL-1β increased among those treated with canakinumab at weeks 4- 24 (p<0.01 for each) and returned to baseline at week 36. There was one death from sepsis in an individual aged 84 with CVD and poorly controlled diabetes who received canakinumab. There were no significant changes in CD4 count, CD8 count, platelet count, creatinine, AST, or ALT by group. Treatment was not associated with a greater reduction in arterial inflammation in the most diseased segment compared to placebo (-6.9%; 95% CI -30.4 to 24.5%; p=0.62). However, bone marrow metabolic activity decreased in the canakinumab group versus placebo (-14.4%, 95% CI -26.5% to -0.2%; p=0.047). Treatment was associated with increased CD163 expression on monocytes at weeks 24 (p=0.03) and 36 (p<0.001), and lower caspase activity at week 36 (p=0.02). There was expansion of anti-inflammatory CD16+ patrolling monocytes that co-express CD163+CX3CR1+ and a decrease in pro-inflammatory CD16+ patrolling monocytes that are Caspase1+CCR2+. Treatment was not associated with differences in hsCRP, IL-6, IL-16, IL-18, MCP-1, sCD14, sCD163, T cell subsets, NK cell subsets, or viral persistence markers. Conclusion Among treated PWH, targeted inhibition of IL-1β using canakinumab results in decreased bone marrow metabolic activity and a shift toward anti-inflammatory monocyte populations. These findings shed light on mechanisms underlying how targeted IL-1β inhibition using canakinumab prevents CVD events by altering monocyte populations and reducing systemic inflammation.

12553 Severe Hyperglycemia After Initiation Of Bictegravir Antiretroviral Therapy With Resolution Upon Discontinuation

Abstract Disclosure: S. Hudson: None. J. Aurora: None. K. Grossman: None. L. Kogelman: None. A.G. Pittas: None. Background: Antiretroviral therapy (ART) containing bictegravir (BIC), a second-generation integrase strand transfer inhibitor (INSTI), is a first-line treatment for HIV. There are mixed reports of INSTIs causing adverse metabolic effects, such as weight gain and hyperglycemia. There are cases of BIC causing hyperglycemia and diabetic ketoacidosis (DKA) within weeks to months following initiation; however, this has not been reported in clinical trials (1). It is unclear whether discontinuing BIC resolves hyperglycemia. We report a case of a patient with prediabetes who developed severe hyperglycemia after switching to a BIC-containing ART. The discontinuation of BIC resulted in significant improvement in glycemia, leading to the de-escalation of diabetes pharmacotherapy. Clinical Case: A 36-year-old woman with obesity was diagnosed with HIV during pregnancy, which was complicated by gestational diabetes mellitus. After pregnancy, she had prediabetes. Her initial ART was darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Due to intolerable GI side effects, six years later, she was switched to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). Laboratory tests four months before starting BIC/FTC/TAF were consistent with prediabetes (HbA1c 6.4%, non-fasting blood glucose of 118 mg/dL). After one month, she was started on metformin when her HbA1c increased to 9.1% with a non-fasting blood glucose of 332 mg/dL. Another month later, HbA1c increased to 12.8% with a non-fasting blood glucose of 685 mg/dL without DKA. She was hospitalized for diabetes management. There were no significant changes in weight, viral load, or CD4 count. A search for secondary causes of hyperglycemia (diabetogenic medications, hypercortisolism, and autoimmune diabetes) was not revealing. She was discharged on metformin and insulin glargine. Her HIV regimen was switched to FTC/TAF and doravirine due to suspicion of BIC-induced hyperglycemia. After five months, she developed symptoms of hypoglycemia, and her estimated HbA1c by continuous glucose monitoring was 6.3%. Insulin glargine was discontinued. While on metformin, HbA1c three months later was 6.3%. Two years later on metformin and linagliptin: HbA1c was 6.1% and beta-cell function did not reveal insulin deficiency or resistance (non-fasting blood glucose 96 mg/dL, insulin 13.5 uIU/mL [RR 2.6-24.9 mIU/mL], C-peptide 3.7 ng/mL [RR 1.1-4.4 ng/mL]). Conclusion: Patients with HIV and a history of obesity and/or dysglycemia who are switched to a BIC-containing ART regimen should be educated and monitored for acute hyperglycemia. This may be due to impaired beta-cell function and/or insulin resistance; however, further research is needed to understand the mechanism. An alternative ART regimen should be considered if hyperglycemia develops. Reference: 1. Nolan NS, et al. Open Forum Infect Dis. 2021;16;8(5): ofab077. Presentation: 6/3/2024

Efficacy and safety of Ibalizumab for the treatment of HIV-1 infected patients: A systematic review

Objectives: Human immunodeficiency virus (HIV) infection is a significant global health concern, due to the emerging complexity in the management of infection. The emergence of novel therapeutic agents, such as ibalizumab, has provided a ray of hope for individuals living with HIV. This systematic review provides a comprehensive analysis of the efficacy and safety of ibalizumab for the treatment of HIV-1-infected patients. Material and Methods: Using online medical literature databases and the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines, four of the 86 articles met the acceptance criteria to be analyzed. Details such as author name, year of publication, demographic characteristics, mode, and dose of drug administration, duration of treatment, comparator if any, baseline CD4 counts, and viral load, change in CD4 count and viral load, and the adverse events were noted in the studies. Results: The total number of patients enrolled in each study ranged from 22 to 82 with a median age ranging from 39 to 53. Except for the open-label dose-ranging cohort study, baseline CD4 counts and post-intervention CD4 counts were assessed in all the studies. The patients who received a higher dose of ibalizumab showed an early significant rise in CD4+T-cell count at week 16 and week 48. Although the viral reduction after ibalizumab injection increases from the dose of 3 mg/kg, it was noted that beyond 10mg/kg the viral load reduction was not increasing proportionately with 25 mg/kg. The adverse effects encountered among the four studies ranged from 45% to 91%. The commonly observed adverse effects were headache, diarrhea, nausea, fatigue, somnolence, and rash. Conclusion: Ibalizumab demonstrates promise as a therapeutic option for individuals with multidrug-resistant HIV-1. Its unique mechanism of action and positive impact on viral load reduction and CD4 cell counts make it a valuable addition to the armamentarium of HIV treatment options.

Evaluation of CD4 Count in HIV Infected Pregnant Women at Kibagabaga Level Two Teaching Hospital

CD4 count measures the degree of immunosuppression in HIV-positive patients and is used to monitor HIV infection progression in human body. HIV is a virus that attacks the body’s immune system and if not treated, can lead to AIDS The rate of CD4 cells destruction is directly proportional to progressive replication of HIV. Pregnant women infected with HIV have high risk of mother to child transmission of HIV infection and are prone to excessive immunosuppression and increased viral load if their CD4 cell count is not properly maintained. Pregnancy may influence CD4 cells count reduction or don’t, that’s why this study focused on evaluation of CD4 count in HIV infected pregnant women. The objectives of this study were to determine the association between pregnancy trimesters and CD4 count among HIV infected pregnant women at KDH. The study was a cross sectional study which included 46 patients who visited kibagabaga level two teaching hospital in 5 months. Data were obtained by collecting venous blood of patients, testing their CD4 count and use of a questionnaire to evaluate the risk factors associated with changes in CD4 count. Data collected were analysed using statistical package for social sciences (SPSS) software version 22.0 and Microsoft word, the presentation of results was done using tables. Variables with p-value less than or equal to 0.05 were considered statistically significant. The study showed that there is an association between pregnancy trimesters and CD4 count among HIV infected pregnant women where 21(45.6%) women were in third trimester and had the highest CD4 count compared to women in the 2nd trimester 14(30.4%) followed by women in 1st trimester 11(24%) with p-value of 0.04 which is statistically significant. In evaluated CD4 count changes, associated risk factors were, antiretroviral treatment intake, diet intake, education level, pregnancy trimester, and closely spaced pregnancies. Which were found to have p-values 0.00, 0.00, 0.04, 0.04 and 0.01 that were statistically significant respectively. Keywords: HIV, CD4 Count, Pregnant women

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.

CD4+ T-cell recovery in HIV/hepatitis C co-infected patients following successful hepatitis C treatment.

Hepatitis C virus (HCV)/HIV co-infection has been identified as a risk for impaired CD4+ T-cell recovery, possibly mediated by HCV-induced liver fibrosis and/or immune activation. As HCV direct-acting antivirals (DAAs) may partially reverse liver fibrosis and immune activation, sustained HCV virological response (SVR) may lead to improved CD4 recovery. We explored the effect of HCV DAA-induced SVR on CD4 recovery among patients living with both HCV and HIV, including those with poor CD4 recovery on antiretroviral therapy (immunological non-responders [INRs]). Subjects aged ≥18 years living with both HIV and HCV who achieved SVR with DAA were included. Pre-DAA CD4 counts were included only after sustained HIV viral suppression and HIV viral suppression was maintained for the duration of the study. Segmented regression of interrupted time series analysis was used to evaluate changes in median CD4 count in the pre-DAA period (-36 months) versus the post-DAA period (+36 months). In total, 156 patients were included. In the full cohort, median CD4 counts increased by 15% (p = 0.002) in the 6-month period following DAA initiation, whereafter CD4 counts decreased by 2.7% per 6-month period (p = 0.004). Among the 13 INRs, there was no immediate effect on median CD4 in the first 6 months after DAA initiation, whereafter there was a sustained CD4 increase (4.1% per 6-month time interval [p = 0.02]). In total, 54% of INRs recorded a post-DAA CD4 count of >350 cells/mm3. Successful DAA therapy induced a modest immediate CD4 immunological reconstitution among this cohort of patients living with both HIV and HCV, although this effect waned with time. By contrast, among INRs, achieving HCV SVR led to slower but sustained CD4 count recovery.

Assessment of the safety of nivolumab in people living with HIV with advanced cancer on antiretroviral therapy: the AIDS Malignancy Consortium 095 Study.

Although immunotherapy has emerged as a therapeutic strategy for many cancers, there are limited studies establishing the safety and efficacy in people living with HIV (PLWH) and cancer. PLWH and solid tumors or Kaposi sarcoma (KS) receiving antiretroviral therapy and a suppressed HIV viral load received nivolumab at 3mg/kg every 2weeks, in two dose deescalation cohorts stratified by CD4 count (stratum 1: CD4 count > 200/µL and stratum 2: CD4 count 100-199/µL). An expansion cohort of 24 participants with a CD4 count > 200/µL was then enrolled. A total of 36 PLWH received nivolumab, including 15 with KS and 21 with a variety of other solid tumors. None of the first 12 participants had dose-limiting toxicity in both CD4 strata, and five patients (14%) overall had grade 3 or higher immune related adverse events. Objective partial response occurred in nine PLWH and cancer (25%), including in six of 15 with KS (40%; 95% CI, 16.3-64.7). The median duration of response was 9.0months overall and 12.5months in KS. Responses were observed regardless of PDL1 expression. There were no significant changes in CD4 count or HIV viral load. Nivolumab has a safety profile in PLWH similar to HIV-negative subjects with cancer, and also efficacy in KS. Plasma HIV remained suppressed and CD4 counts remained stable during treatment and antiretroviral therapy, indicating no adverse impact on immune function. ClinicalTrials.gov Identifier: NCT02408861.

Association of Alcohol Consumption With CD4 Recovery After Antiretroviral Therapy Initiation in St. Petersburg, Russia.

Delayed CD4 recovery after initiating antiretroviral therapy (ART) is a novel potential mechanism by which alcohol consumption leads to increased morbidity and mortality in people with HIV. We hypothesized that alcohol consumption at ART initiation is associated with slower CD4 recovery. We retrospectively analyzed 2 pooled longitudinal alcohol/HIV cohorts (2014-2019) in St. Petersburg, Russia. Eligible participants initiated the first ART during parent studies; had alcohol consumption assessed by the blood biomarker, phosphatidylethanol (PEth), at the last research visit before ART initiation; and had ≥1 CD4 count measurement before and after initiating ART. Participants were stratified by low, moderate, and high PEth (<8, 8-80, and >80 ng/mL, respectively). We used random-effects piecewise linear regression models to estimate CD4 recovery, defined as CD4 count change per 30 days after ART initiation, by the alcohol group. Of 60 eligible participants, median age was 34 years and 28% were female. The median pre-ART PEth in the low, moderate, and high PEth groups were <8, 23, and 232 ng/mL, respectively. After starting ART, the CD4 count increased by 13.60 cells/mm3/mo (95% CI: 0.33 to 26.87) with low PEth, 0.93 cells/mm3/mo (95% CI: -6.18 to 8.04) with moderate PEth, and 2.33 cells/mm3/mo (95% CI: -3.44 to 8.09) with high PEth. Among Russians with HIV, we observed faster CD4 recovery after ART initiation in those with low alcohol consumption compared with those with moderate and high alcohol consumption, as assessed by PEth. This analysis provides further evidence for the possible value of alcohol reduction interventions for people with HIV who are initiating ART.

Evolution of CD4 T-Cell Count With Age in a Cohort of Young People Growing Up With Perinatally Acquired Human Immunodeficiency Virus.

Recent studies have shown a decrease in CD4 count during adolescence in young people with perinatally acquired human immunodeficiency virus (HIV, PHIV). Young people with PHIV in the United Kingdom, followed in the Collaborative HIV Paediatric Study who started antiretroviral therapy (ART) from 2000 onward were included. Changes in CD4 count over time from age 10 to 20 years were analyzed using mixed-effects models, and were compared to published CD4 data for the gerneral population. Potential predictors were examined and included demographics, age at ART start, nadir CD4 z score (age-adjusted) in childhood, and time-updated viral load. Of 1258 young people with PHIV included, 669 (53%) were female, median age at ART initiation was 8.3 years, and the median nadir CD4 z score was -4.0. Mean CD4 count was higher in young people with PHIV who started ART before age 10 years and had a nadir CD4 z score ≥-4; these young people with PHIV had a decline in CD4 count after age 10 that was comparable to that of the general population. Mean CD4 count was lower in young people with PHIV who had started ART before age 10 and had a nadir CD4 z score <-4; for this group, the decline in CD4 count after age 10 was steeper over time. In children, in addition to starting ART at an early age, optimizing ART to maintain a higher CD4 z score during childhood may be important to maximizing immune reconstitution later in life.

Impact of Head and Neck Cancer Treatment on CD4 T Cell Decline and Recovery in People with HIV

The effect of cancer treatment on immunologic decline and recovery in people with HIV (PWH) is not well-described. This study aims to describe the trajectory of treatment-related immunosuppression in PWH treated for HNC predominantly with radiotherapy with or without chemotherapy and/or surgery. We performed a retrospective chart review of 23 PWH diagnosed with nonmetastatic HNC at our institution between 2002 and 2020. Baseline and longitudinal changes in CD4 count from the time of cancer treatment initiation were investigated. Patients were followed for 3 years after treatment completion. Nonparametric Mann-Whitney tests were used to compare median baseline CD4 count, post-treatment nadir CD4 count within 1 year after start of treatment, and peak recovery CD4 count within 3 years. Nonparametric Kruskal-Wallis and Mann-Whitney tests were used to compare median baseline, nadir, and peak recovery CD4 counts stratified by treatment. The majority of patients were male (20 [87%]), were white (13 [57%]), had a smoking history (21 [91%]), and had stage III-IV disease (17 [74%]). The median age was 58 (IQR 55-62). Primary subsites included oropharynx (11 [48%]), larynx (5 [22%]), oral cavity (4 [17%]), hypopharynx (2 [9%]) and nasal sinus (1 [4%]). Treatment comprised of surgery alone (S, n = 2), radiotherapy +/- surgery (RT, n = 6), and chemoradiotherapy +/- surgery (CRT, n = 15), thereby involving radiotherapy in 21 (91%) patients. All patients were on antiretroviral therapy at the time of diagnosis, and baseline HIV load was <200 copies/ml in 20 (87%) patients. Median baseline CD4 count prior to diagnosis was 592 cells/mm3 (IQR 329 to 834). The median nadir CD4 count was 201 cells/mm3 (IQR 104-282) or 34% of baseline (IQR 23-52%) (p<0.0001 compared to baseline), occurring at a median of 3.8 months (IQR 2.5-6.0). The median CD4 counts at 6 months and 1-year post-treatment were 236 cells/mm3 (IQR 135-337) and 274 cells/mm3 (IQR 150-334), respectively, representing 39% (IQR 31-58%) and 50% (IQR 40-63%) of baseline, respectively. The median peak recovery CD4 count was 431 cells/mm3 (IQR 371-561), or 68% of baseline (IQR 59-102%) (p<0.0001 compared to nadir), occurring at a median of 31 months (IQR 22-34). Stratified by treatment, the median nadir CD4 count as a percentage of baseline was 53% (S), 41% (RT), and 34% (CRT) (p = 0.32) and the peak recovery CD4 count as a percentage of baseline was 82% (S), 88% (RT), and 63% (CRT) (p = 0.45). Among PWH with HNC, CD4 count nadirs to a 1/3 of baseline but gradually rebounds to 2/3 of baseline over the subsequent 2-3 years. While this data supports continuing to treat HNC in PWH with standard-of-care management, CD4 count should be monitored closely for several years following HNC radiotherapy.

Clinical Outcomes and Immunotoxicity in People with HIV (PWH) after Definitive Chemoradiation (CRT) for Anal Squamous Cell Carcinoma

Anal cancer disproportionately affects PWH despite antiretroviral therapy. Data on CRT outcomes are limited. Modern IMRT CRT decreases acute toxicity but may exacerbate immune dysregulation from chronic HIV. Although historical CRT has been associated with prolonged CD4 count suppression, little is known about late immunotoxicity in PWH after contemporary CRT. We report clinical outcomes and long term immunotoxicity. Single-center retrospective review of all PWH confirmed on chart review with anal squamous cell carcinoma without prior pelvic irradiation treated with definitive IMRT CRT. Patient and CRT factors including HIV suppression (<200 copies/mL), mean CD4 count (cells/µL), and receipt of capecitabine (C) or 5-fluorouracil (F) +/- mitomycin (M) were summarized with n (%) or median (interquartile range). Progression-free and overall survival (PFS; OS) were estimated per Kaplan-Meier with 95% confidence intervals and compared with log-rank tests. Mean CD4 count and CD4:CD8 were compared by HIV suppression status (Welch's t-test); longitudinal changes in median CD4 count and CD4:CD8 were compared between baseline vs. nadir (within 6 months of CRT start) and 1-year follow-up for patients with complete data (Wilcoxon signed-rank test). A total of 23 PWH were treated between 2010-2022, median age 52, median 16 (13 - 19) years after HIV diagnosis; 4 had unsuppressed HIV; AJCC 8th stage I/II/III/IV 5/5/12/1. Radiation dose was median 54 Gy in 30 fractions over 42 (40 - 44) days. Most had C+M (57%); only 43% had 2×M with either C or F. One had neoadjuvant carboplatin/paclitaxel/pembrolizumab. With 2.9 (1.03 - 3.3) years follow-up, median OS was 6.6 (6.2 - unreached [UR]) years. With 2.2 (0.67 - 2.7) years follow-up, median PFS was UR. OS and PFS were similar regardless of HIV suppression status (both P ≥ 0.09). Overall baseline CD4 count was 458 (226 - 484), and CD4:CD8 was 0.54 (0.2 - 0.7). Nadir CD4 was 100 (59 - 126) and CD4:CD8 was 0.3 (0.2 - 0.4). Baseline and nadir CD4 count and CD4:CD8 were lower if HIV-unsuppressed (each P ≤ 0.04). One year after CRT, CD4 count was 252 (102 - 276), while CD4:CD8 was 0.5 (0.2 - 0.7). For 7 patients with repeated values the change in median from baseline to nadir, 6-, and 12-months post-CRT was -282, -549 (both P = 0.02), -480 (P = 0.9) for CD4 counts, and -0.7, -0.5, -0.4 (each P > 0.5) for CD4:CD8 ratios; none had unsuppressed HIV. Definitive IMRT CRT with guideline-concordant doublet chemotherapy for anal cancer in PWH is effective despite unsuppressed HIV. Treatment leads to prolonged immunological changes that may increase the risk of HIV-related morbidity and mortality. Modifiable treatment-related causes of hematoimmunologic toxicity should be investigated further, and immune surveillance after CRT should be considered to better understand impact on quality of life.

Toward a Prognostic Model for Mortality Risk in Older People Living With HIV: A Prospective Cohort Study From Southwestern China

ObjectiveThe existing prognostic models for mortality risk in people living with HIV (PLWH) may not be applicable for older PLWH because the risk factors were confined to biomarkers and clinical variables. We developed and validated a nomogram for the prognosis of all-cause mortality in older PLWH based on comprehensive predictors. DesignProspective cohort study. Setting and ParticipantsWe included 824 participants aged ≥50 years (mean age, 64.0 ± 7.6 years) from 30 study sites in Sichuan, China, and followed up from Nov 2018 to Mar 2021. MethodsData on demographics, biomarkers, and clinical indicators were extracted from the registry; mental and social factors were assessed by a survey. Elastic net was used to select predictors. A nomogram was developed based on Cox proportional hazards regression model to visualize the relative effect size (points) of the selected predictors. The prognostic index (PI) was calculated by summing points of all predictors to quantify mortality risk. ResultsPredictive performance of PI from the nomogram was good, with area under the curve of 0.76 for the training set, and 0.77 for the validation set. Change in CD4 count, virological failure in antiretroviral therapy, and living with comorbidities were robust predictors. Depressive symptoms were an important predictor in men, those aged ≥65 years, and those with time of diagnosis <1 year; low social capital was an additional predictor in people aged <65. Mortality risk increased approximately 10-fold among participants whose PI was in the fourth quartile compared with those in the first quartile (hazard ratio, 9.5; 95% CI, 2.9–31.5). Conclusion and ImplicationsAlthough biological and clinical factors are crucial predictors, mental and social predictors are essential for specific groups. The developed nomogram is useful for identifying risk factors and groups at risk of mortality in older PLWH.

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.

Nucleoside/nucleotide reverse transcriptase inhibitor sparing regimen with once daily integrase inhibitor plus boosted darunavir is non-inferior to standard of care in virologically-suppressed children and adolescents living with HIV - Week 48 results of the randomised SMILE Penta-17-ANRS 152 clinical trial.

Integrase inhibitor (INSTI) with boosted darunavir (DRV/r), a regimen with a high-resistance barrier, avoiding NRTI toxicities, might be a switching option in children living with HIV (CLWHIV). SMILE is a randomised non-inferiority trial evaluating safety and antiviral efficacy of once-daily INSTI+DRV/r vs. continuing on current standard-of-care (SOC) triple ART (2NRTI+boosted PI/NNRTI) in virologically-suppressed CLWHIV aged 6-18 years. The primary outcome is the proportion with confirmed HIV-RNA ≥50 copies/mL by week 48, estimated by Kaplan-Meier method. Non-inferiority margin was 10%. Registration number for SMILE are: ISRCTN11193709, NCT #: NCT02383108. Between 10th June 2016 and 30th August 2019, 318 participants were enrolled from Africa 53%, Europe 24%, Thailand 15% and Latin America 8%, 158 INSTI+DRV/r [153 Dolutegravir (DTG); 5 Elvitegravir (EVG)], 160 SOC. Median (range) age was 14.7 years (7.6-18.0); CD4 count 782cells/mm3 (227-1647); 61% female. Median follow-up was 64.3 weeks with no loss to follow-up. By 48 weeks, 8 INSTI+DRV/r vs. 12 SOC had confirmed HIV-RNA ≥50 copies/mL; difference (INSTI+DRV/r-SOC)-2.5% (95% CI:-7.6, 2.5%), showing non-inferiority. No major PI or INSTI resistance mutations were observed. There were no differences in safety between arms. By week 48, difference (INSTI+DRV/r-SOC) in mean CD4 count change from baseline was-48.3cells/mm3 (95% CI:-93.4,-3.2; p=0.036). Difference (INSTI+DRV/r-SOC) in mean HDL change from baseline was-4.1mg/dL (95% CI:-6.7,-1.4; p=0.003). Weight and Body Mass Index (BMI) increased more in INSTI+DRV/r than SOC [difference: 1.97kg (95% CI: 1.1, 2.9; p<0.001), 0.66kg/m2 (95% CI: 0.3, 1.0; p<0.001)]. In virologically-suppressed children, switching to INSTI+DRV/r was non-inferior virologically, with similar safety profile, to continuing SOC. Small but significant differences in CD4, HDL-cholesterol, weight and BMI were observed between INSTI+DRV/r vs. SOC although clinical relevance needs further investigation. SMILE data corroborate adult findings and provide evidence for this NRTI-sparing regimen for children and adolescents. Fondazione Penta Onlus, Gilead, Janssen, INSERM/ANRS and UK MRC. ViiV-Healthcare provided Dolutegravir.

Case control study of CD4 cell count and some haematological parameters among hepatitis and non-hepatitis B patients in Oyo State, South-west, Nigeria.

Hepatitis B virus HBV infection is a major cause of chronic liver disease worldwide. CD4 count and haematological parameters (HPs) could be used to monitor the health status of hepatitis B (HB) individuals. This study aimed at assessing levels of CD4 count and some HPs among sufferers of HB patients and controls. Fifty (50) HB patients as cases and 50 age-matched controls were recruited into the study. 5ml of whole blood sample was collected from all eligible participants of which 20µl and 10µl were used for CD4 count and HPs analysis respectively. Pearson correlation analysis was used to assess statistical difference within them using SPSS version 20. There was significant increase between the normal values of the CD4 count of both cases and controls (p<0.05). Significant correlations were found in some HPs such as HCT with WBC; HB and RBC with PLT; RBC, HCT and PLT with WBC. There were no significant differences between the values of the CD4 count and hematological parameters among HB subjects in this study. There is need for future studies to detect changes in CD4 count and other HPs in HB patients to increase options of screening for immunological changes during management.

Predictors of Incomplete Adherence and Immuno-virologic Failure among HIV Infected Patients in Osun State, Nigeria

BACKGROUND: To identify and address modifiable baseline clinical and non- clinical predictors related to negative outcomes, and identify high risk patients who need priority attention in order to prevent future failure of treatment in HIV patients. METHODS: The study was a longitudinal clinical based cohort study of One hundred and forty (140) HIV infected adults who were initially ART naive and commenced ART in June- July 2013 were followed up to June 2014. Three out of the participants were lost to follow up, one participant died and 1 participant was transferred to another treatment centre, while a total of one hundred and thirty-five (135) patients were finally included in the immuno-virologic analysis. Adherence was assessed using both self-report questionnaire and measurement of Mean Cell Volume (MCV) which was obtained using automated haematology analyzer. CD4 counts were analyzed using flow cytometry method and HIV-RNA levels were measured by using the RT-Polymerase Chain Reaction technique. RESULTS: Incomplete adherence was recorded in 28 (20.7%) of the study participants, immunologic failure (decline in CD4 count to or below baseline or CD4 count change &lt; 50 cells/ul at 12 months) was observed in 39 (28.8%) of the participants. Virologic failure rate (viral load &gt; 400 copies/ml) was 27.4% and immuno-virologic failure rate was 31.9%. Using logistic regression model, immunologic failure was associated with male gender (OR=1.29; p=0.008), non-disclosure of status (OR=1.24; p=0.01), baseline anaemia (OR=1.15; p=0.009) and incomplete adherence by self-report (OR=3.28; p=0.001). Virologic failure was associated with no formal education (OR=2.29; p=0.01), non-disclosure of status (OR=1.04; p = &lt; 0.01), non-adherence (OR=2.74; p=0.015), being unemployed (OR=0.57; p=0.04). CONCLUSIONS: The study observed that immunologic recovery and virologic suppression rate within the first year of treatment was significant, although the rate of incomplete adherence obtained still needs improvement. Effort to promote social coping particularly to patients who were unemployed, re-strategizing on improving patient education and counseling especially to patients with no formal education, focusing on campaigns against stigmatization will help in addressing predictors of negative immuno-virologic outcomes. Baseline HIV-RNA level should also be considered in addition to CD4 testing in order to identify virological failure and thus preventing the emergence of drug resistance in HIV/AIDS management.

Factors Affecting Clinical Outcomes Among Patients Infected With HIV and Anal Cancer Treated With Modern Definitive Chemotherapy and Radiation Therapy

PurposeAnal cancer affects a disproportionate percentage of persons infected with human immunodeficiency virus (HIV). We analyzed a cohort of patients with HIV and anal cancer who received modern radiation therapy (RT) and concurrent chemotherapy to assess whether certain factors are associated with poor oncologic outcomes. Patients and MethodsWe performed a retrospective chart review of 75 consecutive patients with HIV infection and anal cancer who received definitive chemotherapy and RT from 2008 to 2018 at a single academic institution. Local recurrence, overall survival, changes in CD4 counts, and toxicities were investigated. ResultsMost patients were male (92%) with large representation from Black patients (77%). The median pretreatment CD4 count was 280 cells/mm3, which was persistently lower at 6 and 12 months’ posttreatment, 87 cells/mm3 and 182 cells/mm3, respectively (P < .001). Most (92%) patients received intensity modulated RT; median dose was 54 Gy (Range, 46.8-59.4 Gy). At a median follow-up 5.4 years (Range, 4.37-6.21 years), 20 (27%) patients had disease recurrence and 10 (13%) had isolated local failures. Nine patients died due to progressive disease. In multivariable analysis, clinically node negative involvement was significantly associated with better overall survival (hazard ratio, 0.39; 95% confidence interval, 0.16-1.00, P = .049). Acute grade 2 and 3 skin toxicities were common, at 83% and 19%, respectively. Acute grade 2 and 3 gastrointestinal toxicities were 9% and 3%, respectively. Acute grade 3 hematologic toxicity was 20%, and one grade 5 toxicity was reported. Several late grade 3 toxicities persisted: gastrointestinal (24%), skin (17%), and hematologic (6%). Two late grade 5 toxicities were noted. ConclusionsMost patients with HIV and anal cancer did not experience local recurrence; however, acute and late toxicities were common. CD4 counts at 6 and 12 months’ posttreatment remained lower than pretreatment CD4 counts. Further attention to treatment of the HIV-infected population is needed.

Safety and efficacy of pharmacotherapy containing INSTIs and chemotherapy drugs in people living with HIV and concomitant colorectal cancer

BackgroundPrevious clinical data have shown that raltegravir-based antiretroviral therapy (ART) with fewer drug-drug interactions (DDIs) and adverse events (AEs) is a good regimen in patients with HIV infection who need cancer chemotherapy. There are currently few data on ART regimens that include Integrase inhibitors (INSTIs) other than RAL among this patient subgroup.MethodsWe evaluated the safety and efficacy of different kinds of INSTI-based regimens among patients with HIV and concomitant colorectal cancer (CRC) who received antineoplastic agents.ResultsFrom January 2020 to November 2021, 66 patients were enrolled. The patients were divided into three groups: 20 patients treated with dolutegravir (DTG)/lamivudine (3TC)/tenofovir (TDF) (group I), 24 patients treated with DTG/albuvirtide (ABT) (group II), and 22 patients treated with bictegravir (BIC)/tenofovir alafenamide (TAF)/emtricitabine (FTC) (group III). The majority of AEs during treatment were of grade 1–2. Treatment‐related AEs of grade 3–4 occurred in 6 patients (9.09%), and no grade 5 AEs occurred. The most common AEs were nausea (100%) and neutrophils (84.85%) attributed to anticancer agents, and there was no significant difference in the incidence of these AEs among the three groups (P > 0.05). Viral load rebound was not observed among pretreated patients during chemotherapy. The viral load of untreated patients who started their ART concomitant with chemotherapy almost decreased to the lower limit of detection 6 months after ART initiation (only one patient in group III had a viral load of 102 copies/ml). At the 6th month, the CD4 count in group I decreased significantly from baseline (P < 0.05). However, the change in CD4 count was not significant in group II (P = 0.457) or group III (P = 0.748).ConclusionsDTG- or BIC-containing regimens are good options for patients with HIV and concomitant CRC.

Third-line antiretroviral therapy, including raltegravir (RAL), darunavir (DRV/r) and/or etravirine (ETR), is well tolerated and achieves durable virologic suppression over 144 weeks in resource-limited settings: ACTG A5288 strategy trial.

IntroductionACTG A5288 was a strategy trial conducted in diverse populations from multiple continents of people living with HIV (PLWH) failing second‐line protease inhibitor (PI)‐based antiretroviral therapy (ART) from 10 low‐ and middle‐income countries (LMICs). Participants resistant to lopinavir (LPV) and/or multiple nucleotide reverse transcriptase inhibitors started on third‐line regimens that included raltegravir (RAL), darunavir/ritonavir (DRV/r) and/or etravirine (ETR) according to their resistance profiles. At 48 weeks, 87% of these participants achieved HIV‐1 RNA ≤200 copies/ml. We report here long‐term outcomes over 144 weeks.MethodsStudy participants were enrolled from 2013 to 2015, prior to the availability of dolutegravir in LMICs. “Extended Follow‐up” of the study started after the last participant enrolled had reached 48 weeks and included participants still on antiretroviral (ARV) regimens containing RAL, DRV/r and/or ETR at that time. RAL, DRV/r and ETR were provided for an additional 96 weeks (giving total follow‐up of ≥144 weeks), with HIV‐1 RNA measured at 48 and 96 weeks and CD4 count at 96 weeks after entry into Extended Follow‐up. Proportion of participants with HIV‐1 RNA ≤200 copies/ml was estimated every 24 weeks, using imputation if necessary to handle the different measurement schedule in Extended Follow‐up; mean CD4 count changes were estimated using loess regression.Results and DiscussionOf 257 participants (38% females), at study entry, median CD4 count was 179 cells/mm3, and HIV‐1 RNA was 4.6 log10 copies/ml. Median follow‐up was 168 weeks (IQR: 156–204); 15 (6%) participants were lost to follow‐up and 9 (4%) died. 27/246 (11%), 26/246 (11%) and 13/92 (14%) of participants who started RAL, DRV/r and ETR, respectively, discontinued these drugs; only three due to adverse events. 87%, 86%, 83% and 80% of the participants had HIV‐1 RNA ≤200 copies/ml at weeks 48, 96, 144 and 168 (95% CI at week 168: 74–85%), respectively. Mean increase from study entry in CD4 count at week 168 was 265 cells/mm3 (95% CI 247–283).ConclusionsThird‐line regimens comprising of RAL, DRV/r and/or ETR were very well tolerated and had high rates of durable virologic suppression among PLWH in LMICs who were failing on second‐line PI‐based ART prior to the availability of dolutegravir.

Weibull Distribution as the Choice Model for State-Specific Failure Rates in HIV/AIDS Progression

This study considered the problem of selecting the best single model for modeling state-specific failure rates in HIV/AIDS progression for patients on antiretroviral therapy with age and gender as risk factors using exponential, twoparameter, and three-parameter Weibull distributions. CD4 count changes in any two consecutive visits, the mean waiting time (μ), and transitional rates (λ) for remaining in the same state or transiting to a better or a worse state were analyzed. Various model selection criteria, namely, Akaike Information Criteria (AIC), Bayesian Information Criteria (BIC), and Log-Likelihood (LL), were used in each specific disease state. The Maximum Likelihood Estimation (MLE) method was applied to obtain the parameters of the distributions used. Plots of State-specific transition rates (λ) depicted constant, increasing, decreasing, and unimodal trends. Three-parameter Weibull distribution was the best for male patients and patients aged (40-69) years transiting in the states 1-2, 3-4, and 4-5, and 1-2, 3-4, and 5-6, respectively, and for male, female patients, and patients aged (40-69), remaining in the same state. Two-parameter Weibull distribution was the best for female patients and patients aged (20-39) years transiting in the states 1-2, 2-3, 4-5, and 1-2, 2-3, 3-4, respectively. Exponential distribution proved inferior to the other two distributions used.