Nadir CD4 Cell Count Research Articles

Fatal Bladder Carcinoma in Woman with Human Immunodeficiency Virus: A Case Report

Background: Chronic human immunodeficiency virus (HIV) infection is associated with an increased incidence of Non-Acquired Immunodeficiency Syndrome (non-AIDS) defining cancers. To date, only a limited number of cases of bladder cancer have been linked with HIV infection in women. We sought to describe the clinical characteristics of HIV-associated bladder cancer. Methods: A 54-year-old female patient presented with symptoms of an occlusive syndrome. Medical examination was followed by a CT scan. The imaging revealed a significant finding. There was a noticeable process within the bladder. Further evaluation and management were recommended. Results: Spontaneous urinary cytology revealed the presence of malignant cells. An endoscopy was performed under spinal anesthesia, uncovering a large sessile tumor with necrotic areas located on the ventral aspect and dome of the bladder. Due to the severity of the condition, a palliative resection was carried out. Subsequent histological examination identified the tumor as a high-grade urothelial carcinoma, with evidence of muscle invasion. This diagnosis confirmed the aggressive nature of the disease, highlighting the necessity for further medical management and intervention. Conclusion: Bladder cancers in HIV-infected patients are rare but can occur in relatively young individuals with a low nadir CD4 cell count. These cancers often exhibit aggressive pathological features and can be fatal.

Identifying risk factors for anal cancer in people with HIV in Spain: a multicentre retrospective cohort study nested in the PISCIS cohort

People with HIV have a substantially higher risk of anal cancer than the general population. We aimed to identify risk factors associated with the development of anal cancer among people with HIV to implement more effective and targeted screening strategies. We conducted a multicentre retrospective cohort study in 16 hospitals across Catalonia and the Balearic Islands, Spain, between Jan 1, 1998, and Dec 31, 2022. Treatment-naive people with HIV nested in the PISCIS cohort aged 16 years and older with biopsy-proven squamous cell carcinoma of the anus or anal canal were eligible for inclusion. Data were retrieved from every hospital registry and were centrally validated in the PISCIS cohort and the Public Data Analysis for Health Research and Innovation Program. The primary outcome was the incidence rate (IR) of histologically confirmed anal cancer. We used Poisson regression to examine the association between the following risk factors and incidence of anal cancer: age, mode of HIV transmission, nadir CD4 cell count, and time period of HIV diagnosis. Among 14 238 people with HIV, 107 (0·8%) developed anal cancer, with an overall IR of 72·5 cases per 100 000 person-years (95% CI 59·4-87·6) and median follow-up of 9·5 years (IQR 4·4-15·7). Of these patients with anal cancer, 37 (34·6%) died, of which 24 (64·9%) deaths were related to anal cancer. Incidence was highest among people with HIV with historical nadir CD4 counts of less than 200 cells per μL (IR 105·0 person-years, 95% CI 82·0-132·5) and lowest among those with counts of more than 350 cells per μL (2·9 person-years, 0·1-16·0). Among men who have sex with men (MSM), the IR was 211·5 person-years (95% CI 151·1-211·7) among those with a CD4 count of less than 200 cells per μL, 37·6 person-years (16·2-74·1) among those with a count of 200-350 cells per μL, and 4·8 person-years (0·1-26·9) among those with a count of more than 350 cells per μL. Among people with HIV younger than 30 years, there were no cases of anal cancer among women or men who do not have sex with men, and one case among MSM with a nadir CD4 count of more than 350 cells per μL (IR 4·8 person-years, 95% CI 0·1-26·9). In the multivariable analysis, people with HIV with nadir CD4 counts of more than 350 cells per μL had the lowest risk of developing anal cancer, compared with people with HIV with counts of less than 200 cells per μL (adjusted IR ratio 0·03, 95% CI 0·00-0·25; p=0·0010) or 200-350 cells per μL (0·30, 0·17-0·55; p<0·0001). Compared with people with HIV younger than 30 years, people with HIV aged 60 years and older had an adjusted IR ratio of 27·6 (3·7-206·9; p=0·0010) and people with HIV aged 45-59 years of 21·6 (3·0-156·4; p=0·0020). Compared with individuals diagnosed after 2015, a diagnosis of HIV before 1998 had an adjusted IR ratio of 33·0 (7·9-137·5; p<0·0001). A nadir CD4 count threshold below 350 cells per μL, particularly less than 200 cells per μL, has the potential to identify people with HIV at heightened risk of developing anal cancer. Customised screening strategies that prioritise screening for individuals at high risk with this surrogate marker could maximise available resources. External validation of these data with other cohorts is required before screening recommendations can be updated. Catalan Health Department, Generalitat de Catalunya.

Clinical Predictors and Outcomes of Invasive Anal Cancer for People With HIV in an Inception Cohort.

Due to the heterogeneity of risk for invasive anal cancer (IAC) among people with human immunodeficiency virus (PWH), we investigated predictors of IAC and described outcomes among those with a cancer diagnosis. Using a longitudinal inception cohort of anal cancer screening, we evaluated risk factors and outcome probabilities for incident IAC in Cox models. Screening included anal cytology and digital anorectal examination, and, if results of either were abnormal, high-resolution anoscopy. Between 30 November 2006 and 3 March 2021, a total of 8139 PWH received care at the University of California, San Diego, with 4105 individuals undergoing screening and subsequently followed up over a median of 5.5 years. Anal cancer developed in 33 of them. IAC was more likely to develop in patients with anal high-grade squamous intraepithelial lesions (aHSILs) on initial or subsequent follow-up cytology (hazard ratio, 4.54) and a nadir CD4 cell count ≤200/µL (2.99). The joint effect of aHSILs and nadir CD4 cell count ≤200/µL amplified the hazard of IAC by 9-fold compared with the absence of both. PWH with time-updated cytology aHSIL and CD4 cell counts ≤200/µL had 5- and 10-year probabilities of IAC of 3.40% and 4.27%, respectively. Twelve individuals with cancer died, 7 (21% of the total 33) due to cancer progression, and they had clinical stage IIIA or higher cancer at initial diagnosis. PWH with both aHSIL and a nadir CD4 cell count ≤200/µL have the highest risk of IAC. PWH who died due to IAC progression had clinical stage IIIA cancer or higher at diagnosis, highlighting the importance of early diagnosis through high-resolution anoscopic screening.

Effectiveness of trichloroacetic acid versus electrocautery for the treatment of anal high-grade squamous intraepithelial lesions in persons with HIV

Purpose This study aimed to compare trichloroacetic acid (TCA) versus electrocautery (ECA) for the treatment of anal high-grade squamous intraepithelial lesions (HSIL). Methods This is an observational, single-center study. All subjects with HIV who had anal HSIL treated with TCA or ECA from 2010 to 2022 were included. Effectiveness was evaluated by on-treatment analysis, defining response as the resolution of HSIL and recurrence as a new diagnosis of HSILs during follow-up. A propensity score analysis was used to adjust for confounding factors. Results In total, 227 and 260 HSIL episodes were treated with ECA and TCA, respectively. Response was observed in 61.7% (95% CI: 55.3–68) of cases treated with ECA and in 73.1% (95% CI: 67.8–78.5) with TCA (p = .004). The effectiveness of TCA was higher in large and multifocal HSILs. Side effects were common with both treatments, but no serious events were described. Tolerability was good in 77.1% and 80.7% of patients treated with ECA and TCA, respectively. At 24 months, recurrent HSIL were observed in 36.3% (95% CI: 27.3–45) and 28% (95% CI: 20.2–35.8) in the ECA and TCA groups (p = .049). A nadir CD4 cell count ≤200 cells/µl was found to be a risk factor for recurrence (OR: 1.77; 95% CI: 1.12–2.78). Conclusions In this study, treatment with TCA showed high effectiveness, low recurrence and good tolerability. Considering the benefits of TCA, it could be considered one of the first-line treatments for anal HSIL.

Peripheral Neuropathy in Virologically Suppressed People Living with HIV: Evidence from the PIVOT Trial.

The aim of this study is to identify the factors associated with peripheral neuropathy and to explore neurofilament light chain (NfL) as a biomarker for peripheral neuropathy (PN) in effectively virologically suppressed adults living with HIV. All protease inhibitor monotherapy versus ongoing triple therapy in the long-term management of HIV infection (PIVOT) trial participants with data on PN at baseline were included in the study. NfL plasma levels (pNfL) were measured in a sub-set of participants. Multivariable logistic regression was used to examine the associations of PN with potential risk factors (including age, sex, nadir CD4 cell count, history of dideoxynucleoside (d-drugs) exposure, and blood glucose levels) and NfL levels. Of the 585 participants included, 131 (22.4%) reported PN during the study period (median of 44 months). The participants were predominantly male (76.6%), White (68.2%), and virologically suppressed for a median period of 37 months (range of 20-63) before recruitment. The age at baseline was 44.3 years (standard deviation (SD) of 9.2). PN was independently associated with age (adjusted odds ratio (aOR) = 1.35, 95% CI of 1.20-1.52; additional 5 years), history of d-drugs (aOR 1.88, 95% CI of 1.12-3.16), height (aOR 1.19, 95% CI of 1.05-1.35; additional 5 cm), nadir CD4 cell count (aOR 1.10 CI of 1.00-1.20; 50 cells fewer), and metabolic syndrome (aOR 2.31, 95% CI of 1.27 4.20), but not pNfL. The excess risk for PN associated with d-drug use remains after the exposure has stopped for years, suggesting non-reversible toxicity. In people with HIV, metabolic syndrome is independently associated with PN. There was no additional value for pNfL as a screening test for peripheral neuropathy in effectively virologically suppressed adults living with HIV.

Bictegravir/Tenofovir Alafenamide/Emtricitabine: A Real-Life Experience in People Living with HIV (PLWH).

Bictegravir (BIC), a recently introduced integrase inhibitor, is available in a single tablet regimen with tenofovir alafenamide (TAF) and emtricitabine (FTC) (BIC-STR). This study aimed to describe a real-life experience with BIC-STR. We retrospectively analyzed the data of people living with HIV (PLWH) on antiretroviral therapy (ART) with BIC-STR followed by the Clinic of Infectious Diseases of Perugia (Perugia, Italy) from September 2019 to February 2023. 270 PLWH were enrolled with a median follow-up time on BIC-STR of 2.2 years (IQR 1.2-2.7). In the overall population, in treatment-experienced (N = 242), in treatment-naïve (N = 28), and in population with age > 60 years old (N = 86), we observed that CD4 cell count improved in absolute number, percentage and CD4/CD8 ratio, under BIC-STR. Patients with viremia < 50 cp/mL increased in all groups. In the overall population, previous ART with TAF and nadir CD4 cell count favored immunological recovery. In the ART-experienced group, time in therapy with BIC-STR was associated with HIV-RNA undetectability. In the older group, previous opportunistic infection and advanced age were associated with lower CD4 count. BIC-STR was demonstrated, in real-life, to be a valid option for a switch, such as initial ART.

Newly diagnosed type 1 diabetes mellitus in a human immunodeficiency virus-infected patient with antiretroviral therapy-induced immune reconstitution inflammatory syndrome: a case report

BackgroundDiabetes that develops in human immunodeficiency virus (HIV)-infected patients who receive antiretroviral therapy (ART) is usually type 2 diabetes mellitus (T2DM); however, autoimmune diabetes, such as type 1 diabetes mellitus (T1DM) can also develop in this population. After treatment with ART, patients might experience clinical deterioration following an increase in the CD4 cell count, which is termed immune reconstitution inflammatory syndrome (IRIS). Here, we describe an HIV-infected patient on ART who developed T1DMat due to IRIS, highlighting the clinical complexity in diagnosis and treatment.Case presentationA 36-year-old man infected with HIV had a nadir CD4 cell count of 15.53/μL before medication, which increased to 429.09/μL after 9 months of regular ART. The fasting serum glucose at 9 months was between 96 mg/dL and 117 mg/dL. After 11 months of ART, the patient was admitted to hospital for diabetic ketoacidosis (DKA) and Graves’ disease (GD). Noninsulin antidiabetics (NIADs) were prescribed following the resolution of DKA. However, poor glycemic control was noted despite well-titrated NIADs. Further investigation demonstrated poor pancreatic beta cell function and elevated anti-glutamic acid decarboxylase (anti-GAD) and anti-tyrosine phosphatase-like insulinoma antigen 2 (anti-IA2) titers. According to the results, he was diagnosed with T1DM and received multiple daily injections(MDI) of insulin. The regimen of MDI was insulin degludec as basal insulin and insulin aspart as prandial insulin. After MDI therapy, his glycemic control was improved.ConclusionIn this case, T1DM was ascribed to IRIS. Although this phenomenon has been demonstrated in previous case reports, further study is necessary to realize the mechanism of this association. Therefore, we emphasize that when HIV-infected patients on ART experience an unstable blood glucose level and abnormal thyroid function, physicians should consider T1DM and GD associated with ART-induced IRIS to reduce the subsequent complications and more serious endocrine dysfunction.

Predicting Factors of Plasma HIV RNA Undetectability after Switching to Co-Formulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide in Experienced HIV-1 Patients: A Multicenter Study.

Switching to bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) from other antiretroviral regimens is safe and effective for virologically suppressed people living with HIV (PLWH). The term virological suppression includes both low but detectable HIV viremia and undetectable HIV viremia, and the latter is possibly associated with a lower immune activation state. Herein, we describe a 24-month follow-up of experienced PLWH with plasma HIV RNA undetectable or detectable < 50 copies/ml switching to BIC/FTC/TAF. A previous 12-month monitoring was available, and the factors correlated with treatment efficacy. This retrospective multicenter study included PLWH who switched to BIC/FTC/TAF in the period of 2019-2022, and who were HBsAg and HCV RNA negative. The follow-up study times were 6 (T6), 12 (T12), 18 (T18), and 24 (T24) months after the switch (T0). Survival analysis with multiple-failure-per-subject design, Kaplan-Meier survival estimates, multivariate analysis of variance, multilevel linear regression, and a hierarchical ordered logistic model were applied. A total of 329 PLWH had plasma HIV RNA which was either undetectable or detectable at <50 copies/mL at T0, and 197 responded to all inclusion criteria: M/F 140/57; the median CD4+ cell count was 677 cells/mm3; and HIV RNA at T0 was undetectable in 108 patients. Most of the 197 patients (122, 61.9%) were on a previous INSTI-based regimen. HIV RNA undetectability was more frequent at each follow-up point in patients with HIV RNA that was undetectable at T0, and it showed a higher frequency throughout the follow-up period in patients with always-undetectable HIV RNA in the 12 months before the switch. A higher nadir CD4 cell count had a predictive role, and HBcAb positivity had no influence. In conclusion, the switch could be programmed and possibly delayed on a case-by-case basis in order to achieve persistent plasma HIV RNA undetectability. Undiagnosed loss of HBcAb has no detrimental consequences on the response to BIC/FTC/TAF.

Trend over time of HIV-1 drug resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and their drivers: A cohort study from Antiviral Response Cohort Analysis (ARCA).

The rise of HIV-1 drug resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) threatens the long-term success of NNRTI-based therapies. Our study aims to describe the circulation of major resistance-associated mutations (RAMs) for NNRTIs in people living with HIV (PLWH) in Italy from 2000 to 2020. We included 5982 naïves and 28 505 genotypes from 9387 treatment-experienced PLWH from the Antiviral Response Cohort Analysis (ARCA) cohort. Transmitted drug resistance (TDR) was found in 12.5% and declined from 17.3% in 2000-2003 to 10.9% in 2016-2020 (p = 0.003). Predictors of TDR were viral subtype B [vs. non-B, adjusted odds ratio (aOR) = 1.94, p < 0.001], zenith viral load (VL) (per 1 log10 higher, aOR = 0.86, p = 0.013), nadir CD4 cell count (per 100 cells/μL increase aOR = 0.95, p = 0.013). At least one RAM for NNRTIs among treatment experienced PLWH was detected in 33.2% and pre-treatment drug resistance (PDR) declined from 43.4% in 2000-2003 to 20.9% in 2016-2020 (p < 0.001). Predictors of PDR were sexual transmission route (vs. others, aOR = 0.78, p < 0.001), time since HIV diagnosis (per 1 month longer, aOR = 1.002, p < 0.001), viral subtype B (vs. non B, aOR = 1.37, p < 0.001), VL (per 1 log10 higher, aOR = 1.12, p < 0.001), nadir CD4 count (per 100 cells/μL increase, aOR = 0.91, p < 0.001), previous exposure to any NNRTI (aOR = 2.31, p < 0.001) and a more recent calendar year sequence (any time span > 2008 vs. 2000-2003, any aOR <1, p < 0.001). Circulation of RAMs to NNRTIs declined during the last 20 years in Italy. NNRTIs remain pivotal drugs for the management of HIV-1 due to safety concerns and long-acting options.

Factors associated with the development of coronary artery disease in people with HIV.

People living with HIV (PLHIV) are at increased risk for coronary artery disease (CAD). This study aimed to describe the features associated with CAD in PLHIV. A case ([n =160] PLHIV with CAD) control ([n =317] PLHIV matched by age and sex without CAD) study was performed at the Alfred Hospital, Melbourne, Australia (January 1996 and December 2018). Data collected included CAD risk factors, duration of HIV infection, nadir and at-event CD4+ T-cell counts, CD4:CD8 ratio, HIV viral load, and antiretroviral therapy exposure. Participants were predominantly male (n =465 [97.4%]), with a mean age of 53years. Traditional risk factors associated with CAD in univariate analysis included hypertension (OR 11.4 [95%CI 5.01, 26.33], P <0.001), current cigarette smoking (OR 2.5 [95% CI 1.22, 5.09], P =0.012), and lower high-density lipoprotein cholesterol (OR 0.14 [95%CI 0.05, 0.37], P <0.001). There was no association between duration of HIV infection, nadir or current CD4 cell count. However, current and ever exposure to abacavir (cases: 55 [34.4%]; controls: 79 [24.9%], P =0.023 and cases: 92 [57.5%]; controls: 154 [48.6%], P =0.048, respectively) was associated with CAD. In conditional logistic regression analysis, current abacavir use, current smoking, and hypertension remained significantly associated (aOR=1.87 [CI=1.14, 3.07], aOR=2.31 [1.32, 4.04], and aOR=10.30 [5.25, 20.20] respectively). Traditional cardiovascular risk factors and exposure to abacavir were associated with CAD in PLHIV. This study highlights that aggressive management of cardiovascular risk factors remains critical for reducing risk in PLHIV.

Predicting Risk of Multidrug-Resistant Enterobacterales Infections Among People With HIV.

BackgroundMedically vulnerable individuals are at increased risk of acquiring multidrug-resistant Enterobacterales (MDR-E) infections. People with HIV (PWH) experience a greater burden of comorbidities and may be more susceptible to MDR-E due to HIV-specific factors.MethodsWe performed an observational study of PWH participating in an HIV clinical cohort and engaged in care at a tertiary care center in the Southeastern United States from 2000 to 2018. We evaluated demographic and clinical predictors of MDR-E by estimating prevalence ratios (PRs) and employing machine learning classification algorithms. In addition, we created a predictive model to estimate risk of MDR-E among PWH using a machine learning approach.ResultsAmong 4734 study participants, MDR-E was isolated from 1.6% (95% CI, 1.2%–2.1%). In unadjusted analyses, MDR-E was strongly associated with nadir CD4 cell count ≤200 cells/mm3 (PR, 4.0; 95% CI, 2.3–7.4), history of an AIDS-defining clinical condition (PR, 3.7; 95% CI, 2.3–6.2), and hospital admission in the prior 12 months (PR, 5.0; 95% CI, 3.2–7.9). With all variables included in machine learning algorithms, the most important clinical predictors of MDR-E were hospitalization, history of renal disease, history of an AIDS-defining clinical condition, CD4 cell count nadir ≤200 cells/mm3, and current CD4 cell count 201–500 cells/mm3. Female gender was the most important demographic predictor.ConclusionsPWH are at risk for MDR-E infection due to HIV-specific factors, in addition to established risk factors. Early HIV diagnosis, linkage to care, and antiretroviral therapy to prevent immunosuppression, comorbidities, and coinfections protect against antimicrobial-resistant bacterial infections.

Antimicrobial-resistant Enterobacterales colonization in people with HIV.

People with HIV (PWH) may be at increased risk for MDR Enterobacterales (MDR-E) infection or colonization, relative to individuals without HIV, due to a greater burden of comorbidities as well as HIV-related intestinal inflammation and microbiota alterations. To characterize antibiotic susceptibility of enteric Enterobacterales and risk factors for antimicrobial-resistant bacterial infections in a sample of PWH attending routine clinic visits. Participants provided self-administered rectal swabs and completed questionnaires regarding healthcare, travel and occupational exposures for the prior 12 months. Rectal samples were processed to identify Enterobacterales species, and susceptibility testing was performed. Among 82 participants, 110 Enterobacterales isolates were obtained. Non-susceptibility was common for penicillins, sulphonamides and first-generation cephalosporins. MDR-E was present in 20% of participants. HIV-related characteristics, including current or nadir CD4 cell count, viral suppression, or AIDS-defining clinical conditions, were not associated with MDR-E. MDR-E colonization is common in this population of PWH. Further research evaluating risk factors for MDR-E in PWH may inform infection prevention approaches to better protect at-risk populations from these difficult-to-treat infections.

Shared Decision-Making Concerning Anal Cancer Screening in Persons With Human Immunodeficiency Virus.

Anal high-grade squamous intraepithelial lesion (aHSIL) is the immediate precursor of anal cancer. Anal cytology is a recommended screening test to identify aHSIL among people with human immunodeficiency virus (HIV; PWH). Heterogeneity of risk for invasive anal cancer among PWH suggests the value of a shared decision-making framework regarding screening. Using a longitudinal HIV cohort with a comprehensive anal cancer screening program, we estimated the adjusted probabilities of having aHSIL on the first anal cytology. We used logistic regression models with inverse probability weighting to account for differential screening in the cohort and to construct a predicted probability nomogram for aHSIL. Sensitivity analysis was performed to estimate aHSIL prevalence corrected for misclassification bias. Of 8139 PWH under care between 2007 and 2020, 4105 (49.8%) underwent at least 1 anal cytology test. First-time cytology aHSIL was present in 502 (12.2%) PWH. The adjusted probability of having aHSIL varied from 5% to 18% depending on patient characteristics. Prespecified factors in the aHSIL prediction model included nadir CD4 cell count, ethnicity, race, age, sex, gender identity, and HIV risk factors. The ability of the model to discriminate cytological aHSIL was modest, with an area under the curve of 0.63 (95% confidence interval, .60-.65). PWH are at increased risk for aHSIL and invasive anal cancer. Risk, however, varies by patient characteristics. Individual risk factor profiles predictive of aHSIL can be modeled and operationalized as nomograms to facilitate shared decision-making conversations concerning anal cancer screening.

Incidence of cervical, breast and colorectal cancers between 2010 and 2015 in people living with HIV in France.

We aimed to evaluate the incidence rates between 2010 and 2015 for invasive cervical cancer (ICC), breast cancer (BC), and colorectal cancer (CRC) in people living with HIV (PLWH) in France, and to compare them with those in the French general population. These cancers are targeted by the national cancer-screening program. This is a retrospective study based on the longitudinal data of the French Dat'AIDS cohort. Standardized incidence ratios (SIR) for ICC and BC, and incidence rates for all three cancers were calculated overall and for specific sub-populations according to nadir CD4 cell count, HIV transmission category, HIV diagnosis period, and HCV coinfection. The 2010-2015 CRC incidence rate was 25.0 [95% confidence interval (CI): 18.6-33.4] per 100,000 person-years, in 44,642 PLWH (both men and women). Compared with the general population, the ICC incidence rate was significantly higher in HIV-infected women both overall (SIR = 1.93, 95% CI: 1.18-3.14) and in the following sub-populations: nadir CD4 ≤ 200 cells/mm3 (SIR = 2.62, 95% CI: 1.45-4.74), HIV transmission through intravenous drug use (SIR = 5.14, 95% CI: 1.93-13.70), HCV coinfection (SIR = 3.52, 95% CI: 1.47-8.47) and HIV diagnosis before 2000 (SIR = 2.06, 95% CI: 1.07-3.97). Conversely, the BC incidence rate was significantly lower in the study sample than in the general population (SIR = 0.56, 95% CI: 0.42-0.73). The present study showed no significant linear trend between 2010 and 2015 in the incidence rates of the three cancers explored in the PLWH study sample. Specific recommendations for ICC screening are still required for HIV-infected women and should focus on sub-populations at greatest risk.

Tailoring care for frail and lonely older people with HIV in Canada: a cross-sectional study.

40-60% of people with HIV report experiencing loneliness, and 5-29% of PWH are frail (depending on the definition used). The risk of death in individuals who are frail and lonely, or frail and socially isolated has recently been estimated to be 1·8 times that in individuals who are not frail, lonely, or socially isolated. The aim of the present study was to determine the prevalence of loneliness, and other vulnerabilities related to ageing, in frail older adults with HIV. We assessed frailty with the Clinical Frailty Scale (CFS) in a cross-sectional, convenience sample of people with HIV aged 50 years or older in Southern Alberta, Canada. All Southern Alberta Clinic patients aged 50 years or older who attended a virtual or in-person clinic visit between March and October, 2020, and who underwent frailty screening were included in the present analyses. Individuals scoring 4 or higher on the CFS then completed a structured questionnaire to provide information on additional co-factors, including loneliness (Three-item Loneliness Scale), falls, impaired gait and balance, polypharmacy, unintentional weight loss, food insecurity, and subjective cognitive concerns. Age, sex, nadir CD4 cell count, duration of known HIV infection, ethnicity, and risk category were evaluated for associations with frailty. We used t tests to compare means and Pearson χ2 tests to compare proportions. Patients gave written informed consent for use of data. The use of data was approved by the University of Calgary Conjoint Heath Research Ethics Board. We assessed frailty in 292 older people with HIV. The mean age was 59 years (range 50-86 years) and 45 (16%) were women. On the basis of a score of 4 or greater on the CFS, 40 (14%) participants were identified as frail. Frail individuals tended to be older than those who were not frail (mean age 61·9 years, SD 8·5 versus 58·4 years, SD 6·3; t test difference 3·5, 95% CI 1·3-5·7; p=0·0011). However, there was no association between frailty status and sex, nadir CD4 cell count, duration of known HIV infection, or self-reported ethnicity. Frail individuals were more likely to report injection drug use as a component of their risk for acquisition than were non-frail individuals. Of the frail participants, 15 (42%) reported loneliness, 15 (42%) had fallen in the past year, and 18 (50%) reported impaired gait or balance. One-fifth (8) reported unintentional weight loss and 12 (33%) experienced food insecurity. Nearly 40% (14) reported subjective memory concerns. In this sample of ageing people with HIV, frailty and loneliness were prevalent. Given the increased risk of death when frailty and loneliness are both present, upstream and targeted interventions are urgently needed. These might include measures to address loneliness, risk of falls, weight loss, food insecurity, and memory concerns. Canadian Foundation for Healthcare Improvement, Advancing Frailty Care in the Community.

Single-Dose 13-Valent Conjugate Pneumococcal Vaccine in People Living With HIV - Immunological Response and Protection.

BackgroundPatients living with HIV (PLHIV) are prone to invasive pneumococcal disease. The 13-valent conjugated pneumococcal vaccine (PCV13) is currently recommended for all PLHIV, followed in most guidelines by a 23-valent polysaccharide pneumococcal vaccine. Data are scarce concerning the immunological efficacy of PCV13 among PLHIV.ObjectiveTo assess the immunological response at one month, and the immunological protection at 1-, 6-, and 12 months in PLHIV with a CD4 cell count above 200 cells/µl after a single dose of PCV13, as measured by both ELISA and opsonophagocytic assay (OPA).MethodsPLHIV with CD4 cell count >200 cells/µl were included. Specific IgG serum concentrations for eight serotypes by ELISA and seven serotypes by OPA were measured at baseline, 1-, 6-, and 12 months after the PCV13 vaccination. Global response was defined as a two-fold increase from baseline of specific IgG antibody levels (μg/ml) assayed by ELISA or as a four-fold increase in OPA titer from baseline, for at least five serotypes targeted by PCV13. Global protection was defined as an IgG-concentration ≥1 µg/ml by ELISA or as an opsonization titer ≥LLOQ by OPA for at least five tested serotypes targeted by PCV13. Factors associated with global response and global protection were assessed using logistic regression.ResultsOf the 38 PLHIV included, 57.9% and 63.2% were global responders, 92.1% and 78.9% were globally protected at one month, and 64.7% and 55.9% were still protected at 12 months, by ELISA and OPA respectively. A CD4/CD8 ratio of >0.8 was significantly associated with a better global response by OPA (OR=6.11, p=0.02), and a CD4 nadir <200 was significantly associated with a poorer global response by ELISA (OR=0.22, p=0.04). A CD4 cell count nadir <200 and age over 50 years were associated with poorer global protection by OPA at M1 (OR=0.18, p=0.04) and M12 (OR= 0.15, p=0.02), respectively. Plasma HIV RNA viral load <40 copies/ml was significantly associated with a better global protection at M1 by ELISA and OPA (OR=21.33, p=0.025 and OR=8.40, p=0.04)ConclusionVaccination with PCV13 in these patients induced immunological response and protection at one month. At one year, more than half of patients were still immunologically protected.

Blood-Brain Barrier Impairment in Patients Living with HIV: Predictors and Associated Biomarkers.

Despite the substantial changes resulting from the introduction of combination antiretroviral therapy (cART), the prevalence of HIV-associated neurocognitive disorders (HAND) remains substantial. Blood–brain barrier impairment (BBBi) is a frequent feature in people living with HIV (PLWH) and it may persist despite effective antiretroviral treatment. A cross-sectional study was performed in PLWH who underwent lumbar puncture for clinical reasons or research protocols and several cerebrospinal fluid biomarkers were studied. BBBi was defined as cerebrospinal fluid-to-serum albumin ratio (CSAR) >6.5 (<40 years) or >8 (>40 years). We included 464 participants: 147 cART-naïve and 317 on cART. Male sex was prevalent in both groups (72.1% and 72.2% respectively); median age was 44 (38–52) years in naïve and 49 (43–57) years in treated subjects. BBBi was observed in 35.4% naïve and in 22.7% treated participants; the use of integrase inhibitors was associated with a lower prevalence (18.3 vs. 30.9%, p = 0.050). At multivariate binary logistic regression (including age and sex) nadir CD4 cell count (p = 0.034), presence of central nervous system (CNS) opportunistic infections (p = 0.024) and cerebrospinal fluid (CSF) HIV RNA (p = 0.002) in naïve participants and male sex (p = 0.021), a history of CNS opportunistic infections (p = 0.001) and CSF HIV RNA (p = 0.034) in treated patients were independently associated with BBBi. CSF cells and neopterin were significantly higher in participants with BBBi. BBBi was prevalent in naïve and treated PLWH and it was associated with CSF HIV RNA and neopterin. Systemic control of viral replication seems to be essential for BBB integrity while sex and treatment influence need further studies.

Prevalence and factors associated with HIV-1 multi-drug resistance over the past two decades in the Italian ARCA database

Despite successful antiretroviral therapy (ART), patients infected with human immunodeficiency virus (HIV) can develop multi-class drug resistance (MDR). This retrospective study aimed to explore the prevalence of HIV-1 drug resistance over the past two decades by focusing on HIV-MDR and its predictors. ART-experienced patients with HIV with results from at least one plasma genotypic resistance test (GRT) from 1998 to 2018, from the Antiviral Response Cohort Analysis database, were included in this study. The temporal trend of resistance to any drug class was evaluated by considering all GRTs. Prevalence and predictors of HIV-MDR were analysed by consideration of cumulative GRTs. Among 15 628 isolates from 6802 patients, resistance to at least one drug class decreased sharply from 1998 to 2010 (1998–2001: 78%; 2008–2010: 59%; P<0.001) and then remained relatively constant at approximately 50% from 2011 to 2018, with the proportion of isolates with HIV-MDR also stable (approximately 9%).By evaluating factors associated with cumulative HIV-MDR, the following factors were found to be associated with increased risk of HIV-MDR on multi-variate analysis: male gender; sexual and vertical transmission; number of previous protease inhibitors, nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and non-NRTIs; previous exposure to integrase strand transfer inhibitors, enfuvirtide and maraviroc; and co-infection with hepatitis B virus. In contrast, a nadir CD4 cell count ≥200 cells/mm3, starting first-line ART in 2008 or later and co-infection with hepatitis C virus were associated with lower risk of HIV-MDR. In conclusion, this study revealed that HIV-1 drug resistance has been stable since 2011 despite its dramatic decrease over the past two decades. HIV-MDR is still present, although at a lower rate, suggesting the need for continuous surveillance and accurate management of ART-experienced patients with HIV.

SARS-CoV-2 infection in persons living with HIV: A single center prospective cohort.

Information about severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in HIV‐infected individuals is scarce. In this prospective study, we included HIV (human immunodefeciency virus)‐infected individuals (people living with HIV [PLWHIV]) with confirmed SARS‐CoV‐2 infection and compared them with PLWHIV negative for SARS‐CoV‐2. We compared 55 cases of SARS‐CoV‐2 infection with 69 asymptomatic PLWHIV negative for SARS‐CoV‐2 reverse transcription‐polymerase chain reaction and/or serology. There was no significant difference between SARS‐CoV‐2 positive or negative patients for age distribution, gender, time with HIV infection, nadir CD4‐cell counts, type and number of co‐morbidities, current CD4 and CD8 counts and type of anti‐HIV therapy. Positive patients presented with a median of three symptoms (interquartile range, 1‐3). Most common symptoms were fever (76%), dyspnea (35%), anosmia (29%) non‐productive cough (27%), fatigue 22%), and ageusia (20%). Ten patients (18%) were completely asymptomatic. Four (7.2%) subjects died of coronavirus disease 2019. Factors significantly (P < .05) associated with death included age and number of co‐morbidities, while time from HIV infection and lower current CD4 counts were significant only in univariate analysis. HIV‐infected individuals are not protected from SARS‐CoV‐2 infection or have a lower risk of severe disease. Indeed, those with low CD4 cell counts might have worse outcomes. Infection is asymptomatic in a large proportion of subjects and this is relevant for epidemiological studies.

Comparison of empirical and dynamic models for HIV viral load rebound after treatment interruption.

To compare empirical and mechanistic modeling approaches for describing HIV-1 RNA viral load trajectories after antiretroviral treatment interruption and for identifying factors that predict features of viral rebound process. We apply and compare two modeling approaches in analysis of data from 346 participants in six AIDS Clinical Trial Group studies. From each separate analysis, we identify predictors for viral set points and delay in rebound. Our empirical model postulates a parametric functional form whose parameters represent different features of the viral rebound process, such as rate of rise and viral load set point. The viral dynamics model augments standard HIV dynamics models-a class of mathematical models based on differential equations describing biological mechanisms-by including reactivation of latently infected cells and adaptive immune response. We use Monolix, which makes use of a Stochastic Approximation of the Expectation-Maximization algorithm, to fit non-linear mixed effects models incorporating observations that were below the assay limit of quantification. Among the 346 participants, the median age at treatment interruption was 42. Ninety-three percent of participants were male and sixty-five percent, white non-Hispanic. Both models provided a reasonable fit to the data and can accommodate atypical viral load trajectories. The median set points obtained from two approaches were similar: 4.44 log10 copies/mL from the empirical model and 4.59 log10 copies/mL from the viral dynamics model. Both models revealed that higher nadir CD4 cell counts and ART initiation during acute/recent phase were associated with lower viral set points and identified receiving a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based pre-ATI regimen as a predictor for a delay in rebound. Although based on different sets of assumptions, both models lead to similar conclusions regarding features of viral rebound process.