Th1 cytokine gene polymorphism and the corresponding plasma cytokine levels: A comparative study in HIV-1 positive and exposed uninfected infants.

The pro-inflammatory (Th1) cytokines namely interleukin (IL)-2, IL-6, IL-12, interferon (IFN)-γ, tumor necrosis factor-α (TNF-α) are vital in the clearance of HIV infection. This prospective cohort study aimed to evaluate the polymorphisms of Th1 cytokine genes and their corresponding plasma cytokine levels in HIV-1 positive and exposed uninfected (EU) infants born to HIV-1 positive mothers. CD4 count, viral load of HIV-1 positive mothers was done using commercially available reagents. Cytokine genotyping analysis and levels were done in 20 HIV-1 positive and 54 EU infants. The polymorphisms of Th1 cytokines were done using the PCR-SSP method. Plasma cytokine levels were estimated using Bio-Plex-Pro cytokine assay (BIO-RAD; USA). Results revealed treatment status of the mothers and viral load were the two confounding factors having a significant effect on HIV status of the infant. TNF-α GG genotype is significantly higher in EU infants as compared with HIV-1 positive infants. GG genotype was associated with high TNF- α levels in HIV-1 positive infants but the difference was not statistically significant. HIV-1 positive infants with -IFN-γ (+874) TT genotype was significantly associated with high IFN-γ levels. To the best of our knowledge, this is the first study reporting the role of Th1 cytokine gene polymorphisms and their corresponding plasma cytokine levels in HIV-1 positive and EU infants from India.

Are HIV-1-Specific Antibody Levels Potentially Useful Laboratory Markers to Estimate HIV Reservoir Size? A Review.

Despite the benefits achieved by the widespread availability of modern antiretroviral therapy (ART), HIV RNA integration into the host cell genome is responsible for the creation of latent HIV reservoirs, and represents a significant impediment to completely eliminating HIV infection in a patient via modern ART alone. Several methods to measure HIV reservoir size exist; however, simpler, cheaper, and faster tools are required in the quest for total HIV cure. Over the past few years, measurement of HIV-specific antibodies has evolved into a promising option for measuring HIV reservoir size, as they can be measured via simple, well-known techniques such as the western blot and enzyme-linked immunosorbent assay (ELISA). In this article, we re-visit the dynamic evolution of HIV-1-specific antibodies and the factors that may influence their levels in the circulation of HIV-positive individuals. Then, we describe the currently-known relationship between HIV-1-specific antibodies and HIV reservoir size based on study of data from contemporary literature published during the past 5 years. We conclude by highlighting current trends, and discussing the individual HIV-specific antibody that is likely to be the most reliable antibody for potential future utilization for quantification of HIV reservoir size.

Reliable Estimation of CD8 T Cell Inhibition of In Vitro HIV-1 Replication.

The HIV-1 viral inhibition assay (VIA) measures CD8 T cell-mediated inhibition of HIV replication in CD4 T cells and is increasingly used for clinical testing of HIV vaccines and immunotherapies. The VIA has multiple sources of variability arising from in vitro HIV infection and co-culture of two T cell populations. Here, we describe multiple modifications to a 7-day VIA protocol, the most impactful being the introduction of independent replicate cultures for both HIV infected-CD4 (HIV-CD4) and HIV-CD4:CD8 T cell cultures. Virus inhibition was quantified using a ratio of weighted averages of p24+ cells in replicate cultures and the corresponding 95% confidence interval. An Excel template is provided to facilitate calculations. Virus inhibition was higher in people living with HIV suppressed on antiretroviral therapy (n=14, mean: 40.0%, median: 43.8%, range: 8.2 to 73.3%; p < 0.0001, two-tailed, exact Mann-Whitney test) compared to HIV-seronegative donors (n = 21, mean: -13.7%, median: -14.4%, range: -49.9 to 20.9%) and was stable over time (n = 6, mean %COV 9.4%, range 0.9 to 17.3%). Cross-sectional data were used to define 8% inhibition as the threshold to confidently detect specific CD8 T cell activity and determine the minimum number of culture replicates and p24+ cells needed to have 90% statistical power to detect this threshold. Last, we note that, in HIV seronegative donors, the addition of CD8 T cells to HIV infected CD4 T cells consistently increased HIV replication, though the level of increase varied markedly between donors. This co-culture effect may contribute to the weak correlations observed between CD8 T cell VIA and other measures of HIV-specific CD8 T cell function.

Serum electrolytes and renal alterations in HIV-seropositive Mexican subjects.

ABSTRACT: To examine potential risk factors associated with biochemical alterations in renal function in a population diagnosed with HIV/AIDS undergoing antiretroviral treatment.This is an observational, transversal, and relational design study that included 179 HIV-seropositive subjects. Glucose serum, cholesterol, triglycerides, total proteins, albumin, creatine, urea, blood urea nitrogen (BUN), and electrolytes levels were determined for each individual. Renal function was evaluated through the glomerular filtration rate (GFR), using the CKD-EPI equation. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate  < 60 mL/min/1.73 m2. Univariate model significant variables, with a 95% confidence interval (CI), were included in a multivariate logistic regression analysis.CKD prevalence in patients was 7.3%, with comorbidities of 7.8% for type 2 diabetes mellitus, 7.3% for arterial hypertension, and 35.2% for dyslipidemia. Additionally, both hypernatremia and hypophosphatemia were detected in 57% (n = 102) of the patients. Multivariate logistic regression suggested that CD4+ T cell count < 200 (P = .02; OR 0.2; CI 95% 0.08-0.8) was associated to hyponatremia; similarly, detectable viral load was associated to hypokalemia (P = .02; OR 5.1; CI 95% 1.2-21.3), hypocalcemia (P = .01; OR 4.1; CI 95% 1.3-12.3), and hypermagnesemia (OR 3.9; CI 95% 1.1-13.6). Patient age was associated to both hypophosphatemia (P = .01; OR 2.4; CI 95% 1.1-5.0) and hypermagnesemia (P = .01; OR 2.8; IC 95% 1.1-7.0), and high creatinine levels were associated to nucleoside reverse transcriptase inhibitor treatment (P = .001; OR 42.5; CI 95% 2.2-806.9). Lastly, high BUN levels were associated to age (P = .03; OR 3.8; CI 95% 1.0-14.4), while GFR 60 to 89 mL/min/1.73 m2 was associated to dyslipidemia (P = .02; OR 2.2; CI 95% 1.1-4.5).CD4+ T cell and viral load were the main factors associated with renal biochemical alterations.

Estimating HIV incidence in the Akwa Ibom AIDS indicator survey (AKAIS), Nigeria using the limiting antigen avidity recency assay.

INTRODUCTION: HIV incidence estimates are important to characterize the status of an epidemic, identify locations and populations at high risk and to guide and evaluate HIV prevention interventions. We used the limiting antigen avidity assay (LAg) as part of a recent infection testing algorithm to estimate HIV incidence in the Akwa Ibom AIDS Indicator Survey (AKAIS), Nigeria. METHODS: In 2017, AKAIS, a cross-sectional population-based study was conducted at the household (HH) level in 31 local government areas (LGAs) of Akwa Ibom state. Of the 8963 participants aged ≥15 years who were administered questionnaires for demographic and behavioural data, 8306 consented to HIV rapid testing. Whole-blood specimens were collected from 394 preliminary HIV-seropositive individuals for CD4+ cell count determination and plasma storage. Samples were shipped to a central quality laboratory for HIV confirmatory testing and viral load determination. A total of 370 HIV-positive specimens were tested for the recent HIV infection using the LAg assay. RESULTS: Of the 8306 consenting adults, the HIV prevalence was 4.8%. Of the 370 HIV-positive samples tested for HIV recency, the median age was 35 years, 48.8% had CD4+ cell count >500/mm3 and 81.3% was not virally suppressed. Viral suppression was greater among females (21%) than for males (13%). A total of 11 specimens were classified as recent based on the LAg assay and HIV viral load ≥1000 copies/mL. The weighted, adjusted HIV-1 incidence was 0.41/100 person-years (95% CI 0.16 to 0.66); translating to 13,000 new cases of HIV infections annually in Akwa Ibom, a state with a population of 5.5 million. The HIV incidence rate was similar in females and males (0.41% and 0.42% respectively). The incidence rate was the highest among participants aged 15 to 49 years (0.44%, 95% CI 0.15 to 0.74) translating to 11,000 new infections annually, about 85% of all new infections in the state. CONCLUSIONS: The finding of the high HIV incidence among the 15 to 49-year age group calls for renewed and innovative efforts to prevent HIV infection among young adults in Akwa Ibom state.

Brief Report: Herpes Simplex Virus Type-2 Shedding and Genital Ulcers During Early HIV in Zimbabwean Women.

BACKGROUND: Herpes simplex virus type-2 (HSV-2) seropositive persons have a 3- to 5-fold higher risk of acquiring HIV, possibly because of HSV-2-induced inflammation and recruitment of susceptible immune cells to exposure sites. We hypothesized that cervical HSV-2 activation (ie, viral DNA shedding and/or ulcers) preceded HIV acquisition in the hormonal contraception and HIV cohort. METHODS: Zimbabwean women who acquired HIV were matched to HIV-negative women on visit, age, and bacterial sexually transmitted infections. Up to 5 cervical swabs bracketing first polymerase chain reaction detection of HIV DNA (the index visit) were selected (t-6months, t-3months, tindex, t+3months, t+6months). Women with HSV-2 immunoglobulin G+ before tindex were polymerase chain reaction tested for viral shedding. Self-reported and clinician-diagnosed ulcers were documented. Multivariable logistic regression, accounting for matching, estimated adjusted odds ratios (aOR) and 95% confidence intervals (CIs) at each visit. RESULTS: Of 387 HSV-2 seropositive women, most had prevalent as compared with incident HSV-2 (91% vs. 9%, respectively). HSV-2 viral shedding was more common among HIV seroconverters than HIV-negative women (26% vs. 14%, P < 0.01). Shedding occurred around HIV acquisition (t-3months aOR, 2.7; 95% CI, 0.8 to 8.8; tindex aOR, 2.6; 95% CI, 1.1 to 6.5; t+3months aOR, 2.6; 95% CI, 1.0 to 6.6). Genital ulcers were reported more often among HIV seroconverters than HIV-negative women (13% vs. 7%; P = 0.06) and detection was after HIV acquisition (t+6months aOR, 14.5; 95% CI, 1.6 to 133.9). CONCLUSIONS: HSV-2 shedding appeared synergistic with HIV acquisition followed by presentation of ulcers. Evaluating all sexually transmitted infections rather than HSV-2 alone may clarify the relationship between inflammation and HIV acquisition.

Seroprevalence of human herpesvirus 8 in Ireland among blood donors, men who have sex with men, and heterosexual genitourinary medicine and infectious diseases clinic attendees.

Human herpesvirus 8 (HHV-8) seroprevalence varies geographically and between subpopulations. High seroprevalence rates have been ascribed to men who have sex with men (MSM), African migrants, and HIV-infected individuals. The objective of this study was to determine the seroprevalence of HHV-8 in an Irish population, including specific risk groups. A cross-sectional study of 200 blood donors and 200 genitourinary medicine (GUM) and infectious diseases (ID) clinic patients was performed, with testing for Immunoglobulin G (IgG) antibodies to HHV-8 lytic antigens using a commercial indirect fluorescence assay (Scimedx Corp.). Verification was performed at the Centers for Disease Control and Prevention (CDC). All 200 blood donor samples were negative for HHV-8 IgG antibodies. 21% of GUM and ID patients were positive for HHV-8 IgG antibodies. One hundred of these patients were MSM, 35% of whom were HHV-8 seropositive (46% of HIV-positive MSM and 24% of HIV-negative MSM). Of 100 heterosexual patients, only 7% were HHV-8 seropositive. The absence of seropositivity in 200 Irish blood donors may suggest that Ireland has a low overall population HHV-8 seroprevalence. The proportion of HHV-8 seropositivity in the MSM population was significantly higher than in the heterosexual population and most marked in HIV-positive MSM.

Oral plasmablastic lymphoma: A case report.

INTRODUCTION: Plasmablastic lymphoma (PBL) is an uncommon and aggressive large B-cell lymphoma commonly diagnosed in human immunodeficiency viruses -positive patients. Oral cavity is the most commonly PBL affected site. Most oral PBLs presented as asymptomatic swellings, frequently associated with ulcerations and bleeding. Most cases lacked B-symptoms, suggesting a more local involvement of the disease. No standard treatment is yet for oral PBL. Five-year survival rate recorded no more than 33.5%. PATIENT CONCERNS: A 39-year-old male presented to Dental Clinic with 1 month swelling of the oral cavity, in absence of any other symptoms or signs. He followed antibiotic therapy just on suspicion of an oral abscess and later oral surgical treatment on suspicion of bone neoplasm. DIAGNOSIS: Surgical specimen analysis highlighted a diffuse infiltrate of large-sized atypical cells with plasmablastic appearance and plasma cell phenotype. Oral cavity PBL was diagnosed. Blood tests recorded mild lymphopenia and positive human immunodeficiency viruses serology. INTERVENTIONS: Patient underwent chemotherapy including intrathecal methotrexate prophylaxis, in addition to a highly active antiretroviral therapy. OUTCOMES: At 12 months from diagnosis, patient recorded complete hematological remission. CONCLUSIONS: Oral PBL diagnosis requires a high level of suspicion and awareness both by physicians and pathologists. They should be aware of the extent of such disease which is often mistaken as oral abscess or infected tooth, thus leading to delay the most appropriate diagnostic evaluation. As PBL is an aggressive non-Hodgkin lymphoma, a delayed diagnosis might negatively impact on both treatment and survival.

Frequent expression of activation-induced cytidine deaminase in diffuse large B-cell lymphoma tissues from persons living with HIV.

OBJECTIVE: The increased risk for persons living with HIV to develop diffuse large B-cell lymphoma (DLBCL) even in the post-antiretroviral therapy eras suggests a role beyond immunosuppression in lymphoma development. However, the mechanisms leading to lymphoma in the HIV setting are not fully understood. HIV is known to induce activation-induced cytidine deaminase (AID) levels in nonneoplastic B cells in vitro and chronic AID expression may play an important role in lymphomagenesis. Although AID expression is observed in B-cell lymphoma, studies in HIV-associated DLBCL are limited. DESIGN: In this study, we conducted a retrospective review of DLBCL tissues from patients with and without HIV infection to compare expression of AID and B-cell receptors potentially involved in HIV and B-cell interaction. METHODS: We evaluated DLBCL formalin-fixed paraffin-embedded tissues from 72 HIV-seropositive and 58 HIV-seronegative patients for AID, DC-SIGN, and CD40 protein expression. BCL2 and MYC, two well established prognostically significant oncoproteins in DLBCL, were also assessed at the protein and mRNA levels. Subset analysis was performed according to DLBCL subtype and EBV status. RESULTS: Of note, AID expression was more frequent in HIV-associated DLBCL compared with non-HIV-associated DLBCL regardless of cell-of-origin subtype, and also displayed significantly less BCL2 expression. Despite no direct correlation with AID expression, the HIV-DLBCL tissues also exhibited high levels of the DC-SIGN receptor. CONCLUSION: Collectively, these findings support a potential role for AID in the pathogenesis of HIV-associated lymphomas and suggest the need of further investigations into the involvement of the DC-SIGN receptor-signaling pathway.

Performance evaluation of the MedMira reveal G4 LAB S/P and POC HIV antibody rapid screening tests using plasma and whole blood specimens.

BACKGROUND: The Reveal G4 antibody rapid test is FDA-approved for HIV-1 detection using the versions LAB S/P and POC in CLIA-moderate complexity settings with serum/plasma and whole blood, respectively. The same Reveal tests are CE-marked for HIV-1 and HIV-2 detection in laboratory and point-of-care (POC) settings. OBJECTIVE: We compared the performance of G4 LAB S/P with plasma and POC with whole blood (blood) for detecting early and established HIV-1/HIV-2 infections. STUDY DESIGN: Matched well-characterized plasma and simulated blood were used to evaluate: sensitivity in 104 HIV-1 and 55 HIV-2 established infections, specificity in 49 HIV-negative, and reactivity in early HIV-1 infection in a performance panel (n=38) and 18 plasma panels from seroconverters (SCs, n=183). Median number of days after first RNA-positive was calculated for 13 SCs. Impact of viral suppression (VS) was evaluated in 3 SCs receiving early antiretroviral therapy (ART). RESULTS: Sensitivity was 100 % for HIV-1 and 98.18 % for HIV-2, while specificity was 100 %. All 38 plasma and blood become reactive by Fiebig stage V. Of 18 SCs, 10 had similar reactivity in plasma/blood, 7 showed delayed reactivity in blood, and 1 was nonreactive in plasma/blood. The median days for a G4-reactive after first RNApositive was 13 for plasma and 14 for blood. Long-term VS had no impact on G4 reactivity. CONCLUSIONS: Overall reactivity in early HIV-1 infections is delayed by one day in blood compared to plasma. If FDA-approved for POC settings, the G4 POC is a fast sensitive screening tool for HIV-1/HIV-2-specific IgG even during VS.

Delineation of Homeostatic Immune Signatures Defining Viremic Non-progression in HIV-1 Infection.

Viremic non-progressors (VNPs), a distinct group of HIV-1-infected individuals, exhibit no signs of disease progression and maintain persistently elevated CD4+ T cell counts for several years despite high viral replication. Comprehensive characterization of homeostatic cellular immune signatures in VNPs can provide unique insights into mechanisms responsible for coping with viral pathogenesis as well as identifying strategies for immune restoration under clinically relevant settings such as antiretroviral therapy (ART) failure. We report a novel homeostatic signature in VNPs, the preservation of the central memory CD4+ T cell (CD4+ T CM ) compartment. In addition, CD4+ TCM preservation was supported by ongoing interleukin-7 (IL-7)-mediated thymic repopulation of naive CD4+ T cells leading to intact CD4+ T cell homeostasis in VNPs. Regulatory T cell (Treg) expansion was found to be a function of preserved CD4+ T cell count and CD4+ T cell activation independent of disease status. However, in light of continual depletion of CD4+ T cell count in progressors but not in VNPs, Tregs appear to be involved in lack of disease progression despite high viremia. In addition to these homeostatic mechanisms resisting CD4+ T cell depletion in VNPs, a relative diminution of terminally differentiated effector subset was observed exclusively in these individuals that might ameliorate consequences of high viral replication. VNPs also shared signatures of impaired CD8+ T cell cytotoxic function with progressors evidenced by increased exhaustion (PD-1 upregulation) and CD127 (IL-7Rα) downregulation contributing to persistent viremia. Thus, the homeostatic immune signatures reported in our study suggest a complex multifactorial mechanism accounting for non-progression in VNPs.

HIV seroconcordance among heterosexual couples in rural KwaZulu-Natal, South Africa: a population-based analysis.

INTRODUCTION: High levels of HIV seroconcordance at the population level reduce the potential for effective HIV transmission. However, the level of HIV seroconcordance is largely unknown among heterosexual couples in sub-Saharan Africa. We aimed to quantify the population level HIV seroconcordance in stable heterosexual couples in rural South Africa. METHODS: We followed adults (≥15 years old) using a population-based, longitudinal and open surveillance system in KwaZulu-Natal, South Africa, from 2003 to 2016. Sexual partnerships and HIV status were confirmed via household surveys and annual HIV surveillance. We calculated the proportions of HIV seroconcordance and serodiscordance in stable sexual partnerships and compared them to the expected proportions under the assumption of random mixing using individual-based microsimulation models. Among unpartnered individuals, we estimated the incidence rates and hazard of sexual partnership formation with HIV-positive or HIV-negative partners by participants' own time-varying HIV status. Competing risks survival regressions were fitted adjusting for sociodemographic and clinical factors. We also calculated Newman's assortativity coefficients. RESULTS: A total of 18,341 HIV-negative and 11,361 HIV-positive individuals contributed 154,469 person-years (PY) of follow-up. Overall, 28% of the participants were in stable sexual partnerships. Of the 677 newly formed stable sexual partnerships, 7.7% (95% CI: 5.8 to 10.0) were HIV-positive seroconcordant (i.e. both individuals in the partnership were HIV-positive), which was three times higher than the expected proportion (2.3%) in microsimulation models based on random mixing. The incidence rates of sexual partnership formation were 0.54/1000PY with HIV-positive, 1.12/1000PY with HIV-negative and 2.65/1000PY with unknown serostatus partners. HIV-positive individuals had 2.39 (95% CI: 1.43 to 3.99) times higher hazard of forming a sexual partnership with an HIV-positive partner than did HIV-negative individuals after adjusting for age, opposite-sex HIV prevalence (by 5-years age groups), HIV prevalence in the surrounding community, ART coverage and other sociodemographic factors. Similarly, forming a sexual partnership with an HIV-negative partner was 1.47 (95% CI: 1.01 to 2.14) times higher in HIV-negative individuals in the adjusted model. Newman's coefficient also showed that assortativity by participant and partner HIV status was moderate (r = 0.35). CONCLUSIONS: A high degree of population level HIV seroconcordance (both positive and negative) was observed at the time of forming new sexual partnerships. Understanding factors driving these patterns may help the development of strategies to bring the HIV epidemic under control.

Epidemiological evidence that common HPV types may be common because of their ability to evade immune surveillance: Results from the Women's Interagency HIV study.

Infection by human papillomavirus (HPV) type 16, the most oncogenic HPV type, was found to be the least affected by HIV-status and CD4 count of any of the approximately 13 oncogenic HPV types. This relative independence from host immune status has been interpreted as evidence that HPV16 may have an innate ability to avoid the effects of immunosurveillance. However, the impact of immune status on other individual HPV types has not been carefully assessed. We studied type-specific HPV infection in a cohort of 2,470 HIV-positive (HIV[+]) and 895 HIV-negative (HIV[-]) women. Semi-annually collected cervicovaginal lavages were tested for >40 HPV types. HPV type-specific prevalence ratios (PRs), incidence and clearance hazard ratios (HRs), were calculated by contrasting HPV types detected in HIV[+] women with CD4 < 200 to HIV[-] women. HPV71 and HPV16 prevalence had the weakest associations with HIV-status/CD4 count of any HPV, according to PRs. No correlations between PRs and HPV phylogeny or oncogenicity were observed. Instead, higher HPV type-specific prevalence in HIV[-] women correlated with lower PRs (ρ = -0.59; p = 0.0001). An alternative (quadratic model) statistical approach (PHIV+ = a*PHIV- + b*PHIV- 2 ; R2 = 0.894) found similar associations (p = 0.0005). In summary, the most prevalent HPV types in HIV[-] women were the types most independent from host immune status. These results suggest that common HPV types in HIV[-] women may have a greater ability to avoid immune surveillance than other types, which may help explain why they are common.

Female genital tract shedding of HIV-1 is rare in women with suppressed HIV-1 in plasma.

OBJECTIVE: Determine the frequency of genital HIV-1 shedding in a large cohort of women on long-term suppressive antiretroviral therapy (ART) and its association with mucosal inflammation. DESIGN: We measured levels of HIV-1 RNA and inflammation biomarkers in cervicovaginal lavage (CVL) from HIV-seropositive women enrolled in the Women's Interagency HIV Study (WIHS). METHODS: HIV-1 was quantified (Abbott RealTime HIV-1 assay) from CVL samples of 332 WIHS participants with and without clinical evidence of genital inflammation at the time of CVL collection; participants had suppressed plasma viral load (PVL; limit of quantitation less than 20-4000 copies/ml depending on year of collection) for a median of 7.1 years [interquartile range (IQR) 3.4-9.8, Group 1] or for a median of 1.0 years (IQR = 0.5-1.0, Group 2). Twenty-two biomarkers of inflammation were measured in CVL to compare with clinical markers. RESULTS: HIV-1 was detected in 47% of 38 pre-ART CVL samples (median 668 copies/ml) and detection in CVL was associated with higher pre-ART PVL. HIV-1 was detected in only 1 of 38 CVL samples from these women on suppressive antiretroviral therapy for 1 year. No HIV-1 RNA was detected in 294 CVL samples from a cross-sectional set of women with suppressed PVL for a median of 7 years. Clinical inflammation markers were correlated with inflammatory biomarkers in CVL specimens, although genital inflammation was not associated with measurable genital HIV-1 shedding in these WIHS participants on ART. CONCLUSION: ART that suppresses HIV-1 in the plasma of women also prevents genital tract HIV-1 shedding, even in the presence of genital tract inflammation.

Evaluation of the concentrations of psychotropic drugs in HIV-infected versus HIV-negative patients: Potential implications for clinical practice.

Objectives: The management of psychiatric illness in HIV-infected patients is clinically challenging because of the risk of potential drug-drug interactions. Here, we aimed to measure the antidepressant and/or antipsychotic drug concentrations in HIV-infected patients during routine outpatient visits.Methods: Six hundred HIV-infected patients were screened during the first 15 months after the introduction of our outpatient polytherapy management service in a search for subjects treated with psychotropic drugs for at least 3 months. The distribution of psychotropic drug concentrations in HIV-infected patients was compared with that observed in a control group of HIV-negative patients monitored over the same period.Results: The search identified 82 HIV-infected patients concomitantly receiving antiretroviral and psychotropic drug treatment, 55% of whom had plasma psychotropic drug concentrations that were below minimum effective levels. The same result was found in only 26% of the samples taken from HIV-negative patients. These results were not affected by patients' gender, age, adherence to therapies or drug-drug interactions.Conclusions: A higher rate of sub-therapeutic antidepressant and/or antipsychotic drugs concentrations were found in HIV-infected patients. The creation of multidiscliplinary specialist teams may contribute to improving the management of such complex patients.

Weight gain and dyslipidemia among virally suppressed HIV-positive patients switching to co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide.

OBJECTIVE: To evaluate the evolution of weight and lipid profiles before and after switch to co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) among virally suppressed HIV-positive patients. METHODS: Patients switching to E/C/F/TAF between March and July 2018 were included. Weight, lipid profile (triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)), and glycated hemoglobin (HbA1c) levels at 48 weeks before and after the switch were analyzed using generalized estimating equations in order to identify the associated factors. RESULTS: A total of 693 patients were included, and a weight gain was noted after the switch at weeks 12 (mean +0.63 kg), 24 (+1.25), 36 (+1.58), and 48 (+1.75) (all p < 0.0001). The weight change after the switch was significantly greater than that observed within the preceding 48-week period before the switch (+1.75 kg vs +0.54, p < 0.0001) and was correlated with switch to E/C/F/TAF (coefficient 0.29), later clinic visit (0.15), baseline weight (0.99), diabetes mellitus (coefficient -0.96), and age (-0.02) (all p < 0.01). At week 48, significant increases were observed for TG (mean +62.93 mg/dl), TC (+22.30), LDL-C (+9.70), HDL-C (+3.65) (all p < 0.01), and HbA1c (+0.08%) (p < 0.05), but not TC/HDL-C ratio (+0.12, p = 0.38). CONCLUSIONS: Virally suppressed HIV-positive patients gained a moderate amount of weight and had significant increases in lipid levels after switching to E/C/F/TAF.

Associations of Viral Seroreactivity with AIDS-Related Non-Hodgkin Lymphoma.

Infection with human immunodeficiency virus (HIV) is associated with substantially increased incidence of non-Hodgkin lymphoma (NHL). This risk may be driven, in part, by reduced immune control over viral infections in the setting of acquired immunodeficiency syndrome (AIDS), although the lymphomagenic mechanisms are not yet established. We used bead-based multiplex assays to measure antibody seroreactivity to 32 viral antigens representing 22 different viral infections (human herpesviruses 1-8, hepatitis B and C virus, human T-lymphotropic virus type-1, and human polyomaviruses) in two prospective HIV cohorts. Incident (n = 28) and prevalent (n = 38) AIDS-related NHL cases were matched by age, sex, race, and CD4 count to 67 HIV-positive control individuals without AIDS-NHL. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations of AIDS-NHL with the number of different viruses to which an individual was seropositive and seroreactivity to individual antigens. Seropositivity to an increasing number of viruses was inversely associated with AIDS-NHL (OR per virus = 0.84, 95% CI = 0.72-0.98). Seroreactivity to herpes simplex virus 2 2mgG unique antigen (OR = 0.47; 95% CI = 0.23-0.97) and to WU polyomavirus viral capsid protein (OR = 0.26, 95% CI = 0.10-0.65) was significantly lower in AIDS-NHL cases compared to controls. In this evaluation of antibodies to multiple viruses, we observed an inverse association between seropositivity to a larger number of viruses and AIDS-NHL. While in need of further evaluation, our data raise the novel hypothesis that insufficient exposures or impaired humoral immune responses to viral infections may be associated with AIDS-related lymphomagenesis.

Elderly HIV-positive women: A gender-based analysis from the Multicenter Italian "GEPPO" Cohort.

BACKGROUND: HIV-positive patients are facing age-and disease-related comorbidities. Since gender differences in viro-immunological, clinical and therapeutic features have been described, aim of this analysis was to explore such differences in elderly HIV-positive females compared to males coming from the same cohort. DESIGN: Cross-sectional study. SETTING: Ten Infectious Diseases Center participating to a new multicenter Italian geriatric Cohort aiming at describing health transition over time in HIV-positive individuals. PARTICIPANTS: HIV-positive patients aged ≥65 years old. MEASUREMENTS: We recorded clinical, viro-immunological and therapeutical data. RESULTS: We included 210 women (17%) out of 1237 patients. Compared to males, elderly females were less likely to present a HIV-RNA <50 copies/mL (74.3% vs. 81.8%, OR 0.64, 95%CI 0.44-0.93); they showed higher CD4+/CD8+ ratio (p = 0.016). Combined antiretroviral therapy (cART) strategies were similar between genders (p>0.05), although women were less likely to be treated with protease Inhibitors (PIs) (p = 0.05); specifically, in triple-drug regimens females received less PIs (28% vs 38% p = 0.022) and more integrase inhibitors (30% vs. 20% p = 0.012). Bone disease was more common in females (p<0.001) while males presented more frequently cardiovascular disease (CVD) (p<0.001). In females with bone disease, PIs and boosted regimens (38% vs. 53.7% p = 0.026 and 30.4 vs 44.0% p = 0.048 respectively) were prescribed less frequently. Polypharmacy was common and similar in both genders (20% vs. 22.8%, p = >0.05). A higher use of lipid-lowering drugs (20.5% vs. 14.8%, p = 0.04) was observed in females and yet they were less likely to receive anti-thrombotic agents (18.6% vs. 26.3%, p = 0.019) even when CVD was recorded (57.1% vs. 83.1%, p = 0.018). In multivariate analysis, we found that female gender was independently associated with a higher CD4+/CD8+ ratio but not with virological suppression. CONCLUSIONS: Elderly HIV-positive women display a worse virologic response despite a better immune reconstitution compared to males. The burden of comorbidities as well as the medications received (including cART) may slightly differ according to gender. Our data suggest that more efforts and focused interventions are needed in this population.

Acquired hypogammaglobulinemia and pathogen-specific antibody depletion after solid organ transplantation in human immunodeficiency virus infection: A brief report.

Hypogammaglobulinemia (HGG) frequently occurs in recipients after types of (SOT). The incidence and significance of HGG in HIV+ recipients of SOT are just being explored. We reported that 12% of the recipients in the SOT in multi-center HIV-TR (HIV-TR) Study developed moderate or severe HGG at 1 year. In LT recipients, this was associated with serious infections and death. We have now further characterized the decreased antibodies in HIV+ SOT recipients who developed HGG. We measured the levels of pathogen-specific antibodies and poly-specific self-reactive antibodies (PSA) in relation to total IgG levels from serial serum samples for 20 HIV+ SOT recipients who developed moderate to severe HGG following SOT. Serum antibody levels to measles, tetanus toxoid, and HIV-1 were determined by EIA. Levels of PSAs were determined by incubating control lymphocytes with patient serum, staining with anti-human IgG Fab-FITC, and analysis by flow cytometry. Levels of PSA were higher compared to healthy, HIV-uninfected controls at pre-transplant baseline and increased by weeks 12 and 26, but the changes were not significant. Likewise, anti-HIV antibody levels remained unchanged over time. In contrast, antibody levels against measles and tetanus were significantly reduced from baseline by week 12, and did not return to baseline, even after 2 years. For HIV patients who develop moderate to severe HGG after transplant, the reduction in IgG levels is associated with a significant decrease in pathogen-specific antibody titers, while PSA levels and anti-HIV antibodies are unchanged. This may contribute to infectious complications and other clinical endpoints.