Diagnosis and Risk Factors of Prediabetes and Diabetes in People Living with HIV- Evaluation of Clinical and Microbiome Parameters.

Diabetes is more common among people living with HIV (PLWH), as compared with healthy individuals. In a prospective multicenter study (N = 248), we identified normoglycemic (48.7%), prediabetic (44.4%) and diabetic (6.9%) PLWH. HbA1c and fasting blood glucose (FBG) sensitivity in defining dysglycemia was 96.8%, while addition of oral glucose tolerance test led to reclassification of only 4 patients. Inclusion of 93 additional PLWH with known DM enabled identification of multiple independent predictors of dysglycemia or diabetes: older age, higher BMI, Ethiopian origin, HIV duration, lower integrase inhibitor exposure and advanced disease at diagnosis. Shotgun metagenomic microbiome analysis revealed 4 species that were significantly expanded with hyperglycemia/hyperinsulinemia, and 2 species that were differentially more prevalent in prediabetic/diabetic PLWH. Collectively, we uncover multiple potential host and microbiome predictors of altered glycemic status in PLWH, while demonstrating that FBG and HbA1C likely suffice for diabetes screening. These potential diabetic predictors merit future prospective validation.

Twelve-month effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in people with HIV: Real-world insights from BICSTaR cohorts.

BACKGROUND: Real-world evidence is an essential component of evidence-based medicine. The aim of the BICSTaR (BICtegravir Single Tablet Regimen) study is to assess effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in antiretroviral treatment-naïve (TN) and treatment-experienced (TE) people with HIV. METHODS: BICSTaR is a prospective, observational cohort study. Participants (≥18 years) are being followed for 24 months. A pooled analysis is presented at 12 months, with the primary endpoint of effectiveness (HIV-1 RNA <50 copies/mL) and secondary endpoints of safety and tolerability (as per protocol). An exploration of patient-reported outcome measures using standardized questionnaires is included. RESULTS: Between June 2018 and May 2021, 1552 people with HIV were enrolled across 12 countries. The analysed population comprised 1509 individuals (279 TN, 1230 TE); most were white (76%), male (84%) and had one or more comorbid conditions (68%). Median age was 47 years. After 12 months of B/F/TAF treatment, HIV-1 RNA was <50 copies/mL in 94% (221/236) of TN participants and 97% (977/1008) of TE participants. Median CD4 cell count increased by 214 cells/µL (p < 0.001) in TN participants and 13 cells/µL (p = 0.014) in TE participants; median CD4/CD8 ratios increased by 0.30 and 0.03, respectively (both p < 0.001). Persistence was high at 12 months (TN, 97%; TE, 95%). No resistance to B/F/TAF emerged. Study drug-related adverse events occurred in 13% of participants through 12 months, leading to B/F/TAF discontinuation in 6%. CONCLUSIONS: The findings of this study provide robust real-world evidence to support the broad use of B/F/TAF in both TN and TE people with HIV.

A third dose of the BNT162b2 mRNA vaccine significantly improves immune responses among liver transplant recipients.

BACKGROUND & AIMS: Immune responses of solid organ transplant recipients to 2 doses of the BNT162b2 mRNA anti-SARS-CoV-2 vaccine are impaired. The immunogenicity and safety of a third dose among liver transplant (LT) recipients are unknown. This work aimed to evaluate the immune response of LT recipients to a third dose of the BNT162b2 mRNA vaccine. METHODS: Consecutive LT recipients (n = 61) in follow-up at Sheba Medical Center were included. Receptor binding domain (RBD) IgG, neutralizing antibody (NA) titers, and T-cell levels before and 21-28 days after a third vaccine dose were determined. Adverse effects after the third dose were monitored. RESULTS: The median age of LT recipients was 65 years and 57.4% were male. The humoral immune response rate improved significantly, with 56% of patients showing a response before the third vaccine dose compared to 98% after the third dose. The cellular response in 12 evaluated patients improved significantly (p = 0.008). The geometric mean of anti-RBD IgG levels, NA levels, and T-cell count also increased significantly after the third dose. NA titers after the third dose negatively correlated with age (p = 0.03), mycophenolate mofetil treatment (p = 0.005), and combined immunosuppression as opposed to calcineurin inhibitor monotherapy (p = 0.001). After the third dose, adverse effects were reported by 37% of recipients and were mostly mild (local pain and fatigue). CONCLUSION: After a third BNT162b2 mRNA vaccine, the immune response improved significantly among LT recipients, without serious adverse effects. Further studies are needed to evaluate immune response durability and to determine the optimal number and schedule of booster vaccine doses. LAY SUMMARY: The Pfizer-Biotech BNT162b2SARS-CoV-2 vaccine induced significant immunity among liver transplant recipients after a third dose. The majority of the patients developed sufficient levels of both humoral and cellular immune responses. Factors that predict non-response were older age and immunosuppressive medications.

Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in haematopoietic stem cell transplantation recipients.

The immunogenicity and safety of Pfizer-BioNTech BNT162b2 mRNA vaccine in allogeneic haematopoietic stem cell transplantation (HSCT) recipients are unknown. We prospectively followed 152 HSCT recipients who were at least six months following transplantation and with no active acute graft-versus-host disease (GVHD). Blood samples were taken 2-4 weeks after the second vaccination and analyzed for receptor-binding domain (RBD) antibodies and neutralizing antibodies (NA). 272 immunocompetent healthcare workers served as controls. At a median of 28 days after the second vaccination, 118 patients (77·6%) developed RBD immunoglobulin G (IgG) with a geometric mean titre (GMT) of 2·61 [95% CI (confidence interval), 2·16-3·16]. In the control group 269/272 (98·9%) developed RBD IgG, with a GMT of 5·98 (95% CI 5·70-6·28), P < 0·0001. The GMT of NA in HSCT recipients and controls was 116·0 (95% CI 76·5-175·9), and 427·9 (95% CI 354·3-516·7) respectively (P < 0001). Multivariate logistic regression analysis revealed that HSCT recipients with no chronic GVHD and no immunosuppressive therapy at the time of vaccination had significantly higher levels of NA following the second vaccination. Adverse events were minimal and were less common than in healthy controls. In conclusion; the BNT162b2 mRNA vaccination is safe and effective in HSCT recipients, especially those who are immunosuppression-free. A significant fraction developed protecting NA.

Immunogenicity and Adverse Effects of the 2-Dose BNT162b2 Messenger RNA Vaccine Among Liver Transplantation Recipients.

The BNT162b2 messenger RNA (mRNA) vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to be safe and effective in immunocompetent patients. The safety and efficacy of this vaccine in liver transplantation (LT) recipients is still under evaluation. The objective of this study was to assess the safety and efficacy of the BNT162b2 vaccine among transplant recipients. The immune responses of 76 LT recipients receiving 2 doses of the vaccine were compared with those of 174 age-matched immunocompetent controls. Postvaccination immunoglobulin G (IgG) antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 and neutralizing antibodies (NA) to the BNT162b2 mRNA vaccine were determined at least 14 days after the second dose of the vaccine. IgG antibody titers ≥1.1 were defined as positive antibodies. Adverse effects were monitored during the study period. Following administration of the second dose, transplant recipients showed reduced immune responses compared with controls (72% versus 94.2%; P < 0.001). At a median time of 38 days after the second vaccination, the geometric mean of RBD IgG and NA titers were 2.1 (95% confidence interval [CI], 1.6-2.6) and 150 (95% CI, 96-234) among transplant recipients and 4.6 (95% CI, 4.1-5.1) and 429 (95% CI, 350-528) in the control group, respectively (P < 0.001). Antibody responses were lower in transplant recipients who were receiving combined immunosuppression therapy and in those with impaired renal function. Among the LT recipients with negative antibody responses, 1 became infected with SARS-CoV-2, but no recipients with positive antibody responses became infected. Overall, most (n = 39 [51%]) adverse effects self-reported by transplant recipients were mild and occurred more often in women than in men. Compared with patients who were immunocompetent, LT recipients had lower immune responses. The durability of immune responses to the BNT162b2 vaccine among LT recipients requires further investigation.

Drop-out of medical follow-up among people living with HIV in Tel-Aviv area.

Access to HIV anti-retroviral treatment (ART) has significantly improved survival and the quality of life of people living with HIV (PLHIV). However, effective therapy necessitates high adherence to ART. The aim of this study was to identify the extent to which PLHIV in Israel were not retained in therapy and their obstacles to accessing care. The Department of Tuberculosis and AIDS (DTA) and the two existing HIV clinics in the Tel-Aviv metropolitan area performed a retrospective study for all PLHIV who were consulted at these clinics during 2008-2011, but were absent in 2012. From that population, 25% were randomly chosen for qualitative interviews. This study included 278 PLHIV not retained in care (13.4% of registered patients), of whom 194 (69.8%) were male, and 58.3% were Israeli citizens. Total number of clinic visits was 1959 (mean: 7.05 visits per patient; range: 1-39; SD: ±7.2) and the total person-years of follow-up for 267 PLHIV was 1,044 (mean: 3.9 py; 0-23; SD: ±4.4). Identified risk groups were: Originating from Generalized Epidemic countries (43.5%, 82.6% were non-Israelis); Men having Sex with Men (22.6%); Injecting Drug Users (12.9%) and Others (28.9%). Among Israelis, major reasons for clinic nonattendance included distance to the clinics and perceived lack of time. The major impediment to seeking care among undocumented migrants was lack of medical insurance. The DTA acted swiftly to make HIV-related services accessible to undocumented migrants. Barriers described by Israeli participants were generally more individual in nature, and should be addressed at the clinic level.

The impact of COVID-19 lockdown on men having sex with men (MSM).

Social distancing including lockdowns are acceptable measures to cope with the COVID-19 pandemic. In this cross sectional study, we surveyed the impact of these measurements on sexual behavior and pre-exposure prophylaxis for HIV (PrEP) use among MSM. A digital questionnaire was distributed via social media and geographically based meeting applications after the first lockdown (March-April 2020). 1194 MSM responded, 91.8% were HIV negative, 19.4% of them used PrEP regularly, and 8.2% were people living with HIV (PLWH). Median age was 34.5 years. 54.4% reported that they kept strictly social distancing guidelines. Low education, hazardous sexual behavior, moderate/severe, and depression predicted low compliance with social distancing guidelines. 66.7% reported a significant decrease in the number of casual sex partners. 55% of those who took PrEP reduced their PrEP intake. Many of the PLWH and PrEP users reduced their medical follow-up. In light of the continuous outbreak and the risk of further outbreaks in the future consideration should be given to provide continuing access to HIV and sexual health clinics.

BNT162b2 Third Booster Dose Significantly Increases the Humoral Response Assessed by Both RBD IgG and Neutralizing Antibodies in Renal Transplant Recipients.

Background: An impaired humoral response to full dose of BNT162b2 vaccine was observed in renal transplant recipients (RTR). Methods: To reveal predictors for humoral response to third vaccine, patients were stratified to positive (N = 85) and negative (N = 14) response groups based on receptor-binding domain (RBD) IgG ≥1.1 and neutralizing antibodies (NA) ≥ 16 dilution versus RBD IgG <1.1 or NA < 16, respectively. NA were detected using a SARS-CoV-2 pseudo-virus. Results: Response rate increased from 32.3% (32/99) before the third dose to 85.9% (85/99) post-third vaccine with a significant rise in geometric mean titers (GMTs) for RBD IgG and NA [0.79 (95% CI 0.65-0.96) vs. 3.08 (95% CI 2.76-3.45), p < 0.001 and 17.46 (95% CI 12.38-24.62) vs. 362.2 (95% CI 220.7-594.6), p < 0.001 respective. 80.6% (54/67) seroconverted and 96.9% (31/32) remained positive following the vaccine with a significant increase in GMTs for RBD IgG and NA. Age, ESRD secondary to diabetic nephropathy (DN) and renal allograft function were independent predictors for antibody response in RTR. Mycophenolic acid (MPA) use and dose had no impact on humoral response following the third booster. AEs were recorded for 70.1% of RTR population. Systemic AEs were more common in recipients with a positive humoral response as opposed to non-responders (45.2% versus 15.4% respectively, p = 0.04). Conclusion: 85.9% of RTR develop NA to BNT162b2 third vaccine, found effective in both negative and positive responders prior to the vaccine. Antigenic re-exposure overcame the suppressive effect of MPA on antibody response in RTR.

Monkeypox DNA levels correlate with virus infectivity in clinical samples, Israel, 2022.

The current monkeypox virus global spread and lack of data regarding clinical specimens' infectivity call for examining virus infectivity, and whether this correlates with results from PCR, the available diagnostic tool. We show strong correlation between viral DNA amount in clinical specimens and virus infectivity toward BSC-1 cell line. Moreover, we define a PCR threshold value (Cq ≥ 35, ≤ 4,300 DNA copies/mL), corresponding to negative viral cultures, which may assist risk-assessment and decision-making regarding protective-measures and guidelines for patients with monkeypox.

The risk for severe COVID 19 in patients with autoimmune and/or inflammatory diseases: First wave lessons.

Data regarding the risk for severe COVID19 in patients with autoimmune or inflammatory diseases are scarce. To estimate the risk of those patients to develop a more severe COVID19 infection All active patients and those with dermatologic and/or rheumatologic autoimmune/inflammatory diseases were identified in a single tertiary center. The charts of those tested positive for COVID19 between 1 March 2020 and 31 May 2020 reviewed including demographics, co-morbidities, and medications. COVID19 outcome of those with dermatologic and/or rheumatologic autoimmune/inflammatory diseases were compared to COVID19 infected matched controls without an autoimmune/inflammatory background. Overall, 974 of 381 268 active patients were tested positive for COVID19, including 35 out of 13 225 with dermatologic and/or rheumatologic autoimmune/inflammatory diseases. No statistically significant difference in severity of COVID19 infection or mortality rate was found. The rate of asymptomatic, mild, moderate, severe/critical and fatal COVID19 infection was 11.4%, 37.1%, 22.8%, 11.4%, and 17.1%, respectively, for the patients with autoimmune diseases and 17.8%, 45.8%, 10.9%, 6.8%, and 18.4%, respectively for the controls . Patients with autoimmune/inflammatory diseases seem not to develop a more severe COVID19 infection than controls.

HIV-1 infection among women in Israel, 2010-2018.

INTRODUCTION: Although women comprise 33% of the HIV-1-carriers in Israel, they have not previously been considered a risk group requiring special attention. Immigration waves from countries in Africa and in East Europe may have changed the local landscape of women diagnosed with HIV-1. Here, we aimed to assess viral and demographic characteristics of HIV-1-positive women identified in Israel between 2010 and 2018. METHODS: All > 16 year-old, HIV-1-infected women, diagnosed in Israel in 2010-2018, (n = 763) registered in the National HIV reference laboratory were included in this cross-sectional study. Demographic and clinical characteristics were extracted from the database. Viral subtypes and transmitted drug resistance mutations (TDRM) were determined in 337 (44.2%) randomly selected samples collected from treatment-naive women. RESULTS: Median age at diagnosis was 38 years. Most (73.3%) women were immigrants from the former Soviet Union (FSU) (41.2%, 314) or sub-Saharan Africa (SSA) (32.2%, 246) and carried subtype A (79.7%) or C (90.3%), respectively. Only 11.4% (87) were Israeli-born women. Over the years, the prevalence of women from SSA decreased while that of women from FSU increased significantly (p < 0.001). The median CD4+ cell count was 263 cells/mm3, and higher (391 cells/mm3) in Israeli-born women. TDRM were identified in 10.4% of the tested samples; 1.8, 3 and 7.1% had protease inhibitors (PI), nucleotide reverse transcriptase inhibitors (NRTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) TDRM, respectively. The prevalence of women with NNRTI TDRM significantly increased from 4.9% in 2010-2012 to 13.3% in 2016-2018. Israeli-born women had the highest prevalence (16.3%) of NNRTI TDRM (p = 0.014). NRTI A62 (5.6%), NNRTI E138 and K103 (5.6 and 4.2%, respectively) were the most prominent mutated sites. CONCLUSIONS: Most HIV-1-positive women diagnosed in Israel in 2010-2018 were immigrants, with the relative ratio of FSU immigrants increasing in recent years. The high proportion of women diagnosed with resistance mutations, particularly, the yearly increase in the frequency of NNRTI mutations, support the national policy of resistance testing at baseline.

Attitudes and perceptions among men having sex with men towards a new non-deferral blood donation policy in Israel.

BACKGROUND: In June 2017, Israel lifted the ban on blood donations from men who have sex with men (MSM) and accepts donations if 12 months have passed since the last sexual contact. Recently, the National Blood Services suggested a novel approach that involves acceptance of MSM blood donations without deferral, keeping solely the frozen plasma in quarantine and releasing it for transfusion if a subsequent donation, at least 4 months later, is found negative for transfusion-transmitted agents. In this study, we examined the attitudes and perceptions of MSM to the new Frozen Plasma Quarantine Policy (FPQP). METHOD: A survey was published on gay-oriented websites, collecting anonymous demographic data, history of blood donations and attitudes towards the new policy. RESULTS: We analysed responses from 1233 MSM. Of these, 13·4% had donated blood at least once during the previous year, almost all of them (89·7%) not complying with the current 12-month deferral. Most respondents (64·5%) supported the suggested new approach and would consider donating blood if it were introduced. Of MSM who had donated blood in the previous year, 85% stated they would agree to reveal their sexual practice in the donor health questionnaire (DHQ) in order to be included in the programme, compared with 8·5% under the current 12-month deferral policy. CONCLUSION: The suggested Plasma Quarantine Policy may be more acceptable to MSM than a 12-month deferral and increase their compliance with the blood services policy. This and retesting of donors may increase blood safety.

Risk factors of syphilis co-infection among HIV-infected men who have sex with men in Tel-Aviv, Israel.

Syphilis incidence in Israel and other industrialized countries has increased in the past decade, mainly among men who have sex with men (MSM) who were co-infected with HIV. This study aimed to assess the demographic characteristics and behavioral risk factors for syphilis infection among HIV-infected MSM in the Tel-Aviv region, Israel. This cross-sectional study compared HIV-infected MSM who were co-infected with syphilis since 2005 with HIV-infected MSM without syphilis, using an anonymous self-administered questionnaire distributed at the AIDS treatment clinic in central Israel in 2016. This study included 75 HIV-infected MSM who were diagnosed with syphilis after their HIV diagnosis and 99 HIV-infected MSM without syphilis. Variables associated with syphilis infection included inadequate adherence to antiretroviral therapy (ART) (OR = 1.8 [1.2-2.4]), frequent unprotected receptive anal intercourse (UAI) with casual sex partners (OR = 2.2 [1.5-8.2]), especially with HIV-infected partner (OR = 3.2 [1.1-7.9]). In conclusion, HIV and syphilis co-infection were associated with frequent UAI with casual sex partners, inadequate adherence to ART and limited partner notification. In order to minimize syphilis transmission among HIV-infected MSM, AIDS clinics should encourage HIV-infected MSM to use condoms, ensure that patients perform periodic syphilis serology testing and improve partner notifications.

Recreational drug and excessive alcohol use among HIV-infected men who have sex with men in Central Israel.

BACKGROUND: HIV-infected men who have sex with men (MSM) who use recreational drugs (RD) or excessive alcohol (EA) may be involved in risky sexual behaviours, including unprotected anal intercourse (UAI). This study describes the prevalence RD/EA-use among HIV-infected MSM, and compares those who used RD/EA with those who did not. METHODS: This cross-sectional study included HIV-infected MSM who were recruited in a convenient sample from two AIDS-treatment centres and events for HIV-infected MSM in Israel in 2016. Participants completed anonymous questionnaires including RD/EA-use and their sexual behaviours. RD/EA-use was defined as consumption of any psychoactive stimulants or dissociative anaesthetics, or an uptake of alcohol until drunkenness before or during sex. RESULTS: Of all 276 HIV-infected MSM, 202 (73.2%) used RD/EA. Those who used RD/EA were younger, reported earlier sexual debut, had more sexual partners, were more likely to perform UAI with casual partners, more commonly involved in paid sex, used psychiatric medications and more likely to be unsatisfied with their health-status compared to those who did not use RD/EA. HIV-infected MSM who used RD/EA reported a lower CD4-count and higher viral-load than those who did not. In a multivariate analysis, being younger, reported earlier sexual debut and been prescribed psychiatric drugs were associated with RD/EA-use among HIV-infected MSM. CONCLUSIONS: A large proportion of HIV-infected MSM used RD/EA and also engaged in risky sexual behaviours. A subset of HIV-infected MSM can benefit from mental support during their routine treatment at the AIDS treatment centres and should also receive harm reduction intervention by their providers in order to minimize potential risks pertaining to RD/EA-use.

Differences in knowledge, attitudes and behaviors of Israeli HIV-uninfected gay men in HIV-discordant vs. concordant steady relationships.

HIV-discordant gay male couples may play an important role in HIV-transmissions. This cross-sectional study compared the knowledge, attitudes and sexual behaviors of HIV-uninfected gay men, between those in HIV-discordant and those in HIV-concordant steady relationships. Anonymous questionnaires were distributed electronically in designated gay-related internet sites and in AIDS-clinics in 2015. The dependent variable was defined as a steady relationship of an HIV-uninfected man with an HIV-infected partner. Risky sexual behavior was defined as unprotected anal intercourse (UAI) with a sex partner whose HIV-status was either positive or unknown. Of 2,319 responders, 460 (20%) were HIV-uninfected gay men in steady relationships, of whom 72 were in HIV-discordant relationships and 388 were in HIV-concordant relationships. Those in HIV-discordant relationships presented better established knowledge regarding HIV-transmission, more lenient attitudes regarding UAI, and reported being involved in riskier sexual behavior, both within and outside their steady relationship compared to men in HIV-concordant relationships. UAI was performed by 48% of the HIV-discordant couples and was associated with the use of sero-positioning strategy and with achieving undetectable viral-load. These findings reflect the complexity of constant use of condoms during long-term sero-discordant relationships. Targeted interventions for HIV-prevention in HIV-discordant couples should be employed for balancing the partners' desire for intimacy and sexual pleasure in the relationship, while reducing the risk for acquiring HIV. ABBREVIATIONS: ART: Antiretroviral therapy; PEP: Post exposure prophylaxis; PrEP: Pre exposure prophylaxis; STI: Sexually transmitted infections; UAI: Unprotected anal intercourse.

HIV infected men who have sex with men in Israel: knowledge, attitudes and sexual behavior.

BACKGROUND: HIV-infected (HIVI) men who have sex with men (MSM) may transmit HIV to their sero-discordant sex partner/s. This study assesses the knowledge, attitudes and sex-practices of Israeli HIVI-MSM. METHODS: This cross-sectional study compared HIVI-MSM to self-reported HIV-uninfected (HIVU) MSM by using anonymous questionnaires that were distributed in AIDS-treatment centers and gay-related internet-sites in 2015. Unprotected anal intercourse (UAI) in the last 6 months was the outcome variable. RESULTS: Of 300 HIVI-MSM and 1299 HIVU-MSM, UAI with sero-discordant/unknown-status partner/s was performed by 12.1% and 17.9%, respectively, p=0.02. UAI with sero-discordant/unknown-status among HIVI-MSM and HIVU-MSM was associated with the type of partnership: 37.7% vs. 52.4% for steady partner/s, 19.0% vs. 39.9% for sex-buddies and 23.5% vs. 24.0% for casual partner/s (p<0.001, p=0.01, p=0.6), respectively. On these occasions, HIVI-MSM were more likely to be receptive during UAI: 92.3%, 87.5% and 83.3% for steady partner/s, sex buddies and casual partner/s, respectively. In cases HIVI-MSM performed UAI, 31.3% expected their partner/s to share responsibility for condom-use vs. 9.7% of HIVU-MSM. HIVI-MSM were involved in risky sexual-behaviors, such as substances-use, earlier sexual debut and sex for money. HIVI-MSM were more likely to disclose their HIV-status with their partner before sex and demonstrated better knowledge about HIV-transmission than HIVU-MSM. CONCLUSION: HIVI-MSM performed UAI with sero-discordant/unknown-status partner/s less frequently than HIVU-MSM. Their condom-use practices were associated with the type of partner, and were lower for casual vs. steady partners or sex-buddies. HIVI-MSM tended to use sero-adaptive strategies to reduce the potential risk of HIV-transmission to their sero-discordant/unknown-status partner/s.

Evaluation of the RealTime HIV-1, Xpert HIV-1, and Aptima HIV-1 Quant Dx Assays in Comparison to the NucliSens EasyQ HIV-1 v2.0 Assay for Quantification of HIV-1 Viral Load.

HIV-1 RNA monitoring, both before and during antiretroviral therapy, is an integral part of HIV management worldwide. Measurements of HIV-1 viral loads are expected to assess the copy numbers of all common HIV-1 subtypes accurately and to be equally sensitive at different viral loads. In this study, we compared for the first time the performance of the NucliSens v2.0, RealTime HIV-1, Aptima HIV-1 Quant Dx, and Xpert HIV-1 viral load assays. Plasma samples (n = 404) were selected on the basis of their NucliSens v2.0 viral load results and HIV-1 subtypes. Concordance, linear regression, and Bland-Altman plots were assessed, and mixed-model analysis was utilized to compare the analytical performance of the assays for different HIV-1 subtypes and for low and high HIV-1 copy numbers. Overall, high concordance (>83.89%), high correlation values (Pearson r values of >0.89), and good agreement were observed among all assays, although the Xpert and Aptima assays, which provided the most similar outputs (estimated mean viral loads of 2.67 log copies/ml [95% confidence interval [CI], 2.50 to 2.84 log copies/ml] and 2.68 log copies/ml [95% CI, 2.49 to 2.86 log copies/ml], respectively), correlated best with the RealTime assay (89.8% concordance, with Pearson r values of 0.97 to 0.98). These three assays exhibited greater precision than the NucliSens v2.0 assay. All assays were equally sensitive for subtype B and AG/G samples and for samples with viral loads of 1.60 to 3.00 log copies/ml. The NucliSens v2.0 assay underestimated A1 samples and those with viral loads of >3.00 log copies/ml. The RealTime assay tended to underquantify subtype C (compared to the Xpert and Aptima assays) and subtype A1 samples. The Xpert and Aptima assays were equally efficient for detection of all subtypes and viral loads, which renders these new assays most suitable for clinical HIV laboratories.

Evaluation of the Bio-Rad Geenius HIV 1/2 assay as an alternative to the INNO-LIA HIV 1/2 assay for confirmation of HIV infection.

The Bio-Rad Geenius HIV 1/2 assay was evaluated as an alternative to the INNO-LIA HIV 1/2 assay for the confirmation of HIV infection in 198 serum samples reactive to 4th-generation HIV enzyme immunoassays (EIAs). The Geenius assay correctly identified 85% of the samples, compared to 75% identified by the INNO-LIA assay, reduced the number of indeterminate results, and shortened the overall turnaround time.

Brain biopsy in AIDS patients: diagnostic yield and treatment applications.

OBJECTIVE: Central nervous system involvement in AIDS patients can present at any stage of the disease. Brain lesions detected in imaging studies are usually treated empirically. A brain biopsy is indicated in the absence of clinical and radiologic improvement. In the present study, 16 AIDS patients underwent brain biopsy. We evaluated the diagnostic yield of the brain biopsy and the changes in the disease course. MATERIALS AND METHODS: Sixteen consecutive AIDS patients (12 men, 4 women; mean age 40.8 years) underwent a brain biopsy at Sheba Medical Center between 1997 and 2009. A retrospective analysis was performed and the clinical outcome was recorded. RESULTS: Median CD4 count before biopsy was 62.6. Magnetic resonance images revealed multiple lesions in 12 patients and enhancing lesions in 12 patients. A total of 19 biopsies were performed in 16 patients. In the present series, the initial procedures provided a diagnostic yield of 81.25% (13 diagnostic cases from 16 procedures in 16 patients). Two of these patients underwent repeated biopsies that were eventually diagnostic . If repeated biopsies were taken into consideration, the diagnostic yield was 93.75% (15 diagnostic cases in 16 patients). The rate of hemorrhagic complications was 10.5% (2 hemorrhages in 19 procedures).Pathologic examination revealed parasitic and fungal infections in 6 patients (6/16; 38%), progressive multifocal leukoencephalopathy in 4 patients (4/16; 25%), AIDS encephalopathy in 4 patients (4/16; 25%), and lymphoma in 1 patient (1/16; 6%). One patient had a nonspecific inflammatory process (6%). The treatment modality was modified in 12 patients and led to clinical and radiologic improvement in 8 patients. CONCLUSIONS: Brain biopsy should be considered when empiric treatment of central nervous system lesions in AIDS patients fails. Biopsy is diagnostic in the majority of patients. The diagnosis allows for treatment modifications, which lead to clinical and radiologic improvement in some patients.