Anti-BLyS Treatment of 36 Israeli Systemic Lupus Erythematosus Patients.

BACKGROUND: Anti-BLyS treatment with the human belimumab monoclonal antibody was shown to be a safe and effective therapeutic modality in lupus patients with active disease (i.e., without significant neurological/renal involvement) despite standard treatment. OBJECTIVES: To evaluate the "real-life" safety and efficacy of belimumab added to standard therapy in patents with active lupus in five Israeli medical centers. METHODS: We conducted a retrospective open-labeled study of 36 lupus patients who received belimumab monthly for at least 1 year in addition to standard treatment. Laboratory tests (C3/C4, anti dsDNA autoantibodies, chemistry, urinalysis and complete blood count) were done every 3-4 months. Adverse events were obtained from patients' medical records. Efficacy assessment by the treating physicians was defined as excellent, good/partial, or no response. RESULTS: The study group comprised 36 lupus patients (8 males, 28 females) with a mean age of 41.6 } 12.2 years. Belimumab was given for a mean period of 2.3 } 1.7 years (range 1-7). None of the patients discontinued belimumab due to adverse events. Four patients (11.1%) had an infection related to belimumab. Only 5 patients (13.9%) stopped taking belimumab due to lack of efficacy. The response was excellent in 25 patients (69.5%) and good/partial in the other 6 (16.6%). Concomitantly, serological response (reduction of C3/C4 and anti-dsDNA autoantibodies) was also observed. Moreover, following belimumab treatment, there was a significant reduction in the usage of corticosteroids (from 100% to 27.7%) and immunosuppressive agents (from 83.3% to 8.3%). CONCLUSIONS: Belimumab, in addition to standard therapy, is a safe and effective treatment for active lupus patients.

Strongyloidiasis-Related IRIS.

Helminthic infection and HIV have been reported to coexist, particularly in sub-Saharan African patients living with HIV. Strongyloidiasis is one of the most common helminths, usually leading to cutaneous and gastrointestinal (GI) symptoms. In the immunocompromised host, this infection can lead to strongyloidiasis hyperinfection syndrome (SHS), not common in HIV-infected patients. Immune reconstitution inflammatory syndrome (IRIS) can follow the initiation of antiretroviral therapy (ART), with a variety of presentations. The authors present here a 32-year-old HIV-infected female who was recently diagnosed with AIDS, started ART, and recovered from SHS. Her upper endoscopy revealed severe duodenitis but no causal agent per biopsy or stool examination. After receiving symptomatic therapy, she showed improvement, a course of events that fit the diagnosis of GI-related IRIS.

A Population-Structured HIV Epidemic in Israel: Roles of Risk and Ethnicity.

BACKGROUND: HIV in Israel started with a subtype-B epidemic among men who have sex with men, followed in the 1980s and 1990s by introductions of subtype C from Ethiopia (predominantly acquired by heterosexual transmission) and subtype A from the former Soviet Union (FSU, most often acquired by intravenous drug use). The epidemic matured over the last 15 years without additional large influx of exogenous infections. Between 2005 and 2013 the number of infected men who have sex with men (MSM) increased 2.9-fold, compared to 1.6-fold and 1.3-fold for intravenous drug users (IVDU) and Ethiopian-origin residents. Understanding contemporary spread is essential for effective public health planning. METHODS: We analyzed demographic and virologic data from 1,427 HIV-infected individuals diagnosed with HIV-I during 1998-2012. HIV phylogenies were reconstructed with maximum-likelihood and Bayesian methods. RESULTS: Subtype-B viruses, but not A or C, demonstrated a striking number of large clusters with common ancestors having posterior probability ≥0.95, including some suggesting presence of transmission networks. Transmitted drug resistance was highest in subtype B (13%). MSM represented a frequent risk factor in cross-ethnic transmission, demonstrated by the presence of Israeli-born with non-B virus infections and FSU immigrants with non-A subtypes. CONCLUSIONS: Reconstructed phylogenetic trees demonstrated substantial grouping in subtype B, but not in non-MSM subtype-A or in subtype-C, reflecting differences in transmission dynamics linked to HIV transmission categories. Cross-ethnic spread occurred through multiple independent introductions, with MSM playing a prevalent role in the transmission of the virus. Such data provide a baseline to track epidemic trends and will be useful in informing and quantifying efforts to reduce HIV transmission.

Evaluation of GS Junior and MiSeq next-generation sequencing technologies as an alternative to Trugene population sequencing in the clinical HIV laboratory.

Population HIV-1 sequencing is currently the method of choice for the identification and follow-up of HIV-1 antiretroviral drug resistance. It has limited sensitivity and results in a consensus sequence showing the most prevalent nucleotide per position. Moreover concomitant sequencing and interpretation of the results for several samples together is laborious and time consuming. In this study, the practical use of GS Junior and MiSeq bench-top next generation sequencing (NGS) platforms as an alternative to Trugene Sanger-based population sequencing in the clinical HIV laboratory was assessed. DeepChek(®)-HIV TherapyEdge software was used for processing all the protease and reverse transcriptase sequences and for resistance interpretation. Plasma samples from nine HIV-1 carriers, representing the major HIV-1 subtypes in Israel, were compared. The total number of amino acid substitutions identified in the nine samples by GS Junior (232 substitutions) and MiSeq (243 substitutions) was similar and higher than Trugene (181 substitutions), emphasizing the advantage of deep sequencing on population sequencing. More than 80% of the identified substitutions were identical between the GS Junior and MiSeq platforms, most of which (184 of 199) at similar frequency. Low abundance substitutions accounted for 20.9% of the MiSeq and 21.9% of the GS Junior output, the majority of which were not detected by Trugene. More drug resistance mutations were identified by both the NGS platforms, primarily, but not only, at low abundance. In conclusion, in combination with DeepChek, both GS Junior and MiSeq were found to be more sensitive than Trugene and adequate for HIV-1 resistance analysis in the clinical HIV laboratory.

Assessment of the knowledge and attitudes regarding HIV/AIDS among pre-clinical medical students in Israel.

BACKGROUND: Today's medical students are the future physicians of people living with HIV/AIDS (PLWHA). It is therefore essential that medical students possess the appropriate knowledge and attitudes regarding PLWHA. This study aims to evaluate knowledge and attitudes of pre-clinical Israeli medical students and to assess whether their knowledge and attitudes change throughout their pre-clinical studies. METHODS: A cross-sectional study was conducted among all pre-clinical medical students from the four medical schools in Israel during the academic year of 2010/2011 (a total of 1,470 students). A self-administered questionnaire was distributed. The questionnaire sought student responses pertaining to knowledge of HIV transmission and non-transmission routes, basic knowledge of HIV/AIDS treatment and attitudes towards HIV/AIDS. RESULTS: The study's response rate was 62.24 percent. Knowledge among pre-clinical medical students was generally high and showed a statistically significant improvement as students progressed through their pre-clinical studies. However, there were some misconceptions, mostly regarding HIV transmission via breastfeeding and knowledge of HIV prevention after exposure to the virus. Students' attitudes were found to include stigmatizing notions. Furthermore, the majority of medical students correlated HIV with shame and fear. In addition, students' attitudes toward HIV testing and providing confidential medical information were contradictory to health laws, protocols and guidelines. Overall, no positive changes in students' attitudes were observed during the pre-clinical years of medical school. CONCLUSION: The knowledge of pre-clinical medical students in Israel is generally high, although there are some knowledge inadequacies that require more emphasis in the curricula of the medical schools. Contrary to HIV-related knowledge, medical students' attitudes are unaffected by their progression through medical school. Therefore, medical schools in Israel should modify their curricula to include teaching methods aimed at improving HIV-related attitudes and adherence to medical professionalism.

[Fertility treatment options for discordant couples living with HIV].

BACKGROUND: Serodiscordant couples live with the risk of HIV infection of the negative partner when attempting to become pregnant. Using density gradient centrifugation (DGC), spermatozoa can be separated from other seminal compartments. Isolated spermatozoa do not contain detectable HIV RNA. DGC followed by artificial insemination may significantly reduce the risk of infection. The Hadassah AIDS Center (HAC) has recently initiated a fertility center for serodiscordant couples. METHODS: Our patient population includes serodiscordant couples in which the male is HIV positive. The male semen is washed using the DGC procedure. Washed semen is tested for HIV by standard PCR methods. Intrauterine insemination (IUI) is attempted using the washed semen. RESULTS: A total of 55 couples have registered for this procedure. This includes 16 men who have sex with men, 7 who have hemophilia and 8 couples of Ethiopian origin. The average female age is 33 years. Seven (12%) men had inadequate sperm counts and were referred for IVF. Overall, 34 semen samples were tested for HIV. Only one was found to be positive. During the procedure, 22 couples underwent at least one IUI attempt and 16 (72%) females became pregnant, 3 of them after the first IUI attempt. All women tested for HIV after IUI were found to be negative. CONCLUSIONS: The pregnancy success rate during the first year of operation was 72%, similar to that reported by other centers in Europe. There were no seroconversions of the female partner. Serodiscordant couples living with HIV in Israel today may consider starting a family, while significantly reducing the risk of infecting the negative female partner.

Hypersensitivity and desensitization to darunavir in a case of HIV infection with triple-class drug resistance: case description and review of the literature.

We report on a case of severe cutaneous reaction to darunavir/r and a successful desensitization protocol. The patient was a 41-yr old female. known to be HIV infective for 18 years and who had received several drug regiments in the past. As a consequence, her virus had triple-class mutations but was susceptible to darunavir/r. Her CD4 was 200 cells/mm(3) and HIV viral load 56,000 copies/mL. Eight days after initiation of darunavir/r the patient developed a severe pruritic vesicular extended cutaneous allergic reaction which required cessation of all drugs. Due to the severity of the allergic reaction no rechallenge was done. After the patient's recovery, the virus was found to be susceptible only to maraviroc, raltegravir, and darunavir/r. Since darunavir/r was an essential component in treating this triple-class mutated virus, a desensitization protocol was applied successfully. Six months after desensitization protocol was applied successfully. Six months after desensitization, the patient is asymptomatic, compliant, and her HIV viral load remains at <20 copies/mL.

A case of possible darunavir/ritonavir-induced peripheral neuropathy: case description and review of the literature.

A 65-year-old man, M.S.M., known as being HIV infected for 20 years, presented with muscle ache and progressive weakness 3 months after initiation of darunavir as a part of his antiretroviral therapy (ART). The patient's treatment included darunavir/ritonavir 600/100 mg twice daily, plus a backbone of didanosine and abacavir which were the backbone in his previous regimen for several years according to his drug resistance profile. Three months after initiation of darunavir/ritonavir the patient exhibited clinical symptoms of severe pain and progressive weakness of his lower limbs; he was unable to walk and was totally wheelchair-bound. Severe sensory peripheral polyneuropathy was revealed on electromyogram (EMG). All medications, including ART, were stopped. Within two months, concomitantly with initiation of raltegravir, etravirine and emcitricabine/tenofovir, the patient recovered, gained weight, resumed walking and his CD4 counts rose from 270 to 450 cells/mm(3). A second EMG study 3 months after initiation of his new ART regimen showed compete recovery of the previously diagnosed peripheral neuropathy. In this report, we present a case of severe HIV-1-related acute demyelinating polyneuropathy which initiated after new generation PI darunavir/ritonavir was given and resolved after cessation of the drug without the use of immune-based therapies. The variety of HIV-related polyneuropathies will be discussed.

[Outcome of treatment with peg-interferon and ribavirin in HIV-HCV co-infected patients: "real life" single center experience].

BACKGROUND AND AIM: Recently, with the emergence of highly effective antiretroviral treatment (ART), chronic liver disease has become the leading cause of morbidity and mortality in co-infected HIV-HCV (Human immunodeficiency virus-Hepatitis C virus) patients. The overall SVR rate in this population remains unsatisfactory. The aim of this study was to evaluate the response to therapy in HIV-HCV co-infected patients in a single center. PATIENTS AND METHODS: Consecutive HIV-HCV co-infected patients were evaluated in the liver clinic between 2003 -2010. Liver needle biopsy was conducted in 100% of the patients. The patients were treated by a multidisciplinary team consisting of immunologists, hepatologists, social workers and nurses and a close follow-up was conducted. The 48 weeks duration of peg-interferon and ribavirin combination was used for all genotypes according to recent guidelines. Weight-adjusted ribavirin doses were applied. Treatment was initiated after stabilization of HIV parameters and successful weaning from drug and alcohol addiction. RESULTS: A total of 86 out of 143 HIV- HCV co-infected patients, were evaluated; 39 completed treatment. Of those 31 (77%) achieved SVR. Out of 22 genotype 1 patients, 18 (82%) achieved SVR. Six patients had spontaneous viral clearance and 8 are still receiving treatment. In 17 non-one genotype patients, the SVR rate was 76.4% (13 of 17 patients); 6 patients were defined as relapsers and non-responders. Overall adherence to the treatment was high. CONCLUSION: Measures, such as the use of a multidisciplinary approach, high adherence of physicians to the guidelines, weight-based ribavirin dose, and selecting patients who are ready to start therapy, can significantly improve the SVR rate in this difficult-to-treat patient population.