Circumcision and penile human papillomavirus prevalence in human immunodeficiency virus-infected men: heterosexual and men who have sex with men

AbstractMale circumcision is associated with a lower risk of penile human papillomavirus (HPV) infection in human immunodeficiency virus (HIV) uninfected men. Few studies have evaluated the role of male circumcision in penile HPV infection in HIV-infected men. The aim of this cross-sectional study was to examine the association between male circumcision and the prevalence of penile HPV infection among HIV-infected men—both men who have sex with men (MSM) and heterosexual men. Samples from 706 consecutive men included in the CARH-MEN cohort (overall 24% circumcised: 26% of MSM, 18% of heterosexual men) were examined by Multiplex-PCR. In the overall group (all HIV-infected men included), the prevalence of any penile HPV infection was 22% in circumcised men and 27% in uncircumcised men (OR = 1.0, 95% CI 0.6–1.6, adjusted analysis). In the circumcised group the overall prevalence of HPV infection was 22% in MSM and 24% in the heterosexual men, whereas in the uncircumcised group the prevalence was 26% and 28%, respectively. The prevalence of high-risk HPV types tended to be lower in the circumcised MSM (14% vs 21%, OR = 0.6, 95% CI 0.3–1.1, p 0.088), but it was similar in the heterosexual men (18% in circumcised vs 20% in uncircumcised). These results suggest that male circumcision may be associated with a lower prevalence of oncogenic high-risk penile HPV infection in HIV-infected MSM

Brain functional abnormality in schizo-affective disorder: an fMRI study.

Background.Schizo-affective disorder has not been studied to any significant extent using functional imaging. The aim of this study was to examine patterns of brain activation and deactivation in patients meeting strict diagnostic criteria for the disorder. METHOD: Thirty-two patients meeting research diagnostic criteria (RDC) for schizo-affective disorder (16 schizomanic and 16 schizodepressive) and 32 matched healthy controls underwent functional magnetic resonance imaging (fMRI) during performance of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups. RESULTS: Controls showed activation in a network of frontal and other areas and also deactivation in the medial frontal cortex, the precuneus and the parietal cortex. Schizo-affective patients activated significantly less in prefrontal, parietal and temporal regions than the controls, and also showed failure of deactivation in the medial frontal cortex. When task performance was controlled for, the reduced activation in the dorsolateral prefrontal cortex (DLPFC) and the failure of deactivation of the medial frontal cortex remained significant. CONCLUSIONS: Schizo-affective disorder shows a similar pattern of reduced frontal activation to schizophrenia. The disorder is also characterized by failure of deactivation suggestive of default mode network dysfunction

Effect of the human immunodeficiency virus type 1 reverse transcriptase polymorphism Leu-214 on replication capacity and drug susceptibility

A negative association between polymorphism Leu-214 and type-1 thymidine analogue mutations (TAM1) and a positive association with a clinically favorable virological response to thymidine analogue-based combination antiretroviral therapy have been described. In this study, the impact of Leu-214 on replication capacity and resistance to zidovudine (ZDV) of viruses containing TAM1 or TAM2 was determined. Leu-214 decreased the growth rate of viruses bearing Tyr-215, as well as their resistance to ZDV. This observation was confirmed by structural and molecular modeling data, suggesting a regulatory role for Leu-214 in the emergence and phenotypic resistance of TAM1

Monotherapy with boosted protease inhibitors as antiretroviral treatment simplification strategy in the clinical setting

Antiretroviral treatment simplification with darunavir/ritonavir or lopinavir/ritonavir monotherapy maintains sustained HIV viremia suppression in clinical trials. However, data about the efficacy of this strategy in routine clinical practice is still limited, and no direct comparison between darunavir/ritonavir and lopinavir/ritonavir has been performed to date. We retrospectively studied all HIV-1-infected subjects who initiated monotherapy with darunavir/ritonavir or lopinavir/ritonavir while having plasma VL<50 c/mL, and had at least 1 subsequent follow-up visit in our clinic. When two consecutive PI-monotherapy regimens were used, each regimen was considered separately. The primary endpoint was the percentage of patients who maintained virological suppression (HIV-1 VL <50 c/mL) through follow-up. Virological failure was defined as at least two consecutive HIV-1 VL >50 c/mL. We also evaluated other reasons for treatment discontinuation. Analyses were performed considering all regimens (full dataset analysis) either as “on treatment” or as “treatment switch equals failure”. Five hundred and seventy-three PI-monotherapy regimens corresponding to 520 subjects were included, 262 with darunavir/ritonavir and 311 with lopinavir/ritonavir. Medians (IQR) follow-up were 50 (26.3–107.6) and 85.6 (36.9–179.1) weeks for subjects on darunavir/ritonavir and lopinavir/ritonavir, respectively (p<0.001). Overall, 67 (11.7%) subjects experienced virological failure, 23 (8.7%) were on darunavir/ritonavir and 42 (13.5%) were on lopinavir/ritonavir (p=0.796). Two hundred and three (77.5%) patients on darunavir/ritonavir and 154 (49.5%) on lopinavir/ritonavir maintained virological suppression in the “treatment switch equals failure” (p=0.002). Other reasons for treatment discontinuation were gastrointestinal toxicity and dyslipidemia in 7.2% and 5.9% of cases, respectively. Gastrointestinal toxicities and dyslipidemia leading to treatment discontinuation were more frequent in patients on lopinavir/ritonavir (10.6% and 10.3%, respectively) than in patients on darunavir/ritonavir (3.1% and 0.8%, respectively). Monotherapy with darunavir/ritonavir or lopinavir/ritonavir as simplification strategy appears to be effective and safe in subjects with virological suppression in clinical practice. Virological efficacy seems to be similar between regimens. However, rates of discontinuation due to toxicities were higher in subjects on lopinavir/ritonavir than darunavir/ritonavir

Multimodal Brain Changes in First-Episode Mania: A Voxel-Based Morphometry, Functional Magnetic Resonance Imaging, and Connectivity Study

Background: Brain structural and functional changes in bipolar disorder (BD) are well-established findings, but it is uncertain whether these changes are already present in first episode mania (FEM). Methods: We compared 31 FEM subjects, with 31 healthy individuals matched for age, sex, and premorbid IQ. Whole-brain voxel-wise morphometry, functional magnetic resonance imaging during the n-back task, and a functional connectivity analysis were performed. Results: There were no volumetric differences between the 2 groups. During the 2-back task, FEM patients did not perform differently from controls and activated similar regions, but they showed less deactivation in the ventromedial prefrontal cortex (vmPFC), the anterior hub of the default mode network (DMN). They showed preserved functional connectivity between the vmPFC and other regions of the DMN, but increased connectivity with the superior frontal gyrus. Conclusions: The absence of volumetric changes in FEM patients suggests that these changes could be related to progression of the illness. On the other hand, the failure of deactivation of the anterior hub of the DMN is present from the onset of the illness and may represent a core pathophysiological feature of BD

Interleukin-2 therapy in patients with HIV infection

BACKGROUND Used in combination with antiretroviral therapy, subcutaneous recombinant interleukin-2 raises CD4+ cell counts more than does antiretroviral therapy alone. The clinical implication of these increases is not known. METHODS We conducted two trials: the Subcutaneous Recombinant, Human Interleukin-2 in HIV-Infected Patients with Low CD4+ Counts under Active Antiretroviral Therapy (SILCAAT) study and the Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT). In each, patients infected with the human immunodeficiency virus (HIV) who had CD4+ cell counts of either 50 to 299 per cubic millimeter (SILCAAT) or 300 or more per cubic millimeter (ESPRIT) were randomly assigned to receive interleukin-2 plus antiretroviral therapy or antiretroviral therapy alone. The interleukin-2 regimen consisted of cycles of 5 consecutive days each, administered at 8-week intervals. The SILCAAT study involved six cycles and a dose of 4.5 million IU of interleukin-2 twice daily; ESPRIT involved three cycles and a dose of 7.5 million IU twice daily. Additional cycles were recommended to maintain the CD4+ cell count above predefined target levels. The primary end point of both studies was opportunistic disease or death from any cause. RESULTS In the SILCAAT study, 1695 patients (849 receiving interleukin-2 plus antiretroviral therapy and 846 receiving antiretroviral therapy alone) who had a median CD4+ cell count of 202 cells per cubic millimeter were enrolled; in ESPRIT, 4111 patients (2071 receiving interleukin-2 plus antiretroviral therapy and 2040 receiving antiretroviral therapy alone) who had a median CD4+ cell count of 457 cells per cubic millimeter were enrolled. Over a median follow-up period of 7 to 8 years, the CD4+ cell count was higher in the interleukin-2 group than in the group receiving antiretroviral therapy alone--by 53 and 159 cells per cubic millimeter, on average, in the SILCAAT study and ESPRIT, respectively. Hazard ratios for opportunistic disease or death from any cause with interleukin-2 plus antiretroviral therapy (vs. antiretroviral therapy alone) were 0.91 (95% confidence interval [CI], 0.70 to 1.18; P=0.47) in the SILCAAT study and 0.94 (95% CI, 0.75 to 1.16; P=0.55) in ESPRIT. The hazard ratios for death from any cause and for grade 4 clinical events were 1.06 (P=0.73) and 1.10 (P=0.35), respectively, in the SILCAAT study and 0.90 (P=0.42) and 1.23 (P=0.003), respectively, in ESPRIT. CONCLUSIONS Despite a substantial and sustained increase in the CD4+ cell count, as compared with antiretroviral therapy alone, interleukin-2 plus antiretroviral therapy yielded no clinical benefit in either study. (ClinicalTrials.gov numbers, NCT00004978 [ESPRIT] and NCT00013611 [SILCAAT study].

From START to FINISH : the influence of osmotic stress on the cell cycle

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