Screening for asymptomatic STIs in HIV-infected men who have sex with men.

We aimed to study the prevalence, characteristics and risk factors of asymptomatic sexually transmitted infections (STIs) in HIV-infected men who have sex with men (MSM). We conducted a prospective cross-sectional study, including asymptomatic HIV-infected MSM attending regular visits between December 2014 and December 2017. Of the 301 patients included, 60 patients (19.9%) presented at least one STI. The most common STI was syphilis (33 of 69 STIs), followed by chlamydia (19 of 69), gonorrhoea (10 of 69), hepatitis C virus (4 of 69) and lymphogranuloma venereum (3 of 69). Illicit drug use during sex was the only variable significantly associated with the presence of an STI on multivariate analysis (OR 2.13; 95% CI 1.17-3.89). We were unable to identify a subgroup of patients where we could potentially avoid STI screening. Our findings support current guidelines that recommend routine screening for all HIV-infected MSM regardless of their self-reported sexual history.

Incidence of malignancy in a Spanish cohort of patients infected by the human immunodeficiency virus. / Incidencia de neoplasias en una cohorte española de pacientes con infección por el virus de la inmunodeficiencia humana.

INTRODUCTION: A higher incidence of malignancies has been described in patients with HIV infection compared to the general population. PATIENTS AND METHODS: Observational retrospective study in patients with HIV infection followed up at the Vall d'Hebron University Hospital (Barcelona, Spain) between 2009 and 2017. The objective of this research was to estimate the incidence of malignancies in HIV patients and their surveillance. Age and sex-adjusted incidence was compared to the incidence calculated by the Spanish Cancer Registry network (REDECAN) in 2015. RESULTS: We included 2,773 patients (41,238 patients-year). Two hundred and eleven malignancies were diagnosed in 182 patients. Non-AIDS defining cancers accounted for 78.2% of the malignancies. The global incidence of cancer was 485 cases per 100,000 person-years. Twenty-year mortality rate was 31.2% in patients with cancer and 7.8% in patients without cancer. In men, adjusted for age, the incidence of malignancies was higher than the incidence in the general population (978.4 vs. 641 cases per 100,000 person-years, P<.001). The most common malignancies in men were lung cancer, Kaposi sarcoma and Hodgkin lymphoma. In women, the incidence of malignancies was not higher than in the general population (340.6 vs. 404.7 cases per 100,000 person-years, P=.27). The most common malignancies among women were lung cancer, head and neck cancer, cervical cancer and Hodgkin's lymphoma. CONCLUSIONS: Men with HIV infection showed a statistically significant higher incidence of malignancies compared to the general Spanish population. Lung cancer was the most common non-AIDS defining cancer.

Expression of CD20 after viral reactivation renders HIV-reservoir cells susceptible to Rituximab.

The identification of exclusive markers to target HIV-reservoir cells will represent a significant advance in the search for therapies to cure HIV. Here, we identify the B lymphocyte antigen CD20 as a marker for HIV-infected cells in vitro and in vivo. The CD20 molecule is dimly expressed in a subpopulation of CD4-positive (CD4+) T lymphocytes from blood, with high levels of cell activation and heterogeneous memory phenotypes. In lymph node samples from infected patients, CD20 is present in productively HIV-infected cells, and ex vivo viral infection selectively upregulates the expression of CD20 during early infection. In samples from patients on antiretroviral therapy (ART) this subpopulation is significantly enriched in HIV transcripts, and the anti-CD20 monoclonal antibody Rituximab induces cell killing, which reduces the pool of HIV-expressing cells when combined with latency reversal agents. We provide a tool for targeting this active HIV-reservoir after viral reactivation in patients while on ART.

Pharmacokinetics of darunavir/cobicistat and etravirine alone and co-administered in HIV-infected patients.

Objectives: To determine the effect of etravirine on the pharmacokinetics of darunavir/cobicistat and vice versa. Safety and tolerability of this combination were also evaluated. Methods: Open-label, fixed-sequence trial in two cohorts of HIV-infected patients on therapy with darunavir/cobicistat 800/150 mg once daily (DRV cohort; n = 15) or etravirine 400 mg once daily (ETR cohort; n = 15). Etravirine or darunavir/cobicistat were added on days 1-14 and 1-7 in participants in the DRV or ETR cohort, respectively. Full pharmacokinetic profiles were obtained on days 0 and 14 in the DRV cohort, and on days 0 and 7 in the ETR cohort. Darunavir, cobicistat and etravirine pharmacokinetic parameters [AUC0-24, Cmax and trough concentrations in plasma (C24)] were calculated for each individual by non-compartmental analysis and were compared using linear mixed-effects models. Adverse events and HIV-1 RNA in plasma were monitored. Results: Etravirine co-administration decreased cobicistat AUC0-24, Cmax and C24 by 30%, 14% and 66%, respectively. Although darunavir AUC0-24 and Cmax were unchanged by etravirine, darunavir C24 was 56% lower for darunavir/cobicistat co-administered with etravirine relative to darunavir/cobicistat alone. Etravirine pharmacokinetics were unchanged by darunavir/cobicistat. Treatments were well tolerated, and HIV-1 RNA remained undetectable in all participants. Conclusions: Although etravirine pharmacokinetics was unchanged by darunavir/cobicistat, there was a significant decrease in cobicistat exposure and in darunavir C24 when darunavir/cobicistat was co-administered with etravirine. Boosting darunavir with ritonavir instead of with cobicistat may be preferred if darunavir is to be combined with etravirine in clinical practice.

Executive summary of the GESIDA/National AIDS Plan Consensus Document on antiretroviral therapy in adults infected by the human immunodeficiency virus (updated January 2015).

In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation vary depending on the CD4+ T-lymphocyte count, the presence of opportunistic infections or comorbid conditions, age, and the efforts to prevent the transmission of HIV. The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should comprise three drugs, namely, two nucleoside reverse transcriptase inhibitors (NRTI) and one drug from another family. Three of the recommended regimens, all of which have an integrase strand transfer inhibitor (INSTI) as the third drug, are considered a preferred regimen; a further seven regimens, which are based on an INSTI, an non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor boosted with ritonavir (PI/r), are considered alternatives. The reasons and criteria for switching ART are presented both for patients with an undetectable PVL and for patients who experience virological failure, in which case the rescue regimen should include three (or at least two) drugs that are fully active against HIV. The specific criteria for ART in special situations (acute infection, HIV-2 infection, pregnancy) and comorbid conditions (tuberculosis and other opportunistic infections, kidney disease, liver disease, and cancer) are updated.

Executive summary of the GeSIDA/National AIDS Plan consensus document on antiretroviral therapy in adults infected by the human immunodeficiency virus (updated January 2014).

In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation varies with clinical circumstances, number of CD4 cells, comorbid conditions and prevention of transmission of HIV. The objective of ART is to achieve an undetectable plasma viral load. Initial ART should always comprise a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors and a third drug from a different family (non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or integrase inhibitor). This update presents the causes and criteria for switching ART in patients with undetectable plasma viral load and in cases of virological failure. An update is also provided for the specific criteria for ART in special situations (acute infection, HIV-2 infection, and pregnancy) and with comorbid conditions (tuberculosis or other opportunistic infections, kidney disease, liver disease, and cancer).

Abacavir coadministration does not interfere with the suppressive activity of ribavirin in an HCV replicon system.

BACKGROUND: HCV is a major cause of morbidity and mortality in HIV-coinfected patients. Several observational studies have suggested that HCV response to pegylated interferon and ribavirin is lower in HIV-coinfected patients treated with abacavir. It has been postulated that abacavir could compete with ribavirin to be phosphorylated, leading to a reduction in the active form of the drug (triphosphorylated ribavirin). Here, we studied the effect of abacavir, tenofovir or lamivudine addition on the suppressive activity of ribavirin in an HCV RNA replicon system. METHODS: We used the human hepatoma HuH-7 cell clone 9B containing the HCV genotype 1b replicon I389/NS3-3'. Cells were treated for 24 h with ribavirin (0, 10 and 50 µM) plus abacavir, tenofovir or lamivudine at doses of 0, 10 and 50 µM and HCV RNA production was quantified by real-time PCR in triplicate assays. Results were expressed as mean±SD of the HCV RNA produced per cell (log(10) IU/cell). Means were compared using the Student's t-test. RESULTS: Ribavirin treatment produced a dose-dependent suppression of HCV RNA production by the replicon system. Combination of ribavirin and interferon resulted in an additive antiviral activity. The addition of abacavir did not modify the suppressive activity of ribavirin on the replicon HCV RNA expression. Similar results were obtained when ribavirin was used in combination with tenofovir or lamivudine. CONCLUSIONS: In a subgenomic HCV RNA replicon system, the antiviral effect of ribavirin was not modified by the addition of abacavir, tenofovir or lamivudine.

HIV-1 infection in subjects older than 70: a multicenter cross-sectional assessment in Catalonia, Spain.

We designed a multicenter cross-sectional study to describe the epidemiological characteristics of the HIV-1-infected population aged 70 years or more in our setting. 179 individuals from eight university hospitals in Barcelona, Spain, were included, representing 1.5% of HIV-1 infected subjects followed during 2008. Most subjects were male (76%) and had acquired HIV infection through sexual intercourse (87%); 69% had been diagnosed with HIV-1 after their sixties. The CD4 cell counts at HIV-1 diagnosis were < 200 cells/mm(3) in 52% of individuals, whereas this was only seen in 34% of subjects from a published cohort including younger HIV- infected adults from the same setting [1]. Most of our patients were on HAART, had undetectable HIV-1 viremia and the most recent median CD4 cell counts were >or= 350 cells/mm(3). 154 subjects had at least one comorbid condition, including dyslipidemia (54%), hypertension (36%), hyperglycemia or diabetes (30%), cardiovascular disease (23%), chronic renal failure (18%), history of neoplasia (17%) and cognitive impairment (11%). Lipodystrophy was reported in 58% of individuals. Rates of hypercholesterolemia, diabetes and cancer were higher than those reported in unselected local population (28%, 17% and 7%, respectively). The study participants were taking an average of 2.97 drugs (range 1-10) other than antiretrovirals. In conclusion, the elder population infected with HIV-1 is likely being diagnosed late and at lower CD4+ counts and is frequently affected by comorbidities and co-medication. Based on our findings, we suggest some recommendations regarding the management of this growing population.

Early monitoring of ribavirin serum concentration is not useful to optimize hepatitis C virus treatment in HIV-coinfected patients.

BACKGROUND: Emerging data suggest that higher ribavirin (RBV) exposure could improve early hepatitis C virus (HCV) response. Furthermore, interindividual RBV bioavailability shows high variation, and dose-limiting haemolytic anaemia is a common adverse event. Therefore, it has been suggested that monitoring RBV serum levels could be used to drive dose modification and to optimize management of HCV-infected patients receiving combination treatment. METHODS: To assess the effect of RBV serum levels on HCV RNA clearance at week 4 and 12 of treatment, and to determine the correlation between RBV serum concentration and haemoglobin decrease, RBV trough levels were measured by HPLC in stored serum samples obtained from 94 HCV-HIV-coinfected patients at week 4 and 12 of treatment with peginterferon-alpha2b (1.5 microg/kg/weekly) pIus ribavirin (800-1,200 mg/day). RESULTS: The median RBV levels increased from 1.70 microg/ml at week 4 to 1.97 microg/ml at week 12 of treatment (P = 0.001) and were independently predicted by weight-adjusted dose of RBV and co-administration of tenofovir. Haemoglobin drop was higher among patients who received zidovudine and weakly correlated with RBV level. Although RBV concentration was lower in genotype 1 or 4 HCV-infected patients who cleared the virus at treatment week 4, the ability of this parameter to discriminate between responders and non-responders at treatment week 4 and 12 was poor. CONCLUSION: Intracellular RBV accumulation early in treatment might improve the kinetics of HCV response in difficult to treat patients. Although this hypothesis and the potential interaction between RBV and tenofovir warrant further research, our data do not support RBV serum monitoring as a tool to optimize treatment in HCV-HIV-coinfected patients.

Amphotericin B lipid complex versus meglumine antimoniate in the treatment of visceral leishmaniasis in patients infected with HIV: a randomized pilot study.

Optimal treatment for HIV-related visceral leishmaniasis (VL) has still to be established. A pilot clinical trial was carried out in 57 HIV-VL coinfected patients to compare the efficacy and safety of amphotericin B lipid complex (ABLC) versus meglumine antimoniate. The patients were randomized to receive either ABLC 3 mg/kg/day for 5 days (ABLC-5, 18 patients), ABLC 3 mg/kg/day for 10 days (ABLC-10, 20 patients) or meglumine antimoniate 20 mg Sbv /kg/day for 28 days (19 patients). Treatment was considered successful if parasites were not detected in a bone marrow aspirate after treatment. Parasitological cure was attained in 33% (95% CI: 13%-59%) of the ABLC-5 group, in 42% (95% CI: 16%-62%) of the ABLC-10 group and in 37% (95% CI: 16%-62%) of the meglumine antimoniate group (P = 0.94). Eight out of 19 patients administered antimoniate discontinued treatment prematurely following serious adverse events, compared with one in the ABLC groups (P = 0.0006). The efficacy of ABLC is similar to meglumine antimoniate, but the severity of toxicity in the treatment of HIV-VL is lower with ABLC.

Clinical course and prognostic factors of progressive multifocal leukoencephalopathy in patients treated with highly active antiretroviral therapy.

We analyzed survival rates, neurologic function, and prognostic factors for 118 consecutive patients with acquired immunodeficiency syndrome-associated progressive multifocal leukoencephalopathy (PML) treated with highly active antiretroviral therapy (HAART) in 11 hospitals throughout Spain. Seventy-five patients (63.6%) remained alive for a median of 114 weeks (2.2 years) after diagnosis of PML. Neurologic function of the survivors was categorized as cure or improvement in 33, stabilization or worsening in 40, and unknown in 2. The baseline CD4+ cell count was the only variable found with prognostic significance. The odds ratio of death was 2.71 (95% confidence interval, 1.19-6.15) for patients with CD4+ cell counts of <100 cells/microL, compared with patients who had CD4+ cell counts of > or =100 cells/microL. One-third of patients with PML died despite receipt of HAART; neurologic function improved in approximately one-half of the survivors. A CD4+ cell count of <100 cells/microL was associated with higher mortality.