Patterns of Sexualized Drug Use among Gay, Bisexual, and Other Men Who Have Sex with Men Living with HIV: Insights from a Comprehensive Study-The U-SEX-2 GESIDA 9416 Study.

BACKGROUND: Sexualized drug use (SDU) has become a public health concern in recent years. This study aimed to estimate the prevalence of SDU in gay, bisexual, and other men who have sex with men living with HIV (HIV + GBMSM) in Madrid during 2019/2020 and compare it with data from 2016/2017 in order to detect changes in patterns. METHODS: We analyzed the frequency of SDU in a sample of HIV + GBMSM attending HIV clinics, who participated in an anonymous online survey regarding sexual behavior and recreational drug use. The association between SDU, sexual risk behaviors, and STIs was evaluated. RESULTS: This study included 424 HIV + GBMSM, with a mean age of 40 (10.43) years. Overall, 94% (396) reported being sexually active. Additionally, 33% (140) had been diagnosed with an STI within the previous year. Moreover, 54% (229) had used drugs in the last year, 25% (107) engaged in SDU, and 16% (17) reported engagement in slamsex. After adjusting for confounding factors, SDU was associated with STIs, fisting, unprotected anal intercourse, and having >24 sexual partners in the last year. According to the DUDIT test scores, 80% (81) probably had problematic drug use (≥6 points), and 8% (8) probable drug dependence (≥25 points). When comparing the U-SEX-1 (2016/2017) data with the U-SEX-2 (2019/2020) data, no significant differences were found in the proportion of participants practicing SDU or slamming. CONCLUSIONS: The prevalence of SDU among HIV + GBMSM has remained high in recent years and without significant changes. The risk of problematic drug use among those who practice SDU is high. We observed a clear association between SDU, high-risk sexual behaviors, and STIs.

Incidence, Characteristics, Laboratory Findings and Outcomes in Acro-Ischemia in COVID-19 Patients.

AIM: In addition to its respiratory impact of SARS-CoV2, skin lesions of probable vascular origin have been described. This study intends to quantify the incidence of acro-ischemic lesions in COVID-19 infected adult subjects in our population, describing clinical patterns and associated findings. METHODS: All adult confirmed cases of COVID-19 infection who presented with acro-ischemic lesions and received care in our institution were prospectively enrolled up to May 15th, 2020. The variables included demographics, comorbidities, analytical parameters, clinical presentations and COVID-19 treatment. RESULTS: We enrolled 24 patients. The overall rate of acro-ischemic findings in COVID-19 patients was 1.2% [0.6% for outpatients and 2.9% for hospitalized (ICU and non-ICU patients)], but the observed incidence for acro-ischemia in ICU patients was remarkably higher (23.0%, p<0.001). We have described four different clinical patterns of acroischemia: atypical Raynaud´s phenomenon (ARP), (4); pseudo-pernio (PP), (5); severe microcirculatory ischemia with preserved pulse (SMI), (6); and dry gangrene with arteriosclerosis obliterans (AO), (9). Kendall´s τ correlation with lung disease severity was 0.877 (95% CI, 0.756 to 0.968); p<0.01). ARP individuals were predominantly female, while SMI appeared lately in elderly hospitalized subjects with better prognosis. AO occurred in patients with more comorbidity and younger than those with SMI. We observed other associated lesions of suggestive ischemic nature in other organs in all groups (15 patients of total sample). Plasma procalcitonin was significantly higher in patients who developed SMI (median and interquartile range: 9.99 (4.2, 12.3) mg/mL vs 0.26 (0.11, 0.89) mg/mL; p<0.001), and D-dimer level at hospital admission was significantly higher in AO patients (median and interquartile range: 1166 (1050, 2111) mg/L vs 502 (448, 777) mg/L; p<0.001). CONCLUSION: The observed risk for acroischemia in COVID-19 is high in ICU patients (23%). We have described four different clinical patterns of acroischemia (ARP, PP, SMI and AO) associated with lung disease severity. Authors have communicated various lesions of suggestive ischemic nature in other organs. Raynaud-like pattern is reported as a "novelty".

Randomised multicentre clinical trial to evaluate voriconazole pre-emptive genotyping strategy in patients with risk of aspergillosis: vorigenipharm study protocol.

INTRODUCTION: Invasive aspergillosis is the most important cause of morbidity and mortality in patients with haematological diseases. At present, voriconazole is the first-line treatment for invasive fungal disease. The pharmacokinetic interindividual variability of voriconazole depends on genetic factors. CYP450 is involved in 70%-75% of total metabolism of voriconazole, mainly CYP3A4 and CYP2C19, with the remaining 25%-30% of metabolism conducted by monooxygenase flavins. CYP2C19 single nucleotide polymorphisms could explain 50%-55% of variability in voriconazole metabolism. MATERIALS AND METHODS: The main objective is to compare efficiency of pre-emptive voriconazole genotyping with routine practice. The primary outcome is serum voriconazole on the fifth day within the therapeutic range. The secondary outcome is the combined variables of therapeutic failure and adverse events within 90 days of first administration, associated with voriconazole. A total of 146 patients at risk of invasive aspergillosis who will potentially receive voriconazole will be recruited, and CYP2C19 will be genotyped. If the patient ultimately receives voriconazole, they will be randomised (1:1 experimental/control). In the experimental arm, patients will receive a dose according to a pharmacogenetic algorithm, including CYP2C19 genotype and clinical and demographic information. In the control arm, patients will receive a dose according to clinical practice guidelines. In addition, a Spanish National Healthcare System (NHS) point-of-view cost-effectiveness evaluation will be performed. Direct cost calculations for each arm will be performed. CONCLUSION: This trial will provide information about the viability and cost-effectiveness of the implementation of a pre-emptive voriconazole genotyping strategy in the Spanish NHS. ETHICS AND DISSEMINATION: A Spanish version of this protocol has been evaluated and approved by the La Paz University Hospital Ethics Committee and the Spanish Agency of Medicines and Medical Devices. Trial results will be submitted for publication in an open peer-reviewed medical speciality-specific publication. TRIAL REGISTRATION NUMBER: Eudra-CT: 2019-000376-41 and NCT04238884; Pre-results.

Physicians' opinions on generic antiretroviral drugs and single-tablet regimen de-simplification for the treatment of HIV infection: a multicentre survey in Spain.

OBJECTIVES: To assess the attitudes and opinions about generic antiretroviral drugs (ARVs) and single-tablet regimen (STR) de-simplification among physicians prescribing HIV treatment in the cohort of the Spanish HIV/AIDS Research Network (CoRIS). METHODS: An online questionnaire with 27 structured questions was sent to all physicians (n=199) who prescribed ARVs among the 45 centres participating in the cohort. RESULTS: A total of 169 (84.9%) physicians answered the questionnaire. Only 4.1% of the physicians would never prescribe generic ARVs, but 53.3% would not prescribe them if the number of pills per day increased and 89.3% would not prescribe them if the number of doses per day increased. However, 84.0% of the physicians agreed to prescribe generic ARVs if doing so would decrease costs for the public healthcare system. The percentages of physicians stating that generic ARVs (compared with branded ones) would be associated with worse adherence, more adverse effects or more probability of virological failure, provided that the number of pills and doses per day would not change, were low: 0.6%, 7.7% and 3.6%, respectively. However, these percentages were much higher if the generic ARV entailed breaking an STR: 63.9%, 18.9% and 42.0%, respectively. Most physicians stated that they needed more information about the effectiveness and safety of generic ARVs and the price difference compared with their branded equivalents. CONCLUSIONS: Although most physicians were confident about prescribing generic ARVs, the majority had strong concerns about de-simplifying STR, and they also needed more information about generic drugs.

Uso de ribavirina en virus distintos de la hepatitis C. Una revisión de la evidencia / Use of ribavirin in viruses other than hepatitis C. A review of the evidence

La ribavirina es una molécula con actividad antiviral sobre diferentes virus. Ha encontrado su hueco en la práctica clínica de forma casi exclusiva para el tratamiento del virus de la hepatitis C, pero existen otras enfermedades que podrían beneficiarse de su empleo. Su disponibilidad para administración por vía oral, por vía intravenosa e inhalada es una característica beneficiosa. En este trabajo se realiza una revisión de las indicaciones en las principales agencias del medicamento (española, europea y americana), así como de otras posibles indicaciones, principalmente sobre fiebres hemorrágicas y coronavirus

Ribavirin is a molecule with antiviral activity against different viruses. In clinical practice, it has made its niche almost exclusively for the treatment of the hepatitis C virus. However, there are other diseases in which it could be of benefit and it has the advantage of being suitable for oral, intravenous and inhaled administration. We conducted a review of the indications of the main drug agencies (Spanish, European and American) and other possible indications, mainly haemorrhagic fevers and coronavirus

Use of ribavirin in viruses other than hepatitis C. A review of the evidence. / Uso de ribavirina en virus distintos de la hepatitis C. Una revisión de la evidencia.

Ribavirin is a molecule with antiviral activity against different viruses. In clinical practice, it has made its niche almost exclusively for the treatment of the hepatitisC virus. However, there are other diseases in which it could be of benefit and it has the advantage of being suitable for oral, intravenous and inhaled administration. We conducted a review of the indications of the main drug agencies (Spanish, European and American) and other possible indications, mainly haemorrhagic fevers and coronavirus.

[Use of ribavirin in viruses other than hepatitis C. A review of the evidence]. / Uso de ribavirina en virus distintos de la hepatitis C. Una revisión de la evidencia.

Ribavirin is a molecule with antiviral activity against different viruses. In clinical practice, it has made its niche almost exclusively for the treatment of the hepatitis C virus. However, there are other diseases in which it could be of benefit and it has the advantage of being suitable for oral, intravenous and inhaled administration. We conducted a review of the indications of the main drug agencies (Spanish, European and American) and other possible indications, mainly haemorrhagic fevers and coronavirus.

Switching from tenofovir containing regimens to boosted protease inhibitor monotherapy: Impact on renal function / Simplificación a monoterapia con inhibidores de la proteasa potenciados desde regímenes con tenofovir: impacto en la función renal

OBJECTIVE: To evaluate the effect on creatinine clearance (CG-CrCl, Cockcroft-Gault equation) of switching to boosted protease inhibitor (PI) monotherapy in patients receiving a triple drug antiretroviral regimen containing TDF. METHODS: All patients who had received a TDF-containing regimen for at least one year and had been switched to PI monotherapy were included. A rapid decrease in CG-CrCl during exposure to TDF was defined as a decrease in CG-CrCl at least five times higher than the expected due to age (0.4 ml/min/year by the years of exposure to TDF). In this subgroup of patients, we considered improvement if the last value of CG-CrCl on PI monotherapy was 10% higher than the last value of CG-CrCl before switching to PI monotherapy. A multivariate logistic regression was constructed to identify factors associated to renal improvement after switching to bPI monotherapy. RESULTS: 64 patients included. The median (IQR) annual change in CG-CrCl during PI monotherapy was significantly lower than the median (IQR) annual change while exposed to TDF [−0.9 (−4.7 to +2.8) ml/min vs. −4 (−8 to −1) ml/min, p = 0.001]. 44 patients experienced a rapid decline during TDF exposition. After switch to PI monotherapy, 15/44 (34%, 95% CI: 21-50%) had an improved CG-CrCl and 16/44 (36%, CI 23-52%) experienced a further decline in CG-CrCl. The only variable associated to CG-CrCl improvement was a more rapid CG-CrCl decline in the last year of exposure to TDF. CONCLUSION: Switching to PI monotherapy partially reversed CG-CrCl decrease associated to TDF use, especially in patients with a more rapid decline while receiving TDF

OBJETIVO: Evaluar el efecto de la retirada de TDF en el aclaramiento de creatinina medido mediante la fórmula de Cockcroft-Gault (CG-ClCr) en pacientes que simplifican a monoterapia con un inhibidor de la proteasa (IP) potenciado. MÉTODOS: Se incluyeron todos los pacientes que habían recibido un regimen con TDF durante al menos un año y que posteriormente habían sido simplificados a monoterapia. Se definió como rápida disminución del CG-CrCl durante la exposición a TDF a una disminución del CG-CrCl de al menos 5 veces mayor de lo esperado para la edad (0.4 ml/min/año por los años de exposición al TDF). En este subgrupo de pacientes, se consideró mejoría si el último valor del CG-CrCl durante la exposición a monoterapia era un 10% más alto que el último valor de CG-CrCl antes de la simplificación. Se construyó una regresión logística multivariante para identificar los factores asociados a mejoría del CG-ClCr. RESULTADOS: Se incluyeron 64 pacientes. La mediana del cambio anual en el CG-CrCl durante la exposición a monoterapia fue significativamente inferior a la mediana del cambio anual durante la exposición a TDF (p = 0.001). 44 pacientes presentaron una rápida disminución del CG-CrCl durante la exposición a TDF. Después de la simplificación, 15/44 (34%, IC 95%: 21-50%) presentaron una mejoría del CG-CrCl y 16/44 (36%, IC 23-52%) continuaron con un empeoramiento en el CG-CrCl. La única variable asociada con mejoría fue haber presentado una disminución más rápida del CG-CrCl en el último año de exposición a TDF. CONCLUSIÓN: La simplificación a monoterapia revierte parcialmente la disminución del CG-CrCl asociada al TDF, especialmente en los pacientes que presentan una disminución más rápida durante la exposición a TDF

Switching from tenofovir containing regimens to boosted protease inhibitor monotherapy: Impact on renal function.

OBJECTIVE: To evaluate the effect on creatinine clearance (CG-CrCl, Cockcroft-Gault equation) of switching to boosted protease inhibitor (PI) monotherapy in patients receiving a triple drug antiretroviral regimen containing TDF. METHODS: All patients who had received a TDF-containing regimen for at least one year and had been switched to PI monotherapy were included. A rapid decrease in CG-CrCl during exposure to TDF was defined as a decrease in CG-CrCl at least five times higher than the expected due to age (0.4ml/min/year by the years of exposure to TDF). In this subgroup of patients, we considered improvement if the last value of CG-CrCl on PI monotherapy was 10% higher than the last value of CG-CrCl before switching to PI monotherapy. A multivariate logistic regression was constructed to identify factors associated to renal improvement after switching to bPI monotherapy. RESULTS: 64 patients included. The median (IQR) annual change in CG-CrCl during PI monotherapy was significantly lower than the median (IQR) annual change while exposed to TDF [-0.9 (-4.7 to +2.8) ml/min vs. -4 (-8 to -1) ml/min, p=0.001]. 44 patients experienced a rapid decline during TDF exposition. After switch to PI monotherapy, 15/44 (34%, 95% CI: 21-50%) had an improved CG-CrCl and 16/44 (36%, CI 23-52%) experienced a further decline in CG-CrCl. The only variable associated to CG-CrCl improvement was a more rapid CG-CrCl decline in the last year of exposure to TDF. CONCLUSION: Switching to PI monotherapy partially reversed CG-CrCl decrease associated to TDF use, especially in patients with a more rapid decline while receiving TDF.

Dual treatment with atazanavir-ritonavir plus lamivudine versus triple treatment with atazanavir-ritonavir plus two nucleos(t)ides in virologically stable patients with HIV-1 (SALT): 48 week results from a randomised, open-label, non-inferiority trial.

BACKGROUND: Problems associated with lifelong antiretroviral therapy, such as need for strict adherence, drug-related toxic effects, difficulties with treatment schedules, and cost, mean that simplification strategies should be sought. We aimed to explore the efficacy and safety of dual treatment with atazanavir-ritonavir plus lamivudine as an option to switch to from standard combination antiretroviral therapy in patients with an HIV-1 infection who are virologically suppressed. METHODS: In this randomised, open-label, non-inferiority trial, we recruited patients aged 18 years and older with chronic HIV-1 infection and no previous treatment failure or resistance, and with HIV-1 RNA of less than 50 copies per mL for at least 6 months, negative hepatitis B virus surface antigen, and good general health, from 30 hospitals in Spain. Exclusion criteria were switch in antiretroviral therapy during the previous 4 months, previous virological failure, pregnancy or breastfeeding, Gilbert's syndrome, use of contraindicated drugs, grade 4 laboratory abnormalities, and previous intolerance to any of the study drugs. We randomly assigned patients (1:1; stratified by active hepatitis C virus infection and previous treatment; computer-generated random number sequence) to dual treatment with oral atazanavir (300 mg once daily) and ritonavir (100 mg once daily) plus lamivudine (300 mg once daily) or triple treatment with oral atazanavir (300 mg once daily) and ritonavir (100 mg once daily) plus two nucleos(t)ide reverse transcriptase inhibitors at the discretion of the investigators. The primary endpoint was virological response, defined as HIV-1 RNA of less than 50 copies per mL at week 48, in the per-protocol population, with a non-inferiority margin of 12%. We included patients who received at least one dose of the study drug in the safety analysis. This study is registered at ClinicalTrials.gov, number NCT01307488. FINDINGS: Between Sept 29, 2011, and May 2, 2013, we randomly assigned 286 patients (143 [50%] to each group). At week 48 in the per-protocol population, 112 (84%) of 133 patients had virological response in the dual-treatment group versus 105 (78%) of 135 in the triple-treatment group (difference 6% [95% CI -5 to 16%), showing non-inferiority at the prespecified level. 14 (5%) patients developed severe adverse events (dual treatment six [4%]; triple treatment eight [6%]), none of which we deemed related to the study drug. Grade 3-4 adverse events were similar between groups (dual treatment 77 [55%] of 140; triple treatment 78 [55%] of 141). Treatment discontinuations were less frequent in the dual-treatment group (three [2%]) than in the triple-treatment group (ten [7%]; p=0·047). INTERPRETATION: In our trial, dual treatment was effective, safe, and non-inferior to triple treatment in patients with an HIV-1 infection who are virologically suppressed who switch antiretroviral therapy because of toxic effects, intolerance, or simplification. This combination has the potential to suppress some of the long-term toxic effects associated with nucleos(t)ide reverse transcriptase inhibitors, preserve future treatment options, and reduce the cost of antiretroviral therapy. FUNDING: Bristol Myers-Squibb and Fundación SEIMC-GESIDA.

A comparative study of neurocognitively impaired patients receiving protease inhibitor monotherapy or triple-drug antiretroviral therapy.

In a cross-sectional study of aviremic neurocognitively impaired patients receiving protease inhibitors as triple-drug therapy (n = 30) or as monotherapy (n = 22), we found no statistically significant differences in the types of cognitive domains involved or severity of cognitive deficit. Cerebrospinal fluid concentrations of total proteins, total tau, myelin basic protein, neuron-specific enolase, ß2 microglobulin, S100B protein, or prevalence of cerebrospinal fluid HIV-RNA detection by standard (6.3% vs 7.1% P = 1) or ultrasensitive assays (50% vs 71.4%, P = 0.28) were similar in both groups. These results do not suggest important differences in the pattern of neurocognitive impairment between groups receiving very different antiretroviral strategies.

A prospective cohort study of neurocognitive function in aviremic HIV-infected patients treated with 1 or 3 antiretrovirals.

BACKGROUND: The evolution of neurocognitive performance in aviremic human immunodeficiency virus (HIV)-positive patients treated with <3 antiretrovirals is unknown. METHODS: We prospectively included aviremic (≥1 year) HIV-positive patients, without concomitant major neurocognitive confounders, currently receiving boosted lopinavir or darunavir as monotherapy (n = 67) or triple antiretroviral therapy (ART) (n = 67) for ≥1 year. We evaluated neurocognitive function (7 domains) at baseline and after 1 year. We performed analysis of covariance to evaluate if 1 additional year of exposure to monotherapy compared with triple ART had an effect on Global Deficit Score (GDS) changes after adjustment for potential confounders. We also compared the evolution of neurocognitive performance and impairment rates. RESULTS: Intention-to-treat analysis showed that monotherapy did not influence 1-year GDS change after adjustment for significant confounders (age, ethnicity, duration of therapy, hepatitis C virus status, and HOMA-IR index); the adjusted effect was -0.04 (95% confidence interval, -.14 to .05; P = .38). Neurocognitive stability was observed with monotherapy and triple therapy (GDS crude mean change, -0.09 [95% confidence interval, -.16 to -.01] vs -0.08 [-.14 to -.02]), after 1 year of follow-up, similar proportions of patients changed neurocognitive status from impaired to unimpaired (monotherapy, 4 of 18 [22.2%]; triple therapy, 4 of 19 [21.1%]; P = .91) and vice versa (monotherapy, 5 of 44 [10.2%] and triple therapy, 3 of 45 [6.3%]; P = .48). Similar results were observed in an on-treatment analysis and with use of clinical ratings instead of GDS changes. CONCLUSIONS: The number of antiretrovirals included in the ART regimen does not seem to influence the evolution of neurocognitive function in HIV-infected patients with suppressed plasma viremia.

Inflammatory, procoagulant markers and HIV residual viremia in patients receiving protease inhibitor monotherapy or triple drug therapy: a cross-sectional study.

BACKGROUND: Protease inhibitor monotherapy is associated with more frequent episodes of viral rebounds above 50 copies/mL than triple therapy. OBJECTIVE: To evaluate if, compared to triple-drug therapy, protease inhibitor monotherapy is associated with increased levels of inflammatory/procoagulant markers and more frequent plasma residual viremia detection. METHODS: In this cross-sectional study, we included patients treated for ≥ 1 year with darunavir/ritonavir or lopinavir/ritonavir as monotherapy (n=72) or with two nucleos(t)ides (n=74). All samples were tested for CRP, IL-6, fibrinogen and D-dimer. Residual viremia was determined using an ultrasensitive qualitative nested-PCR of the HIV pol gene with a limit of detection of 1 copy of HIV-RNA. RESULTS: We found no differences in levels of inflammatory/procoagulant markers or in the proportion of patients with plasma residual viremia detection by treatment group. CONCLUSION: The long-term treatment with protease inhibitor monotherapy in the setting of routine clinical practice is not associated with a higher prevalence of plasma residual viremia or more elevated inflammatory/procoagulant markers levels than triple drug therapy.

Pattern of neurocognitive function in patients receiving boosted protease inhibitor monotherapy: a detailed neuropsychological study.

It is unknown if, compared to a triple drug antiretroviral therapy, boosted protease inhibitor monotherapy leads to worse results in specific neuropsychological processes. In our study, we included patients virologically suppressed (≥1 year), on antiretroviral therapy, without concomitant major neurocognitive confounders, receiving boosted lopinavir or darunavir as monotherapy (n = 96) or as triple therapy with two nucleoside reverse transcriptase inhibitors (n = 95). All patients underwent a comprehensive neuropsychological test battery (14 neuropsychological measures, covering seven domains). Both groups were compared in average score distributions and rates of neuropsychological deficits. Similar comparisons were conducted only for patients with neurocognitive impairment. In the adjusted analysis, we found only small differences between groups in the entire sample: better verbal learning (p = 0.02; d = 0.28) and verbal recall scores (p < 0.01; d = 0.25) in patients on boosted protease inhibitor monotherapy and slightly better motor skills with dominant hand (p = 0.02; d = 0.23) scores in patients on triple therapy. No greater proportion of deficits in the protease inhibitor monotherapy group was found in any neuropsychological measure. In neurocognitively impaired patients, we found similar outcomes in verbal learning, verbal recall, and motor skills with dominant hand but with larger effect sizes. Close similarities in the neurocognitive pattern between groups question the clinical relevance of the number of neuroactive drugs included in the regimen. These results also suggest that peripheral viral load control may be a good indicator of brain protection.

Virological response to short-course maraviroc monotherapy does not predict viral tropism in HIV-1-infected treatment-naive patients.

OBJECTIVES: We aimed to evaluate whether virological response to a short course of maraviroc monotherapy could predict HIV-1 tropism. METHODS: A clinical trial was performed in HIV-1 treatment-naive patients infected with R5- or non-R5-tropic virus determined using the Trofile(®) assay, with >1000 HIV-1 RNA copies/mL. Maraviroc was administered for 10 days. Viral load was measured at baseline and days 4, 7, 10 and 28. The main outcome measurement was the decline in HIV-1 RNA at day 10. The trial was registered in the ClinicalTrials.gov database (NCT01060618; TROPISMVC). RESULTS: Forty patients [30 R5 and 10 dual/mixed (D/M)] were recruited. There was a significant decrease in HIV-1 RNA after 10 days of maraviroc treatment in patients with R5-tropic virus (median 1.52 log10 RNA copies/mL; 95% CI 1.23-1.63; P < 0.0001), but also in patients with D/M-tropic virus (median 1.62 log(10) RNA copies/mL; 95% CI 0.33-1.88; P = 0.00024). The difference in the HIV-1 RNA decrease (-0.16 log(10) RNA copies/mL; 95% CI -0.53 to 0.22) was not significant (P = 0.410). A decrease >0.5 log(10) RNA copies/mL was found in 96.3% of patients with R5-tropic virus and in 70% of patients with D/M-tropic virus (P = 0.052). The differences were not significant when a decline of 1 log(10) RNA copies/mL was considered (92.6% versus 70%; P = 0.11). CONCLUSIONS: Treatment-naive patients infected with R5- or D/M-tropic virus have similar virological responses to a short course of maraviroc monotherapy. This clinical test thus cannot be used as a surrogate marker of viral tropism in this population.

Neurocognitive impairment in patients treated with protease inhibitor monotherapy or triple drug antiretroviral therapy.

BACKGROUND: In patients who remain virologically suppressed in plasma with triple-drug ART a switch to protease inhibitor monotherapy maintains high rates of suppression; however it is unknown if protease inhibitor monotherapy is associated to a higher rate of neurocognitive impairment. METHODS: In this observational, cross-sectional study we included patients with plasma virological suppression (≥ 1 year) without concomitant major neurocognitive confounders, currently receiving for ≥ 1 year boosted lopinavir or darunavir as monotherapy or as triple ART. Neurocognitive impairment was defined as per the 2007 consensus of the American Association of Neurology. The association between neurocognitive impairment and protease inhibitor monotherapy, adjusted by significant confounders, was analysed. RESULTS: Of the 191 included patients--triple therapy: 96, 1-2 years of monotherapy: 40 and >2 years of monotherapy: 55--proportions (95% CI) with neurocognitive impairment were: overall, 27.2% (20.9-33.6); triple therapy, 31.6% (22.1-41.0); short-term monotherapy, 25.0% (11.3-38.7); long-term monotherapy: 21.4% (10.5-32.3); p = 0.38. In all groups, neurocognitive impairment was mildly symptomatic or asymptomatic by self-report. There were not significant differences in Global Deficit Score by group. In the regression model confounding variables for neurocognitive impairment were years on ART, ethnicity, years of education, transmission category and the HOMA index. Adjusted by these variables the Odds Ratio (95% CI) for neurocognitive impairment of patients receiving short-term monotherapy was 0.85 (0.29-2.50) and for long-term monotherapy 0.40 (0.14-1.15). CONCLUSIONS: Compared to triple drug antiretroviral therapy, monotherapy with lopinavir/ritonavir or darunavir/ritonavir in patients with adequate plasma suppression was not associated with a higher rate of asymptomatic neurocognitive impairment than triple drug ART.

Is etravirine and two nucleosides an option for HIV with an isolated K103N mutation?

We report long-term virologic response to etravirine and tenofovir/emtricitabine in four HIV-1-infected patients who had prior standard genotypic resistance testing showing an isolated K103N mutation (three acquired, one transmitted). In three patients tested, the K103N mutation was detected in cellular HIV-1 DNA whereas remaining suppressed on etravirine plus tenofovir/emtricitabine.

Protease inhibitor monotherapy: what is its role?

Protease inhibitor monotherapy has been shown to be effective in maintaining long-term viral suppression in a majority of patients. Withdrawal of nucleoside analogues can prevent long-term toxicity related to these drugs. Clinical trials have recently reported preliminary data on the beneficial effect of protease inhibitor monotherapy on body fat distribution and bone metabolism. Some of the uncertainties possibly associated with protease inhibitor monotherapy such as the increased risk of neurological events and a higher level of subclinical inflammation will be discussed in this review.