Anal Dysplasia Screening in People Living with HIV: Long-Term Follow-Up in a Large Cohort from Northwest Spain.

Anal squamous cell carcinoma (SCC) is not a common disease in the general population, although its incidence is higher in people living with human immunodeficiency virus (PLWH). Anal SCC is caused by human papillomavirus (HPV) infection and arises from premalignant lesions termed squamous intraepithelial lesions (SILs). SIL surveillance programs are based on the early detection and treatment of SILs, especially those with a higher risk of transforming into cancer. An anal surveillance program has been under development in our institution since 2011. In this context, we performed a retrospective cohort study at the anal dysplasia unit of Álvaro-Cunqueiro Hospital (Spain). Epidemiological and clinical data were gathered from our Infectious Diseases Sample Collection (an open sample cohort including PLWH) from January 2011 to January 2022. A total of 493 PLWH were considered, 122 (24.7%) of whom were diagnosed with anal dysplasia at baseline, including 2 cases of anal SCC. Briefly, most of individuals were young men (median age, 38 years old) born in Spain (76%), whose vaccination rate before their inclusion in the program was scarce (<3%). Throughout the study period, 81 (16.4%) cases were diagnosed with high-grade squamous-intraepithelial lesions (HSILs) and 3 with anal SCC. At the baseline, severe immunosuppression (i.e., nadir CD4+ lymphocyte count below 200 cell/µL), and prior diagnosis of condyloma acuminata were more frequent within the group with SILs. Conversely, the baseline CD4+ lymphocyte count was similar among both groups. HPV-16 was related to a higher risk of HSILs (odds ratio: 2.76). At the end of the follow-up, 385 PLWH had been retained in care; one patient had died of anal cancer. Anal dysplasia was common (25% of cases), especially among patients infected by HPV-16, diagnosed with condyloma acuminata, and who were severely immunosuppressed. HPV-16 was the main risk factor for the presentation of HSILs.

Incidence of Anal Cancer and Related Risk Factors in HIV-Infected Patients Enrolled in the National Prospective Spanish Cohort CoRIS.

BACKGROUND: People living with HIV have an increased risk of anal cancer. OBJECTIVE: To estimate anal cancer incidence and related risk factors in a national cohort of HIV-infected patients. DESIGN: Prospective multicenter cohort study. SETTINGS: Multicenter study including patients from the Spanish HIV Research Network. PATIENTS: We collected data from 16,274 HIV-infected treatment-naive adults recruited from January 2004 to November 2020. MAIN OUTCOMES MEASURES: The primary outcome measures of this study were the incidence and prevalence of anal carcinoma. The secondary outcome measures included the associations between baseline and time-dependent covariables and the primary end point. RESULTS: Twenty-six cases of anal cancer were diagnosed, 22 of which were incident cases resulting in a cumulative incidence of 22.29 of 100,000 person-years, which was stable during the study period. At the end of the study, 20 of the 43 centers had screening programs for high-grade anal dysplasia. Patients with anal cancer were males (26/26; 100% vs 13,833/16,248; 85.1%), were mostly men who have sex with men (23/26; 88.5% vs 10,017/16,248; 61.6%), had a median age of 43 years (interquartile range, 35-51), were more frequently previously diagnosed with an AIDS-defining illness (9/26; 34.6% vs 2429/16,248; 15%), and had lower nadir CD4 cell counts (115 vs 303 µL). About a third (34.6%, 9/26) were younger than 35 years. In multivariable analysis, men who have sex with men and patients with previous AIDS-defining illness had an 8.3-fold (95% CI, 1.9-36.3) and 2.7-fold (95% CI, 1.1-6.6) increased HR for developing anal cancer, respectively. Patients with higher CD4 cell counts during the follow-up showed a 28% lower risk per each additional 100 CD4 cell/µL (95% CI, 41%-22%). LIMITATIONS: Lack of information on some potential risk factors, screening, and treatment of high-grade anal dysplasia were not uniformly initiated across centers during the study period. CONCLUSIONS: Although the overall incidence in our study was low, there was a significant number of patients younger than 35 years with anal cancer. In addition to age, other factors, such as men who have sex with men and patients with severe immunosuppression (current or past), should be prioritized for anal cancer screening. INCIDENCIA DEL CNCER DE ANO Y LOS FACTORES DE RIESGO RELACIONADOS CON PACIENTES INFECTADOS POR VIH INCLUIDOS EN LA COHORTE PROSPECTIVA NACIONAL ESPAOLA CORIS: ANTECEDENTES:Las personas portadoras del virus de la inmunodeficiencia humana tienen un mayor riesgo de cáncer anal.OBJETIVO:Nosotros queremos estimar la incidencia de cáncer anal y los factores de riesgo relacionados en una cohorte nacional española de pacientes infectados por VIH.DISEÑO:Estudio de cohortes de tipo multicéntrico y prospectivo.ÁMBITO:Se incluyeron pacientes de la Red Española de Investigación en VIH.PACIENTES:Recolectamos los datos de 16,274 adultos infectados por el VIH que nunca habían recibido tratamiento, reclutados desde enero de 2004 hasta noviembre de 2020.MEDIDAS DE RESULTADO PRINCIPALES:Las medidas de resultado primarias de este estudio fueron la incidencia y la prevalencia del carcinoma anal. Las medidas de resultado secundarias incluyeron las asociaciones entre las covariables basales y dependientes del tiempo y el criterio principal de valoración.RESULTADOS:Se diagnosticaron 26 casos de cáncer anal, de los cuales 22 fueron casos incidentales resultando con una incidencia acumulada de 22,29/100.000 personas-año que se mantuvo estable durante el período de estudio.Al final de nuestro estudio, 20 de los 43 centros referentes tenían programas de detección de displasia anal de alto grado. Los pacientes con cáncer anal eran hombres (26/26; 100% vs 13 833/16 248; 85,1%), en su mayoría hombres que mantenían sexo con otros hombres (23/26; 88,5% vs 10 017/16 248; 61,6%), la mediana de edad fue de 43 años (IQR: 3 -51), 34,6% (9/26) < 35 años, previa y frecuentemente diagnosticados con una enfermedad definitoria de SIDA (9/26; 34,6% vs 2429/16248; 15%) y que tenían un punto opuesto mucho más bajo en el recuentos de células CD4 (115 µL frente a 303 µL).En el análisis multivariable, los hombres que tenían relaciones sexuales con otros hombres y los pacientes con enfermedades definitorias de sida anteriores, tenían un aumento de 8,3 veces (IC del 95%: 1,9 a 36,3) y de 2,7 veces (IC del 95%: 1,1 a 6,6) en el cociente de riesgos instantáneos para desarrollar cáncer anal, respectivamente. Los pacientes con recuentos de células CD4 más altos durante el seguimiento mostraron un riesgo 28 % menor por cada 100 células CD4/µl adicionales (95% IC: 41%- 22%).LIMITACIONES:La falta de información sobre algunos factores potenciales de riesgo, la detección y el tratamiento de la displasia anal de alto grado no se iniciaron uniformemente en todos los centros durante el período de estudio.CONCLUSIONES:Si bien la incidencia general en nuestro estudio fue baja, hubo un número significativo de pacientes de <35 años con cáncer anal. Además de la edad, otros factores como los hombres que tienen sexo con hombres y los pacientes con inmunosupresión severa (actual o pasada) deben priorizarse para la detección del cáncer anal. ( Traducción-Dr. Xavier Delgadillo ).

Effectiveness and safety of integrase strand transfer inhibitors in Spain: a prospective real-world study.

Introduction: Second-generation integrase strand transfer inhibitors (INSTIs) are preferred treatment options worldwide, and dolutegravir (DTG) is the treatment of choice in resource-limited settings. Nevertheless, in some resource-limited settings, these drugs are not always available. An analysis of the experience with the use of INSTIs in unselected adults living with HIV may be of help to make therapeutic decisions when second-generation INSTIs are not available. This study aimed to evaluate the real-life effectiveness and safety of dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), and raltegravir (RAL) in a large Spanish cohort of HIV-1-infected patients. Methods: Real-world study of adults living with HIV who initiated integrase INSTIs DTG, EVG/c, and RAL-based regimens in three settings (ART-naïve patients, ART-switching, and ART-salvage patients). The primary endpoint was the median time to treatment discontinuation after INSTI-based regimen initiation. Proportion of patients experiencing virological failure (VF) (defined as two consecutive viral loads (VL) ≥200 copies/mL at 24 weeks or as a single determination of VL ≥1,000 copies/mL while receiving DTG, EVG/c or RAL, and at least 3 months after INSTI initiation) and time to VF were also evaluated. Results: Virological effectiveness of EVG/c- and RAL-based regimens was similar to that of DTG when given as first-line and salvage therapy. Treatment switching for reasons other than virological failure was more frequent in subjects receiving EVG/c and, in particular, RAL. Naïve patients with CD4+ nadir <100 cells/µL were more likely to develop VF, particularly if they initiated RAL or EVG/c. In the ART switching population, initiation of RAL and EVG/c was associated with both VF and INSTI discontinuation. There were no differences in the time to VF and INSTI discontinuation between DTG, EVG/c and RAL. Immunological parameters improved in the three groups and for the three drugs assessed. Safety and tolerability were consistent with expected safety profiles. Discussion: Whereas second-generation INSTIs are preferred treatment options worldwide, and DTG is one of the treatment of choices in resource-limited settings, first-generation INSTIs may still provide high virological and immunological effectiveness when DTG is not available.

Meningococcal carriage in men who have sex with men presenting at a sexual health unit in Spain.

Neisseria meningitidis (Nm) is asymptomatically carried in the nasopharynx of 5-10% adults, although certain populations, such as men who have sex with men (MSM), exhibit a higher colonisation rate. Interest in Nm carriage has been renewed, owed to meningitis outbreaks within populations of MSM. The aim of this study was to characterise Nm isolates and risk factors for its carriage among MSM attending a sexual health unit. A retrospective cross-sectional study was undertaken between June 2018 and December 2021. We took anal, oropharyngeal, urethral, and blood samples as part of the sexually transmitted infection screening procedures routinely implemented. Nm isolates were subjected to antimicrobial susceptibility testing; the serogroup and genogroup were determined by multi-locus sequence typing. A total of 399 subjects were recruited, and the Nm oropharyngeal carriage rate was 29%, similar among both people living with HIV (PLWH) and uninfected individuals. Nm carriage was less common in vaccinated individuals, especially those who had received the tetravalent vaccine (2.6% vs. 10.6%, p = 0.008). The most frequent serogroups were B (40%) and non-groupable (45%). Most of the isolates were susceptible to ciprofloxacin (96%) and ceftriaxone (100%). However, we identified 21 strains (20%) belonging to hyperinvasive lineages (CC11, CC4821, CC32, CC41/44, CC213, and CC269), most of which belonged to serogroup B. Given that vaccination with MenACWY was associated with a low Nm carriage, we encourage routine vaccination of all MSM. Moreover, the administration of the meningitis B vaccine should also be assessed considering that several invasive lines included in serogroup B are circulating among MSM.

Medicina centrada en la persona en el continuo de la vida / Person-centered medicine on the continuum of life

La alta tecnificación de la asistencia médica en muchos países y la masificación de la atención medica en diferentes servicios de salud y niveles de atención, ha llevado a una deshumanización de la atención médica, con la consecuente actitud de rechazo de los pacientes a esta forma de atención. Como consecuencia de ello, han emergido movimientos mundiales para recuperar la calidez de la atención con un enfoque más profesional, humano y espiritual concibiendo un modelo de atención centrado en la persona como sujeto principal de la atención médica. Este modelo debe ser aplicado en todo el ciclo del continuo de vida de las personas desde que se encuentra en el vientre materno, hasta su muerte. Para ello, es necesario pasar por profundos cambios de mentalidad y actitud por parte de los médicos y otro personal de los servicios de salud. Mas aún se hace necesario enseñar la medicina humanizada desde las instituciones de recursos humanos.

Real-life cohort experience after implementing HIV pre-exposure prophylaxis for one year in northwest Spain.

Introduction: Pre-exposure prophylaxis (PrEP) has become a useful tool to reduce the transmission of human immunodeficiency virus (HIV) in key populations. In this article we assessed the effectiveness, safety, adherence, sexually transmitted infections (STIs) dynamics, and frequency of anal dysplasia among a real-life cohort of PrEP users in Northwest Spain. Methods: A retrospective cohort study was undertaken in the Alvaro-Cunqueiro Hospital, Vigo which included every individual who started daily emtricitabine/tenofovir-disoproxil-fumarate (FTC/TDF) between November-2019 and October-2021. Clinical and epidemiological data were obtained from the patient's medical records. The effectiveness and safety of FTC/TDF were assessed by HIV serology and renal function monitoring every 3 months. Anal, urethral, and oropharyngeal exudates were collected quarterly after the baseline visit. Results: A total of 126 individuals were considered eligible, most of the participants had previously been diagnosed with a STI (60.3%), 22% had consumed recreational drugs in the year prior, and 13% had engaged in chemsex. At the end of the follow-up, no cases of HIV infection were detected; 3 patients had discontinued FTC/TDF because of side effects but none of them had presented renal toxicity. In addition, the diagnosis of STIs during the follow-up was common (100 cases in 54 patients). Moreover, engagement in chemsex was more common within this latter group (22 vs. 6%, p = 0.013). Among the study population included in the anal screening programme, the frequency of dysplasia was 9%. Conclusions: FTC/TDF was effective, safe, and tolerable in a real-life cohort; adherence remained high throughout the study period (79%). However, a high number of STIs were diagnosed, especially among patients who engaged in chemsex.

Factors associated with late presentation for HIV care in adolescents in Spain.

OBJECTIVE: Late presenters (LP) for HIV care are associated with higher morbidity and mortality rates. Our aim was to describe the characteristics associated with LP among adolescents in Spain. Identification of particular features may help in the design of strategies for improvement. METHODS: Late-presenting adolescents diagnosed at 12-19 years of age and enrolled in the Spanish paediatric and adult HIV/AIDS cohorts (CoRIS-CoRISpe) from 2004 to 2019 were selected. LP were defined as those presenting with CD4 count <350 cells/mm3 or an AIDS-defining event in the 6 months following HIV diagnosis. Confirmed low CD4 count in the next 3 months and before antiretroviral treatment initiation defined confirmed LP (cLP). RESULTS: Of 410 adolescents newly diagnosed with HIV, 303 (73.9%) had available data for assessing late presentation. Of these, 34.7% were LP and 23.7% were cLP. The median CD4 count for cLP was 235 cells/mm3 (interquartile range 122-285). In a multivariable analysis, adolescents at the highest risk of late presentation were early adolescents (age 12-14 years; odds ratio [OR] 6.50; 95% confidence interval [CI] 2.61-18.2), middle adolescents (age 15-17 years; OR 1.85; 95% CI 0.92-3.59), and adolescents born abroad (OR 1.71; 95% CI 0.97-3.00), particularly those of African origin (OR 3.08; 95% CI 1.38-6.79). CONCLUSIONS: One-quarter of adolescents presented late for HIV care in Spain. Early adolescents, middle adolescents, and those born abroad presented a sevenfold, twofold, and twofold higher risk of being cLP, respectively. Enhancing the awareness of HIV risk and the access to care, especially for younger and foreign adolescents, could help reduce late presentation and tackle the adolescent HIV epidemic.

Tetanus, analysis of 29 cases

BackgroundTetanus disease is caused by Clostridium tetani, an anaerobe bacteria found in dust and soil. Once reached human body through damaged tissues, C. tetani releases several neurotoxins which block the inhibitory function, leading to an increased muscle tone, ultimately causing respiratory failure. Severe tetanus is a life-threatening disease, especially in low-income-regions.MethodsThis is a retrospective case-series study, undertaken at two hospitals of Vigo (population area 600,000 inhabitants). Tetanus cases were identified through the discharge databases of both hospitals between the years 1995–2019. Epidemiological and clinical data were obtained from the patient's medical records.ResultsA total of 33 cases were identified; median age was 67 years, and most of patients were women (n=16, 55.2%). Generalized tetanus was the most common clinical course, and neck stiffness was the most frequent symptom. A total of 25 patients (86%) were admitted to the Intensive Care Unit, 21 required invasive ventilation and 2 patients died.DiscussionThe incidence of tetanus was low but most of cases were severe. Mortality was slightly higher than previously reported. Interestingly, the deceased patients were old-women, consistent with previously reported research in high-income-regions, while mortality in low-income-countries concentrates in middle-aged men. (AU)

IntroducciónEl tétanos es causado por Clostridium tetani, bacteria anaerobia, ubicada en el suelo. Este microorganismo penetra a través de heridas y libera neurotoxinas que bloquean la función inhibitoria, produciendo espasticidad y fracaso respiratorio. Es una enfermedad grave, especialmente en regiones empobrecidas.MétodosSerie de casos realizada en dos hospitales vigueses (área 600.000 habitantes). Los casos fueron identificados mediante los sistemas de codificación entre 1995-2019. Los datos asistenciales se obtuvieron de la historia clínica.ResultadosSe identificaron 33 casos, mediana de edad, 67 años, la mayoría mujeres (n = 16, 55,2%). El tétanos generalizado fue la forma clínica predominante, la rigidez cervical el síntoma más común. Un total de 25 pacientes requirieron ingreso en UCI, 21 ventilación mecánica, dos fallecieron.DiscusiónEl número de casos fue bajo, pero la mayoría graves. La mortalidad fue ligeramente superior a la informada previamente. La mortalidad se concentró en mujeres ancianas, concordante con otros países desarrollados, mientras que la mortalidad en regiones no-desarrolladas se agrupa en varones de mediana edad. (AU)

Prevalence of HPV genitalia and oral infection in an unvaccinated population of MSM-HIV in Northwest Spain / Prevalencia de la infección genital y oral por VPH en población no vacunada de HSH-VIH en el noroeste de España

Introduction: Human papillomavirus (HPV) infection is the most common sexually transmitted infection (STI), and it is a major risk factor for penile, oropharyngeal and anal cancer. HPV anal infection is common in men-whohave-sex-with-men (MSM), especially in patients living with HIV (MSM-HIV). HPV can also be detected in genitalia and oral tissues. The objective of this cross-sectional study is to analyze the prevalence of HPV genital and oral infection in a HIV-MSM cohort. Methods: This cross-sectional study of HPV infection included 107 HIV-MSM subjects recruited in a HIV follow-up unit of Northwest Spain. HPV-vaccinated subjects were excluded. HPV-DNA was detected with Anyplex™ II HPV28 method. Participants completed a questionnaire on lifestyle and sexual behavior. Results: Median age was 43 years (range 35-54 years); 97 patients received antiretroviral treatment (ART); 81 (75.7%) had undetectable HIV-RNA; median CD4-lymphocyte count was 746 cell/mm3; 70 (65.4%) participants had a previous STI. Genitalia HPV-DNA was detected in n=37 (34.6%) subjects and oral HPV-DNA was detected in 26 (24.3%). In 12 (11.2%) patients, HPVDNA was detected in both locations. High risk HPV (hrHPV) genotypes were detected in 24 (22.4%) and 15 (14%) patients in genitalia and oral samplesrespectively. Genitalia HPV-DNA isolation was more common in HIV virologically non-suppressed patients (65.4% vs 24.7%; p<0.001). Conclusions: HPV genitalia and oral infection is common in unvaccinated HIV-MSM patients. Detectable HIV-RNA was associated with higher HPV prevalence in genitalia. High oncogenic risk HPV genotypes were more common in genitalia than in oral cavity. (AU)

Introducción: La infección por el virus del papiloma humano (VPH) es la infección de transmisión sexual (ITS) más común; y es factor de riesgo para el desarrollo de cáncer de pene, orofaringe y ano. La infección por VPH es frecuente en hombres-que-tienen-sexo-con-hombres (HSH), especialmente en pacientes infectados por VIH (HSH-VIH). Asimismo, el VPH puede infectar genitales y cavidad oral. El objetivo de este estudio transversal es estimar la prevalencia de la infección orogenital por VPH en una cohorte HSH-VIH. Métodos: se incluyeron 107 pacientes de una Unidad de VIH del noroeste de España. Los pacientes vacunados fueron excluidos. El material genético del VPH (ADN-VPH) fue detectado mediante Anyplex™-II HPV-28. Los participantes completaron un cuestionario sobre hábitos sexuales. Resultados: la mediana de edad fue 43 años (rango 35-54); 97 pacientes recibían tratamiento antirretroviral (TAR); 81 (75,7%) presentaban carga viral del VIH suprimida, la mediana de linfocitos-CD4 era de 746 células/mm3, 70 (65,4%) habían padecido una ITS. Se detectó VPH en los genitales de 37 (34.6%) sujetos, en la cavidad oral de 26 (24.3%) y en 12 (11,2%) en ambas localizaciones. Se detectaron genotipos de alto riesgo oncogénico (AR-VPH) en 24 (22,4%) y 15 (14%) sujetos en genitales y cavidad oral respectivamente. El aislamiento del VPH fue más común en pacientes virológicamente no-suprimidos (65.4% vs 24.7%). Conclusiones: la infección orogenital por VPH es frecuente en pacientes HSH-VIH no vacunados. La no-supresión virológica del VIH se asoció con mayor prevalencia de infección genital por VPH. La detección de genotipos AR-VPH fue más común en genitales que cavidad oral. (AU)

Viruses Previously Identified in Brazil as Belonging to HIV-1 CRF72_BF1 Represent Two Closely Related Circulating Recombinant Forms, One of Which, Designated CRF122_BF1, Is Also Circulating in Spain.

Circulating recombinant forms (CRFs) are important components of the HIV-1 pandemic. Those derived from recombination between subtype B and subsubtype F1, with 18 reported, most of them of South American origin, are among the most diverse. In this study, we identified a HIV-1 BF1 recombinant cluster that is expanding in Spain, transmitted mainly via heterosexual contact, which, analyzed in near full-length genomes in four viruses, exhibited a coincident BF1 mosaic structure, with 12 breakpoints, that fully coincided with that of two viruses (10BR_MG003 and 10BR_MG005) from Brazil, previously classified as CRF72_BF1. The three remaining Brazilian viruses (10BR_MG002, 10BR_MG004, and 10BR_MG008) previously identified as CRF72_BF1 exhibited mosaic structures highly similar, but not identical, to that of the Spanish viruses and to 10BR_MG003 and 10BR_MG005, with discrepant subtypes in two short genome segments, located in pol and gp120env. Based on these results, we propose that the five viruses from Brazil previously identified as CRF72_BF1 actually belong to two closely related CRFs, one comprising 10BR_MG002, 10BR_MG004, and 10BR_MG008, which keep their CRF72_BF1 designation, and the other, designated CRF122_BF1, comprising 10BR_MG003, 10BR_MG005, and the viruses of the identified Spanish cluster. Three other BF1 recombinant genomes, two from Brazil and one from Italy, previously identified as unique recombinant forms, were classified as CRF72_BF1. CRF122_BF1, but not CRF72_BF1, was associated with protease L89M substitution, which was reported to contribute to antiretroviral drug resistance. Phylodynamic analyses estimate the emergence of CRF122_BF1 in Brazil around 1987. Given their close phylogenetic relationship and similar structures, the grouping of CRF72_BF1 and CRF122_BF1 in a CRF family is proposed.

Tetanus, analysis of 29 cases.

BACKGROUND: Tetanus disease is caused by Clostridium tetani, an anaerobe bacteria found in dust and soil. Once reached human body through damaged tissues, C. tetani releases several neurotoxins which block the inhibitory function, leading to an increased muscle tone, ultimately causing respiratory failure. Severe tetanus is a life-threatening disease, especially in low-income-regions. METHODS: This is a retrospective case-series study, undertaken at two hospitals of Vigo (population area 600,000 inhabitants). Tetanus cases were identified through the discharge databases of both hospitals between the years 1995-2019. Epidemiological and clinical data were obtained from the patient's medical records. RESULTS: A total of 33 cases were identified; median age was 67 years, and most of patients were women (n=16, 55.2%). Generalized tetanus was the most common clinical course, and neck stiffness was the most frequent symptom. A total of 25 patients (86%) were admitted to the Intensive Care Unit, 21 required invasive ventilation and 2 patients died. DISCUSSION: The incidence of tetanus was low but most of cases were severe. Mortality was slightly higher than previously reported. Interestingly, the deceased patients were old-women, consistent with previously reported research in high-income-regions, while mortality in low-income-countries concentrates in middle-aged men.

Update on the Epidemiological Features and Clinical Implications of Human Papillomavirus Infection (HPV) and Human Immunodeficiency Virus (HIV) Coinfection.

Human papillomavirus (HPV) infection is the most common sexually transmitted infection (STI) worldwide. Although most HPV infections will spontaneously resolve, a considerable proportion of them will persist, increasing the risk of anogenital dysplasia, especially within certain populations, such as patients infected with human immunodeficiency virus (HIV). Furthermore, high-risk oncogenic HPV types (HR-HPV) are the main cause of cervix and other anogenital cancers, such as cancer of the vagina, vulva, penis, or anus. HIV and HPV coinfection is common among people living with HIV (PLWH) but disproportionally affects men who have sex with men (MSM) for whom the rate of persistent HPV infection and reinfection is noteworthy. The molecular interactions between HIV and HPV, as well as the interplay between both viruses and the immune system, are increasingly being understood. The immune dysfunction induced by HIV infection impairs the rate of HPV clearance and increases its oncogenic risk. Despite the availability of effective antiretroviral therapy (ART), the incidence of several HPV-related cancers is higher in PLWH, and the burden of persistent HPV-related disease has become a significant concern in an aging HIV population. Several public health strategies have been developed to reduce the transmission of HIV and HPV and mitigate the consequences of this type of coinfection. Universal HPV vaccination is the most effective preventive tool to reduce the incidence of HPV disease. In addition, screening programs for HPV-related cervical and vulvovaginal diseases in women are well-recognized strategies to prevent cervical cancer. Similarly, anal dysplasia screening programs are being implemented worldwide for the prevention of anal cancer among PLWH. Herein, the main epidemiological features and clinical implications of HIV and HPV coinfection are reviewed, focusing mainly on the relationship between HIV immune status and HPV-related diseases and the current strategies used to reduce the burden of HPV-related disease.

Two-Drug Regimens for HIV-Current Evidence, Research Gaps and Future Challenges.

During the last 30 years, antiretroviral treatment (ART) for human immunodeficiency virus (HIV) infection has been continuously evolving. Since 1996, three-drug regimens (3DR) have been standard-of-care for HIV treatment and are based on a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The effectiveness of first-generation 3DRs allowed a dramatic increase in the life expectancy of HIV-infected patients, although it was associated with several side effects and ART-related toxicities. The development of novel two-drug regimens (2DRs) started in the mid-2000s in order to minimize side effects, reduce drug-drug interactions and improve treatment compliance. Several clinical trials compared 2DRs and 3DRs in treatment-naïve and treatment-experienced patients and showed the non-inferiority of 2DRs in terms of efficacy, which led to 2DRs being used as first-line treatment in several clinical scenarios, according to HIV clinical guidelines. In this review, we summarize the current evidence, research gaps and future prospects of 2DRs.

Identification of CRF66_BF, a New HIV-1 Circulating Recombinant Form of South American Origin.

Circulating recombinant forms (CRFs) are important components of the HIV-1 pandemic. Among 110 reported in the literature, 17 are BF1 intersubtype recombinant, most of which are of South American origin. Among these, all 5 identified in the Southern Cone and neighboring countries, except Brazil, derive from a common recombinant ancestor related to CRF12_BF, which circulates widely in Argentina, as deduced from coincident breakpoints and clustering in phylogenetic trees. In a HIV-1 molecular epidemiological study in Spain, we identified a phylogenetic cluster of 20 samples from 3 separate regions which were of F1 subsubtype, related to the Brazilian strain, in protease-reverse transcriptase (Pr-RT) and of subtype B in integrase. Remarkably, 14 individuals from this cluster (designated BF9) were Paraguayans and only 4 were native Spaniards. HIV-1 transmission was predominantly heterosexual, except for a subcluster of 6 individuals, 5 of which were men who have sex with men. Ten additional database sequences, from Argentina (n = 4), Spain (n = 3), Paraguay (n = 1), Brazil (n = 1), and Italy (n = 1), branched within the BF9 cluster. To determine whether it represents a new CRF, near full-length genome (NFLG) sequences were obtained for 6 viruses from 3 Spanish regions. Bootscan analyses showed a coincident BF1 recombinant structure, with 5 breakpoints, located in p17 gag , integrase, gp120, gp41-rev overlap, and nef, which was identical to that of two BF1 recombinant viruses from Paraguay previously sequenced in NFLGs. Interestingly, none of the breakpoints coincided with those of CRF12_BF. In a maximum likelihood phylogenetic tree, all 8 NFLG sequences grouped in a strongly supported clade segregating from previously identified CRFs and from the CRF12_BF "family" clade. These results allow us to identify a new HIV-1 CRF, designated CRF66_BF. Through a Bayesian coalescent analysis, the most recent common ancestor of CRF66_BF was estimated around 1984 in South America, either in Paraguay or Argentina. Among Pr-RT sequences obtained by us from HIV-1-infected Paraguayans living in Spain, 14 (20.9%) of 67 were of CRF66_BF, suggesting that CRF66_BF may be one of the major HIV-1 genetic forms circulating in Paraguay. CRF66_BF is the first reported non-Brazilian South American HIV-1 CRF_BF unrelated to CRF12_BF.

Factors associated with the number of drugs in darunavir/cobicistat regimens.

BACKGROUND: Darunavir/cobicistat can be used as mono, dual, triple or more than triple therapy. OBJECTIVES: To assess factors associated with the number of drugs in darunavir/cobicistat regimens. METHODS: A nationwide retrospective cohort study of consecutive HIV-infected patients initiating darunavir/cobicistat in Spain from July 2015 to May 2017. Baseline characteristics, efficacy and safety at 48 weeks were compared according to the number of drugs used. RESULTS: There were 761 patients (75% men, 98% were antiretroviral-experienced, 32% had prior AIDS, 84% had HIV RNA <50 copies/mL and 88% had ≥200 CD4 cells/mm3) who initiated darunavir/cobicistat as mono (n=308, 40%), dual (n=173, 23%), triple (n=253, 33%) or four-drug (n=27, 4%) therapy. Relative to monotherapy, triple therapy was more common in men aged <50 years, with prior AIDS and darunavir plus ritonavir use, and with CD4 cells <200/mm3 and with detectable viral load at initiation of darunavir/cobicistat; dual therapy was more common with previous intravenous drug use, detectable viral load at initiation of darunavir/cobicistat and no prior darunavir plus ritonavir; and four-drug therapy was more common with prior AIDS and detectable viral load at initiation of darunavir/cobicistat. Monotherapy and dual therapy showed a trend to better virological responses than triple therapy. CD4 responses and adverse effects did not differ among regimens. DISCUSSION: Darunavir/cobicistat use in Spain has been tailored according to clinical characteristics of HIV-infected patients. Monotherapy and dual therapy have been common and preferentially addressed to older patients with a better HIV status, suggesting that health issues other than HIV infection may have been strong determinants of its prescription.

Screening for precancerous anal lesions with P16/Ki67 immunostaining in HIV-infected MSM.

BACKGROUND: Screening of anal cancer in HIV-infected MSM with anal cytology results in high rates of false positive results and elevated burden of high-resolution anoscopies. High-risk HPV up-regulates p16 and Ki67 expression in epithelial cells. We assessed the usefulness of P16/Ki-67 immunostaining cytology for the diagnosis of precancerous anal lesions. METHODOLOGY: Cross-sectional multicenter study. Concomitant anal liquid cytology with p16/Ki-67 immunostaining and HRA with biopsy of acetowhite lugol-negative lesions was performed in HIV-infected MSM. We compared the diagnostic performance of an abnormal anal cytology and p16/Ki-67 immunostaining relative to HRA-guided biopsy by logistic regression and comparison of ROC areas. RESULTS: We included 328 HIV-infected MSM. HSIL was histologically diagnosed in 72 subjects (25.1%), and 2 (0.6%) were diagnosed with anal cancer. An abnormal cytology showed a sensitivity of 95.6% and a specificity of 58.8% for the diagnosis of biopsy-proven HSIL. P16/Ki67 positivity was associated with the presence of biopsy-proven HSIL (P trend = 0.004) but with low sensitivity (41.2%) and specificity (71%). The combination of standard cytology with P16/Ki67 immunostaining did not increment the predictive value of standard cytology alone (AUC 0.685 vs. 0.673, respectively, P = 0.688). CONCLUSION: In HIV-infected MSM P16/Ki67 immunostaining does not improve the diagnostic accuracy of anal cytology, which shows a high sensitivity yet poor specificity. Other approaches aimed at improving the diagnostic accuracy of current techniques for the diagnostic of precancerous HSIL are warranted.

Hepatic safety of maraviroc in HIV-1-infected patients with hepatitis C and/or B co-infection. The Maraviroc Cohort Spanish Group / Seguridad hepática de maraviroc en pacienes coinfectados con VIH y hepatitis C y/o B. Grupo español de la cohorte de Maraviroc

Introduction: Limited data is available regarding the hepatic safety of maraviroc in patients co-infected with HIV and HCV and/or HBV. Our objective was to compare the hepatic safety profile and fibrosis progression in HIV-mono-infected patients and co-infected with HCV and/or HBV treated with maraviroc. Methods: Retrospective multicentre cohort study of HIV-infected patients receiving treatment with a maraviroc-containing regimen in 27 hospitals in Spain. Results: A total of 667 patients were analyzed, of whom 313 were co-infected with HCV (n=282), HBV (n=14), or both (n=17). Maraviroc main indications were salvage therapy (52%) and drug toxicity (20%). Grade 3-4 hypertransaminasaemia (AST/ALT >5 times ULN) per 100 patient-years of maraviroc exposure, was 5.84 (95% CI, 4.04-8.16) and 1.23 (95% CI, 0.56-2.33) in co-infected and HIV-mono-infected patients, respectively (incidence rate ratio, 4.77; 95% CI, 2.35-10.5). However, the degree of aminotransferase abnormalities remained stable throughout the study in both groups, and no significant between-group differences were seen in the cumulative proportion of patients showing an increase in AST/ALT levels greater than 3.5 times baseline levels. No between-group differences were seen in liver fibrosis over time. With a maraviroc median exposure of 20 months (IQR, 12-41), two patients (0.3%) discontinued maraviroc because of grade 4 hepatitis, and other 2 died due to complications associated to end-stage-liver disease. Conclusions: Maraviroc-containing regimens showed a low incidence of hepatitis in a large Spanish cohort of HIV-infected patients, including more than 300 patients co-infected with HCV and/or HBV. Co-infection did not influence the maximum liver enzyme level or the fibrosis progression throughout the study (AU)

Introducción: La seguridad hepática del maraviroc en pacientes coinfectados por VIH y VHC y/o VHB es poco conocida. Nuestro objetivo es comparar el riesgo de hepatitis y la progresión de la fibrosis hepática en pacientes monoinfectados por VIH y coinfectados por VHC y/o VHB, tratados con maraviroc. Métodos: Estudio de cohortes, retrospectivo, en pacientes infectados por VIH, tratados con maraviroc en 27 hospitales españoles. Resultados: Analizamos 667 pacientes, 313 coinfectados por VHC (n=282), VHB (n=14) o ambos (n=17). El rescate (52%), y la toxicidad farmacológica (20%) fueron las principales indicaciones de tratamiento con maraviroc. La incidencia de hipertransaminasemia de grado 3-4 (AST o ALT >5 veces el LSN), por 100 paciente-años de exposición a maraviroc, fue 5,84 (IC 95%, 4,04-8,16) y 1,23 (IC 95%, 0,56-2,33) en coinfectados y monoinfectados por VIH, respectivamente (razón de tasas, 4,77; IC95%, 2,35-10,5). No se observaron diferencias en la proporción acumulada de pacientes con elevación de AST o ALT mayor de 3,5 veces respecto al valor basal, ni en la progresión de la fibrosis hepática entre ambos grupos. Tras una mediana de tratamiento de 20 meses (AIC, 12-41), dos pacientes (0,3%) discontinuaron el maraviroc por hepatitis de grado 4, y dos pacientes fallecieron por enfermedad hepática. Conclusiones: En una cohorte española de pacientes infectados por VIH que incluye más de 300 pacientes coinfectados por VHC y/o VHB, maraviroc mostró una baja incidencia de hepatitis. La coinfección no afectó al grado de elevación de las transaminasas ni a la progresión de la fibrosis hepática (AU)

Estudio de la prevalencia de marcadores genéticos asociados a la lenta progresión del virus de la inmunodeficiencia humana tipo 1 en la población gallega / Prevalence study of the genetic markers associated with slow progression of human inmunodefiency virus type 1 in the Galician population (Northwest of Spain)

INTRODUCCIÓN: La deleción en el gen CCR5 (CCR5Δ32), el haplotipo HLA-B*27:05 y los polimorfismos rs2395029 y rs9264942 han sido relacionados con la lenta progresión de la infección por VIH-1. MÉTODOS: Analizamos a 408 pacientes en seguimiento. El análisis de la carga viral, linfocitosT CD4+ y demás variables clínicas fueron recogidas desde el diagnóstico. RESULTADOS: La prevalencia de los marcadores genéticos rs9264942, CCR5wt/Δ32, rs2395029 y alelo HLA-B*27:05 fue del 17,9, del 11,5, del 7,6 y del 6,4%, respectivamente. Del total de los pacientes, 354 fueron clasificados como progresores y 46 como no progresores a largo plazo (LTNP). Exceptuando el alelo HLA-B*27:05, los demás marcadores genéticos se relacionaron con la lenta progresión: CCR5wt/Δ32 (p = 0,011) y los SNP rs2395029 y rs9264942 (p < 0,0001), así como su asociación (p < 0,0001). CONCLUSIÓN: La frecuencia hallada del alelo HLA-B*57:01 fue mayor a lo publicado a nivel nacional. Con respecto al alelo HLA-B*27:05, no hemos podido relacionar su presencia con la lenta progresión

INTRODUCTION: The deletion in the CCR5 gene (CCR5Δ32), the HLA-B*27:05, and polymorphisms rs2395029 and rs9264942 have been associated with slower progression of HIV-1. METHODS: An analysis was performed on 408 patients on follow-up. The analysis of viral load, CD4+ Tlymphocytes and other clinical variables since the diagnosis of the infection were collected. RESULTS: The prevalence of the genetic markers rs9264942, CCR5wt/Δ32, rs2395029, HLA-B*27:05 was 17.9%, 11.5%, 7.6%, and 6.4%, respectively. Of all the patients, 354 were classified as progressors and 46 as long-term non-progressors (LTNPs). Except for the HLA-B*27:05 allele, other genetic markers were associated with slower progression: CCR5wt/Δ32 (P=.011) and SNPs rs2395029 and rs9264942 (P<.0001), as well as their association (P<.0001). CONCLUSION: The prevalence of the HLA-B*57:01 allele was higher than described nationally. No association could be found between the HLA-B*27:05 allele and the presence of slower disease progression

[Prevalence study of the genetic markers associated with slow progression of human inmunodefiency virus type 1 in the Galician population (Northwest of Spain)]. / Estudio de la prevalencia de marcadores genéticos asociados a la lenta progresión del virus de la inmunodeficiencia humana tipo 1 en la población gallega.

INTRODUCTION: The deletion in the CCR5 gene (CCR5Δ32), the HLA-B*27:05, and polymorphisms rs2395029 and rs9264942 have been associated with slower progression of HIV-1. METHODS: An analysis was performed on 408 patients on follow-up. The analysis of viral load, CD4+ Tlymphocytes and other clinical variables since the diagnosis of the infection were collected. RESULTS: The prevalence of the genetic markers rs9264942, CCR5wt/Δ32, rs2395029, HLA-B*27:05 was 17.9%, 11.5%, 7.6%, and 6.4%, respectively. Of all the patients, 354 were classified as progressors and 46 as long-term non-progressors (LTNPs). Except for the HLA-B*27:05 allele, other genetic markers were associated with slower progression: CCR5wt/Δ32 (P=.011) and SNPs rs2395029 and rs9264942 (P<.0001), as well as their association (P<.0001). CONCLUSION: The prevalence of the HLA-B*57:01 allele was higher than described nationally. No association could be found between the HLA-B*27:05 allele and the presence of slower disease progression.