Drug resistance mutations in HIV-2 patients failing raltegravir and influence on dolutegravir response.

Background: A broader extent of amino acid substitutions in the integrase of HIV-2 compared with HIV-1 might enable greater cross-resistance between raltegravir and dolutegravir in HIV-2 infection. Few studies have examined the virological response to dolutegravir in HIV-2 patients that failed raltegravir. Methods: All patients recorded in the HIV-2 Spanish cohort were examined. The integrase coding region was sequenced in viraemic patients. Changes associated with resistance to raltegravir and dolutegravir in HIV-1 were recorded. Results: From 319 HIV-2-infected patients recorded in the HIV-2 Spanish cohort, 53 integrase sequences from 30 individuals were obtained (20 raltegravir naive and 10 raltegravir experienced). Only one secondary mutation (E138A) was found in one of the 20 raltegravir-naive HIV-2 patients. For raltegravir-experienced individuals, the resistance mutation profile in 9 of 10 viraemic patients was as follows: N155H + A153G/S (four); Y143G + A153S (two); Q148R + G140A/S (two); and Y143C + Q91R (one). Of note, all patients with Y143G and N155H developed a rare non-polymorphic mutation at codon 153. Rescue therapy with dolutegravir was given to 5 of these 10 patients. After >6 months on dolutegravir therapy, three patients with baseline N155H experienced viral rebound. In two of them N155H was replaced by Q148K/R and in another by G118R. Conclusions: A wide repertoire of resistance mutations in the integrase gene occur in HIV-2-infected patients failing on raltegravir. Although dolutegravir may allow successful rescue in most HIV-2 raltegravir failures, we report and characterize three cases of dolutegravir resistance in HIV-2 patients, emerging variants Q148K and Q148R and a novel change G118R.

Anorectal Lymphogranuloma Venereum in Madrid: A Persistent Emerging Problem in Men Who Have Sex With Men.

BACKGROUND: Since 2003, outbreaks of lymphogranuloma venereum (LGV) with anorectal syndrome have been increasingly recognized in many Western countries. All of them have been classified as LGV serovar L2b, mainly occurring in human immunodeficiency virus (HIV)-infected men who have had sex with men (MSM). We describe a series of 26 diagnosed cases of LGV proctitis in downtown Madrid, Spain, in 2014, after implementing routine diagnostic procedures for this disease in symptomatic MSM. METHODS: We conducted an observational study of patients with symptomatic proctitis attending an outpatient infectious diseases clinic in Madrid, Spain during calendar year 2014. Clinical, epidemiological, laboratory, and therapeutic data were gathered and analyzed. RESULTS: Twenty-six patients were included in the analysis. All were MSM, and 24 of them were HIV-positive. All patients reported having acute proctitis symptoms including tenesmus (85%), pain (88%), constipation (62%), or anal discharge (96%). Proctoscopy showed mucopurulent exudate (25 patients [96%]), and rectal bleeding, with mucosal erythema and/or oedema in all cases. Rectal swabs were obtained from all patients, and LGV serovar L2 was confirmed in all of them. The cure rate was 100% after standard treatments with doxycycline 100 mg twice per day for 3 weeks. Simultaneous rectal infections with other sexually transmitted pathogens (gonorrhoea, herpes simplex virus, Mycoplasma genitalium) and systemic sexually transmitted diseases (STDs) (syphilis, acute HIV, and hepatitis C infections) were also documented in 12 patients (46%), but these co-infections did not appear to influence the clinical manifestations of LGV. CONCLUSIONS: Anorectal LGV is a common cause of acute proctitis and proctocolitis among HIV-infected MSM who practice unprotected anal sex, and it is frequently associated with other rectal STDs. The implementation of routine screening and prompt diagnosis of these rectal infections should be mandatory in all clinical settings attended by HIV and STD patients.

Dolutegravir for the treatment of HIV-2 infection.

BACKGROUND: Therapeutic options are limited for HIV-2 infected persons, largely in part due to the lack of susceptibility to HIV-1 non-nucleoside reverse transcriptase inhibitors and poor susceptibility to some HIV-1 protease inhibitors. This is particularly worrisome for HIV-2 patients with prior antiretroviral failure. OBJECTIVES: Report the virological response to dolutegravir in HIV-2-infected individuals. STUDY DESIGN: Retrospective observational assessment of all HIV-2 individuals treated with dolutegravir in Spain. RESULTS: From 297 HIV-2-infected individuals recorded at the Spanish national registry, 26% received antiretroviral therapy. Six out of 8 failing on raltegravir selected for integrase resistance mutations N155H (4), Y143G (1) and Q148R (1). Two patients bearing N155H subsequently received dolutegravir. Both experienced initially more than 1.5 log drop in plasma HIV-2 RNA and significant CD4 gains. Whereas one kept on undetectable viremia 6 months later, the other experienced viral rebound. CONCLUSION: Dolutegravir may be a good therapeutic option for patients with HIV-2 infection, including those that previously failed other integrase inhibitors.

Valor predictivo y utilidad clínica del genotipado HLA-DQ en el diagnóstico de la enfermedad celiaca en mayores de 50 años / Predictive value and clinical utility of HLA-DQ typing in diagnosis of celiac disease in patients over 50

Introducción. Existe un alto número de casos no diagnosticados de enfermedad celiaca, especialmente en individuos de edad avanzada. El objetivo del presente trabajo es determinar el valor predictivo del genotipado de HLA-DQ en el diagnóstico de la enfermedad celiaca en mayores de 50 años y analizar una posible relación entre la gradación de riesgo atribuida a los alelos y el diagnóstico en edad avanzada. Materiales y métodos. Seiscientos treinta y cinco pacientes fueron estudiados durante 2013 con clínica sugestiva de enfermedad celiaca. El diagnóstico fue confirmado mediante estudios serológicos y biopsia intestinal. El genotipado del HLA-DQ se realizó mediante una técnica PCR-SSOP. Resultados. Un 10,7% de los pacientes estudiados eran mayores de 50 años con un ratio hombre mujer 1:3. La frecuencia de los alelos considerados de riesgo para la enfermedad celiaca (HLA-DQ2.5 y/o HLA-DQ8) fue del 87,5% (56 pacientes), siendo celiacos 13 de ellos. Veintiún pacientes portaban solo un alelo del DQ2.5 (DQA1*05 o DQB1*02) sin confirmarse el diagnóstico de celiaquía. Un paciente celiaco confirmado no expresaba ni DQ2 ni DQ8. El valor predictivo positivo del genotipado de HLA-DQ para el diagnóstico de EC en la población mayor de 50 años fue del 29,27% y el valor predictivo negativo del 93%. Conclusiones. Debido al alto valor predictivo negativo, la determinación del HLA-DQ es un marcador útil en el diagnóstico de la EC en individuos de edad avanzada con clínica asociada. No se encontró relación entre los alelos considerados de menor riesgo y la aparición tardía de la enfermedad (AU)

Introduction. Celiac disease is significantly undiagnosed, especially in older individuals. The aim of this study is to determine the predictive value of HLA-DQ typing in the diagnosis of celiac disease in patients over 50 and analyze the possible relationship between the gradation of risk attributed to the alleles and diagnosis in elderly. Materials and methods. 635 patients were studied during 2013 with suggestive symptoms of celiac disease. The diagnosis was confirmed by serologic studies and small bowel biopsy. The HLA-DQ genotyping was performed using a PCR-SSOP technique. Results. 68 of out 635 patients studied (10.7%) were older than 50 years with a male to female ratio of 1:3. The frequency of the alleles that has been associated with risk of CD (HLA DQ2.5 and/or HLA DQ8) was 87.5% (56 patients), being celiac 13 of them. 21 patients carry the half allele of HLA-DQ2.5 (DQA1*05 or DQB1*02) associated with low risk of celiac disease being none of them celiac. One patient with celiac disease did not carry DQ2.5 or DQ8 heterodimers but was positive for serological and histological analysis. The positive predictive value of the use of HLA testing in the population older than 50 years is 29.27% and the negative predictive value is 93%. Conclusions. Due to the high negative predictive value, the determination of HLA-DQ is a useful marker in the diagnosis of CD, in individuals over 50 with associated clinical. There was no relationship between low risk alleles and late onset of disease (AU)