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.