Discontinuation of dolutegravir, elvitegravir/cobicistat and raltegravir because of toxicity in a prospective cohort.

OBJECTIVES: The aim of the study was to assess the rates of discontinuation of integrase inhibitor regimens because of any neuropsychiatric adverse event (NPAE) and the factors associated with discontinuation. METHODS: A population-based, prospective, multicentre cohort study was carried out. Treatment-naïve subjects starting therapy with a regimen containing integrase inhibitors, or those switching to such a regimen, with plasma HIV-1 RNA < 50 HIV-1 RNA copies/mL in 14 hospitals in Catalonia or the Balearic Islands (Spain) were included in the study. Every discontinuation because of adverse events (AEs) was double-checked directly with treating physicians. Multivariable Cox models identified factors correlated with discontinuation. RESULTS: A total of 4165 subjects (37% treatment-naïve) started regimens containing dolutegravir (n = 1650; 91% with abacavir), raltegravir (n = 930) or elvitegravir/cobicistat (n = 1585). There were no significant differences among regimens in the rate of discontinuation because of any AE. Rates of discontinuation because of NPAEs were low but higher for dolutegravir/abacavir/lamivudine [2.1%; 2.9 (95% confidence interval (CI) 2.0, 4.2) discontinuations/100 patients/year] versus elvitegravir/cobicistat (0.5%; 0.8 (95% CI 0.3, 1.5) discontinuations/100 patients/year], with significant differences among centres for dolutegravir/abacavir/lamivudine and NPAEs (P = 0.003). We identified an association of female gender and lower CD4 count with increased risk of discontinuation because of any AE [Incidence ratio (IR) 2.3 (95% CI 1.4, 4.0) and 1.8 (95% CI 1.1, 2.8), respectively]. Female gender, age > 60 years and abacavir use were not associated with NPAE discontinuations. NPAEs were commonly grade 1-2, and had been present before and improved after drug withdrawal. CONCLUSIONS: In this large prospective cohort study, patients receiving dolutegravir, raltegravir or elvitegravir/cobicistat did not show significant differences in the rate of discontinuation because of any toxicity. The rate of discontinuations because of NPAEs was low, but was significantly higher for dolutegravir than for elvitegravir/cobicistat, with significant differences among centres, suggesting that greater predisposition to believe that a given adverse event is caused by a given drug of some treating physicians might play a role in the discordance seen between cohorts.

[Fever of unknown origin in patients with HIV infection]. / Fiebre de origen desconocido en pacientes con infección por el HIV.

BACKGROUND: The aim of the study was to describe the etiology and clinical characteristics of fever of uncertain origin (FUO) among HIV-infected patients. METHODS: Prospective analysis of 35 episodes of FUO in HIV-infected patients from Balearic Islands that were studied through established guidelines. RESULTS: Most patients were at advanced stages of HIV-1 infection (mean CD4 cell count, 60/mm3). Mean duration of fever until diagnosis was 57 days. Average time of hospitalization until etiological diagnosis of FUO was 26 days (range: 8-127 days). The cause of FUO was identified in 33 cases (94%). Tuberculosis accounted for 18 cases (51%) and visceral leishmaniasis for 8 cases (23%). Other opportunistic infections were the cause of FUO in 8 cases (17%). In one patient, fever was due to Kaposi's sarcoma. Two patients died while febrile, without and identified etiology. Four patients had more than one cause that could contribute to FUO. Imaging techniques that yielded more diagnostic information were abdominal ultrasonography and serial chest X-ray. Leishmania serology and tuberculin skin test showed a high specificity but low sensitivities. Invasive procedures with a highest diagnostic field were fine needle aspirate of lymph nodes, and liver biopsy. CONCLUSIONS: FUO is more frequent in advanced stages of HIV disease. In our area, FUO is caused primarily by endemic opportunistic infections specially TB and visceral leishmaniasis, and rarely can be attributable to HIV or neoplastic diseases.

[Pseudomonas spp. infections in patients with HIV infections]. / Infecciones por Pseudomonas spp. en pacientes con infección por HIV.

BACKGROUND: The aim of this study was to describe the characteristics of the infections by Pseudomonas spp. observed in patients with HIV infection in Spain. METHODS: A retrospective study was performed of the isolations of Pseudomonas spp. in microbiologic samples of patients with HIV infection in three hospitals from Mallorca, Spain, since 1986. RESULTS: Twenty-nine patients with some positive culture for Pseudomonas were reviewed. In 20 cases the infection presented in advanced stages of the disease when the patient fulfilled AIDS criteria. The most frequent foci in both community acquired and nosocomial infection was respiratory (16 and 3 cases, respectively). Fifty percent of the cases presented bacteremia. The classically described predisposing factors for infection by this germ were presented in 19 patients. Pseudomonas aeruginosa was the most frequently isolated type (22 cases). Only 5 patients received the appropriate treatment on admission. Clinical cure was achieved in 23 patients, with recurrence being observed in 10. Five patients died in relation to the infection. CONCLUSIONS: Infections by Pseudomonas spp. in Spain appear to have increased in frequency in patients with HIV infection in the last decade. These infections appear in advanced phases of the disease and mainly involve the lung, with high rates of bacteremia and a high number of recurrence. Empiric treatment of patients with advanced HIV infection with suspicion of bacterial infection should include antipseudomonic drugs.

[Changes in the natural history of AIDS in patients from Mallorca and Ibiza: 1986-1992]. / Cambios en la historia natural del SIDA en pacientes de Mallorca e Ibiza: 1986-1992.

BACKGROUND: Longitudinal follow-up studies in patients with human immunodeficiency virus (HIV) infection and AIDS, which are fundamental for the knowledge of variations the natural history of this disease, have generally been carried out by Public Health Departments and in populations in which homosexual males predominate. The aim of the present study was to analyze the changes in the natural history of the patients diagnosed with AIDS in the islands of Mallorca and Ibiza. METHODS: A prospective study of the adult patients diagnosed with AIDS in Mallorca and Ibiza, from 1986 to 1992 was performed. RESULTS: The annual incidence of the cases of AIDS increased throughout the study. The mean age of the patients did not vary, and neither did that in relation to sexes. A progressive decrease was observed in CD4 lymphocytes at the time of diagnosis (from 0.168 x 10(9)/l in 1986 to 0.079 x 10(9)/l in 1992). There was an increase in heterosexual transmission patients with no known risk factors also increased over the period studied. The incidence of extrapulmonary tuberculosis decreased both as the form of presentation and in its global frequency. Pneumonia by Pneumocystis carinii increased mainly as a initial feature. The median survival was 547 days and did not vary significantly throughout the study. CONCLUSIONS: The epidemiologic and clinical study of AIDS in Mallorca and Ibiza, Spain is similar to that observed in other Mediterranean regions. The incidence of extrapulmonary tuberculosis has decreased.