Impact of reverse transcriptase resistance on the efficacy of TMC125 (etravirine) with two nucleoside reverse transcriptase inhibitors in protease inhibitor-naïve, nonnucleoside reverse transcriptase inhibitor-experienced patients: study TMC125-C227.

OBJECTIVES: TMC125-C227, an exploratory phase II, randomized, controlled, open-label trial, compared the efficacy and safety of TMC125 (etravirine) with an investigator-selected protease inhibitor (PI) in nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant, protease inhibitor-naïve, HIV-1-infected patients. METHODS: Patients were randomized to TMC125 800 mg twice a day (bid) (phase II formulation; n=59) or the control PI (n=57), plus two nucleoside reverse transcriptase inhibitors (NRTIs). RESULTS: In an unplanned interim analysis, patients receiving TMC125 demonstrated suboptimal virological responses relative to the control PI. Therefore, trial enrolment was stopped prematurely and TMC125 treatment discontinued after a median of 14.3 weeks. In this first-line NNRTI-failure population, baseline NRTI and NNRTI resistance was high and reduced virological responses were observed relative to the control PI. No statistically significant relationship was observed between TMC125 exposure and virological response at week 12. TMC125 was better tolerated than a boosted PI for gastrointestinal-, lipid- and liver-related events. CONCLUSIONS: In a PI-naïve population, with baseline NRTI and NNRTI resistance and NRTI recycling, TMC125 was not as effective as first use of a PI. Therefore the use of TMC125 plus NRTIs alone may not be optimal in PI-naïve patients with first-line virological failure on an NNRTI-based regimen. Baseline two-class resistance, rather than pharmacokinetics or other factors, was the most likely reason for suboptimal responses.

Oral Candida flora from Brazilian human immunodeficiency virus-infected patients in the highly active antiretroviral therapy era.

One of the main opportunistic fungal infections amongst immunocompromised individuals is oral candidosis, which has been found in up to 90% of human immunodeficiency virus (HIV)-infected patients. This study employed yeasts isolated from the saliva and oral cavities of 114 HIV-infected patients living in Campinas, São Paulo. Of the isolates, 57.8% were identified as Candida albicans and 42.1% as non-C. albicans. The latter isolates were subsequently identified as C. krusei (7.5%), C. lusitaniae (5.2%), C. tropicalis (4.6%), C. parapsilosis (4.6%), C. glabrata (2.8%), C. kefyr (1.7%), C. guilliermondii (1.7%), C. intermedia (1.1%), C. norvegensis (0.5%), and Rhodotorula rubra (1.7%). Susceptibility of the isolates to amphotericin B, fluconazole, miconazole, and itraconazole was also determined by a microdilution method adopted by the National Committee for Clinical Laboratory Standards. The isolates demonstrated various susceptibilities to the antifungal agents. In particular 29 C. albicans and 13 non-C. albicans isolates showed low susceptibility to FLCZ (> 64 micro g/ml). This study revealed huge diversity of Candida species, in particular the increasing emergence of non-C. albicans associated with the oral flora of HIV-infected patients.

Oral Candida flora from Brazilian human immunodeficiency virus-infected patients in the highly active antiretroviral therapy era

One of the main opportunistic fungal infections amongst immunocompromised individuals is oral candidosis, which has been found in up to 90 percent of human immunodeficiency virus (HIV)-infected patients. This study employed yeasts isolated from the saliva and oral cavities of 114 HIV-infected patients living in Campinas, São Paulo. Of the isolates, 57.8 percent were identified as Candida albicans and 42.1 percent as non-C. albicans. The latter isolates were subsequently identified as C. krusei (7.5 percent), C. lusitaniae (5.2 percent), C. tropicalis (4.6 percent), C. parapsilosis (4.6 percent), C. glabrata (2.8 percent), C. kefyr (1.7 percent), C. guilliermondii (1.7 percent), C. intermedia (1.1 percent), C. norvegensis (0.5 percent), and Rhodotorula rubra (1.7 percent). Susceptibility of the isolates to amphotericin B, fluconazole, miconazole, and itraconazole was also determined by a microdilution method adopted by the National Committee for Clinical Laboratory Standards. The isolates demonstrated various susceptibilities to the antifungal agents. In particular 29 C. albicans and 13 non-C. albicans isolates showed low susceptibility to FLCZ (> 64 æg/ml). This study revealed huge diversity of Candida species, in particular the increasing emergence of non-C. albicans associated with the oral flora of HIV-infected patients.

Prevalence and risk factors for hepatitis C virus (HCV) infection among pregnant Brazilian women.

OBJECTIVES: To determine the prevalence and the risk factors associated with HCV infection among women at childbirth, and to assess potential for infectivity of anti-HCV-positive women. METHODS: A total of 6995 women were interviewed and screened for HCV antibodies. Association and logistic regression analyses were conducted. RESULTS: The anti-HCV prevalence was 1.5% by EIA-3 and 0.8% by RIBA-3; HCV-RNA (RT-PCR) was detected in 74% of the RIBA-positive samples. Blood transfusion, race (blacks), alcohol abuse, a history of STD and anti-HBc positivity were independent risk factors for HCV positivity. Except for parenteral exposure, independent predictors of anti-HCV were a history of STD, anti-HBc positivity, a sex partner with multiple sex partners and a sex partner with a history of hepatitis. CONCLUSIONS: The prevalence of anti-HCV is higher in pregnant women than in blood donors. Sexual exposure may facilitate the spread of HCV and there is a high potential for mother-to-infant transmission.

Randomized, double-blind trial comparing indinavir alone, zidovudine alone and indinavir plus zidovudine in antiretroviral therapy-naive HIV-infected individuals with CD4 cell counts between 50 and 250/mm3.

Treatment with indinavir has been shown to result in marked decreases in viral load and increases in CD4 cell counts in HIV-infected individuals. A randomized double-blind study to evaluate the efficacy of indinavir alone (800 mg q8h), zidovidine alone (200 mg q8h) or the combination was performed to evaluate progression to AIDS. 996 antiretroviral therapy-naive patients with CD4 cell counts of 50-250/mm3 were allocated to treatment. During the trial the protocol was amended to add lamivudine to the zidovudine-containing arms. The primary endpoint was time to development of an AIDS-defining illness or death. The study was terminated after a protocol-defined interim analysis demonstrated highly significant reductions in progression to a clinical event in the indinavir-containing arms, compared to the zidovudine arm (p<0. 0001). Over a median follow-up of 52 weeks (up to 99 weeks), percent reductions in hazards for the indinavir plus zidovudine and indinavir groups compared to the zidovudine group were 70% and 61%, respectively. Significant reductions in HIV RNA and increases in CD4 cell counts were also seen in the indinavir-containing groups compared to the zidovudine group. Improvement in both CD4 cell count and HIV RNA were associated with reduced risk of disease progression. All three regimens were generally well tolerated.

Peripheral T-cell lymphoma in HIV-positive patients.

Two cases of peripheral T-cell lymphomas in HIV-positive patients are reported: one case of T-pleomorphic small cell non-Hodgkin lymphoma in a 27 year-old bisexual male, and one case of a T-pleomorphic medium and large cell non-Hodgkin lymphoma in a 27 year-old female, whose husband was drug addicted. Both cases were studied on a morphological and immunohistological basis.

Estrongiloidiase macica. A proposito de quatro casos. / Massive strongyloidiasis. Apropos of 4 cases

Sao relatados quatro casos de estrongiloidiase macica em pacientes sem diagnostico previo da doenca ou tratamento imunossupressor. A doenca, na maioria dos casos, teve um curso cronico, associada a uma sindrome de ma absorcao. Em um caso a sintomatologia que motivou a internacao foi a de uma meningite purulenta que se repetia pela quarta vez. Nao se sabe ao certo qual o desencadeante de tal situacao nos quatro casos apresentados, porem, discute-se o possivel papel do sistema imunologico na defesa contra a invasao pelo S. stercoralis

Tratamento de escolares com "Hymenolepsis nana" pelo praziquantel. / Treatment of school children with \"Hymenolepsis nana\" with praziquantel

Foi administrado praziquantel a 30 escolares, naturalmente parasitados por Hymenolepsis nana. A droga foi administrada por via oral, em dose unica, 25mg/kg. O controle de cura parasitologica constitui-se nos exames de fezes, praticados no 7o., 14o. e 21o. dias apos o tratamento, utilizando-se as tecnicas de Hoffman, Pons & Janer e de Faust et al. Dos 28 escolares que concluiram os tres controles, constatou-se que 23 (82,1%) tenham sido curados, por nao apresentarem ovos de H. nana nos exames efetuados. Reacoes colaterais quando ocorreram (23,3% dos casos tratados), foram leves e de pequena duracao; a mais frequente foi a queixa de desconforto abdominal. Os resultados deste trabalho confirmam os de outros pesquisadores e sao de molde a se admitir que o praziquantel, no momento, deve ser medicacao preferencial no tratamento da himenolepiase nana do homem