Prévalence de la transmission de virus résistant à la zidovudine en Suisse. L'étude suisse de cohorte VIH

Zidovudine (ZDV) was the most widely used anti-HIV drug between 1987 and 1995, and, as already reported, transmission of ZDV-resistant viruses occurs. Several mutations of the reverse transcriptase gene have been identified; one of them affects the 215 codon and is associated with a high degree of resistance. We have determined, using selective PCR, the prevalence of transmission of 215 mutant isolates in 134 patients with primary HIV infection (PHI) and have identified 8 patients with 215 mutant virus between 1989 and 1995 in Switzerland. Mutant resistant viruses have been isolated from patients treated with most antiviral drugs. A systematic search for mutant viruses may provide useful information for the adaptation of treatment strategies

Combined therapy with zidovudine and L-697,661 in primary HIV infection

OBJECTIVE: To decrease viraemia levels in primary HIV infection by using a combination of zidovudine (ZDV) and L-697,661. DESIGN: Four primary HIV-infected patients were treated for 6 months with ZDV, 250 mg twice daily, in association with the non-nucleoside reverse transcriptase inhibitor L-697,661 500 mg three times daily. Viraemia, proviral DNA, CD4 and CD8 cell counts were measured serially during 18 months. RESULTS: Viraemia decreased to undetectable levels (< 200 RNA copies/ml) in two patients. A third patient had a marked decrease followed by a rebound during therapy; viraemia levels did not vary markedly in the fourth patient. A rebound in viraemia levels was observed within 15 days of discontinuation of therapy in the three responding patients. Proviral levels evolved in parallel with viraemia but were always detectable in all patients. In the three patients with an initial decrease of viraemia, CD4 cell counts were within the normal range 2 months after initiation of therapy and did not markedly decrease after discontinuation of therapy. In the two patients with partial or no response of viraemia, mutations associated with low level of resistance to L-697,661 appeared during treatment. CONCLUSION: A marked decrease of viraemia can be achieved in some primary HIV-infected patients with combined therapy. Six months of treatment does not prevent a rebound of viraemia, which was observed within 15 days of interruption of therapy

Mutations in HIV-1 reverse transcriptase during therapy with abacavir, lamivudine and zidovudine in HIV-1-infected adults with no prior antiretroviral therapy

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Do environmental influences alter motor abilities acquisition? A comparison among children from day-care centers and private schools Influências do ambiente podem alterar a aquisição de habilidades motoras? Uma comparação entre pré-escolares de creches públicas e escolas privadas

Development occurs in a proper rhythm as result of genetic inheritance and environment factors. This study had the aim to identify some environmental risk factors for the motor development in two groups of healthy children. 100 pre-school aged (five years children) from two day-care centers and a private school were evaluated, in Recife-PE. All the children underwent to a motor skills assessment and their parents answered a questionnaire. The children from the public nursery remained behind in fine motor skills. The results showed that the biologically healthy children development can suffer negative influence of the environmental risk factors. In this research these factors were: the father absence, improper toys use to the correct age, the place were the child was kept in the early childhood, the lack of pedagogical guidance and extra-parental socialization and low familiar socioeconomic status.<br>O desenvolvimento ocorre num ritmo resultante da interação entre herança genética e fatores ambientais. Este estudo teve por objetivo identificar alguns fatores de risco ambientais para o desenvolvimento motor, em dois grupos de crianças saudáveis. Foram avaliadas 100 crianças (idade:5 anos) provenientes de duas creches públicas e uma escola particular, em Recife-PE. Todas as crianças foram submetidas a uma avaliação das habilidades motoras e seus pais responderam a um questionário. As crianças da creche pública mostraram atraso no campo das habilidades motoras finas. Os resultados indicaram que o desenvolvimento das crianças biologicamente saudáveis pode sofrer influência negativa dos fatores de risco ambientais. Os fatores encontrados foram: a ausência do pai; a utilização de brinquedos inadequados para faixa etária; o local onde a criança era mantida em idades precoces da infância; a falta de orientação pedagógica e de socialização extra-familiar precoce, e a baixa condição socioeconômica familiar

Mutations in HIV-1 Reverse Transcriptase during Therapy with Abacavir, Lamivudine and Zidovudine in HIV-1-Infected Adults with No Prior Antiretroviral Therapy

Objective To evaluate HIV-1 reverse transcriptase (RT) drug resistance in patients receiving abacavir, lamivudine and zidovudine therapy. Methods In a randomized, double-blind study, 173 anti-retroviral treatment-naive HIV-1-infected adults received abacavir/lamivudine/zidovudine or lamivudine/zidovudine for up to 48 weeks. After week 16, patients could switch to open-label abacavir/lamivudine/zidovudine, and those with plasma HIV-1 RNA (vRNA) >400 copies/ml could add other antiretrovirals. From weeks 16 to 48, samples with vRNA >400 copies/ml were collected for genotyping and phenotyping. Results At baseline, 90% of isolates were wild-type (WT). At week 16, vRNA was >400 copies/ml in seven of 72 (10%) patients receiving abacavir/lamivudine/zidovudine and in 41 of 66 (62%) receiving lamivudine/ zidovudine. At week 16, the genotypes in isolates from the abacavir/lamivudine/zidovudine group were M184V alone ( n=3 cases), WT ( n=3) and M184V plus thymidine analogue mutations (TAMs) ( n=1). The genotypes in isolates from the lamivudine/zidovudine group were M184V alone ( n=37), WT ( n=1) and M184V plus TAMs ( n=3). In the four cases where M184V plus TAMs were detected some mutations were present at baseline. Despite detectable M184V in 74% of patients on lamivudine/zidovudine, addition of abacavir with or without another antiretroviral therapy resulted in a reduction in vRNA, with 42 of 65 (65%) patients having week 48 vRNA <400 copies/ml (intent-to-treat with missing=failure). At week 48, the most common genotype was M184V alone in the abacavir/ lamivudine/zidovudine group (median vRNA 1–2 log 10 below baseline), and M184V with or without TAMs in patients originally assigned to lamivudine/zidovudine. At week 48, phenotypic results were obtained for 11 isolates for patients from both arms, and all had reduced susceptibility to lamivudine but all remained sensitive to stavudine, all protease inhibitors and all non-nucleoside reverse transcriptase inhibitors. Three, three and two isolates had reduced susceptibility to abacavir, didanosine and zidovudine, respectively. Conclusions Abacavir retained efficacy against isolates with the M184V genotype alone. TAMs did not develop during 48 weeks of abacavir/lamivudine/zidovudine therapy and were uncommon when abacavir was added after 16 weeks of lamivudine/zidovudine therapy. Limited mutations upon rebound on this triple nucleoside combination allows for several subsequent treatment options