9 research outputs found
Estudo duplo-cego, randĂ´mico comparando indinavir, zidovudina e indinavir mais zidovudina na terapia anti-retroviral de indivĂduos HIV+ sem tratamento anterior, com contagem de cĂ©lulas CD4 entre 50 e 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.Foi demonstrado que o tratamento com indinavir resulta em importante redução da carga viral e aumentos das cĂ©lulas CD4 em pacientes infectados pelo HIV. Foi realizado um estudo duplo-cego, randĂ´mico para avaliar a eficácia do indinavir isoladamente (800 mg cada 8h), zidovudina isoladamente (200 mg cada 8h) ou a combinação, para avaliar a progressĂŁo para AIDS. Foram distribuidos para tratamento 996 pacientes virgens de tratamento antiretroviral, com contagens de CD4 entre 50 e 250 cĂ©lulas/mm3. Durante o estudo, o protocolo foi modificado para adicionar lamivudina aos braços contendo zidovudina. O "endpoint" primário foi o tempo para o desenvolvimento de uma doença-definidora de AIDS ou morte. O estudo foi interrompido apĂłs uma análise preliminar definida no protocolo ter demonstrado reduções significativas na progressĂŁo para um evento clĂnico nos grupos contendo indinavir, comparado ao grupo da zidovudina (p< 0,0001). ApĂłs uma mediana de seguimento de 52 semanas (chegando a 99 semanas), as reduções percentuais nas ocorrĂŞncias para indinavir+zidovudina e indinavir, comparado com zidovudina foram de 70% e 61%, respectivamente. Reduções significativas na medida do RNA viral e aumentos nas contagens de CD4 tambĂ©m foram observadas nos grupos contendo indinavir, em relação ao da zidovudina. A melhora nas cĂ©lulas CD4 e RNA viral foram ambas associadas a risco reduzido de progressĂŁo da doença. Os trĂŞs tratamentos foram geralmente bem tolerados
Subgroup and Resistance Analyses of Raltegravir for Resistant HIV-1 Infection
Background: We evaluated the efficacy of raltegravir and the development of viral resistance in
two identical trials involving patients who were infected with human immunodeficiency
virus type 1 (HIV-1) with triple-class drug resistance and in whom antiretroviral
therapy had failed.
Methods: We conducted subgroup analyses of the data from week 48 in both studies according
to baseline prognostic factors. Genotyping of the integrase gene was performed
in raltegravir recipients who had virologic failure.
Results: Virologic responses to raltegravir were consistently superior to responses to placebo,
regardless of the baseline values of HIV-1 RNA level; CD4 cell count; genotypic
or phenotypic sensitivity score; use or nonuse of darunavir, enfuvirtide, or both in
optimized background therapy; or demographic characteristics. Among patients in the
two studies combined who were using both enfuvirtide and darunavir for the first
time, HIV-1 RNA levels of less than 50 copies per milliliter were achieved in 89% of
raltegravir recipients and 68% of placebo recipients. HIV-1 RNA levels of less than 50
copies per milliliter were achieved in 69% and 80% of the raltegravir recipients and
in 47% and 57% of the placebo recipients using either darunavir or enfuvirtide for
the first time, respectively. At 48 weeks, 105 of the 462 raltegravir recipients (23%)
had virologic failure. Genotyping was performed in 94 raltegravir recipients with
virologic failure. Integrase mutations known to be associated with phenotypic resistance
to raltegravir arose during treatment in 64 patients (68%). Forty-eight of
these 64 patients (75%) had two or more resistance-associated mutations.
Conclusions: When combined with an optimized background regimen in both studies, a consistently
favorable treatment effect of raltegravir over placebo was shown in clinically
relevant subgroups of patients, including those with baseline characteristics that typically
predict a poor response to antiretroviral therapy: a high HIV-1 RNA level, low
CD4 cell count, and low genotypic or phenotypic sensitivity score. (ClinicalTrials.gov
numbers, NCT00293267 and NCT00293254.
Raltegravir with Optimized Background Therapy for Resistant HIV-1 Infection
Background: Raltegravir (MK-0518) is an inhibitor of human immunodeficiency virus type 1 (HIV-1)
integrase active against HIV-1 susceptible or resistant to older antiretroviral drugs.
Methods: We conducted two identical trials in different geographic regions to evaluate the
safety and efficacy of raltegravir, as compared with placebo, in combination with
optimized background therapy, in patients infected with HIV-1 that has triple-class
drug resistance in whom antiretroviral therapy had failed. Patients were randomly
assigned to raltegravir or placebo in a 2:1 ratio.
Results: In the combined studies, 699 of 703 randomized patients (462 and 237 in the raltegravir
and placebo groups, respectively) received the study drug. Seventeen of the 699
patients (2.4%) discontinued the study before week 16. Discontinuation was related
to the study treatment in 13 of these 17 patients: 7 of the 462 raltegravir recipients
(1.5%) and 6 of the 237 placebo recipients (2.5%). The results of the two studies
were consistent. At week 16, counting noncompletion as treatment failure, 355 of
458 raltegravir recipients (77.5%) had HIV-1 RNA levels below 400 copies per milliliter,
as compared with 99 of 236 placebo recipients (41.9%, P<0.001). Suppression of
HIV-1 RNA to a level below 50 copies per milliliter was achieved at week 16 in
61.8% of the raltegravir recipients, as compared with 34.7% of placebo recipients,
and at week 48 in 62.1% as compared with 32.9% (P<0.001 for both comparisons).
Without adjustment for the length of follow-up, cancers were detected
in 3.5% of
raltegravir recipients and in 1.7% of placebo recipients. The overall frequencies of
drug-related adverse events were similar in the raltegravir and placebo groups.
Conclusions: In HIV-infected patients with limited treatment options, raltegravir plus optimized
background therapy provided better viral suppression than optimized background
therapy alone for at least 48 weeks. (ClinicalTrials.gov numbers, NCT00293267 and
NCT00293254.
Estudo duplo-cego, randĂ´mico comparando indinavir, zidovudina e indinavir mais zidovudina na terapia anti-retroviral de indivĂduos HIV+ sem tratamento anterior, com contagem de cĂ©lulas CD4 entre 50 e 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.Foi demonstrado que o tratamento com indinavir resulta em importante redução da carga viral e aumentos das cĂ©lulas CD4 em pacientes infectados pelo HIV. Foi realizado um estudo duplo-cego, randĂ´mico para avaliar a eficácia do indinavir isoladamente (800 mg cada 8h), zidovudina isoladamente (200 mg cada 8h) ou a combinação, para avaliar a progressĂŁo para AIDS. Foram distribuidos para tratamento 996 pacientes virgens de tratamento antiretroviral, com contagens de CD4 entre 50 e 250 cĂ©lulas/mm3. Durante o estudo, o protocolo foi modificado para adicionar lamivudina aos braços contendo zidovudina. O endpoint primário foi o tempo para o desenvolvimento de uma doença-definidora de AIDS ou morte. O estudo foi interrompido apĂłs uma análise preliminar definida no protocolo ter demonstrado reduções significativas na progressĂŁo para um evento clĂnico nos grupos contendo indinavir, comparado ao grupo da zidovudina (p< 0,0001). ApĂłs uma mediana de seguimento de 52 semanas (chegando a 99 semanas), as reduções percentuais nas ocorrĂŞncias para indinavir+zidovudina e indinavir, comparado com zidovudina foram de 70% e 61%, respectivamente. Reduções significativas na medida do RNA viral e aumentos nas contagens de CD4 tambĂ©m foram observadas nos grupos contendo indinavir, em relação ao da zidovudina. A melhora nas cĂ©lulas CD4 e RNA viral foram ambas associadas a risco reduzido de progressĂŁo da doença. Os trĂŞs tratamentos foram geralmente bem tolerados.273