Effectiveness and risk factors for virological outcome of darunavir-based therapy for treatment-experienced HIV-infected patients.

OBJECTIVE: We evaluated the effectiveness of darunavir (DRV) treatment plus an optimized background regimen in 120 HIV-1 treatment-experienced patients. DESIGN: Retrospective cohort, multicenter study. METHODS: Adults >16 years with virological treatment failure starting therapy with a DRV-containing regimen were included. Effectiveness was evaluated as the percentage of patients with an undetectable HIV-1 RNA viral load (<50 and <200 copies/mL) after 48 weeks, and changes in CD4+ cell counts. We evaluated the risk factors associated with treatment failure. RESULTS: Of the cohort, 83 % were men with a median age of 45 years (interquartile range, IQR 40-51). They had experienced treatment for a median of 13 years (IQR 9-17) with a median of six previous regimens (IQR 4-7), all using protease inhibitors. After treatment, 82 % (95 % confidence interval, CI 74-88 %) of patients had an HIV-1 RNA viral load <200 copies/mL and 69 % (95 % CI 60-76 %) had <50 copies/mL. The CD4+ cell count increased by 378 cells/µL (IQR 252-559; P < 0.001 vs. baseline). Risk factors associated with poor outcome were age >40 years [odds ratio, OR 0.15 (95 % CI 0.10-0.78); P = 0.015], use of raltegravir in the regimen [OR 0.37 (95 % CI 0.10-0.97); P = 0.046], and baseline CD4+ cell count <200 cells/µL [OR 2.79 (95 % CI 1.11-6.97); P = 0.028]. CONCLUSION: In this Mexican cohort Darunavir was metabolically safe, well tolerated and achieved high rates of virological suppression in highly treatment-experienced patients infected with HIV-1.

[Identification of Mycobacterium avium-intracellulare complex by PCR of AIDS and disseminated mycobacteriosis]. / Identificación del complejo Mycobacterium avium-intracellulare por PCR en SIDA y micobacteriosis diseminada.

OBJECTIVE: The aim of this study is to differentially identify MAC by PCR in patients with AIDS and disseminated mycobacteriosis. METHODS: A cross sectional study was conducted in Mexico to identify MAC by Molecular Biology. Two sets of primers were synthesized: MAV and MIN, for M. avium and M. intracellulare, respectively. Whole-cell DNAs obtained from 29 clinical isolates and clinical serum specimens from other 24 patients with AIDS and disseminated mycobacterial infection were extracted and amplified by PCR with the MAV and MIN primers. The MAV and MIN primers each amplified one highly specific 1.3-kb segment of the homologous DNA, respectively. RESULTS: Twenty-nine DNAs from MAC clinical isolates identified by Gen-Probe AccuProbes were amplified with the MAV primers. Of the 24 clinical samples, 3 were positive for M. avium and 6 for M. tuberculosis. CONCLUSIONS: Our results demonstrated that PCR technique could be applied for the differentiation of M. avium and M. intracellulare by specific 16S rRNA primers. In patients with advanced stage AIDS and in whom disseminated mycobacteriosis is suspected, the presence of anemia (even with negative cultures), elevated alkaline phosphatase and a median CD4 count of 15.9/mL, the diagnosis of infection by MAC should be strongly considered; we suggest that in accordance with our findings, a more precise stratification of patients in terms of their CD4 T cell counts is warranted.

Introducción: el objetivo de este artículo es Identificar y diferenciar el complejo MAC por PCR en pacientes con SIDA y micobacteriosis diseminada. Métodos: se llevó a cabo un estudio transversal para identificar MAC por biología molecular. Se sintetizaron dos conjuntos de iniciadores: MAV y MIN, para M. avium y M. intracellulare, respectivamente. El ADN total de células obtenidas de 29 aislados clínicos y muestras de suero de otros 24 pacientes con SIDA e infección micobacteriana diseminada fue extraído y se amplificó por PCR con los iniciadores MAV y MIN. Cada uno de los iniciadores MAV y MIN amplificó un segmento altamente específico de 1.3 kb del ADN homólogo, respectivamente. Resultados: veintinueve ADN de los aislados clínicos de MAC identificadas por Gen-Probe AccuProbes se amplificaron con los iniciadores MAV (M. avium). De las 24 muestras clínicas, 3 fueron positivas para M. avium y 6 para M. tuberculosis. Conclusiones: nuestros resultados demostraron que la técnica de PCR se puede aplicar para la diferenciación de M. avium y M. intracellulare por iniciadores específicos 16S rRNA. En pacientes con estadio avanzado de SIDA y en quienes se sospecha micobacteriosis diseminada, la presencia de anemia (incluso con cultivos negativos) fosfatasa alcalina elevada y una mediana de CD4 de 15.9/ml, se debe considerar seriamente el diagnóstico de infección por MAC; sugerimos que, de acuerdo con nuestros resultados, se justifica una estratificación más precisa de los pacientes en términos de sus recuentos de células T CD4.

Effectiveness of etravirine-based therapy for treatment-experienced HIV-infected patients.

INTRODUCTION: Treatment options are limited for HIV-1-infected individuals who have received extensive previous antiretroviral therapy. ETV has shown significant clinical benefits in treatment-experienced HIV-1+ patients with antiretroviral resistance. The aim of this study was to evaluate the effectiveness of ETV plus optimized background regimen in real-life conditions in a cohort of highly HIV-1 antiretroviral-experienced patients. METHODOLOGY: Retrospective cohort of treatment-experienced HIV-1-infected adults with virological failure who started therapy with an ETV-containing regimen. The effectiveness was evaluated using HIV-1 RNA viral load and changes in CD4+ cell count after 48 weeks of treatment. RESULTS: Forty-two patients ≥ 16 years of age were included; 74% were men, and the median age was 45 years (IQR 41-53). All participants had prior non-nucleoside reverse transcriptase inhibitor use (55% nevirapine, 83%, efavirenz, and 28% both). Baseline median HIV-1 RNA viral load was 15,598 copies/mL (IQR 2651-84,175) and CD4+ cell count was 276 cells/mL (IQR 155-436). After 48 weeks of treatment, 90.5% (95% CI 78-96) of patients had HIV-1 RNA viral load < 200 copies/mL and 76% (95% CI 61-86) had < 50 copies/mL. CD4+ cell counts increased from baseline to 48 weeks of treatment to a median of 407 cells/mL (IQR 242-579); p < 0.001. Virological outcome was associated with virological failure at baseline HIV-1 RNA viral load ≥ 100,000 copies/mL (OR 7.6; 95% CI 1.2-44.80; p = 0.025). CONCLUSIONS: Our study provides clinically important evidence of the effectiveness and safety of ETV in highly antiretroviral-experienced HIV-1-infected patients.