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

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          Abstract

          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.

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          Most cited references13

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          Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection.

          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. 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. 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. 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.) 2008 Massachusetts Medical Society
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            Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trials.

            The continuing, randomised, multinational, phase IIB POWER 1 and 2 studies aim to evaluate efficacy and safety of darunavir in combination with low-dose ritonavir in treatment-experienced HIV-1-infected patients. We did a pooled subgroup analysis to update results at week 48 for patients receiving the recommended dose of darunavir-ritonavir compared with those receiving other protease inhibitors (PIs). After 24-week dose-finding phases and primary efficacy analyses, patients randomised to receive darunavir-ritonavir were given 600/100 mg twice daily, and patients receiving control PIs continued on assigned treatment into the longer-term, open-label phase; all patients continued on optimised background regimen. We assessed patients who had reached week 48 or discontinued earlier at the time of analysis; for the darunavir-ritonavir group, only patients who received 600/100 mg twice daily from baseline were included. Analyses were intention-to-treat. The POWER 2 study (TMC114-C202) is registered with ClinicalTrials.gov (NCT00071097). At week 48, 67 of 110 (61%) darunavir-ritonavir patients compared with 18 of 120 (15%) of control PI patients had viral load reductions of 1 log10 copies per mL or greater from baseline (primary endpoint; difference in response rates 46%, 95% CI 35%-57%, p<0.0001). Based on a logistic regression model including stratification factors (baseline number of primary PI mutations, use of enfuvirtide, baseline viral load) and study as covariates, the difference in response was 50% (odds ratio 11.72, 95% CI 5.75-23.89). In the darunavir-ritonavir group, rates of adverse events were mostly lower than or similar to those in the control group when corrected for treatment exposure. No unexpected safety concerns were identified. Efficacy responses with darunavir-ritonavir 600/100 mg twice daily plus optimised background regimen were greater than those with control PI and were sustained to at least week 48, with favourable safety and tolerability in treatment-experienced patients. This regimen could expand the treatment options available for such patients.
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              Aging, antiretrovirals, and adherence: a meta analysis of adherence among older HIV-infected individuals.

              Older adults are generally considered to be at greater risk for medication non-adherence due to factors such as medication complexity, side effects, cost, and cognitive decline. However, this generalization may not apply to older adults with human immunodeficiency virus (HIV). Regardless of age, suboptimal adherence to antiretroviral therapy (ART) can lead to increased viral load, immunosuppression, drug-resistant viral strains, co-morbidities, and opportunistic infections. Understanding trends of adherence to ART among older adults is critical, especially as the population of people living with HIV grows older. The purpose of this systematic review and meta-analysis is to determine if older individuals with HIV are less likely to be non-adherent to antiretroviral therapy than younger individuals with HIV. A systematic search in PubMed, Embase, and PsycINFO was conducted to identify peer-reviewed articles evaluating adherence to ART in older adults. Two independent reviewers screened abstracts, applied inclusion criteria, and appraised study quality. The bibliographies of qualifying studies were searched. Data were abstracted from studies by two independent authors. Meta-analyses were conducted, and adherence levels were reported as the relative risk of non-adherence in older individuals compared to younger individuals. The systematic search yielded 1,848 abstracts. Twelve studies met full inclusion criteria. The overall meta-analysis found that older age reduced risk for nonadherence by 27 % (relative risk (RR) 0.72, 95 % confidence interval (CI) 0.64–0.82). Studies assessing both short-term and long-term adherence demonstrated a significant reduction in non-adherence among older patients (RR 0.75, 95 % CI 0.64–0.87 and RR 0.65, 95 % CI 0.50–0.85, respectively). Older adults with HIV have a reduced risk for non-adherence to ART than their younger counterparts. Future studies should seek to elucidate contributing factors of adherence among older individuals with HIV.
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                Author and article information

                Contributors
                + 52-5557245900 , jamatamarin@gmail.com
                gloriahuerta@gmail.com
                cardomher@gmail.com
                marcelino347@hotmail.com
                marcobandalara@gmail.com
                nohemis74@yahoo.com.mx
                javkike@hotmail.com
                escribo_a_jorge@yahoo.com.mx
                cima.dr@gmail.com
                aorjavillagomez@hotmail.com
                manjarreztellez@gmail.com
                jgaytanmtz@yahoo.com.mx
                Journal
                AIDS Res Ther
                AIDS Res Ther
                AIDS Research and Therapy
                BioMed Central (London )
                1742-6405
                24 September 2015
                24 September 2015
                2015
                : 12
                : 31
                Affiliations
                [ ]Infectious Diseases Department, National Medical Center “La Raza”, IMSS, Mexico Distrito Federal, Mexico
                [ ]Pediatric Infectious Diseases Department, National Medical Center “Siglo XXI”, IMSS, Mexico Distrito Federal, Mexico
                [ ]Infectious Diseases Department, Third Level Hospital No. 25, IMSS, Monterrey, NL Mexico
                [ ]AIDS Clinic, General Hospital No 2, IMSS, San Luis Potosí, S.L.P. Mexico
                [ ]AIDS Clinic, General Hospital No-24, IMSS, Mexico Distrito Federal, Mexico
                [ ]AIDS Clinic, General Hospital No.72, IMSS, Mexico Distrito Federal, Mexico
                [ ]AIDS Clinic, Regional Hospital No. 1, IMSS, Culiacán, Sinaloa Mexico
                [ ]Seris y Jacarandas s/n, Colonia “La Raza”, Del Azcapotzalco, CP 02990 Ciudad de México D.F., Mexico
                Article
                72
                10.1186/s12981-015-0072-9
                4582634
                725300bc-b255-4608-833d-aca05221005d
                © Mata-Marín et al. 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 25 April 2015
                : 10 September 2015
                Categories
                Research
                Custom metadata
                © The Author(s) 2015

                Infectious disease & Microbiology
                darunavir,hiv,drug resistance,hiv-1 rna,virological outcome
                Infectious disease & Microbiology
                darunavir, hiv, drug resistance, hiv-1 rna, virological outcome

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