Updating our understanding of pulmonary disease associated with HIV infection.

Arch Bronconeumol. 2012 Apr  V.48 N.4 P.126-32.

Estébanez-Muñoz M, Soto-Abánades CI, Ríos-Blanco JJ, Arribas JR.

Unidad de VIH, Servicio de Medicina Interna, Hospital Universitario La Paz, IdiPAZ, Madrid, España. mestebanez.hulp@salud.madrid.org

Abstract

The introduction of highly active antiretroviral therapy (HAART) has resulted in a reduction of opportunistic infections associated with cellular and humoral immunosuppression. However, what is still unclear is the impact of HAART on the development of other diseases not associated with AIDS, such as lung cancer and COPD. The aim of this paper is to review the most innovative and relevant aspects of lung pathology in patients infected with HIV.

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http://www.archbronconeumol.org/watermark/ctl_servlet?_f=10&pident_articulo=90107870&pident_usuario=0&pident_revista=260&fichero=260v48n04a90107870pdf001.pdf&ty=104&accion=L&origen=abn_eng&web=www.archbronconeumol.org&lan=en

Treatment of advanced HIV infection.

J Antimicrob Chemother. 2003 Feb  V.51 N.2 P.225-7.

Pulido F, Arribas JR.

HIV CareUnit, Hospital Universitario 12 de Octubre, Ctra. Andalucia Km 5.4, 28041-Madrid, Spain. fpulido@palmedico.com

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http://jac.oxfordjournals.org/content/51/2/225.full.pdf+html

 

The rise and fall of triple nucleoside reverse transcriptase inhibitor (NRTI) regimens.

J Antimicrob Chemother. 2004 Sep  V.54 N.3 P.587-92.

Arribas JR.

HIV Unit, La Paz Hospital, Paseo de la Castellana 261, 28046 Madrid, Spain. josearribas@telefonica.net

Abstract

Triple nucleoside reverse transcriptase inhibitor (NRTI) regimens have attracted much interest due to their potential to (1) simplify dosing, with potential gains in adherence to treatment, and (2) reduce or even reverse dyslipidaemia associated with protease inhibitor (PI) therapy. A variety of triple NRTI combinations have been investigated, in both antiretroviral-naive and antiretroviral-experienced HIV-infected patients. Many of these trials have generated disappointing results, and some have been prematurely discontinued due to poor efficacy. This article reviews the background to the development of triple NRTI regimens, and the mounting evidence that this approach is suboptimal for antiretroviral-naive patients. Indeed, some triple NRTI regimens should never be used in this population. A role for triple NRTI combinations as a simplification strategy in treatment-experienced patients whose HIV is well controlled has been suggested, but emerging evidence indicates that such an approach can, under adequate selection pressure, lead to the emergence of mutations and viral load rebound. This commentary discusses the factors that appear to influence patients’ responses to triple NRTI therapy, and their implications for patient selection.

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http://jac.oxfordjournals.org/content/54/3/587.full.pdf+html

Causes and consequences of incomplete HIV RNA suppression in clinical trials.

HIV Clin Trials. 2009 Sep-Oct  V.10 N.5 P.289-98.

Pozniak A, Gupta RK, Pillay D, Arribas J, Hill A.

Chelsea and Westminster Hospital, London, United Kingdom.

Abstract

The current goal of antiretroviral treatment is suppression of HIV RNA below 50 copies/mL. However, there is evidence for residual low-level plasma viraemia below 50 copies/mL for people with HIV RNA suppression on antiretroviral treatment. It is not clear whether more profound suppression of HIV RNA would lead to a lower risk of virological failure on antiretroviral treatment or emergent drug resistance. There is high variability in the currently used HIV RNA PCR assays for samples with HIV RNA levels close to the detection lower limit of 40-50 copies/mL. For patients who have HIV RNA levels just above 50 copies/mL (often called “single blips”), a repeat sample should be taken to investigate the possibility of technical error. In a systematic review of 48-week efficacy from randomized clinical trials (N = 8,083), patients were significantly more likely to show HIV RNA levels between 50-400 copies/mL while taking fi rst-line boosted PI-based HAART (7.3%) compared with fi rst-line NNRTI-based HAART (4.5%) (p < 0.01). However in a systematic review of emergent drug resistance at failure in the same trials, there was also a significantly lower risk of emerging drug resistance after virological failure of boosted PI-based HAART (p < 0.01). Therefore, HIV RNA blips between 50-400 copies/mL may have different consequences for different classes of antiretrovirals. The most widely used method to analyse HIV RNA in clinical trials – time to loss of virological response (TLOVR) – uses two consecutive HIV RNA measurements to define both virological success and failure. However, other methods may improve precision and increase statistical power.

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http://thomasland.metapress.com/content/4326nn455t683x50/fulltext.pdf

The future of antiretroviral therapy: challenges and needs.

J Antimicrob Chemother. 2010 May  V.65 N.5 P.827-35.

Moreno S, López Aldeguer J, Arribas JR, Domingo P, Iribarren JA, Ribera E, Rivero A, Pulido F; HIV 2020 Project.

Collaborators (38)

Department of Infectious Diseases, Hospital Ramón y Cajal, Carretera de Colmenar Km 9.100, 28034 Madrid, Spain. smoreno.hrc@salud.madrid.org

Abstract

The introduction of combination antiretroviral therapy (cART) has substantially modified the natural history of HIV infection. At the beginning of the cART era the objective was focused on HIV-1-associated mortality and morbidity, but as this objective was accomplished other issues emerged, including toxicity, resistance and compliance with treatment. Moreover, the participation of other disease mechanisms, such as proinflammatory activity, in the so-called non-AIDS events is becoming increasingly important. To overcome these issues, therapeutic options have dramatically expanded, which has made the management of HIV-1-infected patients increasingly complex. The intense changes seen raise the question of what will be the future of HIV infection and its treatment. A projection into the future may help to reflect on current limitations, needs and research priorities, to optimize patient care. To debate on this topic a group of 38 experts has initiated The HIV 2020 Project, with the aim of reflecting on the future of HIV infection and identifying the needs that should be the attention of research in different areas. This document summarizes the group’s conclusions on the future of antiretroviral treatment, presented as 20 relevant questions. Each question includes the current status of the topic and our vision for the future.

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http://jac.oxfordjournals.org/content/65/5/827.full.pdf+html

Effectiveness of protease inhibitor monotherapy versus combination antiretroviral maintenance therapy: a meta-analysis.

PLoS One. 2011 V.6 N.7 e22003.

Mathis S, Khanlari B, Pulido F, Schechter M, Negredo E, Nelson M, Vernazza P, Cahn P, Meynard JL, Arribas J, Bucher HC.

Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.

Abstract

BACKGROUND:

The unparalleled success of combination antiretroviral therapy (cART) is based on the combination of three drugs from two classes. There is insufficient evidence whether simplification to ritonavir boosted protease inhibitor (PI/r) monotherapy in virologically suppressed HIV-infected patients is effective and safe to reduce cART side effects and costs.

METHODS:

We systematically searched Medline, Embase, the Cochrane Library, conference proceedings and trial registries to identify all randomised controlled trials comparing PI/r monotherapy to cART in suppressed patients. We calculated in an intention to treat (loss-of follow-up, discontinuation of assigned drugs equals failure) and per-protocol analysis (exclusion of protocol violators following randomisation) and based on three different definitions for virological failure pooled risk ratios for remaining virologically suppressed.

FINDINGS:

We identified 10 trials comparing 3 different PIs with cART based on a PI/r plus 2 reverse transcriptase inhibitors in 1189 patients. With the most conservative approach (viral load <50 copies/ml on two consecutive measurements), the risk ratios for viral suppression at 48 weeks of PI/r monotherapy compared to cART were in the ITT analysis 0.94 8 (95% CI 0.89 to 1.00) p = 0.06; risk difference -0.06 (95%CI -0.11 to 0) p = 0.05, p for heterogeneity  = 0.08, I(2) = 43.1%) and in the PP analysis 0.93 ((95%CI 0.90 to 0.97) p<0.001; risk difference -0.07 (95%CI -0.10 to -0.03) p<0.001, p for heterogeneity  = 0.44, I(2) = 0%). Reintroduction of cART in 44 patients with virological failure led in 93% to de-novo viral suppression.

INTERPRETATION:

Virologically well suppressed HIV-infected patients have a lower chance to maintain viral suppression when switching from cART to PI/r monotherapy. Failing patients achieve high rates of de-novo viral suppression following reintroduction of reverse transcriptase inhibitors.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139616/pdf/pone.0022003.pdf