María José Galindo

Reversible posterior leukoencephalopathy secondary to indinavir-induced hypertensive crisis: a case report.

Reversible posterior leukoencephalopathy syndrome (RPLS) is an uncommon entity related to multiple and different pathologies, the most common being hypertensive crisis. It is believed to be secondary to the breakdown on the blood-brain barrier. At the beginning, it is undistinguishable from other leukoencephalopathies. However, the disappearance of brain lesions after removal of the potential cause, establish the differential diagnosis with other leukoencephalopathies. We present the case of an HIV-infected patient with a RPLS related to a hypertensive crisis short after the initiation of indinavir-containing highly active antiretroviral therapy. Once blood pressure was controlled and indinavir replaced by nelfinavir, white matter lesions at magnetic resonance imaging disappeared. The clinical and radiologic evolution excludes other diagnosis as progressive multifocal leukoencephalopathy and points indinavir as a potential hypertension-inducing agent in HIV-infected predisposed subjects.

Ambulatory blood pressure during diseases of the kidney.

During the last few years there has been a renewal of interest in blood-pressure-induced kidney damage due to a progressive increase in the incidence and prevalence of hypertension and vascular diseases as a cause of end-stage renal disease (ESRD). The need to prevent ESRD demands a continuation of effort to make the early identification of hypertensives who are at risk possible and to provide them with effective antihypertensive therapy. Since ambulatory blood pressure monitoring has been used successfully to assess blood pressure and identify risk markers for cardiovascular diseases, a logical approach would be to use it also to identify the risk markers for ESRD. Higher than normal percentages of non-dippers have been found among subjects with renal failure, during dialysis (haemofiltration, peritoneal dialysis and continuous ambulatory peritoneal dialysis), among cases of renovascular hypertension or cystic kidney disease and among cases of renal transplantation. Although this non-dipping pattern might be related to the presence of severe hypertension in some patients, such as those who have renovascular hypertension, in other cases the abnormal circadian variability is present with milder forms of hypertension or even in the absence of hypertension. Monitoring ambulatory blood pressure could offer advantages for protection of renal function during antihypertensive treatment of subjects with mild renal insufficiency. Furthermore, ambulatory blood pressure monitoring seems to have been prognostic for the development of proteinuria in a group of refractory hypertensives. Whether higher than normal nocturnal blood pressures and the non-dipping pattern are causes or consequences of renal disease should be addressed in prospective studies. The above notwithstanding, assessment of nocturnal blood pressure seems to be an important aid in the management of patients with hypertension-related renal disease and of patients who are susceptible to developing it.

Cardiovascular toxicity of abacavir: a clinical controversy in need of a pharmacological explanation

&NA; There is a long-lasting controversy surrounding an association between abacavir (ABC) and an increased risk of cardiovascular disease in HIV-positive patients. Although differing in their specifics, a number of published cohort studies and clinical trials support such an association, usually relating it to recent exposure to the drug, independently of traditional predisposing factors. However, other clinical trials have failed to reveal such a relation and have pointed to methodological differences to explain discrepancies. Significantly, the controversy has been fueled by the lack of a credible mechanism of action to justify the putative detrimental actions of ABC. There is a myriad of contradictory clinical indicators which are not clearly compatible with known profiles of either vascular physiopathology or pharmacological interference. However, basic research has recently hinted at altered homeostatic mechanisms, though this requires clinical validation. In particular, recurrent evidence – both clinical and experimental – relates ABC with vascular inflammation, a leading contributor to the atherosclerotic plaque and thrombosis. ABCs chemical structure is very close to that of endogenous purines (ATP, ADP and AMP), major paracrine signaling molecules capable of triggering prothrombotic and proinflammatory vascular programs. Other proposed mechanisms are a competitive inhibition of guanylyl cyclase in platelets and a subsequent decrease in cyclic guanosine monophosphate (cGMP). The present review aims to shed light on this complex subject by summarizing and critically evaluating all the available clinical data regarding a relationship between ABC and cardiovascular disease, and to put forward potential pharmacological explanations compatible with both the clinical scenario and experimental findings.

Alteración renal en la infección por el virus de la inmunodeficiencia humana

Fundamento y objetivo: Aunque la enfermedad renal se esta convirtiendo en un problema emergente en la poblacion infectada por el virus de la inmunodeficiencia humana (VIH), se tiene muy escasa informacion sobre su curso natural. El objetivo del presente estudio es analizar las lesiones renales en una serie de autopsias de pacientes con infeccion por el VIH en ausencia de tratamiento antirretroviral. Pacientes y metodo: Se han revisado retrospectivamente datos de las autopsias de 61 sujetos infectados por el VIH (edad media [DE], 36,9 [8,4] anos; un 58,6% eran adictos a drogas por via parenteral y el 84%, varones) fallecidos en nuestro hospital entre 1984 y 1997. Ningun paciente recibio tratamiento antirretroviral. Se reviso especificamente la totalidad de las muestras autopsicas renales. Resultados: En el momento del ingreso previo al fallecimiento el 9,8% de los pacientes presentaba insuficiencia renal, y un 44,3% la presento en algun momento del ingreso. La causa principal de fallecimiento correspondio a cuadros infecciosos (76%). La mayoria de los pacientes (93,4%) presento alteraciones renales en las muestras autopsicas. Las lesiones encontradas destacaron por su elevada heterogeneidad, con predominio de las alteraciones tubulares (96,7%) y del intersticio (60,7%) frente a las glomerulares (55,7%). Los diagnosticos anatomopatologicos mas frecuentes fueron necrosis tubular aguda (16,4%) y nefritis septica-abscesos (16,4%), seguidos de nefritis tubulointersticial (9%); 2 pacientes (3,3%) presentaron nefropatia asociada al VIH. No hubo diferencias anatomopatologicas al considerar la existencia de insuficiencia renal. Conclusiones: La afeccion renal es frecuente en la infeccion por el VIH. La heterogeneidad de las lesiones renales es muy alta, con afeccion predominante de tubulos, seguidos de intersticio y mesangio. La principal causa de lesion renal son las infecciones, si bien los germenes oportunistas raramente se localizan en este organo. No existe relacion entre la presencia de dano renal microscopico y presencia de alteraciones analiticas de funcion renal.

Executive summary of the GeSIDA/National AIDS Plan consensus document on antiretroviral therapy in adults infected by the human immunodeficiency virus (updated January 2018)

This update to the document on antiretroviral therapy (ART) in adults, which has been prepared jointly by GeSIDA and the Spanish National AIDS Plan for the last two decades, supersedes the document published in 2017.1 The update provides physicians treating HIV-1-infected adults with evidence-based recommendations to guide their therapeutic decisions. The main difference with respect to the previous document concerns recommended initial ART regimens, only three of which are maintained as preferential. All three include dolutegravir or raltegravir, together with emtricitabine/tenofovir alafenamide or abacavir/lamivudine. Other differences concern the section on switching ART in patients with suppressed viral replication, which now includes new two- and three-drug regimens, and the antiretroviral drugs recommended for pregnant women and patients with tuberculosis. A recommendation has also been added for patients who present with acute HIV infection after pre-exposure prophylaxis.

Abacavir/Lamivudine plus Rilpivirine Is an Effective and Safe Strategy for HIV-1 Suppressed Patients: 48 Week Results of the SIMRIKI Retrospective Study

Objectives Based on data from clinical practice, we evaluated the effectiveness and safety of switching to abacavir/lamivudine plus rilpivirine (ABC/3TC+RPV) treatment in virologically suppressed HIV-1-infected patients. Methods We performed a multicenter, non-controlled, retrospective study of HIV-1-infected patients who switched treatment to ABC/3TC+RPV. Patients had an HIV-RNA <50 copies/mL for at least 24 weeks prior to changing treatments. The primary objective was HIV-1 RNA <50 copies/mL at week 48. Effectiveness was analyzed by intention-to-treat (ITT), missing = failure and on-treatment (OT) analyses. The secondary objectives analyzed were adverse effects changes in renal, hepatic or lipid profiles, changes in CD4+ cell count and treatment discontinuations. Results Of the 205 patients included, 75.6% were men and the median age was 49. At baseline, before switching to ABC/3TC+RPV, median time since HIV diagnosis was 13.1 years, median time with undetectable HIV-1 RNA was 6.2 years and median time of previous antiretroviral regimen was 3.1 years (48.3% patients were taking efavirenz and ABC/3TC was the most frequent backbone coformulation in 69.7% of patients). The main reasons for switching were drug toxicity/poor tolerability (60.5%) and simplification (20%). At week 48, the primary objective was achieved by 187 out of 205 (91.2%) patients by ITT analysis, and 187 out of 192 (97.4%) patients by OT analysis. The CD4+ lymphocyte count and CD4+ percentage increased significantly from baseline to week 48 by a median of 48 cells/μL (−50 to 189) and 1.2% (−1.3% to 4.1%), respectively, P<0.001. Thirty-eight adverse events (AE) were detected in 32 patients. Of these, 25 had no clear association with treatment. Three patients interrupted therapy due to AE. We observed a decrease in all lipid parameters, P<0.001, and a slight improvement in the glomerular filtration rate, P<0.01. Therapy was considered to have failed in 18 patients owing to virological failure (5 [2.4%]), toxicity/poor tolerability (4 [2%]), clinical decision (3 [1.5%]), loss to follow-up (3 [1.5%]), death (1 [0.5%]), and no clinical data (2 [1%]). Conclusions The results of this study confirms that ABC/3TC+RPV is an effective, safe, and cost-effective option for the treatment of patients with virologically stable HIV-1 infection.

Efavirenz: What is known about the cellular mechanisms responsible for its adverse effects

&NA; The HIV infection remains an important health problem worldwide. However, due to the efficacy of combined antiretroviral therapy (cART), it has ceased to be a mortal condition, becoming a chronic disease instead. Efavirenz, the most prescribed non‐nucleoside analogue reverse transcriptase inhibitor (NNRTI), has been a key component of cART since its commercialization in 1998. Though still a drug of choice in many countries, its primacy has been challenged by the arrival of newer antiretroviral agents with better toxicity profiles and treatment adherence. The major side effects related to EFV have been widely described in clinical studies, however the mechanisms that participate in their pathogenesis remain largely ununderstood. This review provides an insight into the cellular and molecular mechanisms responsible for the development of the most significant undesired effects induced by efavirenz, both short‐ and long‐term, revealed by in vitro and in vivo experimental pharmacological research. Growing evidence implicates the drug in energy metabolism, mitochondrial function, and other cellular processes involved in stress responses including oxidative stress, inflammation and autophagy.

High quality of life, treatment tolerability, safety and efficacy in HIV patients switching from triple therapy to lopinavir/ritonavir monotherapy: A randomized clinical trial

Trial design The QoLKAMON study evaluated quality of life, efficacy and treatment safety in HIV patients receiving lopinavir/ritonavir in monotherapy (MT) versus continuing combined antiretroviral triple treatment with a boosted protease inhibitor (TT). Methods This was a 24-week, open-label, multicentre study in virologically-suppressed HIV-infected participants (N = 225) with a 2:1 randomization: 146 patients who switched to MT were compared with 79 patients who remained on a TT regimen. The primary endpoint was change in patient-reported outcomes in quality of life as measured by the MOS-HIV and EQ-5D questionnaires. Secondary endpoints included treatment adherence, patient satisfaction, incidence of adverse events and differences in plasma HIV-1 RNA viral load (VL) and CD4 cell counts. Results Baseline quality of life, measured with the MOS-HIV score, was very good (overall score of 83 ± 10.5 in the MT arm and 82.3 ± 11.3 in the TT arm) and suffered no change during the study in any of the arms (at week 24, 83.5 ± 12.2 in MT arm and 81.9 ± 12.7 in TT arm), without statistically significant differences when compared. In regards to adherence to therapy and patient satisfaction, some aspects (number of doses forgotten in the last week and satisfaction of treatment measured with the CESTA score, dimension 1) improved significantly with MT. There were also no differences in the incidence and severity of adverse events, even though 22.8% of those in the MT arm switched their treatment when they were included in the study. Moreover, there was also no significant difference between the immunological and virological evolution of MT and TT. In the MT arm, the VL was always undetectable in 83% of patients (vs 90.7% in the TT arm) and there were only 6.7% of virological failures with VL > 50 copies/mL (vs 2.3% in the TT arm), without resistance mutations and with resuppression of VL after switching back to TT. Conclusions In a new clinical trial, monotherapy as a treatment simplification strategy in HIV-1 infected patients with sustained viral suppression has demonstrated quality of life, safety and efficacy profiles comparable to those of conventional triple therapy regimens.

Hepatocellular carcinoma after sustained virological response with interferon-free regimens in Hiv/hcv-coinfected patients

Objective: To assess the possible association between the use of direct antiviral agents (DAA) and the risk of hepatocellular carcinoma (HCC) in HIV/hepatitis C virus (HCV)-coinfected patients. Methods: The GEHEP-002 cohort recruits HCC cases in HIV-infected patients from 32 centers from Spain. Three analyses were performed: the proportion of HCC cases after sustained virological response (SVR) and the evolution of this proportion over time, the frequency of HCC after SVR in HIV/HCV-coinfected patients with cirrhosis, and the probability of HCC recurrence after curative therapies among those undergoing HCV therapy. Results: Forty-two (13%) out of 322 HCC cases in HIV/HCV-coinfected patients occurred after SVR. Twenty-eight (10%) out of 279 HCC cases diagnosed during the years of use of IFN-based regimens occurred after SVR whereas this occurred in 14 (32.6%) out of the 43 HCC cases diagnosed in the all-oral DAA period (Pu200a<u200a0.0001). One thousand, three hundred and thirty-seven HIV/HCV-coinfected patients with cirrhosis achieved SVR in the cohort. The frequency of HCC after SVR declined from 15% among those cured with pegylated-IFN with ribavirin to 1.62 and 0.87% among those cured with DAA with and without IFN, respectively. In patients with previous HCC treated with curative therapies, HCC recurrence occurred in two (25%) out of eight patients treated with IFN-based regimens and four (21%) out of 19 treated with DAA-IFN-free regimens (Pu200a=u200a1.0). Conclusion: The frequency of HCC emergence after SVR has not increased after widespread use of DAA in HIV/HCV-coinfected patients. DAA do not seem to impact on HCC recurrence in the short-term among those with previously treated HCC.

Executive summary of the consensus document on osteoporosis in HIV-infected individuals

Osteoporosis has become an emerging comorbid condition in people living with HIV (PLWH). The increase in survival and the progressive aging of PLWH will make this complication more frequent in the near future. In addition to the traditional risk factors affecting the general population, factors directly or indirectly associated with HIV infection, including antiretroviral therapy, can increase the risk of osteoporosis. The present article is an executive summary of the document that updates the previous recommendations on the prevention and treatment of osteoporosis in PLWH. This document is intended for all professionals who work in clinical practice in the field of HIV infection.