Posts filed under ‘HIV/SIDA Infeccion Aguda / Reciente’

HIV-1 persistence following extremely early initiation of antiretroviral therapy (ART) during acute HIV-1 infection: An observational study.

PLoS Med. November 4, 2017 V.14 N.11 e1002417.     

Henrich TJ1, Hatano H2, Bacon O2,3, Hogan LE1, Rutishauser R1,2, Hill A4, Kearney MF5, Anderson EM5, Buchbinder SP2,3, Cohen SE2,3, Abdel-Mohsen M2,6, Pohlmeyer CW7, Fromentin R8, Hoh R2, Liu AY2,3, McCune JM1, Spindler J5, Metcalf-Pate K7, Hobbs KS1, Thanh C1, Gibson EA1, Kuritzkes DR9,10, Siliciano RF11,12, Price RW13, Richman DD14,15, Chomont N8, Siliciano JD10, Mellors JW16, Yukl SA17,18, Blankson JN7, Liegler T2, Deeks SG2.

Author information

1 Division of Experimental Medicine, University of California, San Francisco, California, United States of America.

2 Division of HIV, Infectious Diseases and Global Medicine, University of California, San Francisco, California, United States of America.

3 San Francisco Department of Public Health, San Francisco, California, United States of America.

4 Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts, United States of America.

5 HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.

6 The Wistar Institute, Philadelphia, Pennsylvania, United States of America.

7 Center for AIDS Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.

8 Centre de Recherche du CHUM and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Quebec, Canada.

9 Division of Infectious Diseases, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America.

10 Harvard Medical School, Boston, Massachusetts, United States of America.

11 Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.

12 Howard Hughes Medical Institute, Baltimore, Maryland, United States of America.

13 Department of Neurology, University of California, San Francisco, California, United States of America.

14 University of California San Diego, La Jolla, California, United States of America.

15 Veterans Affairs San Diego Healthcare System, San Diego, California, United States of America.

16 Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

17 San Francisco Veterans Affairs Medical Center, San Francisco, California, United States of America.

18 University of California, San Francisco, California, Unites States of America.

Abstract

BACKGROUND:

It is unknown if extremely early initiation of antiretroviral therapy (ART) may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from a pre-exposure prophylaxis (PrEP) program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male) and 12 days (Participant B; 31-year-old male) after infection with peak plasma HIV RNA of 220 copies/mL and 3,343 copies/mL, respectively. Extensive testing of blood and tissue for HIV persistence was performed, and PrEP Participant A underwent analytical treatment interruption (ATI) following 32 weeks of continuous ART.

METHODS AND FINDINGS:

Colorectal and lymph node tissues, bone marrow, cerebral spinal fluid (CSF), plasma, and very large numbers of peripheral blood mononuclear cells (PBMCs) were obtained longitudinally from both participants and were studied for HIV persistence in several laboratories using molecular and culture-based detection methods, including a murine viral outgrowth assay (mVOA). Both participants initiated PrEP with tenofovir/emtricitabine during very early Fiebig stage I (detectable plasma HIV-1 RNA, antibody negative) followed by 4-drug ART intensification. Following peak viral loads, both participants experienced full suppression of HIV-1 plasma viremia. Over the following 2 years, no further HIV could be detected in blood or tissue from PrEP Participant A despite extensive sampling from ileum, rectum, lymph nodes, bone marrow, CSF, circulating CD4+ T cell subsets, and plasma. No HIV was detected from tissues obtained from PrEP Participant B, but low-level HIV RNA or DNA was intermittently detected from various CD4+ T cell subsets. Over 500 million CD4+ T cells were assayed from both participants in a humanized mouse outgrowth assay. Three of 8 mice infused with CD4+ T cells from PrEP Participant B developed viremia (50 million input cells/surviving mouse), but only 1 of 10 mice infused with CD4+ T cells from PrEP Participant A (53 million input cells/mouse) experienced very low level viremia (201 copies/mL); sequence confirmation was unsuccessful. PrEP Participant A stopped ART and remained aviremic for 7.4 months, rebounding with HIV RNA of 36 copies/mL that rose to 59,805 copies/mL 6 days later. ART was restarted promptly. Rebound plasma HIV sequences were identical to those obtained during acute infection by single-genome sequencing. Mathematical modeling predicted that the latent reservoir size was approximately 200 cells prior to ATI and that only around 1% of individuals with a similar HIV burden may achieve lifelong ART-free remission. Furthermore, we observed that lymphocytes expressing the tumor marker CD30 increased in frequency weeks to months prior to detectable HIV-1 RNA in plasma. This study was limited by the small sample size, which was a result of the rarity of individuals presenting during hyperacute infection.

CONCLUSIONS:

We report HIV relapse despite initiation of ART at one of the earliest stages of acute HIV infection possible. Near complete or complete loss of detectable HIV in blood and tissues did not lead to indefinite ART-free HIV remission. However, the small numbers of latently infected cells in individuals treated during hyperacute infection may be associated with prolonged ART-free remission.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675377/pdf/pmed.1002417.pdf

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December 11, 2017 at 8:42 am

Fiebre de origen desconocido en pacientes HIV positivos

ANALES DE MEDICINA INTERNA (Madrid), 2001 V.18 N.4 P.181-186

BARBA, J. GÓMEZ-RODRIGO, J. MARCO, P. RONDÓN, G. EROLES,

LÓPEZ-VARAS, R. TORRES

Departamento de Medicina Interna y Enfermedades Infecciosas. Hospital Severo Ochoa.

Leganés. Madrid

RESUMEN

Objetivos

Describir la presentación clínica y la utilidad de los de tests diagnósticos habitualmente recomendados en el estudio de la fiebre de origen desconocido (FOD) en los pacientes VIH positivos.

Pacientes y métodos

Incluimos en el estudio a los 54 pacientes con infección por el VIH que ingresaron en nuestro Hospital por FOD durante un periodo de 23 meses. La FOD fue definida de acuerdo con los criterios modificados de Petersdorf´s.

Resultados

La causa de la fiebre se identificó en 48 casos (89%). La tuberculosis, la micobacteriosis atípica y la leishmaniasis pueden explicar el 68% de los casos. El aspirado de médula ósea, la punción aspiración o la biopsia de los ganglios linfáticos y los cultivos para micobacterias fueron las pruebas diagnósticas más rentables.

Conclusiones

La infección por micobacterias debe ser el primer diagnóstico de sospecha en los pacientes VIH positivos con FOD. Es posible precedir el diagnóstico de tuberculosis con una alta precisión (90,5%) con un modelo de regresión logística basado en datos clínicos y analíticos fácilmente obtenibles.

PDF

http://scielo.isciii.es/pdf/ami/v18n4/original2.pdf

November 21, 2017 at 8:41 am

FIEBRE DE ORIGEN DESCONOCIDO EN PACIENTES INFECTADOS CON EL VIRUS DE LA INMUNODEFICIENCIA HUMANA

MEDICINA (Buenos Aires) 2000 V.60 N.5 P.623-630

SEBASTIAN A. MATHURIN, SERGIO LUPO, HECTOR O. ALONSO

Primera Cátedra de Clínica Médica y Terapéutica, Facultad de Ciencias Médicas, Universidad Nacional de Rosario; Hospital Provincial del Centenario, Rosario

La fiebre de origen desconocido (FOD) es frecuente en pacientes infectados por el HIV. Existen numerosas causas que pueden originar FOD y su frecuencia relativa depende de múltiples factores. Usualmente se debe a una infección oportunista agregada.

La evaluación diagnóstica depende de la presentación clínica y del estadio de la infección por HIV. Existe una asociación entre el recuento de linfocitos CD4 y ciertas enfermedades oportunistas que pueden originar FOD.

El área geográfica y la prevalencia local de infecciones endémicas es un factor importante. Las infecciones de distribución mundial como la tuberculosis siempre deben ser consideradas y otras como la histoplasmosis diseminada son causa frecuente de FOD en áreas endémicas como la Argentina.

La mayor utilidad diagnóstica se obtiene con los cultivos de esputo y hemocultivos para micobacterias, y entre los métodos invasivos con cultivos a partir de la aspiración/biopsia de ganglio linfático, la biopsia de médula ósea y la biopsia hepática.

La eficacia del tratamiento empírico ha sido documentada en ciertas infecciones.

FULL TEXT

http://www.medicinabuenosaires.com/revistas/vol60-00/5-1/fiebredeorigen.htm

November 21, 2017 at 8:34 am

HIV-1 persistence following extremely early initiation of antiretroviral therapy (ART) during acute HIV-1 infection: An observational study.

PLoS Med November 7, 2017 V.14 P.e1002417.

Henrich TJ et al.

Abstract

Background

It is unknown if extremely early initiation of antiretroviral therapy (ART) may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from a pre-exposure prophylaxis (PrEP) program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male) and 12 days (Participant B; 31-year-old male) after infection with peak plasma HIV RNA of 220 copies/mL and 3,343 copies/mL, respectively. Extensive testing of blood and tissue for HIV persistence was performed, and PrEP Participant A underwent analytical treatment interruption (ATI) following 32 weeks of continuous ART.

Methods and findings

Colorectal and lymph node tissues, bone marrow, cerebral spinal fluid (CSF), plasma, and very large numbers of peripheral blood mononuclear cells (PBMCs) were obtained longitudinally from both participants and were studied for HIV persistence in several laboratories using molecular and culture-based detection methods, including a murine viral outgrowth assay (mVOA). Both participants initiated PrEP with tenofovir/emtricitabine during very early Fiebig stage I (detectable plasma HIV-1 RNA, antibody negative) followed by 4-drug ART intensification. Following peak viral loads, both participants experienced full suppression of HIV-1 plasma viremia. Over the following 2 years, no further HIV could be detected in blood or tissue from PrEP Participant A despite extensive sampling from ileum, rectum, lymph nodes, bone marrow, CSF, circulating CD4+ T cell subsets, and plasma. No HIV was detected from tissues obtained from PrEP Participant B, but low-level HIV RNA or DNA was intermittently detected from various CD4+ T cell subsets. Over 500 million CD4+ T cells were assayed from both participants in a humanized mouse outgrowth assay. Three of 8 mice infused with CD4+ T cells from PrEP Participant B developed viremia (50 million input cells/surviving mouse), but only 1 of 10 mice infused with CD4+ T cells from PrEP Participant A (53 million input cells/mouse) experienced very low level viremia (201 copies/mL); sequence confirmation was unsuccessful. PrEP Participant A stopped ART and remained aviremic for 7.4 months, rebounding with HIV RNA of 36 copies/mL that rose to 59,805 copies/mL 6 days later. ART was restarted promptly. Rebound plasma HIV sequences were identical to those obtained during acute infection by single-genome sequencing. Mathematical modeling predicted that the latent reservoir size was approximately 200 cells prior to ATI and that only around 1% of individuals with a similar HIV burden may achieve lifelong ART-free remission. Furthermore, we observed that lymphocytes expressing the tumor marker CD30 increased in frequency weeks to months prior to detectable HIV-1 RNA in plasma. This study was limited by the small sample size, which was a result of the rarity of individuals presenting during hyperacute infection.

Conclusions

We report HIV relapse despite initiation of ART at one of the earliest stages of acute HIV infection possible. Near complete or complete loss of detectable HIV in blood and tissues did not lead to indefinite ART-free HIV remission. However, the small numbers of latently infected cells in individuals treated during hyperacute infection may be associated with prolonged ART-free remission.

FULL TEXT

http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002417

PDF

http://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1002417&type=printable

 

 

November 21, 2017 at 7:27 am

Brief Report: Enhanced Normalization of CD4/CD8 Ratio With Earlier Antiretroviral Therapy at Primary HIV Infection.

J Acquir Immune Defic Syndr. 2016 Sep 1;73(1):69-73.

Thornhill J1, Inshaw J, Kaleebu P, Cooper D, Ramjee G, Schechter M, Tambussi G, Fox J, Samuel M, Miro JM, Weber J, Porter K, Fidler S.

1 *Department of Medicine, Imperial College, London, United Kingdom; †Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom; ‡Medical Research Council/Uganda Virus Research Institute Research Unit on AIDS, Entebbe, Uganda; §Kirby Institute University of New South Wales and Centre for Applied Medical Research, St Vincent’s Hospital, Sydney, Australia; ‖HIV Prevention Unit, Medical Research Council, Durban, South Africa; ¶Projeto Praça Onze, Hospital Escola Sao Francisco de Assis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; #Division of Infectious Diseases, Ospedale San Raffaele, Milan, Italy; **Department of HIV, Faculty of Medicine, Guys and St Thomas’ NHS Trust/Kings College London, United Kingdom; and ††Hospital Clinic – IDIBAPS, University of Barcelona, Barcelona, Spain.

Abstract

BACKGROUND:

Total CD4 T-cell counts predict HIV disease progression but do not necessarily reflect normalization of immune function. CD4/CD8 ratio is a marker of immune dysfunction, a prognostic indicator for non-AIDS mortality, and reflects viral reservoir size. Despite antiretroviral therapy (ART), recovery of CD4/CD8 ratio in chronic HIV infection is incomplete; we hypothesize enhanced CD4/CD8 ratio recovery with earlier treatment initiation in recently infected individuals.

METHODS:

CD4 count and CD4/CD8 ratio were analyzed using data from 2 cohorts: SPARTAC trial and the UK HIV Seroconverters Cohort where primary HIV infection (PHI) was defined as within 6 months from estimated date of infection. Using time-to-event methods and Cox proportional hazard models, we examined the effect of CD4/CD8 ratio at seroconversion on disease progression (CD4 <350 cells per cubic millimeter/ART initiation) and factors associated with time from ART initiation to CD4/CD8 normalization (ratio >1.0).

FINDINGS:

Of 573 seroconverters, 482 (84%) had abnormal CD4/CD8 ratios at HIV seroconversion. Individuals with higher CD4/CD8 ratio at seroconversion were significantly less likely to reach the disease progression endpoint [adjusted hazard ratio (aHR) (95% CI) = 0.52 (0.32 to 0.82), P = 0.005]. The longer the interval between seroconversion and ART initiation [HR (95% CI) = 0.98 per month increase (0.97, 0.99), P < 0.001], the less likely the CD4/CD8 ratio normalization. ART initiation within 6 months from seroconversion was significantly more likely to normalize [HR (95% CI) = 2.47 (1.67 to 3.67), P < 0.001] than those initiating later.

INTERPRETATION:

Most individuals presenting in PHI have abnormal CD4/CD8 ratios. The sooner the ART is initiated in PHI, the greater the probability of achieving normal CD4/CD8 ratio.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981213/pdf/qai-73-069.pdf

March 11, 2017 at 6:39 pm

2016 BHIVA GUIDELINES for the treatment of HIV-1-positive Adults with antiretroviral therapy

The British HIV Association

Writing Group

Laura Waters (Chair)

N Ahmed, B Angus, M Boffito, M Bower, D Churchill, D Dunn, S Edwards, C Emerson, S Fidler, †M Fisher, R Horne, S Khoo, C Leen, N Mackie, N Marshall, F Monteiro, M Nelson, C Orkin, A Palfreeman, S Pett, A Phillips, F Post, A Pozniak, I Reeves, C Sabin, R Trevelion, J Walsh, E Wilkins, I Williams, A Winston

†Professor Martin Fisher died in April 2015 – he made a significant contribution to these, many other guidelines and our speciality as a whole – he is greatly missed.

Introduction

The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of adults with HIV infection on antiretroviral therapy (ART).

The scope includes: (i) guidance on the initiation of ART in those previously naïve to therapy; (ii) support of people living with HIV (PLWH) on treatment; (iii) management of individuals experiencing virological failure; and (iv) recommendations in specific populations where other factors need to be taken into consideration.

The guidelines are aimed at clinical professionals directly involved with and responsible for the care of adults with HIV infection, and at community advocates responsible for promoting the best interests and care of HIV-positive adults. They should be read in conjunction with other published BHIVA guidelines.

The 2016 interim update to the 2015 BHIVA antiretroviral guidelines has been published online to include tenofovir-alafenamide/emtricitabine as a preferred NRTI backbone for first-line therapy. Changes were based on new data and the consensus opinion of the writing committee. All changes to the guideline are highlighted and include updates to the chronic kidney disease and bone disease sections of special populations and some small changes to managing virological failure. The next formal update to the guidelines in anticipated in 2017.

PDF

http://www.bhiva.org/documents/Guidelines/Treatment/2016/treatment-guidelines-2016-interim-update.pdf

December 3, 2016 at 9:33 am

2016-07-14 Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents

Key Updates

What to Start: Initial Combination Regimens for the Antiretroviral-Naive Patient

The approval of 3 fixed-dose combination products containing tenofovir alafenamide (an oral prodrug of tenofovir) and emtricitabine (TAF/FTC) prompted several changes in the What to Start section. The key changes are highlighted below:

– TAF/FTC was added as a 2-NRTI option in several Recommended and Alternative regimens, as noted in Table 6 of the guidelines. The addition of TAF/FTC to these recommendations is based on data from comparative trials demonstrating that TAF-containing regimens are as effective in achieving or maintaining virologic suppression as tenofovir disoproxil fumarate (TDF)-containing regimens and with more favorable effects on markers of bone and renal health.

– In the What to Start section, the evidence quality rating “II” was expanded to include “relative bioavailability/bioequivalence studies or regimen comparisons from randomized switch studies.” This evidence rating was broadened because not all recommended regimens were evaluated in randomized, controlled trials in antiretroviral therapy (ART)-naive patients. The Panel on Antiretroviral Guidelines for Adults and Adolescents (the Panel) based their recommendations for some regimens on either data from bioequivalence or relative bioavailability studies, or by extrapolating results from randomized “switch” studies that evaluated a drug’s or regimen’s ability to maintain virologic suppression in patients whose HIV was suppressed on a previous regimen. Guidance for clinicians on choosing between abacavir (ABC)-, TAF-, and TDF-containing regimens was added to What to Start.

– The lopinavir/ritonavir (LPV/r) plus 2-NRTI regimen was removed from the list of Other regimens because regimens containing this protease inhibitor (PI) combination have a larger pill burden and greater toxicity than other currently available options.

Regimen Switching

– Based on the most current data, this section was simplified to focus on switch strategies for virologically suppressed patients. The strategies are categorized as Strategies with Good Supporting Evidence, Strategies Under Evaluation, and Strategies Not Recommended.

HIV-Infected Women

– The Panel emphasizes that ART is recommended for all HIV-infected patients, including all HIV-infected women.

– The Panel also stresses the importance of early treatment for HIV-infected women during pregnancy and continuation of ART after pregnancy.

– This section was updated to include new data on interactions between antiretroviral (ARV) drugs and hormonal contraceptives.

Hepatitis B Virus (HBV)/HIV Coinfection

– This section was updated to include TAF/FTC as a treatment option for patients with HBV/HIV coinfection. Data on the virologic efficacy of TAF for the treatment of HBV in persons without HIV infection and TAF/FTC in persons with HBV/HIV coinfection are discussed.

– The Panel no longer recommends adefovir or telbivudine as options for HBV/HIV coinfected patients, as there is limited safety and efficacy data on their use in this population. In addition, these agents have a higher incidence of toxicities than other recommended treatments.

Hepatitis C Virus (HCV)/HIV Coinfection

– The text and Table 12 in this section were updated with information regarding the potential pharmacokinetic (PK) interactions between different ARV drugs and the recently approved hepatitis C drugs daclatasvir and the fixed-dose combination product of elbasvir and grazoprevir.

– Peginterferon alfa and ribavirin were removed from Table 12, as these agents do not have significant PK interactions with ARV drugs.

Tuberculosis (TB)/HIV Coinfection

– This section was updated to include a discussion on the treatment of latent tuberculosis infection (LTBI) in HIV-infected persons. The added discussion notes that a 12-week course of once-weekly rifapentine and isoniazid is an option for patients receiving either an efavirenz (EFV)- or a raltegravir (RAL)-based regimen.

– This section addresses the data from the TEMPRANO and START studies demonstrating a potential role of ART in reducing TB disease.

The recommendations and discussion regarding when to initiate ART in patients with active TB were simplified.

– As rifamycins are potent inducers of P-glycoprotein (P-gp), and TAF is a P-gp substrate, coadministration of TAF and rifamycins is not recommended.

Additional Updates

Minor revisions were made to the following sections:

– Laboratory Testing for Initial Assessment and Monitoring of HIV-Infected Patients on Antiretroviral Therapy

– Drug Resistance Testing

– Adverse Effects of Antiretroviral Agents and Tables 14 and 15

– Monthly Average Wholesale Price of Commonly Used Antiretroviral Drugs (Table 16)

– Drug Interaction Tables 18, 19a-e, and 20b

– Drug Characteristics Tables (Appendix B, Tables 1–7)

PDF

https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf

 

July 25, 2016 at 2:17 pm

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