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

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

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society–USA Panel

JAMA July 12, 2016 V.316 N.2 P.191-210

Special Communication

Huldrych F. Günthard, MD; Michael S. Saag, MD; Constance A. Benson, MD; Carlos del Rio, MD; Joseph J. Eron, MD; Joel E. Gallant, MD, MPH; Jennifer F. Hoy, MBBS, FRACP; Michael J. Mugavero, MD, MHSc; Paul E. Sax, MD; Melanie A. Thompson, MD; Rajesh T. Gandhi, MD; Raphael J. Landovitz, MD; Davey M. Smith, MD; Donna M. Jacobsen, BS; Paul A. Volberding, MD

1University Hospital Zurich and Institute of Medical Virology, University of Zurich, Zurich, Switzerland

2University of Alabama at Birmingham, Birmingham

3University of California San Diego School of Medicine, San Diego

4Emory University Rollins School of Public Health and School of Medicine, Atlanta, Georgia

5University of North Carolina at Chapel Hill School of Medicine, Chapel Hill

6Southwest CARE Center, Santa Fe, New Mexico

7Alfred Hospital and Monash University, Melbourne, Australia

8Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts

9AIDS Research Consortium of Atlanta, Atlanta, Georgia

10Massachusetts General Hospital and Harvard Medical School, Boston

11University of California Los Angeles

12University of California San Diego, La Jolla

13International Antiviral Society–USA, San Francisco, California

14University of California San Francisco

Importance 

New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults.

Objective 

To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis.

Evidence

Review  A panel of experts in HIV research and patient care convened by the International Antiviral Society–USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence.

Findings 

Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory assessments are recommended before treatment, and monitoring during treatment is recommended to assess response, adverse effects, and adherence. Approaches are recommended to improve linkage to and retention in care are provided. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. When indicated, postexposure prophylaxis should be started as soon as possible after exposure.

Conclusions and Relevance 

Antiretroviral agents remain the cornerstone of HIV treatment and prevention. All HIV-infected individuals with detectable plasma virus should receive treatment with recommended initial regimens consisting of an InSTI plus 2 NRTIs. Preexposure prophylaxis should be considered as part of an HIV prevention strategy for at-risk individuals. When used effectively, currently available ARVs can sustain HIV suppression and can prevent new HIV infection. With these treatment regimens, survival rates among HIV-infected adults who are retained in care can approach those of uninfected adults.

FULL TEXT

http://jama.jamanetwork.com/article.aspx?articleid=2533073

July 17, 2016 at 4:30 pm

Initiating antiretroviral therapy for HIV at a patient’s first clinic visit – The RapIT randomized controlled trial.

PLoS Med 2016 May 10; 13:e1002015

Sydney Rosen , Mhairi Maskew, Matthew P. Fox, Cynthia Nyoni, Constance Mongwenyana, Given Malete, Ian Sanne, Dorah Bokaba, Celeste Sauls, Julia Rohr, Lawrence Long

Background

High rates of patient attrition from care between HIV testing and antiretroviral therapy (ART) initiation have been documented in sub-Saharan Africa, contributing to persistently low CD4 cell counts at treatment initiation. One reason for this is that starting ART in many countries is a lengthy and burdensome process, imposing long waits and multiple clinic visits on patients. We estimated the effect on uptake of ART and viral suppression of an accelerated initiation algorithm that allowed treatment-eligible patients to be dispensed their first supply of antiretroviral medications on the day of their first HIV-related clinic visit.

Methods and Findings

RapIT (Rapid Initiation of Treatment) was an unblinded randomized controlled trial of single-visit ART initiation in two public sector clinics in South Africa, a primary health clinic (PHC) and a hospital-based HIV clinic. Adult (≥18 y old), non-pregnant patients receiving a positive HIV test or first treatment-eligible CD4 count were randomized to standard or rapid initiation. Patients in the rapid-initiation arm of the study (“rapid arm”) received a point-of-care (POC) CD4 count if needed; those who were ART-eligible received a POC tuberculosis (TB) test if symptomatic, POC blood tests, physical exam, education, counseling, and antiretroviral (ARV) dispensing. Patients in the standard-initiation arm of the study (“standard arm”) followed standard clinic procedures (three to five additional clinic visits over 2–4 wk prior to ARV dispensing). Follow up was by record review only. The primary outcome was viral suppression, defined as initiated, retained in care, and suppressed (≤400 copies/ml) within 10 mo of study enrollment. Secondary outcomes included initiation of ART ≤90 d of study enrollment, retention in care, time to ART initiation, patient-level predictors of primary outcomes, prevalence of TB symptoms, and the feasibility and acceptability of the intervention. A survival analysis was conducted comparing attrition from care after ART initiation between the groups among those who initiated within 90 d. Three hundred and seventy-seven patients were enrolled in the study between May 8, 2013 and August 29, 2014 (median CD4 count 210 cells/mm3). In the rapid arm, 119/187 patients (64%) initiated treatment and were virally suppressed at 10 mo, compared to 96/190 (51%) in the standard arm (relative risk [RR] 1.26 [1.05–1.50]). In the rapid arm 182/187 (97%) initiated ART ≤90 d, compared to 136/190 (72%) in the standard arm (RR 1.36, 95% confidence interval [CI], 1.24–1.49). Among 318 patients who did initiate ART within 90 d, the hazard of attrition within the first 10 mo did not differ between the treatment arms (hazard ratio [HR] 1.06; 95% CI 0.61–1.84). The study was limited by the small number of sites and small sample size, and the generalizability of the results to other settings and to non-research conditions is uncertain.

Conclusions

Offering single-visit ART initiation to adult patients in South Africa increased uptake of ART by 36% and viral suppression by 26%. This intervention should be considered for adoption in the public sector in Africa.

Trial Registration

ClinicalTrials.gov NCT01710397, and South African National Clinical Trials Register DOH-27-0213-4177.

 

FULL TEXT

http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002015

PDF

http://journals.plos.org/plosmedicine/article/asset?id=10.1371%2Fjournal.pmed.1002015.PDF

May 28, 2016 at 9:30 am

Prospective Study of Acute HIV-1 Infection in Adults in East Africa and Thailand

N Engl J Med May 18,  2016

Merlin L. Robb, M.D., Leigh A. Eller, Ph.D., Hannah Kibuuka, M.B., Ch.B., Kathleen Rono, M.B., Ch.B., Lucas Maganga, M.B., Ch.B., Sorachai Nitayaphan, M.D., Eugene Kroon, M.D., Fred K. Sawe, M.B., Ch.B., Samuel Sinei, M.B., Ch.B., Somchai Sriplienchan, M.D., Linda L. Jagodzinski, Ph.D., Jennifer Malia, Dr.Ph., Mark Manak, Ph.D., Mark S. de Souza, Ph.D., Sodsai Tovanabutra, Ph.D., Eric Sanders-Buell, B.S., Morgane Rolland, Ph.D., Julie Dorsey-Spitz, B.S., Michael A. Eller, Ph.D., Mark Milazzo, B.A., Qun Li, M.Sc., Andrew Lewandowski, Ph.D., Hao Wu, Ph.D., Edith Swann, Ph.D., Robert J. O’Connell, M.D., Sheila Peel, Ph.D., Peter Dawson, Ph.D., Jerome H. Kim, M.D., and Nelson L. Michael, M.D., Ph.D., for the RV 217 Study Team*

BACKGROUND

Acute human immunodeficiency virus type 1 (HIV-1) infection is a major contributor to transmission of HIV-1. An understanding of acute HIV-1 infection may be important in the development of treatment strategies to eradicate HIV-1 or achieve a functional cure.

METHODS

We performed twice-weekly qualitative plasma HIV-1 RNA nucleic acid testing in 2276 volunteers who were at high risk for HIV-1 infection. For participants in whom acute HIV-1 infection was detected, clinical observations, quantitative measurements of plasma HIV-1 RNA levels (to assess viremia) and HIV antibodies, and results of immunophenotyping of lymphocytes were obtained twice weekly.

RESULTS

Fifty of 112 volunteers with acute HIV-1 infection had two or more blood samples collected before HIV-1 antibodies were detected. The median peak viremia (6.7 log10 copies per milliliter) occurred 13 days after the first sample showed reactivity on nucleic acid testing. Reactivity on an enzyme immunoassay occurred at a median of 14 days. The nadir of viremia (4.3 log10 copies per milliliter) occurred at a median of 31 days and was nearly equivalent to the viral-load set point, the steady-state viremia that persists durably after resolution of acute viremia (median plasma HIV-1 RNA level, 4.4 log10 copies per milliliter). The peak viremia and downslope were correlated with the viral-load set point. Clinical manifestations of acute HIV-1 infection were most common just before and at the time of peak viremia. A median of one symptom of acute HIV-1 infection was recorded at a median of two study visits, and a median of one sign of acute HIV-1 infection was recorded at a median of three visits.

CONCLUSIONS

The viral-load set point occurred at a median of 31 days after the first detection of plasma viremia and correlated with peak viremia. Few symptoms and signs were observed during acute HIV-1 infection, and they were most common before peak viremia. (Funded by the Department of Defense and the National Institute of Allergy and Infectious Diseases.)

abstract

http://www.nejm.org/doi/10.1056/NEJMoa1508952

PDF

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1508952

May 19, 2016 at 8:21 am

Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection

N Engl J of Medic Aug. 27, 2015 V.73 P.795-807

The INSIGHT START Study Group

BACKGROUND

Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter.

METHODS

We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non–AIDS-related event, or death from any cause.

RESULTS

A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non–AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P=0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions.

CONCLUSIONS

The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.)

PDF

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1506816

August 26, 2015 at 8:12 pm

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