Posts filed under ‘Antirretrovirales’

Same-day HIV testing with initiation of antiretroviral therapy versus standard care for persons living with HIV: A randomized unblinded trial.

PLoS Med. 2017 Jul 25;14(7):e1002357.

Koenig SP1,2, Dorvil N1, Dévieux JG3, Hedt-Gauthier BL4, Riviere C1, Faustin M1, Lavoile K1, Perodin C1, Apollon A1, Duverger L1, McNairy ML5,6, Hennessey KA1, Souroutzidis A7, Cremieux PY7, Severe P1, Pape JW1,5.

Author information

1 Haitian Study Group for Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti.

2 Division of Global Health Equity, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America.

3 AIDS Prevention Program, Florida International University, Miami, Florida, United States of America.

4 Department of Global Health and Social Medicine, Harvard Medical School, Harvard University, Boston, Massachusetts, United States of America.

5 Center for Global Health, Department of Medicine, Weill Cornell Medical College, Cornell University, New York, New York, United States of America.

6 Division of General Internal Medicine, Department of Medicine, Weill Cornell Medical College, Cornell University, New York, New York, United States of America.

7 Analysis Group, Boston, Massachusetts, United States of America.

Abstract

BACKGROUND:

Attrition during the period from HIV testing to antiretroviral therapy (ART) initiation is high worldwide. We assessed whether same-day HIV testing and ART initiation improves retention and virologic suppression.

METHODS AND FINDINGS:

We conducted an unblinded, randomized trial of standard ART initiation versus same-day HIV testing and ART initiation among eligible adults ≥18 years old with World Health Organization Stage 1 or 2 disease and CD4 count ≤500 cells/mm3. The study was conducted among outpatients at the Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic infections (GHESKIO) Clinic in Port-au-Prince, Haiti. Participants were randomly assigned (1:1) to standard ART initiation or same-day HIV testing and ART initiation. The standard group initiated ART 3 weeks after HIV testing, and the same-day group initiated ART on the day of testing. The primary study endpoint was retention in care 12 months after HIV testing with HIV-1 RNA <50 copies/ml. We assessed the impact of treatment arm with a modified intention-to-treat analysis, using multivariable logistic regression controlling for potential confounders. Between August 2013 and October 2015, 762 participants were enrolled; 59 participants transferred to other clinics during the study period, and were excluded as per protocol, leaving 356 in the standard and 347 in the same-day ART groups. In the standard ART group, 156 (44%) participants were retained in care with 12-month HIV-1 RNA <50 copies, and 184 (52%) had <1,000 copies/ml; 20 participants (6%) died. In the same-day ART group, 184 (53%) participants were retained with HIV-1 RNA <50 copies/ml, and 212 (61%) had <1,000 copies/ml; 10 (3%) participants died. The unadjusted risk ratio (RR) of being retained at 12 months with HIV-1 RNA <50 copies/ml was 1.21 (95% CI: 1.04, 1.38; p = 0.015) for the same-day ART group compared to the standard ART group, and the unadjusted RR for being retained with HIV-1 RNA <1,000 copies was 1.18 (95% CI: 1.04, 1.31; p = 0.012). The main limitation of this study is that it was conducted at a single urban clinic, and the generalizability to other settings is uncertain.

CONCLUSIONS:

Same-day HIV testing and ART initiation is feasible and beneficial in this setting, as it improves retention in care with virologic suppression among patients with early clinical HIV disease.

TRIAL REGISTRATION:

This study is registered with ClinicalTrials.gov number NCT01900080.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526526/pdf/pmed.1002357.pdf

Advertisements

September 7, 2017 at 8:15 am

Enhanced prophylaxis plus antiretroviral therapy for advanced HIV infection in Africa

N Engl J Med July 20, 2017 V.377 P.233-245.

James Hakim, F.R.C.P., Victor Musiime, Ph.D., Alex J. Szubert, M.Sc., Jane Mallewa, M.D., Abraham Siika, M.Med., Clara Agutu, M.B., Ch.B., M.P.H., Simon Walker, M.Sc., Sarah L. Pett, Ph.D., Mutsa Bwakura-Dangarembizi, M.Med., Abbas Lugemwa, M.D., Symon Kaunda, M.B., Ch.B., Mercy Karoney, M.Sc., Godfrey Musoro, M.Sc., Sheila Kabahenda, M.B., Ch.B., Kusum Nathoo, M.B., Ch.B., Kathryn Maitland, Ph.D., Anna Griffiths, Ph.D., Margaret J. Thomason, Ph.D., Cissy Kityo, M.Sc., Peter Mugyenyi, Ph.D., Andrew J. Prendergast, D.Phil., A. Sarah Walker, Ph.D., and Diana M. Gibb, M.D., for the REALITY Trial Team*

BACKGROUND

In sub-Saharan Africa, among patients with advanced human immunodeficiency virus (HIV) infection, the rate of death from infection (including tuberculosis and cryptococcus) shortly after the initiation of antiretroviral therapy (ART) is approximately 10%.

METHODS

In this factorial open-label trial conducted in Uganda, Zimbabwe, Malawi, and Kenya, we enrolled HIV-infected adults and children 5 years of age or older who had not received previous ART and were starting ART with a CD4+ count of fewer than 100 cells per cubic millimeter. They underwent simultaneous randomization to receive enhanced antimicrobial prophylaxis or standard prophylaxis, adjunctive raltegravir or no raltegravir, and supplementary food or no supplementary food. Here, we report on the effects of enhanced antimicrobial prophylaxis, which consisted of continuous trimethoprim–sulfamethoxazole plus at least 12 weeks of isoniazid–pyridoxine (coformulated with trimethoprim–sulfamethoxazole in a single fixed-dose combination tablet), 12 weeks of fluconazole, 5 days of azithromycin, and a single dose of albendazole, as compared with standard prophylaxis (trimethoprim–sulfamethoxazole alone). The primary end point was 24-week mortality.

RESULTS

A total of 1805 patients (1733 adults and 72 children or adolescents) underwent randomization to receive either enhanced prophylaxis (906 patients) or standard prophylaxis (899 patients) and were followed for 48 weeks (loss to follow-up, 3.1%). The median baseline CD4+ count was 37 cells per cubic millimeter, but 854 patients (47.3%) were asymptomatic or mildly symptomatic. In the Kaplan–Meier analysis at 24 weeks, the rate of death with enhanced prophylaxis was lower than that with standard prophylaxis (80 patients [8.9% vs. 108 [12.2%]; hazard ratio, 0.73; 95% confidence interval [CI], 0.55 to 0.98; P=0.03); 98 patients (11.0%) and 127 (14.4%), respectively, had died by 48 weeks (hazard ratio, 0.76; 95% CI, 0.58 to 0.99; P=0.04). Patients in the enhanced-prophylaxis group had significantly lower rates of tuberculosis (P=0.02), cryptococcal infection (P=0.01), oral or esophageal candidiasis (P=0.02), death of unknown cause (P=0.03), and new hospitalization (P=0.03). However, there was no significant between-group difference in the rate of severe bacterial infection (P=0.32). There were nonsignificantly lower rates of serious adverse events and grade 4 adverse events in the enhanced-prophylaxis group (P=0.08 and P=0.09, respectively). Rates of HIV viral suppression and adherence to ART were similar in the two groups.

CONCLUSIONS

Among HIV-infected patients with advanced immunosuppression, enhanced antimicrobial prophylaxis combined with ART resulted in reduced rates of death at both 24 weeks and 48 weeks without compromising viral suppression or increasing toxic effects. (Funded by the Medical Research Council and others; REALITY Current Controlled Trials number, ISRCTN43622374.)

abstract

http://www.nejm.org/doi/10.1056/NEJMoa1615822

PDF

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1615822

 

N Engl J Med  July 20, 2017 V.377 P.283-284

EDITORIAL – The enduring challenge of advanced HIV infection.

Nathan Ford, M.P.H., Ph.D., and Meg Doherty, M.D., Ph.D.

Until recently, progress in the fight against human immunodeficiency virus (HIV) infection was primarily measured in terms of the number of patients who were started on antiretroviral therapy (ART). Major efforts to increase access to ART in the low- and middle-income countries that are most affected by HIV infection began in 2000, and over the following 15 years, an estimated 8 million HIV-related deaths were averted. In countries with a high burden of disease, this decline translated into important increases in life expectancy.1

Notwithstanding these gains, the decrease in HIV-associated deaths appears to have plateaued in recent years. HIV still causes more than 1 million deaths per year worldwide and remains a leading cause of death and complications in sub-Saharan Africa.1 A key explanation for this enduring high mortality is that despite an evolution toward offering treatment earlier in the course of the disease,2 HIV continues to be identified in a substantial number of patients with advanced infection (which is defined by the World Health Organization [WHO] as a CD4+ count of fewer than 200 cells per cubic millimeter). A recent study of trends across 55 countries showed that more than a third (37%) of the patients who initiated ART in 2015 already had advanced HIV infection.3 Such patients are at high risk for death, even after starting ART (which can increase the inflammatory response), and the risk increases with a decreasing CD4+ count.3 A worrisome new trend that has been observed in countries with long-standing HIV treatment programs is an increase in the number of patients who present for care with advanced HIV infection after a period of treatment interruption…..

abstract

http://www.nejm.org/doi/10.1056/NEJMe1707598

PDF

http://www.nejm.org/doi/pdf/10.1056/NEJMe1707598

 

August 11, 2017 at 8:27 am

2017-07 Guidelines for the managing advanced HIV disease and rapid initiation of antiretroviral therapy. WHO 56 pags

Overview

The objectives of these guidelines are to provide recommendations outlining a public health approach to managing people presenting with advanced HIV disease, and to provide guidance on the timing of initiation of antiretroviral therapy (ART) for all people living with HIV.

The first set of recommendations addresses the specific needs of people with advanced HIV disease and defines a package of interventions aimed at reducing HIV-associated morbidity and mortality. WHO recommends that a package of screening, prophylaxis, rapid ART initiation and intensified adherence interventions be offered to everyone living with HIV presenting with advanced disease. This is a strong recommendation that applies to all populations and age groups. The guidelines also include an algorithm to support decision making for providing care for people with advanced HIV disease.

The second set of recommendations defines how rapidly ART should be initiated within the context of the “treat all” policy, especially when coinfections are present. WHO strongly recommends that rapid ART initiation should be offered to people living with HIV following confirmed diagnosis and clinical assessment. Rapid initiation of ART is defined as within seven days of HIV diagnosis. WHO further strongly recommends ART initiation on the same day as HIV diagnosis based on the person’s willingness and readiness to start ART immediately, unless there are clinical reasons to delay treatment. Both of these recommendations apply to all populations and age groups. People with advanced HIV disease should be given priority for clinical assessment and treatment initiation.

PDF

http://apps.who.int/iris/bitstream/10665/255884/1/9789241550062-eng.pdf?ua=1

August 7, 2017 at 9:56 am

HIV DRUG RESISTANCE REPORT 2017 – WHO – CDC – The Global Fund 82 pags.

Antimicrobial resistance (AMR) is a growing global public health threat, which urgently requires collective action to ensure effective prevention and treatment of infections. Minimizing the emergence and transmission of HIV drug resistance (HIVDR) is a critical aspect of the broader global response to AMR. Prevention, monitoring and response to HIVDR is key to building and sustaining gains in HIV treatment scale-up, and achieving the global 90-90-90 targets for treatment. These widely adopted targets reflect the global community’s commitment to expanding access to antiretroviral therapy (ART) including: diagnosing 90% of all people with HIV infection; providing treatment to 90% of those diagnosed; and ensuring 90% of people on treatment achieve virological suppression, by 2020. By the end of 2016, 70% of people living with HIV (PLHIV) were diagnosed,77% of those who knew their HIV status received ART, and 82% of those on treatment were virally suppressed…

PDF

http://apps.who.int/iris/bitstream/10665/255896/1/9789241512831-eng.pdf

August 7, 2017 at 8:03 am

EDITOR’S CHOICE – Practical Review of Recognition and Management of Obesity and Lipohypertrophy in Human Immunodeficiency Virus Infection.

Clin Inf Dis May 15, 2017 V.64 N.10

Jordan E. Lake; Takara L. Stanley; Caroline M. Apovian; Shalendar Bhasin; Todd T. Brown …

Obesity and lipohypertrophy are common disease states in treated HIV infection that may have overlapping pathophysiologies and/or synergistic metabolic consequences. This is a consensus opinion on the epidemiology, diagnosis, and treatment of excess adiposity in adults with treated HIV infection.

PDF

https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/cid/64/10/10.1093_cid_cix178/2/cix178.pdf?Expires=1494189161&Signature=Z86YQmq8fpG3rQeDTAgf-6dxeGAza3rir8VbdzT6~Y8BIIegZ9YFhVmvfCuuioUe6flXY~hkwOyW7VuLWzgwbl7oy15P8wEYUEyQ2~C6byqQrWFGAUGBe8sNOThSWkwuZhd-XSRlqUHu6mJlvYckWuaPcXk~BQ3NPGQNOgYlyfTs-ZiwqMg5SQThms7YEmJz2WzX8t3bXBFqazRAFCyGRixH~xhOTwmUm-Rmb1yBBo1Cvo0a0RmSK4juCMpxjC8U2b~LA2taJsD77csu3AsNFu4yG2r2X8vWA-QankHJZyzkO~aRfQNNx8913ZMbOUOsmf7nUemdLsBx-kXkO4LCHw__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q

May 6, 2017 at 3:50 pm

Correspondence: Multidrug-resistant HIV-1 infection despite preexposure prophylaxis.

N Engl J Med 2017 Feb 2; 376:501

Knox DC et al.

To the Editor:

Preexposure prophylaxis with emtricitabine (FTC)–tenofovir disoproxil fumarate (TDF) has been shown to be efficacious in preventing human immunodeficiency virus type 1 (HIV-1) infection in men who have sex with men and in whom adherence to treatment is high, as measured by levels of tenofovir diphosphate (TFV-DP) in dried blood spots.1 We describe a case of HIV-1 infection despite FTC-TDF–based preexposure prophylaxis.2

A 43-year-old man in Toronto who reported having sex with men began to receive oral daily FTC-TDF in April 2013 and had seven nonreactive fourth-generation HIV screening tests over the next 21 months. Pharmacy dispensation records provided support for his report of “perfect” adherence to preexposure prophylaxis over 24 months……

PDF

http://www.nejm.org/doi/pdf/10.1056/NEJMc1611639

March 14, 2017 at 7:35 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

Older Posts


Calendar

September 2017
M T W T F S S
« Aug    
 123
45678910
11121314151617
18192021222324
252627282930  

Posts by Month

Posts by Category