Posts filed under ‘HIV/SIDA HAART’

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: No Evidence That HIV-1 Subtype C Infection Compromises the Efficacy of Tenofovir-Containing Regimens: Cohort Study in the United Kingdom

Journal of Infectious Diseases November 1, 2016 V.214 N.9 P.1302-1308

Ellen White, Erasmus Smit, Duncan Churchill, Simon Collins, Clare Booth, Anna Tostevin, Caroline Sabin, Deenan Pillay, and David T. Dunn on behalf of the UK HIV Drug Resistance Database and UK Collaborative HIV Cohort Study

1MRC Clinical Trials Unit at UCL

2Department of Infection and Population Health

3Division of Infection and Immunity, University College London

4HIV i-Base

5Health Service Laboratories, Royal Free Hospital, London

6Public Health England, Birmingham Heartlands Hospital

7Brighton and Sussex Hospitals NHS Trust, United Kingdom

8Africa Centre for Population Health, University of KwaZulu-Natal, Durban, South Africa

Concern has been expressed that tenofovir-containing regimens may have reduced effectiveness in the treatment of human immunodeficiency virus type 1 (HIV-1) subtype C infections because of a propensity for these viruses to develop a key tenofovir-associated resistance mutation.

We evaluated whether subtype influenced rates of virological failure in a cohort of 8746 patients from the United Kingdom who received a standard tenofovir-containing first-line regimen and were followed for a median of 3.3 years.

In unadjusted analyses, the rate of failure was approximately 2-fold higher among patients infected with subtype C virus as compared to those with subtype B virus (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.50–2.31; P < .001). However, the increased risk was greatly attenuated in analyses adjusting for demographic and clinical factors (adjusted HR, 1.14; 95% CI, .83–1.58; P = .41).

There were no differences between subtypes C and subtypes non-B and non-C in either univariate or multivariate analysis. These observations imply there is no intrinsic effect of viral subtype on the efficacy of tenofovir-containing regimens.

PDF

http://jid.oxfordjournals.org/content/214/9/1302.full.pdf+html

 

J Infect Dis. (2016) 214 (9): 1289-1291

Editor’s Choice: HIV-1 Subtype C, Tenofovir, and the Relationship With Treatment Failure and Drug Resistance

Huldrych F. Günthard and Alexandra U. Scherrer

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich and Institute of Medical Virology, Switzerland

Tenofovir disoproxil fumarate (TDF) has emerged as a cornerstone of initial antiretroviral therapy (ART) [1, 2].

However, human immunodeficiency virus type 1 (HIV) subtype C, the most prevalent worldwide subtype, accounting for >50% of all HIV infections, harbors polymorphisms in reverse transcriptase codons 64, 65, and 66, which lead to more-rapid in vitro selection of the K65R mutation [3], the signature mutation conferring resistance to TDF [4].

Subtype C viruses may only require a single point mutation at position 65 to select for K65R.

Several clinical studies have suggested that this mechanism may contribute to higher treatment failure rates and higher rates of the emergence of the K65R mutations observed in HIV subtype C–infected, compared with subtype B–infected, individuals treated with TDF-containing regimens [5–9], although others could not confirm different response rates between subtype B and C [10–12].

In this issue of The Journal of Infectious Diseases, White et al report a comprehensive study on this issue [13].

They analyzed data from the UK Collaborative HIV Cohort (CHIC) Study (available at: http://www.ukchic.org.uk) and included 8746 patients who had initiated ART containing TDF, plus lamivudine or emtricitabine and either a nonnucleoside reverse transcriptase inhibitor (NNRTI; efavirenz or nevirapine) or a ritonavir-boosted protease inhibitor (lopinavir, atazanavir, or darunavir), and were followed for a median of 3.3 years.

Unadjusted analyses indicated an approximately 2-fold higher virological failure rate for subtype C–infected individuals as compared to subtype B–infected individuals. However, when they adjusted …

PDF

http://jid.oxfordjournals.org/content/214/9/1289.full.pdf+html

December 22, 2016 at 8:17 am

Impact of Cigarette Smoking and Smoking Cessation on Life Expectancy Among People With HIV: A US-Based Modeling Study

Journal of Infectious Diseases December 1, 2016 V.214 N.11 P.1672-1681

Krishna P. Reddy, Robert A. Parker, Elena Losina, Travis P. Baggett, A. David Paltiel, Nancy A. Rigotti, Milton C. Weinstein, Kenneth A. Freedberg, and Rochelle P. Walensky

1Medical Practice Evaluation Center

2Division of Pulmonary and Critical Care Medicine

3Division of General Internal Medicine

4Biostatistics Center

5Tobacco Research and Treatment Center

6Mongan Institute for Health Policy

7Division of Infectious Diseases, Massachusetts General Hospital

8Harvard Medical School

9Department of Orthopedic Surgery

10Division of Infectious Diseases, Brigham and Women’s Hospital

11Department of Biostatistics

12Department of Epidemiology, Boston University School of Public Health

13Boston Health Care for the Homeless Program

14Department of Health Policy and Management, Harvard T. H. Chan School of Public Health, Boston, Massachusetts

15Yale School of Public Health, New Haven, Connecticut

Background

In the United States, >40% of people infected with human immunodeficiency virus (HIV) smoke cigarettes.

Methods

We used a computer simulation of HIV disease and treatment to project the life expectancy of HIV-infected persons, based on smoking status. We used age- and sex-specific data on mortality, stratified by smoking status. The ratio of the non-AIDS-related mortality risk for current smokers versus that for never smokers was 2.8, and the ratio for former smokers versus never smokers was 1.0–1.8, depending on cessation age. Projected survival was based on smoking status, sex, and initial age. We also estimated the total potential life-years gained if a proportion of the approximately 248 000 HIV-infected US smokers quit smoking.

Results

Men and women entering HIV care at age 40 years (mean CD4+ T-cell count, 360 cells/µL) who continued to smoke lost 6.7 years and 6.3 years of life expectancy, respectively, compared with never smokers; those who quit smoking upon entering care regained 5.7 years and 4.6 years, respectively. Factors associated with greater benefits from smoking cessation included younger age, higher initial CD4+ T-cell count, and complete adherence to antiretroviral therapy. Smoking cessation by 10%–25% of HIV-infected smokers could save approximately 106 000–265 000 years of life.

Conclusions

HIV-infected US smokers aged 40 years lose >6 years of life expectancy from smoking, possibly outweighing the loss from HIV infection itself. Smoking cessation should become a priority in HIV treatment programs.

PDF

http://jid.oxfordjournals.org/content/214/11/1672.full.pdf+html

December 11, 2016 at 8:29 pm

Editorial – The Shifting Paradigm of Care for Adults Living With HIV – Smoking Cessation for Longer Life

Journal of Infectious Diseases December 1, 2016 V.214 N.11 P.1618-1620

Keri N. Althoff

Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

There are few truths in medical science that are as agreed upon as this: smoking is bad for health. In persons with human immunodeficiency virus (HIV) infection, smoking is a scourge, with recent prevalence estimates of 42%, which Reddy et al, in this issue of The Journal of Infectious Diseases, translated to an estimated 247 586 smokers among those in HIV care in the United States [1, 2]. It is hypothesized that adults living with HIV start smoking at younger ages, smoke more heavily and for a longer duration, and have lower rates of cessation than the general population in the United States. However, population-based estimates are not available. The problem may seem insurmountable, particularly because a delay in the manifestations of harm from smoking creates a lack of urgency for cessation. Because the HIV infection paradigm has changed from an acutely terminal illness to a chronic infection with a life expectancy approaching that of uninfected adults, the paradigm of how we protect the health of people living with HIV has also evolved.

Reddy et al estimate a gain in life expectancy of 5.7 years among men and 4.6 years among women who quit smoking upon entering into HIV care [2]. The authors predict that if a quarter of HIV-infected adults quit smoking, 265 000 years of life could be regained at the population level. It is reasonable to assume that there is also an increased quality of life, not only quantity of life, given the strong associations of smoking with a poorer immunologic response to antiretroviral therapy (ART) and the development of cancer, cardiovascular disease, chronic obstructive pulmonary disease, and lower respiratory tract infections [3]. After accounting for nonadherence to …

PDF

http://jid.oxfordjournals.org/content/214/11/1618.full.pdf+html

December 11, 2016 at 8:28 pm

2016 BHIVA GUIDELINES for the routine investigation and monitoring of Adult HIV-1-positive individuals 72 pags

British HIV Association

Writing Group: Brian Angus (Chair), Gary    Brook (Vice-chair), Funmi Awosusi, Gary Barker, Marta Boffito, Satyajit Das, Lucy Dorrell, Esther Dixon-Williams, Charlotte Hall, Bridie Howe, Sebastian Kalwij, Nashaba Matin, Eleni Nastouli, Frank Post, Melinda Tenant-Flowers, Erasmus Smit, Dan Wheals

NHS Evidence has accredited the process used by the British HIV Association (BHIVA) to produce guidelines.

Accreditation is valid for five years from July 2012 and is applicable to guidance produced using the processes described in the British HIV Association (BHIVA) Guideline Development Manual. More information on accreditation can be viewed at www.nice.org.uk/accreditation

PDF

http://www.bhiva.org/documents/Guidelines/Monitoring/2016-BHIVA-Monitoring-Guidelines.pdf

December 3, 2016 at 9:35 am

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