Timing of antiretroviral therapy after diagnosis of

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Boletín de la Sociedad de Enfermedades Infecciosas de la Comunidad Valenciana
VOLUMEN 3
NÚ M E R O 7
JULIO 2014
Timing of antiretroviral therapy after diagnosis of
cryptococcal meningitis.
Boulware DR, et al
N Engl J Med. 2014 Jun 26;370(26):2487-98 (enlace)
IMPACTOS EN ESTE
NÚMERO:
1. Ya conocemos cuál es el
momento óptimo de iniciar el tratamiento antirretroviral en los pacientes con meningitis criptocócica (portada)
2. Impactos (y enlaces) a
artículos de interés
Que el Boletín de la
SEICV sea de útil
Deferring ART for 5 weeks after the diagnosis of cryptococcal meningitis was associated with significantly improved survival, as compared with initiating ART at 1 to
2 weeks, especially among patients with a paucity of
white cells in cerebrospinal fluid.
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ASPECTOS GENERALES
Association of Azithromycin with Mortality and Cardiovascular Events among Older
Patients Hospitalized With Pneumonia
Eric M. Mortensen et al
JAMA. 2014; 311(21):2199-2208 (enlace)
Fracture risk in hepatitis C virus infected persons: Results from the DANVIR cohort
study
Ann-Brit Eg Hansen
Journal of Hepatology 2014; 61: 15–21
Association Between Efavirenz as Initial Therapy for HIV-1 Infection and Increased
Risk for Suicidal Ideation or Attempted or Completed Suicide. An Analysis of Trial
Data
Katie R. Mollan, et al
Ann Intern Med. 2014;161:1-10. doi:10.7326/M14-0293
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Hepatitis C virus itself is a causal risk factor for chronic kidney disease beyond traditional risk factors: a 6-year nationwide cohort study across Taiwan
Yi-Chun Chen, et al
BMC Nephrology 2013, 14:187 (enlace)
Conclusions: HCV infection is associated with increased risk for CKD beyond the wellknown traditional CKD risk factors. HCV patients should be informed of their increased risk for development of CKD and should be more closely monitored
BACTERIAS
Improving Outcomes for Multidrug-Resistant Tuberculosis: Aggressive Regimens
Prevent Treatment Failure and Death
Gustavo E. Velásquez, et al
Clin Infect Dis 2014 59: 9-15 (enlace)
In this retrospective cohort study of patients treated for multidrug-resistant tuberculosis in the Russian Federation, we found that monthly exposure to an aggressive
multidrug-resistant tuberculosis regimen was a robust predictor of decreased risk of
death or failure during treatment.
Is Asymptomatic Bacteriuria a Risk Factor for Prosthetic Joint Infection?
Ricardo Sousa, et al
In this large study of about 2500 total joint arthroplasty candidates, we found a
12.1% prevalence of preoperative asymptomatic bacteriuria. It was associated with
higher risk of prosthetic joint infection, and appropriate preoperative antibiotics
were not effective in reducing the risk.
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Epidemiology and clinical management of Legionnaires' disease
Phin N, et al
Lancet Infect Dis. 2014 Jun 23. pii: S1473-3099(14)70713-3. (enlace)
VIRUS
Addressing the Achilles' Heel in the HIV Care Continuum for the Success of a Testand-Treat Strategy to Achieve an AIDS-Free Generation
Jean B. Nachega, et al
Clin Infect Dis 2014 59: S21-S27 (enlace)
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Antiretroviral Chemoprophylaxis: State of Evidence and the Research Agenda
Kenneth H. Mayer
Clin Infect Dis 2014 59: S47-S51 (enlace)
Management of HIV Infection in Patients With Cancer Receiving Chemotherapy
Harrys A. Torres and Victor Mulanovich
Treating human immunodeficiency virus (HIV)-infected cancer patients simultaneously with antiretrovirals and chemotherapy is complicated. Little has been published on this topic. Clinicians should individualize decisions regarding HIV treatment
according to clinical and laboratory findings, chemotherapy plan, comorbidities, potential toxic effects, and patient preference.
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Heterosexual Risk of HIV Transmission per Sexual Act under Combined Antiretroviral Therapy: Systematic Review and Bayesian Modeling
Virginie Supervie, et al
We show that the per-act risk of HIV transmission through condom-unprotected sex
with HIV-infected individuals on combination antiretroviral therapy (cART) in comprehensive care for >6 months is <13:100 000. Available data do not support zero
HIV transmission risk under cART.
Figure 2. Upper-bound cumulative risk of human immunodeficiency virus (HIV) transmission within a
heterosexual serodiscordant couple where the partner had been on combination antiretroviral therapy (cART) in care for >6 months vs the number of condom-unprotected sexual acts. We considered 2
interpretations of current data. In case 1, the HIV transmission reported by Apondi et al [18] occurred
within the first 6 months of cART (continuous line), whereas in case 2, the HIV transmission reported
by Apondi et al [18] occurred after 6 months of cART (dashed line). Hence, in case 1, no HIV transmission occurred beyond 6 months of cART, whereas in case 2, 1 HIV transmission occurred beyond 6
months of cART. The gray area indicates upper-bound cumulative risk <1%.
Immunogenicity and Safety of the Quadrivalent Human Papillomavirus Vaccine in
HIV-1–Infected Women
Erna Milunka Kojic, et al
This multicenter prospective trial among HIV-1–infected women aged 13–45 years
found that the quadrivalent human papillomavirus vaccine was highly immunogenic,
but women with CD4 counts <200 cells/µL had lower seroconversion rates compared
with women with higher CD4 cell counts.
Delay in cART Initiation Results in Persistent Immune Dysregulation and Poor Recovery of T-Cell Phenotype Despite a Decade of Successful HIV Suppression.
Ndumbi P, et al
PLoS One. 2014 Apr 7;9(4):e94018 (enlace)
Conclusions: Failure to normalize the complete T-cell phenotype was most apparent
in patients who initiated cART with a CD4+ T-cell count 200 cells/mm3. The impact
of this impaired T-cell phenotype on life-long immune function and potential
comorbidities remains to be elucidated.
Timing of Antiretroviral Therapy after Diagnosis of Cryptococcal Meningitis
David R. Boulware, et al
N Engl J Med 2014; 370:2487-2498 (enlace)
Deferring ART for 5 weeks after the
diagnosis of cryptococcal meningitis
was associated with significantly improved survival, as compared with
initiating ART at 1 to 2 weeks, especially among patients with a paucity of
white cells in cerebrospinal fluid.
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A randomized open-label study of 3- versus 5-drug combination antiretroviral therapy in newly HIV-1-infected individuals
Markowitz M, et al.
J Acquir Immune Defic Syndr 66(2):140-7 (enlace)
Intensified 5-drug cART initiated during early infection fails to significantly further
impact virologic or immunologic responses beyond those achieved with standard 3drug PI-based cART.
Progression of Liver Fibrosis in Women Infected With Hepatitis C: Long-Term
Benefit of Estrogen Exposure
Vincent Di Martino, et al
Hepatology 2004;40:1426 –1433
Conclusion, menopause appears to be associated with accelerated liver fibrosis progression in HCV-infected women, an effect that may be prevented by HRT. Pregnancies may have a beneficial impact on the long-term progression of liver fibrosis.
Incidence, Clearance, and Disease Progression of Genital Human Papillomavirus
Infection in Heterosexual Men
Edson Duarte Moreira, et al
J Infect Dis 2014 210: 192-199 (enlace)
The study results suggest that the acquisition of HPV 6, 11, 16, and/or 18 in males is
common and that many of these so-called
infections are subsequently cleared, similar to findings for women. Nevertheless,
given the high rate of HPV detection
among young men, HPV vaccination of
males may reduce infection in men and
reduce the overall burden of HPVassociated disease in the community.
Prognostic Value of Vitamin D Level for All-cause Mortality, and Association With
Inflammatory Markers, in HIV-infected Persons
Leah Shepherd, et al
J Infect Dis. 2014; 210 (2): 234-243 (enlace)
Low Vitamin D predicts short term mortality in HIV-positive persons. Effectiveness of
vitamin D supplementation on inflammation and patient outcomes should be investigated.
25-Hydroxyvitamin D Insufficiency and Deficiency is Associated With HIV Disease
Progression and Virological Failure Post-Antiretroviral Therapy Initiation in Diverse
Multinational Settings
Fiona Havers, et al.
J Infect Dis. (2014) 210 (2): 244-253.
Low 25(OH)D is common in diverse HIV-infected populations and is an independent
risk factor for clinical and virologic failure. Studies examining the potential benefit of
vitamin D supplementation among HIV patients initiating cART are warranted.
Evidence for Camel-to-Human Transmission of MERS Coronavirus
Esam I. Azhar, et al
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Middle East Respiratory Syndrome Coronavirus: A Case-Control Study of Hospitalized Patients
Jaffar A. Al-Tawfiq, et al
This case-control study of hospitalized
patients compared underlying conditions,
symptoms, signs, laboratory data, and
radiographic presentations between Middle East respiratory syndrome coronavirus
(MERS-CoV)–positive and –negative patients. Those with MERS-CoV were more
likely to be overweight and to have diabetes mellitus, end-stage renal disease,
tachypnea, and a normal white blood cell
count on bivariate analysis.
Complications Among Adults Hospitalized With Influenza: A Comparison of
Seasonal Influenza and the 2009 H1N1 Pandemic
Carrie Reed, et al
Adults hospitalized with 2009 pandemic influenza were younger than those hospitalized in previous influenza seasons and more likely to have lower respiratory tract
complications and corresponding indicators of severe illness including intensive care
admission, mechanical ventilation, or death.
Hepatitis (en NEJM)
Therapy of Hepatitis C — Back to the Future
T. Jake Liang, M.D., and Marc G. Ghany, M.D., M.H.Sc.
A book on hepatitis C would read like a marriage of an Orson Welles mystery and a
Shakespearean play — awash in enigma, tragedy, despair, resilience, redemption,
and triumph. It is only fitting that treatment of hepatitis C virus (HCV) infection
stands at center stage of such a book. After the initial introduction of interferon alfa
as the mainstay of therapy….
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Sofosbuvir and ribavirin in HCV genotypes 2 and 3.
Zeuzem S, et al.
N Engl J Med. 2014 May 22;370(21):1993-2001 (Enlace)
Therapy with sofosbuvir–
ribavirin for 12 weeks in patients
with HCV genotype 2 infection
and for 24 weeks in patients with
HCV genotype 3 infection resulted in high rates of sustained
virologic response
ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV.
Ferenci P, et al
N Engl J Med. 2014 May 22;370(21):1983-92 (enlace)
Twelve weeks of treatment with ABT-450/r–
ombitasvir and dasabuvir without ribavirin
was associated with high rates of sustained
virologic response among previously untreated patients with HCV genotype 1 infection.
Rates of virologic failure were higher without
ribavirin than with ribavirin among patients
with genotype 1a infection but not among
those with genotype 1b infection.
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ABT-450/r–Ombitasvir and Dasabuvir with Ribavirin for Hepatitis C with Cirrhosis
Fred Poordad, et al
In this phase 3 trial of an oral, interferon-free regimen evaluated exclusively in patients with HCV genotype 1
infection and cirrhosis, multitargeted
therapy with the use of three new
antiviral agents and ribavirin resulted
in high rates of sustained virologic
response. Drug discontinuations due
to adverse events were infrequent.
Retreatment of HCV with ABT-450/r–Ombitasvir and Dasabuvir with Ribavirin
Stefan Zeuzem, et al
Rates of response to a 12-week interferon-free combination regimen were more than 95% among previously treated patients with HCV genotype 1 infection, including patients with a prior null response.
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Ledipasvir and Sofosbuvir for Previously Treated HCV Genotype 1 Infection
Nezam Afdhal, et al
Treatment with a once-daily,
single-tablet regimen of ledipasvir and sofosbuvir resulted
in high rates of sustained virologic response among patients
with HCV genotype 1 infection
who had not had a sustained
virologic response to prior
interferon-based treatment.
Ledipasvir and Sofosbuvir for Untreated HCV Genotype 1 Infection
Nezam Afdhal, et al
Once-daily ledipasvir–
sofosbuvir with or without
ribavirin for 12 or 24 weeks
was highly effective in previously untreated patients with
HCV genotype 1 infection
Ledipasvir and Sofosbuvir for 8 or 12 Weeks for Chronic HCV without Cirrhosis
Kris V. Kowdley, et al
Ledipasvir–sofosbuvir for 8 weeks
was associated with a high rate of
sustained virologic response among
previously untreated patients with
HCV genotype 1 infection without
cirrhosis. No additional benefit was
associated with the inclusion of ribavirin in the regimen or with extension of the duration of treatment to
12 weeks.
Treatment of HCV with ABT-450/r–Ombitasvir and Dasabuvir with Ribavirin
Jordan J. Feld, et al
In previously untreated patients with
HCV genotype 1 infection and no cirrhosis, a 12-week multitargeted regimen of
ABT-450/r–ombitasvir and dasabuvir
with ribavirin was highly effective and
was associated with a low rate of treatment discontinuation
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HONGOS
Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis (portada)
Boulware DR, et al
N Engl J Med. 2014 Jun 26;370(26):2487-98 (enlace)
Deferring ART for 5 weeks after the diagnosis of cryptococcal meningitis was associated with significantly improved survival, as compared with initiating ART at 1 to 2
weeks, especially among patients with a paucity of white cells in cerebrospinal fluid.
PARASITOS
Failure of Miltefosine in Visceral Leishmaniasis Is Associated With Low Drug Exposure
Thomas P. C. Dorlo, et al
J Infect Dis 2014 210: 146-153 (enlace)
Figure 3. Probability of treatment failure versus miltefosine exposure. The solid line represents the logistic model predicted probability of treatment failure, and the gray area denotes
the 90% confidence interval. The transparent bars indicate the interval of the observed time
that the miltefosine concentration is >10 times the half maximal effective concentration (T >
10× EC) is covered by the bins, with approximately 25 observations in each bin, whereas the
filled circles on top of the bins indicate the mean observed data-based probabilities of
treatment failure per bin at the mean
T > 10× EC 50 50 of the bin.
Conclusions. Achieving a sufficient exposure to miltefosine is a significant and
critical factor for VL treatment success, suggesting an urgent need to evaluate
the recently proposed optimal allometric miltefosine dosing regimen. This
study establishes the first evidence for a drug exposure-effect relationship for
miltefosine in the treatment of VL.
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EVENTOS RECIENTES

Timing of antiretroviral therapy after diagnosis of

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