Posts filed under ‘HIV/SIDA’

Effects of Pre-exposure Prophylaxis for the Prevention of Human Immunodeficiency Virus Infection on Sexual Risk Behavior in Men Who Have Sex With Men: A Systematic Review and Meta-analysis

Clinical Infectious Diseases September 1, 2018 V.67 N.5 P.676–686

EDITOR’S CHOICE

Michael W Traeger; Sophia E Schroeder; Edwina J Wright; Margaret E Hellard; Vincent J Cornelisse..

This systematic review and meta-analysis of 17 open-label studies published to 2017 found that daily HIV pre-exposure prophylaxis use among men who have sex with men is associated with increased sexually transmitted infection diagnoses and an increase in condomless sex.

Background

Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) is effective in reducing HIV risk in men who have sex with men (MSM). However, concerns remain that risk compensation in PrEP users may lead to decreased condom use and increased incidence of sexually transmitted infections (STIs). We assessed the impact of PrEP on sexual risk outcomes in MSM.

Methods

We conducted a systematic review of open-label studies published to August 2017 that reported sexual risk outcomes in the context of daily oral PrEP use in HIV-negative MSM and transgender women. Pooled effect estimates were calculated using random-effects meta-analysis, and a qualitative review and risk of bias assessment were performed.

Results

Sixteen observational studies and 1 open-label trial met selection criteria. Eight studies with a total of 4388 participants reported STI prevalence, and 13 studies with a total of 5008 participants reported change in condom use. Pre-exposure prophylaxis use was associated with a significant increase in rectal chlamydia (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.19–2.13) and an increase in any STI diagnosis (OR, 1.24; 95% CI, .99–1.54). The association of PrEP use with STI diagnoses was stronger in later studies. Most studies showed evidence of an increase in condomless sex among PrEP users.

Conclusion

Findings highlight the importance of efforts to minimize STIs among PrEP users and their sexual partners. Monitoring of risk compensation among MSM in the context of PrEP scale-up is needed to assess the impact of PrEP on the sexual health of MSM and to inform preventive strategies.

FULL TEXT

https://academic.oup.com/cid/article/67/5/676/4917600

PDF (CLIC en PDF)

Advertisements

September 2, 2018 at 10:36 am

Bioequivalence of a Fixed-Dose Combination Tablet of the Complete Two-Drug Regimen of Dolutegravir and Rilpivirine for Treatment of HIV-1 Infection

Antimicrobial Agents and Chemotherapy September 2018 V.62 N.9

Rashmi Mehta, Allen Wolstenholme, Kristin Di Lullo, Caifeng Fu, Shashidhar Joshi, Herta Crauwels, Naomi Givens, Simon Vanveggel, Brian Wynne and Kimberly Adkison

A complete 2-drug regimen of dolutegravir at 50 mg and rilpivirine at 25 mg was approved to treat HIV-1 infection in virologically suppressed patients after demonstrating acceptable efficacy and tolerability.

This study investigated the bioequivalence and pharmacokinetics of the fixed-dose combination tablet compared with those of separate tablets. Secondary endpoints were the tolerability and safety of the fixed-dose combination tablet.

In this open-label, randomized-sequence, 2-way crossover trial, single doses of the fixed-dose combination tablet (the test treatment) and the combination of separate tablets (the reference treatment) were administered to healthy adults after a moderate-fat meal, with a 21-day washout between treatments.

Pharmacokinetic samples were collected through 12 days after dosing. The primary endpoints were the area under the plasma concentration-time curve (AUC) and the maximum concentration of drug in plasma (Cmax). The study employed a prespecified sample size reestimation based on a blind midpoint review of Cmax variability to update the enrollment size to achieve statistical power.

Of 118 participants enrolled, 113 received both treatments and underwent pharmacokinetic assessment.

The 90% confidence intervals for the geometric least-squares mean ratios for the AUC from 0 h to infinity, the AUC from 0 h to the last quantifiable measurement, and Cmax (test treatment versus reference treatment) were within the bioequivalence range of 0.80 to 1.25 for both drugs, indicating bioequivalence.

In this study, a single dose of either treatment was well tolerated overall, with 4% (n = 5) and 3% (n = 3) of participants reporting adverse events considered related to the test and reference treatments, respectively.

The dolutegravir-rilpivirine fixed-dose combination tablet is bioequivalent to a combination of separate tablets, and no new safety signals emerged.

(This study has been registered at ClinicalTrials.gov under identifier NCT02741557.)

FULL TEXT

https://aac.asm.org/content/62/9/e00748-18?etoc=

PDF

https://aac.asm.org/content/aac/62/9/e00748-18.full.pdf

August 29, 2018 at 3:45 pm

Human Immunodeficiency Virus Drug Resistance: 2018 Recommendations of the International Antiviral Society-USA Panel.

Clinical Infectious Diseases July 20, 2018             

Günthard HF1, Calvez V2, Paredes R3,4, Pillay D5, Shafer RW6, Wensing AM7, Jacobsen DM8, Richman DD9.

Author information

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

2 Pierre et Marie Curie University and Pitié-Salpêtriere Hospital, Paris, France.

3 Infectious Diseases Service and IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.

4 Africa Health Research Institute, KwaZulu Natal, South Africa.

5 University College London, United Kingdom.

6 Stanford University Medical School, California.

7 University Medical Center Utrecht, The Netherlands.

8 International Antiviral Society-USA, San Francisco.

9 Veterans Affairs San Diego Healthcare System and University of California San Diego.

Abstract

BACKGROUND:

Contemporary antiretroviral therapies (ART) and management strategies have diminished both human immunodeficiency virus (HIV) treatment failure and the acquired resistance to drugs in resource-rich regions, but transmission of drug-resistant viruses has not similarly decreased. In low- and middle-income regions, ART roll-out has improved outcomes, but has resulted in increasing acquired and transmitted resistances. Our objective was to review resistance to ART drugs and methods to detect it, and to provide updated recommendations for testing and monitoring for drug resistance in HIV-infected individuals.

METHODS:

A volunteer panel of experts appointed by the International Antiviral (formerly AIDS) Society-USA reviewed relevant peer-reviewed data that were published or presented at scientific conferences. Recommendations were rated according to the strength of the recommendation and quality of the evidence, and reached by full panel consensus.

RESULTS:

Resistance testing remains a cornerstone of ART. It is recommended in newly-diagnosed individuals and in patients in whom ART has failed. Testing for transmitted integrase strand-transfer inhibitor resistance is currently not recommended, but this may change as more resistance emerges with widespread use. Sanger-based and next-generation sequencing approaches are each suited for genotypic testing. Testing for minority variants harboring drug resistance may only be considered if treatments depend on a first-generation nonnucleoside analogue reverse transcriptase inhibitor. Different HIV-1 subtypes do not need special considerations regarding resistance testing.

CONCLUSIONS:

Testing for HIV drug resistance in drug-naive individuals and in patients in whom antiretroviral drugs are failing, and the appreciation of the role of testing, are crucial to the prevention and management of failure of ART.

FULL TEXT

https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciy463/5055715

PDF (CLIC en PDF)

August 21, 2018 at 8:09 am

Increased Risk of HIV Acquisition Among Women Throughout Pregnancy and During the Postpartum Period: A Prospective Per-Coital-Act Analysis Among Women With HIV-Infected Partners

The Journal of Infectious Diseases July 1, 2018 V.218 N.1 P.16-25

EDITOR’S CHOICE

Kerry A Thomson; James Hughes; Jared M Baeten; Grace John-Stewart; Connie Celum

The risk of human immunodeficiency virus type 1 (HIV-1) acquisition by women per condomless sex act was 3-fold and 4-fold higher during late pregnancy and the postpartum period, respectively, relative to the nonpregnant period. Enhanced HIV-1 prevention and testing strategies are needed during pregnancy and the postpartum period.

FULL TEXT

https://academic.oup.com/jid/article/218/1/16/4915924

PDF (CLIC en PDF)

August 13, 2018 at 6:16 pm

Risk of HIV Acquisition During Pregnancy and Postpartum: A Call for Action

The Journal of Infectious Diseases July 1, 2018 V.218 N.1 P.1-4

EDITOR’S CHOICE

Lynne M Mofenson

Prospective studies exploring the relationship between pregnancy and HIV acquisition in women have had inconsistent results, with some studies documenting an increased risk [1–3], while others finding no increase in risk — or even lower risk — after controlling for sexual behavior and other confounding factors such as sexually transmitted infections [4–7]. A meta-analysis of 19 cohort studies estimated a pooled HIV incidence during pregnancy and postpartum of 3.9 per 100 person-years (4.7 per 100 person-years during pregnancy and 2.9 per 100 person-years postpartum) [8], similar to that defined as “substantial risk” in nonpregnant individuals, such as female sex workers, by the World Health Organization (WHO) [9]. The pooled meta-analysis reported that HIV incidence was not significantly higher among pregnant or postpartum women than among nonpregnant/nonpostpartum women, but only 5 studies had appropriate data and were not able to control for a variety of confounding factors, limiting the power to detect associations…

FULL TEXT

https://academic.oup.com/jid/article/218/1/1/4913312

PDF (CLIC en PDF)

August 13, 2018 at 6:15 pm

Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted HIV-1 Drug Resistance in a Large U.S. Clinic Population.

Clin Infect Dis. May 28, 2018

Rhee SY1, Clutter D1, Fessel WJ2, Klein D3, Slome S4, Pinsky BA5, Marcus JL6, Hurley L7, Silverberg MJ7, Kosakovsky Pond SL8, Shafer RW1.

Author information

1 Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA.

2 Department of Internal Medicine, Kaiser Permanente Northern California, San Francisco, CA.

3 Department of Infectious Diseases, Kaiser Permanente Northern California, San Leandro, CA.

4 Department of Infectious Diseases, Kaiser Permanente Northern California, Oakland, CA.

5 Department of Pathology, Stanford University, Stanford, CA.

6 Harvard Medical School and Harvard Pilgrim Health Care Institute, Oakland, CA.

7 Division of Research, Kaiser Permanente Northern California, Oakland, CA.

8 Department of Biology, Temple University, Philadelphia, PA.

Abstract

BACKGROUND:

There are few large studies of transmitted drug resistance (TDR) prevalence and the drug resistance mutations (DRMs) responsible for TDR in the U.S.

METHODS:

HIV-1 RT and protease sequences were obtained from 4,253 antiretroviral therapy (ART)-naïve individuals in a California clinic population from 2003-2016. Phylogenetic analyses were performed to study linkages between TDR strains and selection pressure on TDR-associated DRMs.

RESULTS:

From 2003-2016, there was a significant increase in overall (odds ratio [OR]=1.05 per year; 95% CI: 1.03 – 1.08; p<0.001) and nonnucleoside RT inhibitor (NNRTI)-associated TDR (OR=1.11 per year; 95% CI: 1.08 – 1.15; p<0.001). Between 2012 and 2016, TDR rates to any drug class ranged from 15.7%-19.2%, and class-specific rates ranged from 10.0%-12.8% for NNRTIs, 4.1%-8.1% for nucleoside RT inhibitors (NRTIs), and 3.6%-5.2% for protease inhibitors. K103N/S, Y181C, Y188L, and G190A mutations accounted for 88.5% of NNRTI-associated TDR. The thymidine analog mutations, M184V/I, and the tenofovir-associated DRMs K65R and K70E/Q/G/N/T accounted for 82.9%, 7.3%, and 1.4% of NRTI-associated TDR, respectively. The proportions of individuals with low-level resistance or higher to boosted atazanavir and darunavir were 2.2% and 0.3%, respectively. 37% of TDR strains clustered with other TDR strains sharing the same DRMs.

CONCLUSIONS:

Although TDR has increased significantly in this large cohort, many TDR strains are unlikely to influence the activity of currently preferred first-line ART regimens. The high proportion of DRMs associated with infrequently used regimens combined with the clustering of TDR strains suggest that some TDR strains are being transmitted between ART-naïve individuals.

FULL TEXT

https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciy453/5005024

PDF (CLIC en PDF)

July 2, 2018 at 6:45 pm

Cancer Risk in Older Persons Living With Human Immunodeficiency Virus Infection in the United States

Clinical Infectious Diseases July 1, 2018 V.67 N.1 P.50–57

Parag Mahale; Eric A Engels; Anna E Coghill; Amy R Kahn; Meredith S Shiels

El riesgo de cáncer en 183.542 personas mayores que vivían con la infección por el virus de la inmunodeficiencia humana se evaluó utilizando datos del estudio de compatibilidad del cáncer de VIH/SIDA. El riesgo relativo de la mayoría de los cánceres disminuyó con la edad, pero los riesgos absolutos fueron más altos para algunos cánceres.

Background

Cancer risk is increased in persons living with human immunodeficiency virus (HIV) (PLWH). Improved survival has led to an aging of PLWH. We evaluated the cancer risk in older PLWH (age ≥50 years).

Methods

We included data from the HIV/AIDS Cancer Match Study (1996–2012) and evaluated risks of Kaposi sarcoma (KS), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma, and cervical, anal, lung, liver, oral cavity/pharyngeal, breast, prostate, and colon cancers in older PLWH with risk in the general population by calculating standardized incidence ratios (SIRs) and excess absolute risks (EARs). Cancer risk by time since HIV diagnosis was estimated using Poisson regression.

Results

We identified 10371 cancers among 183542 older PLWH. Risk was significantly increased for KS (SIR, 103.34), NHL (3.05), Hodgkin lymphoma (7.61), and cervical (2.02), anal (14.00), lung (1.71), liver (2.91), and oral cavity/pharyngeal (1.66) cancers, and reduced for breast (0.61), prostate (0.47), and colon (0.63) cancers. SIRs declined with age for all cancers; however, EARs increased with age for anal, lung, liver, and oral cavity/pharyngeal cancers. Cancer risk was highest for most cancers within 5 years after HIV diagnosis; risk decreased with increasing time since HIV diagnosis for KS, NHL, lung cancer, and Hodgkin lymphoma.

Conclusions

Cancer risk is elevated among older PLWH. Although SIRs decrease with age, EARs are higher for some cancers, reflecting a greater absolute excess in cancer incidence among older PLWH. High risk in the first 5 years after HIV diagnosis for some cancers highlights the need for early HIV diagnosis and rapid treatment initiation.

abstract

https://academic.oup.com/cid/article/67/1/50/4793024

PDF (CLIC en PDF)

June 28, 2018 at 9:09 am

Older Posts


Calendar

September 2018
M T W T F S S
« Aug    
 12
3456789
10111213141516
17181920212223
24252627282930

Posts by Month

Posts by Category