Drug Resistance Factors Into HIV Treatment Failures

Ob Gyn News ◽  
2005 ◽  
Vol 40 (21) ◽  
pp. 45
Author(s):  
HEIDI SPLETE
2010 ◽  
Vol 55 (3) ◽  
pp. 1114-1119 ◽  
Author(s):  
Jia Liu ◽  
Michael D. Miller ◽  
Robert M. Danovich ◽  
Nathan Vandergrift ◽  
Fangping Cai ◽  
...  

ABSTRACTRaltegravir is highly efficacious in the treatment of HIV-1 infection. The prevalence and impact on virologic outcome of low-frequency resistant mutations among HIV-1-infected patients not previously treated with raltegravir have not been fully established. Samples from HIV treatment-experienced patients entering a clinical trial of raltegravir treatment were analyzed using a parallel allele-specific sequencing (PASS) assay that assessed six primary and six secondary integrase mutations. Patients who achieved and sustained virologic suppression (success patients,n= 36) and those who experienced virologic rebound (failure patients,n= 35) were compared. Patients who experienced treatment failure had twice as many raltegravir-associated resistance mutations prior to initiating treatment as those who achieved sustained virologic success, but the difference was not statistically significant. The frequency of nearly all detected resistance mutations was less than 1% of viral population, and the frequencies of mutations between the success and failure groups were similar. Expansion of pre-existing mutations (one primary and five secondary) was observed in 16 treatment failure patients in whom minority resistant mutations were detected at baseline, suggesting that they might play a role in the development of drug resistance. Two or more mutations were found in 13 patients (18.3%), but multiple mutations were not present in any single viral genome by linkage analysis. Our study demonstrates that low-frequency primary RAL-resistant mutations were uncommon, while minority secondary RAL-resistant mutations were more frequently detected in patients naïve to raltegravir. Additional studies in larger populations are warranted to fully understand the clinical implications of these mutations.


Parasitology ◽  
1977 ◽  
Vol 74 (2) ◽  
pp. 205-213 ◽  
Author(s):  
L. P. Joyner ◽  
C. C. Norton

Experiments are described which support the view that, in Eimeria maxima, drug resistance factors are transferred at zygote formation. The phenomenon occurred between infections which were initiated by the inoculation of merozoites. It also took place between variants of the same, but not between different species. Transference of drug resistance wsa not affected by the treatment of the chicks with acriflavine.


eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Alison F Feder ◽  
Soo-Yon Rhee ◽  
Susan P Holmes ◽  
Robert W Shafer ◽  
Dmitri A Petrov ◽  
...  

In the early days of HIV treatment, drug resistance occurred rapidly and predictably in all patients, but under modern treatments, resistance arises slowly, if at all. The probability of resistance should be controlled by the rate of generation of resistance mutations. If many adaptive mutations arise simultaneously, then adaptation proceeds by soft selective sweeps in which multiple adaptive mutations spread concomitantly, but if adaptive mutations occur rarely in the population, then a single adaptive mutation should spread alone in a hard selective sweep. Here, we use 6717 HIV-1 consensus sequences from patients treated with first-line therapies between 1989 and 2013 to confirm that the transition from fast to slow evolution of drug resistance was indeed accompanied with the expected transition from soft to hard selective sweeps. This suggests more generally that evolution proceeds via hard sweeps if resistance is unlikely and via soft sweeps if it is likely.


2021 ◽  
Vol 19 ◽  
Author(s):  
Giuseppa Visalli ◽  
Alessio Facciolà ◽  
Maria Giovanna Costanzo ◽  
Angela Di Pietro

Aims: To evaluate the frequency of the InSTIs mutations in a large cohort of HIV-infected people. Background: The Highly Active Anti-Retroviral Therapy (HAART) allow turning HIV infection from a fatal disease to a chronic infection and Integrase Strand Transfer Inhibitors (InSTIs) represent the cornerstone of this treatment. However, the spread of HIV-1 drug resistance mutations represents an emerging threat to the long-term success of HIV treatment programs. Objectives: To evaluate the trend of the HIV drug resistance to InSTIs in a large cohort of HIV-positive people in order to assess the risk represented by these subjects in the spread of the HIV infection to the community. Methods: A cross-sectional study was conducted analysing all the InSTIs resistance tests performed in HIV positive subjects in the period 2017-2019 by the HIV Laboratory of the University Hospital "Gaetano Martino" of Messina, Italy. Results: In 2017-2019, 252 InSTIs resistance tests were performed of which 59 (23.4%), 88 (34.9%) and 105 (41.7%) respectively in the three considered years. Overall, 28 (11.1%) samples showed resistance to at least one of the four InSTIs. We observed a significant percentage increase of 95% about the resistance to all the four drugs. Conclusion: Because the InSTI resistance is not rare, a continuous surveillance can represent nowadays, together with an incessant health education and a wide offer of the HIV test, the most important tool in the fight against HIV infection.


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