scholarly journals Reverse Transcriptase Mutations in HIV-1 Infected Patients Treated with Two Nucleoside Analogues: The Smart Study

2002 ◽  
Vol 15 (2) ◽  
pp. 129-139 ◽  
Author(s):  
N. Gianotti ◽  
M. Setti ◽  
P.E. Manconi ◽  
F. Leoncini ◽  
F. Chiodo ◽  
...  

Resistance to nucleoside reverse transcriptase inhibitors (NRTIs) was studied in 527 HIV-1-infected patients, 342 responder and 185 non-responder to two NRTIs. Responders were followed for one year to assess the incidence of clinical failure. The prevalence of the 215Y/F substitution was higher among non-responder, compared to responder patients (33.7% vs. 17%, P = 0.0005), whereas the prevalence of the 184V and of the 70R mutations was comparable between these two groups. The 74V substitution was never observed and the 75T mutation was detected in only two subjects non-responder to a stavudine including regimen. Reduced susceptibility to didanosine or stavudine was infrequent. Reduced susceptibility to zidovudine was observed in 25% of individuals failing a zidovudine including regimen, whereas reduced susceptibility to lamivudine was detected in all subjects failing a lamivudine including regimen. In the prospective analysis, patients with undetectable viral load at enrollment had a lower incidence of failure rate over one year compared to those with detectable HIV-RNA at entry (P < 0.0001). A detectable viral load at enrollment was the only independent variable that predicted clinical failure over one year (P < 0.0001).

2013 ◽  
Vol 4 ◽  
pp. VRT.S12677 ◽  
Author(s):  
Georgina N. Odaibo ◽  
Isaac F. Adewole ◽  
David O. Olaleye

Plasma HIV-1 RNA concentration, or viral load, is an indication of the magnitude of virus replication and largely correlates with disease progression in an infected person. It is a very useful guide for initiation of therapy and monitoring of response to antiretroviral drugs. Although the majority of patients who are not on antiretroviral therapy (ART) have a high viral load, a small proportion of ART naive patients are known to maintain low levels or even undetectable viral load levels. In this study, we determined the rate of undetectable HIV-1 RNA among ART naive HIV positive patients who presented for treatment at the University College Hospital (UCH), Ibadan, Nigeria from 2005 to 2011. Baseline viral load and CD4 lymphocyte cell counts of 14,662 HIV positive drug naive individuals were determined using the Roche Amplicor version 1.5 and Partec easy count kit, respectively. The detection limits of the viral load assay are 400 copies/mL and 750,000 copies/mL for lower and upper levels, respectively. A total of 1,399 of the 14,662 (9.5%) HIV-1 positive drug naive individuals had undetectable viral load during the study period. In addition, the rate of non-detectable viral load increased over the years. The mean CD4 counts among HIV-1 infected individuals with detectable viral load (266 cells/μL; range = 1 to 2,699 cells/μL) was lower than in patients with undetectable viral load (557 cells/μL; range = 1 to 3,102 cells/μL). About 10% of HIV-1 infected persons in our study population had undetectable viral load using the Roche Amplicor version 1.5.


2019 ◽  
Vol 74 (7) ◽  
pp. 2039-2046 ◽  
Author(s):  
Antonella Castagna ◽  
Camilla Muccini ◽  
Laura Galli ◽  
Alba Bigoloni ◽  
Andrea Poli ◽  
...  

AbstractObjectivesDespite the fact that there are individuals who have chronic HIV infection, few studies have investigated ART interruption in this setting. The aim of this study was to evaluate the ability to spontaneously control viral replication during analytical treatment interruption (ATI) in adults with chronic HIV-1 infection, on ART, with suppressed viraemia for >10 years and with a low reservoir.Patients and methodsThis was a prospective, open-label, single-arm, non-randomized, proof-of-concept study (NCT03198325) of subjects with chronic HIV-1 infection, HIV-RNA <50 copies/mL for ≥10 years, without residual viraemia for ≥5 years, CD4+ >500 cells/mm3, HIV-DNA <100 copies/106 PBMCs and without comorbidities or AIDS-defining diseases. Enrolled patients were strictly monitored. The ART regimen in use at ATI was resumed in the case of confirmed viral rebound (CVR, two consecutive HIV-RNA >50 copies/mL). Results are reported as median (IQR).ResultsNine patients underwent ATI. All participants experienced CVR [4.84 (IQR: 3.47–6.47) HIV-RNA log10 copies/mL] after ATI at a median time of 21 days (range 14–56) and restarted ART. After ART resumption, all the subjects achieved HIV-RNA <50 copies/mL in a median of 88 days (range 15–197). No serious adverse event occurred; one subject experienced acute retroviral syndrome. No significant correlation between baseline factors and time to viral rebound was observed, while the magnitude of viral rebound was significantly associated with pre-ART HIV-1 RNA (Spearman r = 0.786, P = 0.036), nadir CD4+ (Spearman r = −0.800, P = 0.010), baseline CD4+ (Spearman r = −0.667, P = 0.049) and years with undetectable viral load (Spearman r = −0.717, P = 0.030).ConclusionsDespite a long period of HIV viral load suppression and a low viral reservoir, early and consistent viral rebound was observed during ATI in all subjects.


AIDS ◽  
2001 ◽  
Vol 15 (6) ◽  
pp. 665-673 ◽  
Author(s):  
Nicole Ngo-Giang-Huong ◽  
Christiane Deveau ◽  
Isabelle Da Silva ◽  
Isabelle Pellegrin ◽  
Alain Venet ◽  
...  

2017 ◽  
Vol 3 (1) ◽  
pp. 34-39 ◽  
Author(s):  
W. Snippenburg ◽  
F.J.B. Nellen ◽  
C. Smit ◽  
A.M.J. Wensing ◽  
M.H. Godfried ◽  
...  

2014 ◽  
Vol 8 (03) ◽  
pp. 339-348
Author(s):  
Jacques M Mokhbat ◽  
Nada M. Melhem ◽  
Ziad El-Khatib ◽  
Pierre Zalloua

Introduction: Antiretroviral therapy (ART) has been successful at decreasing the morbidity and mortality associated with human immunodeficiency virus type 1 (HIV-1) infection. HIV-1 drug resistance (HIVDR) among ART-naive patients has been documented to compromise the success of initial therapy. This study was conducted to determine the prevalence of HIVDR mutations among newly diagnosed drug-naive HIV-infected individuals in Lebanon. Methodology: Plasma samples from 37 newly diagnosed participants at various stages of HIV-1 infection were used to determine HIV-1 RNA viral load, isolate viral RNA, and amplify DNA by RT-PCR. Purified PCR products were used to perform genotypic resistance tests. Results: The prevalence of resistance mutations to nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRT), and protease inhibitors (PI) were 5.4%, 10.8%, and 8%, respectively. The major mutations detected in the study participants conferred resistance to NRTIs and NNRTIs recommended for HIV-1 treatment.  No significant relationship between HIV-1 viral load of participants and the mode of HIV-1 transmission or between the occurrence of HIVDR and the mode of transmission was found. Conclusions: To our knowledge, this is the first study on HIVDR mutations among newly diagnosed HIV-infected persons in Lebanon. The overall prevalence of HIVDR mutations detected in our study was 16%. Our results are important for evaluating the utility of the standard first-line regimens in use, determining the feasibility of HIVDR testing before the initiation of ART, as well as minimizing the emergence and transmission of HIVDR.


2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Beatrice N Vetter ◽  
Cyril Shah ◽  
Jon B Huder ◽  
Jürg Böni ◽  
Jörg Schüpbach

Viruses ◽  
2017 ◽  
Vol 9 (12) ◽  
pp. 392 ◽  
Author(s):  
Brunna Alves ◽  
Juliana Siqueira ◽  
Marianne Garrido ◽  
Ornella Botelho ◽  
Isabel Prellwitz ◽  
...  

Author(s):  
Brunna M. Alves ◽  
Juliana D. Siqueira ◽  
Marianne M. Garrido ◽  
Ornella M. Botelho ◽  
Isabel M. Prellwitz ◽  
...  

Increased access to highly active antiretroviral therapy (HAART) by HIV+ individuals has become a reality worldwide. In Brazil, ART currently reaches over half of the HIV-infected subjects. In the context of a remarkable HIV-1 genetic variability, highly related variants, called quasispecies, are generated. HIV quasispecies generated during infection can influence virus persistence and pathogenicity, representing a challenge to treatment. However, the clinical relevance of minority quasispecies is still uncertain. For this study, we have determined the archived proviral sequences, viral subtype and drug resistance mutations from a cohort of HIV+ patients with undetectable viral load undergoing HAART as first-line therapy using next-generation sequencing for near full-length virus genome (NFLG) assembly. HIV-1 consensus sequences representing NFLG were obtained for eleven patients, while for another twelve varying genome coverage rates were obtained. Phylogenetic analysis showed the predominance of subtype B (83%; 19/23). Considering the minority variants, 18 patients carried archived virus harboring at least one mutation conferring antiretroviral resistance; for six patients, the mutations correlated with the current ARVs used. These data highlight the importance of monitoring HIV minority drug resistant variants and their clinical impact, to guide future regimen switches and improve HIV treatment success.


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