scholarly journals Early Virological Failure in Naive Human Immunodeficiency Virus Patients Receiving Saquinavir (Soft Gel Capsule)-Stavudine-Zalcitabine (MIKADO Trial) Is Not Associated with Mutations Conferring Viral Resistance

2000 ◽  
Vol 38 (7) ◽  
pp. 2726-2730 ◽  
Author(s):  
M. Mouroux ◽  
A. Yvon-Groussin ◽  
G. Peytavin ◽  
C. Delaugerre ◽  
M. Legrand ◽  
...  
Keyword(s):  
Viral Load ◽  
Virological Failure ◽  
Viral Resistance ◽  
Resistance Testing ◽  
Genotypic Resistance ◽  
Phenotypic Resistance ◽  
Genotypic Resistance Testing ◽  
Immunodeficiency Virus ◽  
Group 2 ◽  
Group 1

The MIKADO trial was designed to evaluate the efficacy of stavudine-zalcitabine-saquinavir (soft gel capsule) [d4T-ddC-SQV(SGC)] in 36 naive patients (−3.3 log10units at week 24 [W24]). Among the 29 patients remaining on d4T-ddC-SQV(SGC) until W24, 10 harbored a virological failure (viral load of >200 copies/ml at W24) (group 1). To determine the reasons for therapeutic failure, genotypic and phenotypic resistance test results and SQV concentrations in plasma were analyzed and compared to those in successfully treated patients (viral load of <200 copies/ml at W24) (group 2). Reverse transcriptase and protease genotypic analyses in group 1 revealed the acquisition of only one SQV-associated mutation (L90M) in only two patients. There was no significant increase in the 50 or 90% inhibitory concentration of SQV in patients with or without the L90M mutation. However, the fact that two patients developed an L90M mutation only 4 weeks after relapse points to the need for genotypic resistance testing in the context of an initial failure of the antiretroviral regimen. At W24, the median SQV concentration in group 1 (71 ng/ml) was significantly lower than in group 2 (475 ng/ml), and the plasma SQV concentration was correlated with the viral load at W24 (r = −0.5; P < 0.05) and with the drop in viral load between day 0 and W24 (r = −0.5; P < 0.01). These results and the fact that the plasma SQV concentrations in the two groups prior to relapse (W12) were not significantly different strongly suggest that the early failure of this combination is not due to viral resistance but to a lack of compliance, pharmacological variability, and drug interactions or a combination of these factors.

scholarly journals Distribution of Human Immunodeficiency Virus Type 1 Protease and Reverse Transcriptase Mutation Patterns in 4,183 Persons Undergoing Genotypic Resistance Testing

2004 ◽  
Vol 48 (8) ◽  
pp. 3122-3126 ◽  
Author(s):  
Soo-Yon Rhee ◽  
Tommy Liu ◽  
Jaideep Ravela ◽  
Matthew J. Gonzales ◽  
Robert W. Shafer
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Resistance Testing ◽  
Resistance Mutations ◽  
Genotypic Resistance ◽  
Drug Resistance Mutations ◽  
Genotypic Resistance Testing ◽  
Immunodeficiency Virus

ABSTRACT In a sample of 6,156 sequences from 4,183 persons, the top 30 patterns of protease inhibitor, nucleoside reverse transcriptase (RT) inhibitor, and nonnucleoside RT inhibitor mutations accounted for 55, 46, and 66%, respectively, of sequences with drug resistance mutations. Characterization of the phenotypic and clinical significance of these common patterns may lead to improved treatment recommendations for a large proportion of patients for whom antiretroviral therapy is failing.

scholarly journals HIV-1 Genotypic Resistance Testing on Low Viral Load Specimens Using the Abbott ViroSeq HIV-1 Genotyping System

2008 ◽  
Vol 39 (11) ◽  
pp. 671-673 ◽  
Author(s):  
Zhen Yang ◽  
Richard Morrison ◽  
Carl Oates ◽  
Juan Sarria ◽  
Janak Patel ◽  
...  
Keyword(s):  
Viral Load ◽  
Resistance Testing ◽  
Genotypic Resistance ◽  
Genotypic Resistance Testing ◽  
Hiv 1

scholarly journals SAT0140 SAFETY OF TOFACITINIB THERAPY IN HBSAG CARRIERS WITH RHEUMATOID ARTHRITIS: A PROSPECTIVE STUDY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1008.2-1008
Author(s):  
L. Fang ◽  
Z. Lin ◽  
Z. Liao ◽  
O. Jin ◽  
Y. Pan ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Viral Load ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Infection ◽  
Hbsag Carriers ◽  
B Virus ◽  
Group 2 ◽  
A Prospective Study ◽  
Group 1

Background:Targeted synthetic DMARDs (ts-DMARDs) are becoming more available and affordable in developing countries, where the prevalence of hepatitis B virus (HBV) infection is still an important public health issue. The safety of ts-DMARDs therapy in terms of the reactivation of hepatitis B virus (HBV) infection need more concern. Rare data from a prospective study focus on the use of ts-DMARDs in patients with concurrent rheumatoid arthritis (RA) and HBV infection were available by now.Objectives:To evaluate the influence of tofacitinib on reactivation of HBV infection in HBsAg carriers with RA.Methods:In this 52 weeks observation, HBsAg carriers with active RA (DAS28>5.1) despite failed combined treatment with MTX and other non-biological DMARDs were enrolled. Patients must have normal liver function prior to study. All patients received therapy with tofacitinib (5mg twice daily) and concomitant MTX (10-12.5mg/w). Entecavir was prescribed preventively for patients who had a baseline HBV load >2000 copy/ml (group 1), and Lamivudin for patients with HBV load ≤ 2000 copy/ml (group 2). Liver enzymes (AST/ALT) and HBV viral load were monitored every 4 weeks. Increased viral load and abnormal liver function were managed according to expert opinion.Results:Thirteen patients (10 female) were recruited. Nine patients had a baseline viral load >2000 copy/ml (group 1, with preventive Entecavir), and the other 4 patients had a viral load ≤ 2000 copy/ml (group 2, with preventive Lamivudin). Two patients from group 1 discontinued tofacitinib at week 12 due to ineffectiveness, and both continued taking Entecavir for another 3 months after the discontinuation of tofacitinib.No reactivation of hepatitis B was observed in patients from group 1. One patients (female, 54 years old) from group 2 underwent a mild increase of both ALT and AST (67 and 56 IU/L, respectively) at week 16. An elevated viral load (4.9e6 copies/ml, baseline 1.4e3) and a HBV YMDD mutant was also found. The tofacitinib treatment continued. After prescription of Adefovir (combined with the pre-existing Lamivudin), both liver enzyme and viral load decreased to normal range in 8 weeks and remained normal throughout the study.Conclusion:An aggressive Tofacitinib + MTX therapy may be a safe option for HBsAg carriers with cs-DMARDs refractory RA. More active and effective prophylaxis strategy may be recommended to reduce the risk of HBV reactivation during the treatment.References:[1]Chen YM, Huang WN, Wu YD, et al. Reactivation of hepatitis B virus infection in patients with rheumatoid arthritis receiving tofacitinib: a real-world study. Ann Rheum Dis 2018; 77:780-2.Disclosure of Interests: :None declared

scholarly journals Replicative phenotyping adds value to genotypic resistance testing in heavily pre-treated HIV-infected individuals - the Swiss HIV Cohort Study

2011 ◽  
Vol 9 (1) ◽  
pp. 14 ◽  
Author(s):  
Jan Fehr ◽  
Tracy R Glass ◽  
S�verine Louvel ◽  
Fran�ois Hamy ◽  
Hans H Hirsch ◽  
...  
Keyword(s):  
Cohort Study ◽  
Resistance Testing ◽  
Genotypic Resistance ◽  
Genotypic Resistance Testing

scholarly journals Mamu-B*17+Rhesus Macaques Vaccinated withenv,vif, andnefManifest Early Control of SIVmac239 Replication

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Mauricio A. Martins ◽  
Damien C. Tully ◽  
Núria Pedreño-Lopez ◽  
Benjamin von Bredow ◽  
Matthias G. Pauthner ◽  
...  
Keyword(s):  
T Cells ◽  
Rhesus Macaques ◽  
Chronic Phase ◽  
Virologic Suppression ◽  
Mhc I ◽  
Immunodeficiency Virus ◽  
Genes Encoding ◽  
Siv Infection ◽  
Group 2 ◽  
Group 1

ABSTRACTCertain major histocompatibility complex class I (MHC-I) alleles are associated with spontaneous control of viral replication in human immunodeficiency virus (HIV)-infected people and simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs). These cases of “elite” control of HIV/SIV replication are often immune-mediated, thereby providing a framework for studying anti-lentiviral immunity. In this study, we examined how vaccination impacts SIV replication in RMs expressing the MHC-I alleleMamu-B*17. Approximately 21% ofMamu-B*17+and 50% ofMamu-B*08+RMs control chronic-phase viremia after SIVmac239 infection. Because CD8+T cells targeting Mamu-B*08-restricted SIV epitopes have been implicated in virologic suppression inMamu-B*08+RMs, we investigated whether this might also be true forMamu-B*17+RMs. Two groups ofMamu-B*17+RMs were vaccinated with genes encoding Mamu-B*17-restricted epitopes in Vif and Nef. These genes were delivered by themselves (group 1) or together withenv(group 2). Group 3 included MHC-I-matched RMs and served as the control group. Surprisingly, the group 1 vaccine regimen had little effect on viral replication compared to group 3, suggesting that unlikeMamu-B*08+RMs, preexisting SIV-specific CD8+T cells alone do not facilitate long-term virologic suppression inMamu-B*17+RMs. Remarkably, however, 5/8 group 2 vaccinees controlled viremia to <15 viral RNA copies/ml soon after infection. No serological neutralizing activity against SIVmac239 was detected in group 2, although vaccine-elicited gp140-binding antibodies correlated inversely with nadir viral loads. Collectively, these data shed new light on the unique mechanism of elite control inMamu-B*17+RMs and implicate vaccine-induced, nonneutralizing anti-Env antibodies in the containment of immunodeficiency virus infection.IMPORTANCEA better understanding of the immune correlates of protection against HIV might facilitate the development of a prophylactic vaccine. Therefore, we investigated simian immunodeficiency virus (SIV) infection outcomes in rhesus macaques expressing the major histocompatibility complex class I alleleMamu-B*17. Approximately 21% ofMamu-B*17+macaques spontaneously controlled chronic phase viremia after SIV infection, an effect that may involve CD8+T cells targeting Mamu-B*17-restricted SIV epitopes. We vaccinatedMamu-B*17+macaques with genes encoding immunodominant epitopes in Vif and Nef alone (group 1) or together withenv(group 2). Although neither vaccine regimen prevented SIV infection, 5/8 group 2 vaccinees controlled viremia to below detection limits shortly after infection. This outcome, which was not observed in group 1, was associated with vaccine-induced, nonneutralizing Env-binding antibodies. Together, these findings suggest a limited contribution of Vif- and Nef-specific CD8+T cells for virologic control inMamu-B*17+macaques and implicate anti-Env antibodies in containment of SIV infection.

scholarly journals Plasmodium falciparum Infection Does Not Affect Human Immunodeficiency Virus Viral Load in Coinfected Rwandan Adults

2014 ◽  
Vol 1 (2) ◽  
Author(s):  
Krishanthi Subramaniam ◽  
Rebeca M. Plank ◽  
Nina Lin ◽  
Adam Goldman-Yassen ◽  
Emil Ivan ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Viral Load ◽  
Malaria Infection ◽  
Hiv Transmission ◽  
Falciparum Infection ◽  
Resistance Testing ◽  
Plasmodium Falciparum Infection ◽  
Immunodeficiency Virus

Abstract Background.  Plasmodium falciparum infection has been reported to increase human immunodeficiency virus (HIV) viral load (VL), which can facilitate HIV transmission. We prospectively studied the impact of mild P falciparum coinfection on HIV VL in Rwanda. Methods.  We measured plasma HIV VL at presentation with malaria infection and weekly for 4 weeks after artemether-lumefantrine treatment in Rwandan adults infected with HIV with P falciparum malaria. Regression analyses were used to examine associations between malaria infection and HIV VL changes. Samples with detectable virus underwent genotypic drug-resistance testing. Results.  We enrolled 28 HIV-malaria coinfected patients and observed 27 of them for 5 weeks. Three patients (11%) were newly diagnosed with HIV. Acute P falciparum infection had no significant effect on HIV VL slope over 28 days of follow-up. Ten patients with VL &lt;40 copies/mL at enrollment maintained viral suppression throughout. Seventeen patients had a detectable VL at enrollment including 9 (53%) who reported 100% adherence to ARVs; 3 of these had detectable genotypic drug resistance. Conclusions.  Unlike studies from highly malaria-endemic areas, we did not identify an effect of P falciparum infection on HIV VL; therefore, malaria is not likely to increase HIV-transmission risk in our setting. However, routine HIV testing should be offered to adults presenting with acute malaria in Rwanda. Most importantly, we identified a large percentage of patients with detectable HIV VL despite antiretroviral (ARV) therapy. Some of these patients had HIV genotypic drug resistance. Larger studies are needed to define the prevalence and factors associated with detectable HIV VL in patients prescribed ARVs in Rwanda.

scholarly journals Virtual Inhibitory Quotient Predicts Response to Ritonavir Boosting of Indinavir-Based Therapy in Human Immunodeficiency Virus-Infected Patients with Ongoing Viremia

2002 ◽  
Vol 46 (12) ◽  
pp. 3907-3916 ◽  
Author(s):  
Nancy Shulman ◽  
Andrew Zolopa ◽  
Diane Havlir ◽  
Ann Hsu ◽  
Cheryl Renz ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
Combination Therapy ◽  
Drug Exposure ◽  
Virologic Response ◽  
Virologic Suppression ◽  
Time Curve ◽  
Minimum Concentration ◽  
Phenotypic Resistance ◽  
Immunodeficiency Virus

ABSTRACT Depending on the degree of underlying resistance present, optimization of the pharmacokinetics of protease inhibitors may result in improved virologic suppression. Thirty-seven human immunodeficiency virus (HIV)-infected subjects who had chronic detectable viremia and who were receiving 800 mg of indinavir three times a day (TID) were switched to 400 mg of indinavir BID with 400 mg of ritonavir two times a day (BID) for 48 weeks. Full pharmacokinetic evaluations were obtained for 12 subjects before the switch and 3 weeks after the switch. Combination therapy increased the indinavir predose concentrations in plasma by 6.47-fold, increased the minimum concentration in serum by 3.41-fold, and reduced the maximum concentration in serum by 57% without significantly changing the area under the plasma concentration-time curve at 24 h. At week 3, 58% (21 of 36) of the subjects for whom postbaseline measurements were available achieved a viral load in plasma of <50 copies/ml or a reduction from the baseline load of ≥0.5 log10 copies/ml. Of these subjects, 82% (14 of 17) whose viruses had three or fewer protease inhibitor mutations and 88% (14 of 16) whose viruses had an indinavir virtual phenotypic susceptibility test of more than sixfold less than that for the baseline isolate were considered virologic responders. The indinavir virtual inhibitory quotient, which is a function of baseline indinavir phenotypic resistance (estimated by virtual phenotype) and the indinavir predose concentration in plasma achieved with indinavir-ritonavir combination therapy, was the best predictor of a viral load reduction. Sixteen subjects discontinued the study by week 48 due to adverse events, predominantly related to hyperlipidemia. Pharmacokinetic intensification of indinavir-based therapy with ritonavir reduced the viral loads in subjects but added toxicity. The virtual inhibitory quotient, which incorporates both baseline viral resistance and the level of drug exposure in plasma, was superior to either baseline resistance or drug exposure alone in predicting the virologic response.

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