scholarly journals 2509. Pooled Resistance Analyses of Darunavir (DRV) Once Daily (QD) Regimens and Formulations Across 10 Clinical Studies of Treatment-Naïve (TN) and Treatment-Experienced (TE) Patients with Human Immunodeficiency Virus (HIV)-1 Infection

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S870-S871 ◽  
Author(s):  
Erkki Lathouwers ◽  
Sareh Seyedkazemi ◽  
Donghan Luo ◽  
Kimberley Brown ◽  
Sandra De Meyer ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Virologic Failure ◽  
Transcriptase Inhibitor ◽  
Resistance Testing ◽  
Resistance Development ◽  
Single Tablet Regimen ◽  
Treatment Naïve ◽  
Tenofovir Alafenamide ◽  
Hiv 1 ◽  
Phenotypic Susceptibility

Abstract Background DRV has demonstrated high efficacy and barrier to resistance development across diverse populations, from TN to heavily TE patients. We evaluated resistance data from 10 clinical studies of different DRV 800 mg QD–based antiretroviral regimens and formulations. Methods The analysis included patients from 10 phase 2/3 studies (48–192 weeks in duration) of ritonavir- and cobicistat-boosted DRV 800 mg QD–based regimens in TN and virologically failing or suppressed TE patients with HIV-1 (table). Three were phase 3 studies of the DRV/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg single-tablet regimen (STR). Post-baseline resistance was evaluated in patients experiencing protocol-defined virologic failure (PDVF); definitions and criteria for resistance testing varied slightly among studies. Resistance-associated mutations (RAMs) were based on respective International Antiviral Society–USA mutation lists over time. Results Of the 3,635 patients evaluated, 250 met PDVF criteria and 205 had post-baseline genotypes/phenotypes. Overall, 4 (0.1%) patients developed (or had identified [switch studies]) ≥1 DRV and/or primary protease inhibitor (PI) RAM (table), and only 1 (< 0.1%, ODIN) patient lost DRV phenotypic susceptibility; this TE patient had prior VF with lopinavir. Among those who used a nucleos(t)ide reverse transcriptase inhibitor (NRTI) backbone (mostly emtricitabine [FTC] + tenofovir [TFV]), 12 (0.4%) patients had ≥1 NRTI RAM, including 10 with M184I/V associated with FTC resistance. No TFV RAMs were observed. Among patients receiving D/C/F/TAF (n = 1,949), none had post-baseline DRV, primary PI, or TFV RAMs; only 2 (0.1%) patients developed an FTC RAM. Conclusion Across a large, diverse population using DRV 800 mg QD–based regimens and formulations, resistance development remains rare; 0.1% of patients had ≥1 DRV and/or primary PI RAM post-baseline. Among 3 trials of the D/C/F/TAF STR, no patients developed a DRV or primary PI RAM. After > 10 years of investigating DRV 800 mg QD–based regimens in clinical trials, loss of phenotypic susceptibility to DRV has never been observed in TN or TE virologically suppressed patients and was only once observed in a TE patient with prior VF on multiple antiretrovirals, including a PI. Disclosures All authors: No reported disclosures.

scholarly journals Discordance between Etravirine Phenotype and Genotype-Based Predicted Phenotype for Subtype C HIV-1 from First-Line Antiretroviral Therapy Failures in South Africa

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Kevin D. McCormick ◽  
Kerri J. Penrose ◽  
Chanson J. Brumme ◽  
P. Richard Harrigan ◽  
Raquel V. Viana ◽  
...  
Keyword(s):  
Virologic Failure ◽  
Transcriptase Inhibitor ◽  
Subtype C ◽  
Genotypic Resistance ◽  
Low Level ◽  
Nnrti Resistance ◽  
Subtype B ◽  
Treatment Naïve ◽  
Hiv 1 ◽  
Interpretation Systems

ABSTRACT Etravirine (ETR) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) used in treatment-experienced individuals. Genotypic resistance test-interpretation systems can predict ETR resistance; however, genotype-based algorithms are derived primarily from HIV-1 subtype B and may not accurately predict resistance in non-B subtypes. The frequency of ETR resistance among recombinant subtype C HIV-1 and the accuracy of genotypic interpretation systems were investigated. HIV-1LAI containing full-length RT from HIV-1 subtype C-positive individuals experiencing virologic failure (>10,000 copies/ml and >1 NNRTI resistance-associated mutation) were phenotyped for ETR susceptibility. Fold change (FC) was calculated against a composite 50% effective concentration (EC50) from treatment-naive individuals and three classifications were assigned: (i) <2.9-FC, susceptible; (ii) ≥2.9- to 10-FC, partially resistant; and (iii) >10-FC, fully resistant. The Stanford HIVdb-v8.4 was used for genotype predictions merging the susceptible/potential low-level and low-level/intermediate groups for 3 × 3 comparison. Fifty-four of a hundred samples had reduced ETR susceptibility (≥2.9-FC). The FC correlated with HIVdb-v8.4 (Spearman’s rho = 0.62; P < 0.0001); however, 44% of samples were partially (1 resistance classification difference) and 4% completely discordant (2 resistance classification differences). Of the 34 samples with an FC of >10, 26 were HIVdb-v8.4 classified as low-intermediate resistant. Mutations L100I, Y181C, or M230L were present in 27/34 (79%) of samples with an FC of >10 but only in 2/46 (4%) of samples with an FC of <2.9. No other mutations were associated with ETR resistance. Viruses containing the mutation K65R were associated with reduced ETR susceptibility, but 65R reversions did not increase ETR susceptibility. Therefore, genotypic interpretation systems were found to misclassify ETR susceptibility in HIV-1 subtype C samples. Modifications to genotypic algorithms are needed to improve the prediction of ETR resistance for the HIV-1 subtype C.

scholarly journals Management of HIV-2 resistance to antiretroviral therapy in a HIV-1/HIV-2/HBV co-infected patient

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Margarida Cardoso ◽  
Joana Vasconcelos ◽  
Teresa Baptista ◽  
Isabel Diogo ◽  
Fátima Gonçalves ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Virologic Failure ◽  
Standard Of Care ◽  
Resistance Testing ◽  
Current Standard ◽  
Viral Loads ◽  
B Virus ◽  
Tenofovir Alafenamide ◽  
Viral Load Determination ◽  
Hiv 1

Abstract Background The current standard of care is to start antiretroviral therapy in all patients diagnosed with HIV-1, as for HIV-2 current DHHS guideline suggests ART for HIV-2 as soon as diagnosis is established, although this practice is not universal, for instance, in Portugal there are specific criteria to start treatment. Case presentation We present a case of a man, chronically infected with HIV-1, HIV-2 and hepatitis B virus who developed resistance to HIV-2 while maintaining HIV-1 under control. 6 years after starting antiretroviral therapy he had his first virologic failure. We performed HIV-2 resistance tests that revealed high-grade resistance to all nucleoside reverse-transcriptase inhibitors except tenofovir and to all protease inhibitors except darunavir. After a decade of permanent poor adherence to therapy he developed resistance to both tenofovir and darunavir. We put together a new regiment with tenofovir alafenamide + emtricitabine + dolutegravir + maraviroc and nowadays he is with undetectable HIV-1 and HIV-2 viral loads. Conclusions This shows the importance of having access to HIV-2 viral load determination and HIV-2 resistance testing.

scholarly journals No Emergent Resistance in HIV-1 Infected Virologically-Suppressed Subjects Who Switched to R/F/TAF

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S427-S427
Author(s):  
Danielle Porter ◽  
Rima Kulkarni ◽  
Huyen Cao ◽  
Devi Sengupta ◽  
Kirsten White
Keyword(s):  
Dna Analysis ◽  
Virologic Failure ◽  
Success Rates ◽  
Resistance Mutations ◽  
Double Blind ◽  
Resistance Development ◽  
Safety And Efficacy ◽  
Proviral Dna ◽  
Tenofovir Alafenamide ◽  
Hiv 1

Abstract Background GS-US-366-1216 and GS-US-366-1160 are randomized, double-blind, phase 3b studies evaluating the safety and efficacy of switching to rilpivirine/emtricitabine/tenofovir alafenamide (R/F/TAF) from R/F/tenofovir disoproxil fumarate (TDF) or efavirenz (EFV)/F/TDF, respectively, in HIV-1-infected virologically-suppressed subjects. At Week 48, switching to R/F/TAF was non-inferior to staying on R/F/TDF (94% vs. 94%, respectively) or EFV/F/TDF (90% vs. 92%) for HIV-1 RNA &lt;50 c/mL (virologic success) by FDA snapshot analysis. Here, we present integrated resistance analyses of these two studies through Week 48. Methods Historical genotypes were collected when available. Subjects in the resistance analysis population (subjects with HIV-1 RNA ≥400 c/mL at virologic failure, discontinuation, or Week 48) had genotypic/phenotypic analyses at failure for protease and reverse transcriptase (RT; PhenoSense GT, Monogram). Subjects with post-baseline resistance mutations detected had their baseline proviral DNA analyzed retrospectively (GenoSure Archive, Monogram). Results Of the 1504 randomized and treated subjects, resistance development was analyzed for 7 subjects (0.9%; 7/754) on R/F/TAF, 1 subject (0.3%; 1/313) on R/F/TDF, and 2 subjects (0.5%; 2/437) on EFV/F/TDF. No R/F/TAF (0%) or R/F/TDF (0%) subjects developed primary NNRTI or NRTI resistance mutations. One EFV/F/TDF subject (0.2%; 1/437) developed primary NNRTI and NRTI resistance mutations (NNRTI: Y188L; NRTI: M184V). Three subjects on R/F/TAF had virologic rebound with mutations also detected at baseline by proviral DNA analysis. Historical genotypes were available for 527 subjects; virologic success rates were high among subjects with pre-existing mutations (Table 1). Conclusion No emergent resistance to any of the components of R/F/TAF was detected through 48 weeks after switching. Virologic success rates were high among subjects with pre-existing mutations. Disclosures D. Porter, Gilead Sciences, Inc.: Employee and Shareholder, Salary; R. Kulkarni, Gilead Sciences, Inc.: Employee and Shareholder, Salary; H. Cao, Gilead Sciences, Inc.: Employee and Shareholder, Salary; D. Sengupta, Gilead Sciences Inc.: Employee and Shareholder, Salary; K. White, Gilead Sciences, Inc.: Employee and Shareholder, Salary

scholarly journals Switching to Bictegravir, Emtricitabine, and Tenofovir Alafenamide in Virologically Suppressed Adults With Human Immunodeficiency Virus

2020 ◽  
Author(s):  
Paul E Sax ◽  
Jürgen K Rockstroh ◽  
Anne F Luetkemeyer ◽  
Yazdan Yazdanpanah ◽  
Douglas Ward ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Weight Change ◽  
Transcriptase Inhibitor ◽  
Recommended Treatment ◽  
Single Tablet Regimen ◽  
Immunodeficiency Virus ◽  
Effective Option ◽  
Tenofovir Alafenamide ◽  
Double Blinded ◽  
Hiv 1

Abstract Background Bictegravir (B)/emtricitabine (F)/tenofovir alafenamide (TAF) is guideline-recommended treatment for human immunodeficiency virus type 1 (HIV-1). We evaluated whether people receiving dolutegravir (DTG) plus F/TAF or F/TDF (tenofovir disoproxil fumarate) with viral suppression can switch to B/F/TAF without compromising safety or efficacy, regardless of preexisting nucleoside reverse transcriptase inhibitor (NRTI) resistance. Methods In this multicenter, randomized, double-blinded, active-controlled, noninferiority trial, we enrolled adults who were virologically suppressed for ≥6 months before screening (with documented/suspected NRTI resistance) or ≥3 months before screening (with no documented/suspected NRTI resistance) on DTG plus either F/TDF or F/TAF. We randomly assigned (1:1) participants to switch to B/F/TAF or DTG + F/TAF once daily for 48 weeks, each with matching placebo. The primary endpoint was proportion of participants with plasma HIV-1 RNA ≥50 copies/mL at week 48 (snapshot algorithm); the prespecified noninferiority margin was 4%. Results Five hundred sixty-seven adults were randomized; 565 were treated (284 B/F/TAF, 281 DTG + F/TAF). At week 48, B/F/TAF was noninferior to DTG + F/TAF, as 0.4% (1/284) vs 1.1% (3/281) had HIV-1 RNA ≥50 copies/mL (difference, −0.7% [95.001% confidence interval {CI}, −2.8% to 1.0%]). There were no significant differences in efficacy among participants with suspected or confirmed prior NRTI resistance (n = 138). No participant had treatment-emergent drug resistance. Median weight change from baseline at week 48 was +1.3 kg (B/F/TAF) vs +1.1 kg (DTG + F/TAF) (P = .46). Weight change differed by baseline NRTIs (+2.2 kg [F/TDF] and +0.6 kg [F/TAF], P &lt; .001), with no differences between B/F/TAF and DTG + F/TAF. Conclusions The single-tablet regimen B/F/TAF is a safe, effective option for people virologically suppressed on DTG plus either F/TDF or F/TAF, including in individuals with preexisting resistance to NRTIs. Clinical Trials Registration NCT03110380.

scholarly journals 1448. Forgiveness of BIC/FTC/TAF: In Vitro Simulations of Intermittent Poor Adherence Find Limited HIV-1 Breakthrough and High Barrier to Resistance

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S726-S727
Author(s):  
Andrew Mulato ◽  
Rima K Acosta ◽  
Stephen R Yant ◽  
Tomas Cihlar ◽  
Kirsten L White
Keyword(s):  
Virologic Failure ◽  
Resistance Development ◽  
Drug Concentrations ◽  
Suboptimal Adherence ◽  
Trough Concentrations ◽  
Tenofovir Alafenamide ◽  
Emergence Of Resistance ◽  
Perfect Adherence ◽  
Hiv 1

Abstract Background Short lapses in adherence to ARVs can lead to virologic failure and emergence of resistance. Previous in vitro studies of regimen “forgiveness” simulated drug exposures of perfect adherence or short-term suboptimal adherence with bictegravir+emtricitabine+tenofovir alafenamide (BIC+FTC+TAF) and with dolutegravir and lamivudine (DTG+3TC). Here, viral breakthrough (VB) and resistance development were evaluated under alternating high and low drug exposures simulating variable adherence levels. Methods Wild-type HIV-1 (IIIb)-infected MT-2 cells were exposed to drug combinations and monitored for VB. Experiments alternated between high and low drug concentrations of either BIC+FTC+TAF or DTG+3TC (Table 1). Drug concentrations for each regimen were determined using human plasma-free adjusted clinical trough concentrations (Cmin), at simulated Cmin after missing 2 or 4 consecutive doses (Cmin-2 and Cmin-4) based on drug half-lives. Emergent HIV-1 were genotyped by deep sequencing and a 2% threshold. Results In these experiments, constant drug concentrations corresponding to full adherence (Cmin) did not lead to VB. Using Cmin concentrations for one week followed by constant Cmin-2 exposures for 4 weeks, DTG+3TC had VB and emergence of M184V/I in reverse transcriptase (RT) but there was no VB for BIC+FTC+TAF. Using alternating drug exposures of Cmin (weeks 1 and 3) and Cmin-2 or Cmin -4 (weeks 2, 4, and 5), VB was not observed with BIC+FTC+TAF, and VB was decreased or delayed with DTG+3TC compared to DTG+3TC held at Cmin-2 or Cmin-4. Resistance development was observed in some cultures with VB: 1 culture with BIC+FTC+TAF had G163R in IN and 19 cultures with DTG+3TC had INSTI and RT resistance including 10 with M184V/I. Table 1. Summary of Breakthrough Frequency and Resistance Development Conclusion BIC+FTC+TAF has high in vitro forgiveness and consistent protection against emergence of drug resistance during simulations of short lapses in adherence. Higher DTG+3TC exposure, whether constant or intermittent, was better at preventing or delaying VB than lower DTG+3TC exposures, but DTG+3TC was less forgiving than BIC+FTC+TAF. Prevention of viral replication and resistance development is necessary to maintain lifelong viral suppression, particularly in the real world where drug adherence is often imperfect. Disclosures Andrew Mulato, BS, MBA, Gilead Sciences, Inc. (Employee, Shareholder) Rima K. Acosta, BS, Gilead Sciences, Inc. (Employee, Shareholder) Stephen R. Yant, PhD, Gilead Sciences, Inc. (Employee, Shareholder) Tomas Cihlar, PhD, Gilead Sciences, Inc. (Employee, Shareholder) Kirsten L. White, PhD, Gilead Sciences, Inc. (Employee, Shareholder)

scholarly journals Resistance Analysis of Bictegravir-Emtricitabine-Tenofovir Alafenamide in HIV-1 Treatment-Naive Patients through 48 Weeks

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Rima K. Acosta ◽  
Madeleine Willkom ◽  
Ross Martin ◽  
Silvia Chang ◽  
Xuelian Wei ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Transcriptase Inhibitor ◽  
Virologic Suppression ◽  
Strand Transfer ◽  
Primary Drug Resistance ◽  
Treatment Naïve ◽  
Tenofovir Alafenamide ◽  
Inhibitor Resistance ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1

ABSTRACT In clinical studies GS-US-380-1489 (study 1489) and GS-US-380-1490 (study 1490), bictegravir-emtricitabine-tenofovir alafenamide (B-F-TAF), dolutegravir-abacavir-lamivudine (DTG-ABC-3TC), and dolutegravir plus emtricitabine-tenofovir alafenamide (DTG+F-TAF) treatment achieved high rates of virologic suppression in HIV-1 treatment-naive participants through week 48. Preexisting primary drug resistance was present at levels of 1.3% integrase strand transfer inhibitor resistance (INSTI-R), 2.7% nucleoside reverse transcriptase inhibitor resistance (NRTI-R), 14.1% nonnucleoside reverse transcriptase inhibitor resistance (NNRTI-R), and 3.5% protease inhibitor resistance (PI-R) in the 1,274 participants from these studies. These mutations did not affect treatment outcomes. Resistance analyses in 13 virologic failures found no emergent resistance to study drugs.

Three-year study of pre-existing drug resistance substitutions and efficacy of bictegravir/emtricitabine/tenofovir alafenamide in HIV-1 treatment-naive participants

2021 ◽  
Author(s):  
Rima K Acosta ◽  
Grace Q Chen ◽  
Silvia Chang ◽  
Ross Martin ◽  
Xinxin Wang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Treatment Outcomes ◽  
Study Drug ◽  
Resistance Testing ◽  
Strand Transfer ◽  
Double Blind ◽  
Primary Drug Resistance ◽  
Treatment Naïve ◽  
Tenofovir Alafenamide ◽  
Hiv 1

Abstract Objectives Two Phase 3, randomized, double-blind, active-controlled studies of initial HIV-1 treatment demonstrated that bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) was non-inferior to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC; Study 1489) or to DTG+F/TAF (Study 1490) through 144 weeks. In both studies, there was no emergent resistance to study drugs. Here, the 3 year resistance analysis and impact of baseline resistance substitutions on treatment response are described. Methods Population sequencing of HIV-1 protease and reverse transcriptase (RT) was performed at screening. Retrospective baseline next generation sequencing of protease, RT and integrase (IN) was analysed at a ≥15% cutoff. Resistance analyses were performed on participants with confirmed viral rebound of HIV-1 RNA ≥200 copies/mL through Week 144 or last visit who did not resuppress to &lt;50 copies/mL while on study drug. Results Transmitted primary drug resistance substitutions were present in the following proportions of participants: integrase strand transfer inhibitor (INSTI) resistance (-R) in 1.3% (17/1270) of participants; NRTI-R in 2.7% (35/1274); NNRTI-R in 14.1% (179/1274); and PI-R in 3.5% (44/1274). These pre-existing resistance substitutions not associated with study drug did not affect treatment outcomes. One participant in the B/F/TAF group had pre-existing bictegravir and dolutegravir resistance substitutions (Q148H+G140S in integrase) at baseline and suppressed and maintained HIV-1 RNA &lt;50 copies/mL through Week 144. In total, 21 participants qualified for resistance testing [1.3% (8/634) B/F/TAF; 1.9% (6/315) DTG/ABC/3TC; 2.2% (7/325) DTG+F/TAF]; none had emergent resistance to study drugs. Conclusions Treatment with B/F/TAF, DTG/ABC/3TC, or DTG+F/TAF achieved high, durable rates of virological suppression in HIV-1 treatment-naive participants. The presence of pre-existing resistance substitutions did not affect treatment outcomes, and there was no treatment-emergent resistance.

Diversity of HIV-1 subtypes and transmitted drug-resistance mutations among minority HIV-1 variants in a Turkish cohort

2021 ◽  
Vol 19 ◽  
Author(s):  
Rabia Can Sarinoglu ◽  
Uluhan Sili ◽  
Ufuk Hasdemir ◽  
Burak Aksu ◽  
Guner Soyletir ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Transcriptase Inhibitor ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Treatment Naïve ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1

Background: The World Health Organization (WHO) recommends the surveillance of transmitted drug resistance mutations (TDRMs) to ensure the effectiveness and sustainability of HIV treatment programs. Objective: Our aim was to determine the TDRMs and evaluate the distribution of HIV-1 subtypes using and compared next-generation sequencing (NGS) and Sanger-based sequencing (SBS) in a cohort of 44 antiretroviral treatment-naïve patients. Methods: All samples that were referred to the microbiology laboratory for HIV drug resistance analysis between December 2016 and February 2018 were included in the study. After exclusions, 44 treatment-naive adult patients with a viral load of >1000 copies/mL were analyzed. DNA sequencing for reverse transcriptase and protease regions was performed using both DeepChek ABL single round kit and Sanger-based ViroSeq HIV-1 Genotyping System. The mutations and HIV-1 subtypes were analyzed using the Stanford HIVdb version 8.6.1 Genotypic Resistance software, and TDRMs were assessed using the WHO surveillance drug-resistance mutation database. HIV-1 subtypes were confirmed by constructing a maximum-likelihood phylogenetic tree using Los Alamos IQ-Tree software. Results: NGS identified nucleos(t)ide reverse transcriptase inhibitor (NRTI)-TDRMs in 9.1% of the patients, non-nucleos(t)ide reverse transcriptase inhibitor (NNRTI)-TDRMs in 6.8% of the patients, and protease inhibitor (PI)-TDRMs in 18.2% of the patients at a detection threshold of ≥1%. Using SBS, 2.3% and 6.8% of the patients were found to have NRTI- and NNRTI-TDRMs, respectively, but no major PI mutations were detected. M41L, L74I, K65R, M184V, and M184I related to NRTI, K103N to NNRTI, and N83D, M46I, I84V, V82A, L24I, L90M, I54V to the PI sites were identified using NGS. Most mutations were found in low-abundance (frequency range: 1.0% - 4.7%) HIV-1 variants, except M41L and K103N. The subtypes of the isolates were found as follows; 61.4% subtype B, 18.2% subtype B/CRF02_AG recombinant, 13.6% subtype A, 4.5% CRF43_02G, and 2.3% CRF02_AG. All TDRMs, except K65R, were detected in HIV-1 subtype B isolates.. Conclusion: The high diversity of protease site TDRMs in the minority HIV-1 variants and prevalence of CRFs were remarkable in this study. All minority HIV-1 variants were missed by conventional sequencing. TDRM prevalence among minority variants appears to be decreasing over time at our center.

scholarly journals Week 96 results of a phase 3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients

AIDS ◽  
2020 ◽  
Vol 34 (5) ◽  
pp. 707-718 ◽  
Author(s):  
Chloe Orkin ◽  
Joseph J. Eron ◽  
Jürgen Rockstroh ◽  
Daniel Podzamczer ◽  
Stefan Esser ◽  
...  
Keyword(s):  
Phase 3 ◽  
Treatment Naïve ◽  
Tenofovir Alafenamide ◽  
Hiv 1

scholarly journals Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Maja Oroz ◽  
Josip Begovac ◽  
Ana Planinić ◽  
Filip Rokić ◽  
Maja M. Lunar ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Single Case ◽  
Clinical Care ◽  
Resistance Testing ◽  
Transmitted Drug Resistance ◽  
Strand Transfer ◽  
Primary Drug Resistance ◽  
Treatment Naïve ◽  
Pre Treatment ◽  
Hiv 1

AbstractMolecular epidemiology of HIV-1 infection in treatment-naive HIV-1 infected persons from Croatia was investigated. We included 403 persons, representing 92.4% of all HIV-positive individuals entering clinical care in Croatia in 2014–2017. Overall prevalence of transmitted drug resistance (TDR) was estimated at 16.4%. Resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside RTI (NNRTIs) and protease inhibitors (PIs) was found in 11.4%, 6.7% and 2.5% of persons, respectively. Triple-class resistance was determined in 2.2% of individuals. In addition, a single case (1.0%) of resistance to integrase strand-transfer inhibitors (InSTIs) was found. Deep sequencing was performed on 48 randomly selected samples and detected additional TDR mutations in 6 cases. Phylogenetic inference showed that 347/403 sequences (86.1%) were part of transmission clusters and identified forward transmission of resistance in Croatia, even that of triple-class resistance. The largest TDR cluster of 53 persons with T215S was estimated to originate in the year 1992. Our data show a continuing need for pre-treatment HIV resistance testing in Croatia. Even though a low prevalence of resistance to InSTI was observed, surveillance of TDR to InSTI should be continued.

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