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

Günthard, Huldrych F.; Cálvez, Vincent; Paredes, Roger; Pillay, Deenan; Shafer, Robert W.; Wensing, Annemarie M. J.; Jacobsen, Donna M.; Richman, Douglas D.

doi:10.1093/cid/ciy463

Cited by 170 publications

(142 citation statements)

References 106 publications

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“…86 For virologic failure of InSTI containing ART, integrase resistance testing is recommended (evidence rating AIII). 1,87–89 Once a new regimen is started, HIV RNA level should be checked 4 to 6 weeks after initiation, following the same schedule as for monitoring of initial therapy (evidence rating AIII). 1 …”

Section: Laboratory Monitoringmentioning

confidence: 99%

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

Saag

Benson

Gandhi

et al. 2018

JAMA

518

287

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IMPORTANCE Antiretroviral therapy (ART) is the cornerstone of prevention and management of HIV infection. OBJECTIVE To evaluate new data and treatments and incorporate this information into updated recommendations for initiating therapy, monitoring individuals starting therapy, changing regimens, and preventing HIV infection for individuals at risk. EVIDENCE REVIEW New evidence collected since the International Antiviral Society–USA 2016 recommendations via monthly PubMed and EMBASE literature searches up to April 2018; data presented at peer-reviewed scientific conferences. A volunteer panel of experts in HIV research and patient care considered these data and updated previous recommendations. FINDINGS ART is recommended for virtually all HIV-infected individuals, as soon as possible after HIV diagnosis. Immediate initiation (eg, rapid start), if clinically appropriate, requires adequate staffing, specialized services, and careful selection of medical therapy. An integrase strand transfer inhibitor (InSTI) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) is generally recommended for initial therapy, with unique patient circumstances (eg, concomitant diseases and conditions, potential for pregnancy, cost) guiding the treatment choice. CD4 cell count, HIV RNA level, genotype, and other laboratory tests for general health and co-infections are recommended at specified points before and during ART. If a regimen switch is indicated, treatment history, tolerability, adherence, and drug resistance history should first be assessed; 2 or 3 active drugs are recommended for a new regimen. HIV testing is recommended at least once for anyone who has ever been sexually active and more often for individuals at ongoing risk for infection. Preexposure prophylaxis with tenofovir disoproxil fumarate/emtricitabine and appropriate monitoring is recommended for individuals at risk for HIV. CONCLUSIONS AND RELEVANCE Advances in HIV prevention and treatment with antiretroviral drugs continue to improve clinical management and outcomes for individuals at risk for and living with HIV.

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Section: Laboratory Monitoringmentioning

confidence: 99%

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

Saag

Benson

Gandhi

et al. 2018

JAMA

518

287

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“…All subjects received first-line ART regimen according to Chinese guidelines for diagnosis and treatment of HIV/AIDS [26]. This included two nucleoside reverse transcriptase inhibitors (NRTIs) and a non-nucleoside reverse transcriptase inhibitor (NNRTI) that are widely used globally [27][28][29][30][31]. All participants were followed up every 3 to 6 months for evaluation of VL, CD4 + T cell counts, and other routine clinical parameters.…”

Section: Study Populationmentioning

confidence: 99%

Factors associated with high-risk low-level viremia leading to virologic failure: 16-year retrospective study of a Chinese antiretroviral therapy cohort

Zhang

Ding

et al. 2020

BMC Infect Dis

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Background: Low level viremia (LLV) often occurs during antiretroviral therapy (ART) against HIV-1. However, whether LLV increases the risk of virologic failure (VF) is controversial because of the non-uniform definitions of LLV and VF. Methods: A long-term first line regimen ART cohort from 2002 to 2018 from Shenyang, northeast China, was retrospectively studied. All participants were followed up every 3 to 6 months to evaluate the treatment effect. The high-risk LLV subgroups leading to VF (with strict standards) were explored with Cox proportional hazards model and linear mixed-effect model. The association factors of high-risk LLV were further explored using multivariate logistic regression analyses. Results: A total of 2155 HIV-1 infected participants were included; of these, 38.7% showed LLV. Both high level LLV (HLLV) and any other level LLV coupled with high level blip (HLB) showed higher risk of VF (hazards ratios, HR HLLV = 5.93, and HR HLB = 2.84, p < 0.05 respectively). Moreover, HR increased with prolonged duration of LLV. Independent factors associated with high-risk LLV included the zenith baseline viral load (VL) above 6 log copies/ml (aOR = 3.49, p = 0.002), nadir baseline CD4 + T cell counts below 200 cells/mm 3 (aOR = 1.78, p = 0.011), Manchu (aOR = 2.03, p = 0.003), ART over 60 months (aOR = 1.81, p = 0.004), AZT + 3TC + NVP (aOR = 2.26, p < 0.001) or DDI-based regimen (aOR = 9.96, p = 0.002), and subtype B′ infection (aOR = 8.22, p = 0.001). Conclusions: In case of VF with strict standards, high-risk LLV leading to VF includes VL above 400 copies/ml, occurring at least once. Serious laboratory indicators or advanced stage of infection, long term ART and subtype B′ infection might also predict the occurrence of high-risk LLV.

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“…Numerous previous studies have demonstrated NGS methods detect more resistance-associated mutations at low frequencies that Sanger is unable to detect (11-20). However, the predictive value of detectable low frequency mutations for virological failure or other clinical outcomes remains unclear (21-23).…”

Section: Introductionmentioning

confidence: 99%

Limited marginal utility of deep sequencing for HIV drug resistance testing in the age of integrase inhibitors

Dalmat

Makhsous

Pepper

et al. 2018

Preprint

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word count: 287 24 Body word count: 4,683 25 60 Instead, virological failure was entirely explained by medication non-adherence. While 61 larger studies are required, we suggest that detection of low frequency variants by NGS 62 presents limited marginal clinical utility when compared to standard of care. 63 64 129 RNA PCR kit (Perkin-Elmer, Foster City, CA) according to the manufacturer's protocol. 130 Nested PCR amplification was performed in 50ul volume reactions, consisting of 5ul 131 10X PCR buffer (with 15mM MgCl 2 ), 8 ul dNTP's (1.25mM each), 1ul each forward and 132 reverse primer (20pmol/ul), 0.5 ul Taq (2.5 units per 10μl cDNA sample for first-round 133 PCR; 2.5 units per 5μl PCR product for second round PCR), and nuclease free water. A list of 134 primers is provided in SupplementaryTable S-1. A thermal cycler protocol programmed for 135 94°C x 5 minutes for initial denaturation, followed by 35 cycles of 15 seconds at 94°C for 136 denaturation, 30 seconds at 57°C for annealing, 2 min at 72 °C for extension, and final 137 extension at 72 °C for 7 minutes. An annealing temperature of 55 °C was used for second 138 round nested PCR. 139

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

Abstract: 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.

Cited by 170 publications

References 106 publications

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

Factors associated with high-risk low-level viremia leading to virologic failure: 16-year retrospective study of a Chinese antiretroviral therapy cohort

Limited marginal utility of deep sequencing for HIV drug resistance testing in the age of integrase inhibitors

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