literature

HIV mutation literature information.

Switching efavirenz to rilpivirine in virologically suppressed adolescents with HIV: a multi-centre 48-week efficacy and safety study in Thailand.

PMID: 35001501 2022 Journal of the International AIDS Society

Method: We excluded individuals with prior evidence of NNRTI-associated resistance mutations based on the IAS-USA HIV drug-resistance mutations list (2019) (V90I, A98G, L100I, K101E/H/P/Q/R/N, K103N/S, V106A/M/I, V108I, E138K/A/G/Q/R, V179D/F/L/T, Y181C/I/V, Y188L/C/H, G190A/S/E,H221Y, P225H, F227L/C/R,

Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study.

PMID: 34694877 2022 Antimicrobial agents and chemotherapy

Table: E138A/K

Table: E138K

Figure: a, K160T was observed in 4 of 13 clones containing G118R, E138K, and R263K integrase substitutions but is not a prespecified dolutegravir resistance-associated substitution.

Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study.

PMID: 34694878 2022 Antimicrobial agents and chemotherapy

Abstract: G118R reduced dolutegravir susceptibility and integrase replication capacity more than R263K and demonstrated greater reduction in susceptibility and integrase replication capacity when present with specific secondary integrase substitutions, including L74M, T66I, and E138E/K.

Result: Additional integrase

Discussion: Treatment-emergent G118R in combination with either L74M or T66I was associated with reduced dolutegravir susceptibility compared with G118R alone or with E138E/K.

Phase 2 Open-Label Study of Long-Term Safety, Tolerability, and Antiviral Activity of Rilpivirine in Antiretroviral-Naive Adolescents Living with HIV-1.

PMID: 34871089 2022 Antimicrobial agents and chemotherapy

Method: Patients with previously documented HIV-2 infection, with active AIDS, and with documented genotypic evidence of >=1 NNRTI resistance-associated mutation (RAM) from a predefined list of the following NNR

Result: The most frequent treatment-emergent RPV RAM at the last post-baseline time point was E138K (5/15 patients [33.3%]).

Result: Three patients had both treatment-emergent RPV RAM E138K and NRTI RAM M184V at the last post-baseline time point with genotypic data.

Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials.

PMID: 34897227 2022 Journal of acquired immune deficiency syndromes (1999)

Table: E138K/A

Discussion: In the 3 real-world cases, other INSTI-R substitutions were also noted, including L74I, E138K, S147G, and H51Y, along with M184V in RT.

Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine.

PMID: 34978890 2022 Antimicrobial agents and chemotherapy

Result: However, when E138K was introduced into either clone, EC50 values against rilpivirine were above the biological cutoff, with fold change values of 2.38 and 2.21 for the viruses with PR/RT genes from NL4-3 and 92UG307, respectively.

Result: Therefore, the known E138K and K101E mutations conferred EC50 fold change values consistent with in vitro resistance to rilpivirine equally across clones containing PR/RT genes from HIV-1 subtypes B and A1 (https://hivdb.stanford.edu/dr-summary/resistance-notes/NNRTI/).

Discussion: As the presence of E138K alone has been associated with decreased susceptibility to rilpivirine, the discrepancy observed between observations

Management of a human immunodeficiency virus case with discordant antiviral drug resistance profiles in cerebrospinal fluid compared with plasma: a case report.

PMID: 35164871 2022 Journal of medical case reports

Conclusion: The HIV-1 pol gene genotypic resistance analysis showed development of the NRTI M184V mutation, and NNRTI K103N and E138EK mutations in plasma, respectively.

Conclusion: The nonpolymorphic NNRTI K103N mutation causes high-level resistance to efavirenz (EFV), and E138K mutation causes potential low-level cross-resistance to EFV, which was discontinued together with 3TC.

High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort.

PMID: 35215866 2022 Viruses

Res

Result: For example, E138K, a well-known escape mutation, was first identified in participant ML874 (A*68:02+) in the blood sample collected in 1996, and this DRM was also detected in the samples collected in 2003 from the same participant.

Result: The HLA-DRM associations involving HLA alleles at >10% frequency in Kenya are A*68:02 with DRMs G190ES (p = 0.008), IN E138K (p = 0.042), C*17:01 with DRMs M46I (p = 0.018), and IN E138K (p = 0.021).

Could Long-Acting Cabotegravir-Rilpivirine Be the Future for All People Living with HIV? Response Based on Genotype Resistance Test from a Multicenter Italian Cohort.

PMID: 35207677 2022 Journal of personalized medicine

Method: Furthermore, we excluded people with the following mutations for NNRTI: L100I, K101E/H/NP/Q, E138A/G/K/Q/R, V179L, Y181C/F/G/I/S/V, Y188L, G190A/C/E/Q/S/T/V, H221Y, F227C/L, and M230L.

Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia.

PMID: 35458459 2022 Viruses

Result: In this study,19 substitutions conferring major resistance to DTG at 10 amino acid positions in the IN (T66A/I/K, E92G, G118R, E138K/A/T, G140S/A/C, Y143R/C/H, S147G, Q148H/R/K, N155H, and R263K) were assessed to explore the genetic barrier to DTG.

Result: No major DRMs known to be associated with DTG resistance (T66K, E92Q, G118R, E138K/A/T, G140S/A/C<

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