Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance.
Discussion: reported that 11 amino acid substitutions, V11I, V32I, L33F, I47V, I50V, I54L/M, G73S, L76V, I84V, and L89V, which appear to be associated with HIV-1 resistance against DRV, were identified among HIV-1 variants isolated from patients treated with DRV-including regimens on POWER studies.
Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128).
Abstract: Only L76V was a major mutation, and K70N/E and V179D/E are known to cause low-level resistance to RT inhibitors.
Abstract: Six transmitted drug-resistant mutations were found, including two mutations (L33F and L76V) in the protease region and four (K70N/E and V179D/E) in the RT region.
HIV-1 Transmitted Drug Resistance Mutations in Newly Diagnosed Antiretroviral-Naive Patients in Turkey.
PMID: 26414663
2016
AIDS research and human retroviruses
Abstract: Nonnucleoside reverse transcriptase inhibitor-associated TDRMs were detected in 3.3% (44/1,306) of patients (L100I, K101E/P, K103N/S, V179F, Y188H/L/M, Y181I/C, and G190A/E/S) and TDRMs to protease inhibitors were detected in 2.3% (30/1,306) of patients (M46L, I50V, I54V, Q58E, L76V, V82A/C/L/T, N83D, I84V, and L90M
Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance.
Introduction: The latest International AIDS Society (IAS)-USA panel list shows 11 mutations associated with DRV resistance: V11I, V32I, L33F, I47V, I50V, I54M/L, T74P, L76V, I84V, and L89V (Wensing et al.,).
Result: The other minor variants had I47V mutation and either of I50V or L76V mutation although the other sequences were similar to that of the major virus.
Treatment Outcomes and Resistance Patterns of Children and Adolescents on Second-Line Antiretroviral Therapy in Asia.
PMID: 27355415
2016
Journal of acquired immune deficiency syndromes (1999)
Result: Data on PI resistance mutations were available among 50 (68%) children, and included any major LPV mutation (L76V, V82A, V82S; 8%), >=6 LPV mutations (2%), any major darunavir (DRV) mutation (I84V, L76V; 2%), and any major ATV mutation (I84V, N88S; 4%) (Table 2).
Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics.
Abstract: PRS17 has none of the major mutations (I47V, I50V, I54ML, L76V and I84V) associated with darunavir resistance, but has 10,000-fold weaker binding affinity relative to the wild type
Conclusion: In contrast to other highly resistant proteases like PR20, PRS17 has none of the major mutations (I47V, I50V, I54ML, L76V and I84V) associated with DRV resistance, although it exhibits 10,000-fold weaker binding affinity for DRV relative to the wild type PR.
Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations.
Result: It is noteworthy that several major mutations associated to high level resistance to NRTIs (K65R, L74V, Y115F, M184V and T215Y), to NNRTIs (l100I, K101E, K103N/S, V106M, Y181C, Y188L and G190A) and to PIs (D30N, M46I/L, I54V/T, L76V, V82A, I84V, N88D
The use of dried blood spot specimens for HIV-1 drug resistance genotyping in young children initiating antiretroviral therapy.
PMID: 26192603
2015
Journal of virological methods
Introduction: Only one specimen was predicted to be resistant to protease inhibitors (PI) due to the presence of major and minor PI mutations (L10F, M46I, I54V, L76V and V82A) while 8 specimens had minor PI mutations (A71T (n=3), L10I/V (n=3) and M46L/T (n=2)).
The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil.
Abstract: Most common protease mutations were M46I, V82A, I54V, L90M, I84V, M46L, and L76V.
Discussion: On the other hand, in multifailed individuals, seven major PI mutations associated with resistance were documented:
Discussion: Previous PI-based treatments might have contributed to the emergence of PI major mutations M46I, V82A, L90M, I84V, M46L, and L76V, associated with resistance to APV/r.
HIV mutation literature information.
PMID: 
2018
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