Effect of human immunodeficiency virus type 1 protease inhibitor therapy and subtype on development of resistance in subtypes B and G

Palma, Ana Carolina; Abecasis, Ana; Vercauteren, Jürgen; Carvalho, Ana Patrícia; Cabanas, Joaquim; Vandamme, Anne‐Mieke; Camacho, Ricardo Jorge

doi:10.1016/j.meegid.2009.06.019

Cited by 9 publications

(8 citation statements)

References 21 publications

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“…_Consistently, previous studies in Brazil highlight that prevalence of subtype B is around 70-80% through the country followed by subtypes F1, C and recombinants BF1 [24][25][26][27]. Interestingly, we found 9% of Brazilian migrants infected with HIV-1 subtype G. Given the high prevalence of this subtype in Portugal [28] and its rarity in Brazil, this could indicate infections potentially acquired in Portugal, after migration. We are further performing phylogenetic studies to describe transmission networks and get robust information concerning the place of acquisition of infection among migrants.…”

Section: Discussionsupporting

confidence: 90%

Molecular Epidemiology of HIV-1 Infected Migrants Followed Up in Portugal: Trends between 2001–2017

Pimentel

Pingarilho

Alves

et al. 2020

Viruses

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Migration is associated with HIV-1 vulnerability. Objectives: To identify long-term trends in HIV-1 molecular epidemiology and antiretroviral drug resistance (ARV) among migrants followed up in Portugal Methods: 5177 patients were included between 2001 and 2017. Rega, Scuel, Comet, and jPHMM algorithms were used for subtyping. Transmitted drug resistance (TDR) and Acquired drug resistance (ADR) were defined as the presence of surveillance drug resistance mutations (SDRMs) and as mutations of the IAS-USA 2015 algorithm, respectively. Statistical analyses were performed. Results: HIV-1 subtypes infecting migrants were consistent with the ones prevailing in their countries of origin. Over time, overall TDR significantly increased and specifically for Non-nucleoside reverse transcriptase inhibitor (NNRTIs) and Nucleoside reverse transcriptase inhibitor (NRTIs). TDR was higher in patients from Mozambique. Country of origin Mozambique and subtype B were independently associated with TDR. Overall, ADR significantly decreased over time and specifically for NRTIs and Protease Inhibitors (PIs). Age, subtype B, and viral load were independently associated with ADR. Conclusions: HIV-1 molecular epidemiology in migrants suggests high levels of connectivity with their country of origin. The increasing levels of TDR in migrants could indicate an increase also in their countries of origin, where more efficient surveillance should occur.

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Section: Discussionsupporting

confidence: 90%

Molecular Epidemiology of HIV-1 Infected Migrants Followed Up in Portugal: Trends between 2001–2017

Pimentel

Pingarilho

Alves

et al. 2020

Viruses

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“…50 In contrast, a study by Palma et al in 2009 found that genetic background played a role in different treatment-associated mutations that developed in subtypes B and G in Portuguese patients. 51 In a study of patients from Rio Grande do Sul, Brazil, in a population infected by subtypes B and C, a lower rate of accumulation of mutations was found in subtype C than subtype B. 52 However, certain NRTI mutations such as K65R have been shown to develop more quickly in subtype C than in other subtypes.…”

Section: Hiv-1 Subtype On Drug Resistance Mutations In Nigeriamentioning

confidence: 99%

“…50,54 Some of these non-subtype B-specific protease polymorphisms have been previously noted, but studies of non-subtype B patients on PR inhibitor regimens are uncommon in the literature so that the clinical significance of these baseline minor mutations is still being evaluated. 15,16,18,51 Although none of the subtype-specific polymorphisms in the PR are considered major PI mutations, many are minor mutations to PR inhibitors commonly used in resourcelimited settings such as Nigeria, including indinavir/ritonavir and lopinavir/ritonavir.…”

Section: Hiv-1 Subtype On Drug Resistance Mutations In Nigeriamentioning

confidence: 99%

Impact of HIV Type 1 Subtype on Drug Resistance Mutations in Nigerian Patients Failing First-Line Therapy

Chaplin

Eisen

Idoko

et al. 2011

AIDS Research and Human Retroviruses

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A diverse array of non-subtype B HIV-1 viruses circulates in Africa and dominates the global pandemic. It is important to understand how drug resistance mutations in non-B subtypes may develop differently from the patterns described in subtype B. HIV-1 reverse transcriptase and protease sequences from 338 patients with treatment failure to first-line ART regimens were evaluated. Multivariate logistic regression was used to examine the effect of subtype on each mutation controlling for regimen, time on therapy, and total mutations. The distribution of HIV-1 subtypes included CRF02_AG (45.0%), G (37.9%), CRF06_cpx (4.4%), A (3.6%), and other subtypes or recombinant sequences (9.2%). The most common NRTI mutations were M184V (89.1%) and thymidine analog mutations (TAMs). The most common NNRTI mutations were Y181C (49.7%), K103N (36.4%), G190A (26.3%), and A98G (19.5%). Multivariate analysis showed that CRF02_AG was less likely to have the M41L mutation compared to other subtypes [adjusted odds ratio (AOR) ¼ 0.35; p ¼ 0.022]. Subtype A patients showed a 42.5-fold increased risk (AOR ¼ 42.5, p ¼ 0.001) for the L210W mutation. Among NNRTI mutations, subtype G patients had an increased risk for A98G (AOR ¼ 2.40, p ¼ 0.036) and V106I (AOR ¼ 6.15, p ¼ 0.010), whereas subtype CRF02_AG patients had an increased risk for V90I (AOR ¼ 3.16; p ¼ 0.003) and a decreased risk for A98G (AOR ¼ 0.48, p ¼ 0.019). Five RT mutations were found to vary significantly between different non-B West African subtypes. Further study to understand the clinical impact of subtype-specific diversity on drug resistance will be critically important to the continued success of ART scale-up in resource-limited settings.

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“…However, a recent study of the differences in the impact of several PI-selected mutations on subtypes B and G in 500 patients showed that the mutation L90M confers different levels of resistance in subtypes B and G (Santos et al, 2009). Another recent study indicated that even though in general drug selective pressure and resistance pathways are relatively similar in subtypes B and G some differences do occur, leading to subtype-dependent substitutions (Palma et al, 2009). With respect to the development of drug-resistance mutations (DRMs), a recent study showed that non-B subtypes tend to select for the same DRMs as described in subtype B in PR and reverse transcriptase (RT), although in distinct proportions (Dumans et al, 2009;Kantor et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Structure of the unbound form of HIV-1 subtype A protease: comparison with unbound forms of proteases from other HIV subtypes

Robbins

Coman

Bracho-Sanchez

et al. 2010

Acta Crystallogr D Biol Cryst

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The crystal structure of the unbound form of HIV-1 subtype A protease (PR) has been determined to 1.7 Å resolution and refined as a homodimer in the hexagonal space group P6 1 to an R cryst of 20.5%. The structure is similar in overall shape and fold to the previously determined subtype B, C and F PRs. The major differences lie in the conformation of the flap region. The flaps in the crystal structures of the unbound subtype B and C PRs, which were crystallized in tetragonal space groups, are either semi-open or wide open. In the present structure of subtype A PR the flaps are found in the closed position, a conformation that would be more anticipated in the structure of HIV protease complexed with an inhibitor. The amino-acid differences between the subtypes and their respective crystal space groups are discussed in terms of the differences in the flap conformations.

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Effect of human immunodeficiency virus type 1 protease inhibitor therapy and subtype on development of resistance in subtypes B and G

Cited by 9 publications

References 21 publications

Molecular Epidemiology of HIV-1 Infected Migrants Followed Up in Portugal: Trends between 2001–2017

Molecular Epidemiology of HIV-1 Infected Migrants Followed Up in Portugal: Trends between 2001–2017

Impact of HIV Type 1 Subtype on Drug Resistance Mutations in Nigerian Patients Failing First-Line Therapy

Structure of the unbound form of HIV-1 subtype A protease: comparison with unbound forms of proteases from other HIV subtypes

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