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Camacho RJ

Comparative performance of the REGA subtyping tool version 2 versus version 1

The REGA HIV-1 subtyping tool is a phylogenetic-based method for subtyping HIV-1 genomic sequences that was published in 2005. The subtyping tool combines phylogenetic approaches with recombination detection methods.
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Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients.

BACKGROUND:
The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore are expected to revert quickly. Compensatory mutations, often already polymorphic in wild-type viruses, do not tend to revert after transmission.
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The demise of multidrug- resistant HIV-1: The national time trend in Portugal

Despite a decreasing mortality and morbidity in treated HIV-1 patients, highly active antiretroviral treatment (HAART) can still fail due to the development of drug resistance. Especially, multidrug-resistant viruses pose a threat to efficient therapy. We studied the changing prevalence of multidrug resistance (MDR) over time in a cohort of HIV-1-infected patients in Portugal.
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HIV-1 subtype is an independent predictor of reverse transcriptase mutation k65r in HIV-1 patients treated with combination antiretroviral therapy including tenofovir

Subtype-dependent selection of HIV-1 reverse transcriptase resistance mutation K65R was previously observed in cell culture and small clinical investigations. We compared K65R prevalence across subtypes A, B, C, F, G, and CRF02_AG separately in a cohort of 3,076 patients on combination therapy including tenofovir. K65R selection was significantly higher in HIV-1 subtype C. This could not be explained by clinical and demographic factors in multivariate analysis, suggesting subtype sequence-specific K65R pathways.
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Decreasing population selection rates of resistance mutation K65R over time in HIV-1 patients receiving com- bination therapy including tenofovir

The use of tenofovir is highly associated with the emergence of mutation K65R, which confers broad resistance to nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs), especially when tenofovir is combined with other NRTIs also selecting for K65R. Although recent HIV-1 treatment guidelines discouraging these combinations resulted in reduced K65R selection with tenofovir, updated information on the impact of currently recommended regimens on the population selection rate of K65R is presently lacking.
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Molecular Epidemiological Analysis of Paired pol/env Sequences from Portuguese HIV Type 1 Patients

The advent of new therapeutic approaches targeting env and the search for efficient anti-HIV-1 vaccines make it necessary to identify the number of recombinant forms using genomic regions that were previously not frequently sequenced.
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HIV-1 sub- type distribution and its demographic determinants in newly diagnosed patients in Europe suggest highly compartmentalized epidemics

Understanding HIV-1 subtype distribution and epidemiology can assist preventive measures and clinical decisions. Sequence variation may affect antiviral drug resistance development, disease progression, evolutionary rates and transmission routes.
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Predicted residual activity of rilpivirine in HIV-1 infected patients failing therapy including NNRTIs efavirenz or nevirapine

Rilpivirine is a second-generation nonnucleoside reverse-transcriptase inhibitor (NNRTI) currently indicated for first-line therapy, but its clinical benefit for HIV-1 infected patients failing first-generation NNRTIs is largely undefined.This study quantified the extent of genotypic rilpivirine resistance in viral isolates from 1212 patients upon failure of efavirenz- or nevirapine-containing antiretroviral treatment, of whom more than respectively 80% and 90% showed high-level genotypic resistance to the failing NNRTI.
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Characterization of amino acids Arg, Ser and Thr at position 70 within HIV-1 reverse transcriptase

The amino acid position 70 in HIV-1 reverse transcriptase (RT) plays an important role in nucleoside RT inhibitor (NRTI) resistance. K70R is part of the thymidine analog mutations, but also other amino acid changes have been associated with NRTI resistance, such as K70E and K70G. In this study, we investigated the in vivo selection of the HIV-1 RT mutations K70S and K70T and their in vitro effect on drug resistance and replication capacity.
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