HIV-1 Genetic Diversity and Transmitted Drug Resistance in Health Care Settings in Maputo, Mozambique

Bártolo, Inês; Casanovas, J; Bastos, Ronaldo Rocha; Rocha, Cheila; Abecasis, Ana; Folgosa, Elena; Mondlane, Jose; Manuel, Rolanda; Taveira, Nuno

doi:10.1097/qai.0b013e3181a24906

Cited by 23 publications

(23 citation statements)

References 48 publications

(61 reference statements)

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“…This is in accordance with previous studies showing that subtype C is the most frequent in Mozambique 14,15 and is consistent with previous studies showing the existence of this subtype in neighboring countries such as South Africa, with the exception to Tanzania where subtype A1 predominates. 16,17 Similarly, in Mozambique subtype G has previously been found in drug-naive patients enrolled from 2002 to 2004 and subtype A1 was recently introduced from patients enrolled in 2010.…”

Section: Aids Research and Human Retrovirusessupporting

confidence: 82%

“…16,17 Similarly, in Mozambique subtype G has previously been found in drug-naive patients enrolled from 2002 to 2004 and subtype A1 was recently introduced from patients enrolled in 2010. 15,18 Furthermore, recombinant analysis using the jpHMM program showed that one (Sequence ID A037) of the sequences was a mosaic form composed of subtypes C/A1. The C/A1 mosaic form identified in this study could represent a new CRF or URF, but full genomic analysis and further studies in other regions of Mozambique are required to confirm this finding.…”

Section: Aids Research and Human Retrovirusesmentioning

confidence: 99%

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Genetic Analysis and Natural Polymorphisms in HIV-1 gp41 Isolates from Maputo City, Mozambique

Ismael

Bila

Mariani

et al. 2014

AIDS Research and Human Retroviruses

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Enfuvirtide was the first fusion inhibitor approved by the Food and Drug Administration (FDA) in 2003 for HIV-1 infection in treatment-experienced patient. It is the first approved antiviral agent to attack the HIV life cycle in its early stages. For HIV fusion to occur, the HR1 and HR2 domains in the gp41 region need to interact. Enfuvirtide is a synthetic peptide that corresponds to 36 amino acids of the HR2, which competitively binds to HR1 inhibiting the interaction with the HR2 domain thus preventing fusogenic conformation and inhibiting viral entry into host cells. Resistance to enfuvirtide is conferred by mutations occurring in the HR1 region involving residues 36-45. Mozambique, a sub-Saharan country, with an HIV prevalence of 11.5%, provides first line and second line antiretroviral therapy (ART)-based treatment. In poor resource settings such as Mozambique the lack of adequate infrastructures, the high costs of viral load tests, and the availability of salvage treatment have hindered the intended objective of monitoring HIV treatment, suggesting an important concern regarding the development of drug resistance. The general aim of this study was to evaluate naturally occurring polymorphisms and resistance-associated mutations in the gp41 region of HIV-1 isolates from Mozambique. The study included 78 patients naive to ARV treatment and 28 patients failing first line regimen recruited from Centro de Saú de Alto-Maé situated in Maputo. The gp41 gene from 103 patients was sequenced and resistance-associated mutations for enfuvirtide were screened. Subtype analysis revealed that 96% of the sequences were classified as subtype C, 2% as subtype G, 1% as subtype A1, and the other 1% as a mosaic form composed of A1/C. No enfuvirtide resistance-associated mutations in HR1 of gp41 were detected. The major polymorphisms in the HR1 were N42S, L54M, A67T, and V72I. This study suggests that this new class of antiviral drug may be effective as a salvage therapy in patients failing first line regimens in Mozambique. However, further phenotypic studies are required to determine the clinical relevance of the polymorphisms detected in this study. 1 Mozambique, a sub-Saharan country, faces serious HIV epidemics with a national prevalence of 11.5% of adults aged 15-49 years; the overall prevalence rate is 17.8% in the southern region, 12.5% in the central region, and 5.6% in the northern region.2 Thus, according to the Ministry of Health in 2010 the number of people receiving antiretroviral treatment (ART) was approximately 211,000 adults and 16,800 children and the ART coverage for people in need of treatment was 40% for adults and 26% for children. 3As recommended by the WHO, the first line ART regimen in Mozambique consists of two nucleoside reverse transcriptase inhibitors (NRTIs) and one nonnucleoside reverse transcriptase inhibitor (NNRTI) and the second line ART regimen consists of a boosted protease inhibitor (PIs) and two NRTIs for patients failing the first line regimen. However, due to the rapid expansion...

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Section: Aids Research and Human Retrovirusessupporting

confidence: 82%

Section: Aids Research and Human Retrovirusesmentioning

confidence: 99%

Genetic Analysis and Natural Polymorphisms in HIV-1 gp41 Isolates from Maputo City, Mozambique

Ismael

Bila

Mariani

et al. 2014

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

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“…84 Phylogenetic analyses have been employed in TDR prevalence studies primarily to characterize the extensive genetic diversity in specific regions 90–94 and the dominance of HIV-1C in southern Africa. 95–99 Few studies have evaluated transmission lineages of drug resistant strains through transmission cluster analysis to support or refute epidemiological linkages.…”

Section: Phylogenetics and Transmission Dynamics In Generalized Epidementioning

confidence: 99%

Phylogenetic Studies of Transmission Dynamics in Generalized HIV Epidemics

Dennis

Herbeck

Brown

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Efficient and effective HIV prevention measures for generalized epidemics in sub-Saharan Africa have not yet been validated at the population-level. Design and impact evaluation of such measures requires fine-scale understanding of local HIV transmission dynamics. The novel tools of HIV phylogenetics and molecular epidemiology may elucidate these transmission dynamics. Such methods have been incorporated into studies of concentrated HIV epidemics to identify proximate and determinant traits associated with ongoing transmission. However, applying similar phylogenetic analyses to generalized epidemics, including the design and evaluation of prevention trials, presents additional challenges. Here we review the scope of these methods and present examples of their use in concentrated epidemics in the context of prevention. Next, we describe the current uses for phylogenetics in generalized epidemics, and discuss their promise for elucidating transmission patterns and informing prevention trials. Finally, we review logistic and technical challenges inherent to large-scale molecular epidemiological studies of generalized epidemics, and suggest potential solutions.

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“…The study participants harboring the M36I mutation did not show a particular predominance of any HIV-1 subtype (subtype A, n = 4; subtype B, n = 3; subtype CRF-02AG, n = 4; subtype CRF-02AD, n = 1). R41K, H69K, L89M, and I15V were reported to be more frequent in subtype C [25,36]. In this study, one patient was infected with HIV-1C harboring R41K, H69K, and I15V.…”

Section: Drug Resistance Mutations Among the Study Participantsmentioning

confidence: 93%

“…These samples were used to determine HIV-1 RNA viral load, which was determined via quantification of HIV-1 viral RNA using COBAS AMPLICOR HIV-1 MONITOR Test version 1.5 (Roche Molecular Diagnostics, Basel, Switzerland) [24,25].…”

Section: Clinical and Virologic Characteristicsmentioning

confidence: 99%

Screening for antiretroviral drug resistance among treatment-naive human immunodeficiency virus type 1-infected individuals in Lebanon

Mokhbat

Melhem

El‐Khatib

et al. 2014

J Infect Dev Ctries

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Introduction: Antiretroviral therapy (ART) has been successful at decreasing the morbidity and mortality associated with human immunodeficiency virus type 1 (HIV-1) infection. HIV-1 drug resistance (HIVDR) among ART-naive patients has been documented to compromise the success of initial therapy. This study was conducted to determine the prevalence of HIVDR mutations among newly diagnosed drug-naive HIV-infected individuals in Lebanon. Methodology: Plasma samples from 37 newly diagnosed participants at various stages of HIV-1 infection were used to determine HIV-1 RNA viral load, isolate viral RNA, and amplify DNA by RT-PCR. Purified PCR products were used to perform genotypic resistance tests. Results: The prevalence of resistance mutations to nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRT), and protease inhibitors (PI) were 5.4%, 10.8%, and 8%, respectively. The major mutations detected in the study participants conferred resistance to NRTIs and NNRTIs recommended for HIV-1 treatment. No significant relationship between HIV-1 viral load of participants and the mode of HIV-1 transmission or between the occurrence of HIVDR and the mode of transmission was found. Conclusions: To our knowledge, this is the first study on HIVDR mutations among newly diagnosed HIV-infected persons in Lebanon. The overall prevalence of HIVDR mutations detected in our study was 16%. Our results are important for evaluating the utility of the standard first-line regimens in use, determining the feasibility of HIVDR testing before the initiation of ART, as well as minimizing the emergence and transmission of HIVDR.

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HIV-1 Genetic Diversity and Transmitted Drug Resistance in Health Care Settings in Maputo, Mozambique

Cited by 23 publications

References 48 publications

Genetic Analysis and Natural Polymorphisms in HIV-1 gp41 Isolates from Maputo City, Mozambique

Genetic Analysis and Natural Polymorphisms in HIV-1 gp41 Isolates from Maputo City, Mozambique

Phylogenetic Studies of Transmission Dynamics in Generalized HIV Epidemics

Screening for antiretroviral drug resistance among treatment-naive human immunodeficiency virus type 1-infected individuals in Lebanon

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