Naturally occurring resistance mutations to HIV-1 entry inhibitors in subtypes B, C, and CRF31_BC

Araújo, Leonardo Augusto Luvison; Junqueira, Dennis Maletich; Medeiros, Rúbia Marília de; Matte, Maria Cristina Cotta; Almeida, Sabrina Esteves de Matos

doi:10.1016/j.jcv.2012.01.005

Cited by 23 publications

(21 citation statements)

References 28 publications

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“…20 Similar to Araú jo and collaborators, 19 several polymorphisms within the HR2 domain were observed: polymorphism L130I in 13% (n = 13) of the sequences, S129N in 31% (n = 32) of the sequences, E137K in 6% (n = 6) of the sequences, and S138A in 4% (n = 4) of the sequences (Fig. 3); these recently detected sequences were related to decreased susceptibility to ENF.…”

Section: Genetic Diversity Of the Gp41 Region In Mozambiquesupporting

confidence: 67%

“…Notably, further studies are required to clarify whether the genetic background of HIV subtypes affects the efficiency of treatment with fusion inhibitors, especially in Mozambique where subtype C is most frequent. 19 These results demonstrate that the HIV-1 epidemic in Mozambique is quite homogeneous with regard to the subtype mostly composed of C clade viruses influenced by foreign and neighboring countries. In addition, the recent introduction of other subtypes and mosaic forms suggests that the genetic complexity in Mozambique is evolving rapidly.…”

Section: Figmentioning

confidence: 66%

“…previously associated with increased susceptibility to ENF 19 were detected in 90% (n = 89) of the sequences (Fig. 2).…”

Section: Genetic Diversity Of the Gp41 Region In Mozambiquementioning

confidence: 70%

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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: Genetic Diversity Of the Gp41 Region In Mozambiquesupporting

confidence: 67%

Section: Figmentioning

confidence: 66%

See 1 more Smart Citation

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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“…Due to the low usage, the development of fusion inhibitor testing is further limited. Moreover, naturally occurring drug resistance is found in certain HIV-1 subtypes, restricting susceptibility to this class [76][77][78].…”

Section: Drug Resistance Monitoring (Integrase and Fusion Inhibitors)mentioning

confidence: 99%

Current Assays for HIV-1 Diagnostics and Antiretroviral Therapy Monitoring: Challenges and Possibilities

Chen

Yam

2013

Future Virol.

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In 2011, there were over 34 million people living with HIV infections, placing a heavy burden on public health sectors. HIV infection is a lifelong threat that cannot be prevented by vaccination or cured by antiretroviral drugs. The infected patients rely on daily antiretroviral therapy to suppress HIV viral replication. Hence, it is important to diagnose HIV infections as early as possible and to monitor the efficacy of antiretroviral therapy every 3–6 months. Different immunoassays detecting HIV antigens and antibodies have been modified to offer better sensitivity and more rapid diagnosis. Several clinical and virological parameters, including CD4+ cell counts, viral load and drug resistance mutations, are also used for treatment monitoring. Many molecular assay optimizations are now being utilized to improve patient care. This review will focus on the most updated HIV diagnostic assays, as well as discussing the upcoming possibilities of other advanced technologies.

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“…19,20 Primary mutations associated with resistance to maraviroc and vicriviroc are also found to be prevalent in adult therapy naive patients. 21,22 However, the prevalence and transmission of primary mutations to HIV-1 entry inhibitors- maraviroc and vicriviroc during MTCT are unclear, and both may have a profound impact on the clinical management of maraviroc.…”

Section: Introductionmentioning

confidence: 99%

Analysis of primary resistance mutations to HIV-1 entry inhibitors in therapy naive subtype C HIV-1 infected mother–infant pairs from Zambia

Guo

Liu

et al. 2013

Journal of Clinical Virology

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Background Small molecular CCR5 inhibitors represent a new class of drugs for treating HIV-1 infection. The evaluation of the primary resistance mutations associated with entry inhibitors during HIV-1 perinatal transmission is required because they may have a profound impact on the clinical management in MTCT. Objectives To evaluate the primary resistance mutations to maraviroc and vicriviroc during perinatal transmission and analyze the sensitivity of Env derived from mother–infant pairs to maraviroc. Study design Nine MIPs infected by subtype C HIV-1 were recruited to analyze the prevalence and transmission of primary resistance mutations to maraviroc and vicriviroc. Moreover, Env derived from six MIPs were employed to construct provirus clones and to analyze the sensitivity to maraviroc. Results Mutations A316T, conferring partial resistance to maraviroc, T307I and R315Q, both conferring partial resistance to vicriviroc are prevalent in mother and infant cohorts, indicating the transmission of primary resistance mutations during HIV-1 perinatal transmission. However, the mutations of acutely infected mothers seem to directly transmit to their corresponding infants, while some mutations at low frequency of chronically infected mothers would be lost during transmission. Moreover, provirus clones derived from acutely infected MIPs are less susceptible to maraviroc than those from chronically infected MIPs. Conclusions Our study suggests that the transmission mode of primary resistance mutations and the sensitivity to maraviroc are dependent on infection status of MIPs either acutely or chronically infected. These results may indicate that higher dose of maraviroc could be needed for treatment of acutely infected MIPs compared to chronically infected MIPs.

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Naturally occurring resistance mutations to HIV-1 entry inhibitors in subtypes B, C, and CRF31_BC

Cited by 23 publications

References 28 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

Current Assays for HIV-1 Diagnostics and Antiretroviral Therapy Monitoring: Challenges and Possibilities

Analysis of primary resistance mutations to HIV-1 entry inhibitors in therapy naive subtype C HIV-1 infected mother–infant pairs from Zambia

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