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Genetic analysis and natural polymorphisms in HIV-1 gp41 isolates from Maputo City, Mozambique.

ABSTRACT: 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 Saúde 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.

SUBMITTER: Ismael N

PROVIDER: S-EPMC4046211 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Genetic analysis and natural polymorphisms in HIV-1 gp41 isolates from Maputo City, Mozambique.

Ismael Nália N Bila Dulce D Mariani Diana D Vubil Adolfo A Mabunda Nedio N Abreu Celina C Jani Ilesh I Tanuri Amilcar A

AIDS research and human retroviruses 20131221 6

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 ...[more]

PMID: 24188582

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Project description:BACKGROUND:Irrational use of antibiotics is a major driver of antimicrobial resistance (AMR) worldwide. Sub-Saharan Africa, where the risk of spread of AMR is highest, lacks data on the knowledge, attitudes and practices regarding antibiotic prescription and use. This is the first study in Mozambique to address this gap. METHODS:A cross-sectional study was conducted in 2016 in 1091 adults (age ?18 years) living in five districts in peri-urban areas of Maputo City. Three stage cluster sampling was used to select the households. A semi-structured questionnaire was used to collect information on the knowledge, attitudes and practices regarding antibiotics and their use and socio-demographic data. RESULTS:Of the 1091 participants, 20.9% (228/1091) had used non-prescribed antibiotics. Most of the non-prescribed antibiotics were purchased in pharmacies (199/228; 87.3%). The proportion of use of non-prescribed antibiotics was higher in those who purchased from informal markets (82.6%; 14/17) and home stores (66.7%; 12/18), compared to pharmacies (24.6%; 199/810) (p = 0.000). Variables significantly associated with use of non-prescribed antibiotics were male gender (p = 0.004), living in the Central A (p<0.001), Aeroporto B (p<0.001) or 25 de Junho (p<0.001) neighborhoods, purchase of antibiotics in informal markets (p<0.002) or obtaining from home stores (p = 0.026), not completing the course (p<0.001) and having poor knowledge on the use of antibiotics (p<0.001). Main reasons for use of non-prescribed antibiotics were a perception that there was no need to attend a health facility (26.8%), followed by someone else's advice (7.7%), symptoms similar to a previous episode (6.2%) and poor quality of care in health facilities (6.7%). CONCLUSIONS:Our study shows for the first time that knowledge regarding antibiotics is poor in Maputo City. Purchase of non-prescribed antibiotics is a common practice and most are sold in pharmacies, indicating deficient inspection. Interventions to reinforce adherence by pharmacies to current legislation for dispensing antibiotics, combined with community education are urgently needed.

Project description:IntroductionVaccine efficacy testing requires engagement of willing volunteers with high disease incidence. We evaluated factors associated with willingness to participate in potential future HIV vaccine trials in Maputo, Mozambique.MethodsAdults aged 18-35 years without HIV and who reported at least two sexual partners in the 3 months prior to screening were enrolled into a 24-month observational study. They were asked at screening and exit if they would be willing to participate in a theoretical HIV vaccine study. Bivariate and multivariate logistic regression analyses were done between willingness to participate, demographic, sexual behavior, and motivational factors for screening visit data. Logistic regression with generalized estimating equations (GEE) was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors potentially associated with willingness to participate for data from both visits.ResultsA total of 577 participants without HIV were eligible, including 275 (48%) women. The mean age was 22.2 (SD ± 3.9) years. At screening 529 (92%) expressed willingness to participate and the proportion remained stable at 378 (88%) of the 430 participants retained through the exit visit (p = 0.209). Helping the country (n = 556) and fear of needles (n = 26) were the top motive and barrier for willingness to participate, respectively. Results from the GEE binary logistic regression (screening visit and exit visit) showed that wanting to learn how to avoid risk behaviors (aOR 3.33, 95% CI: 1.61-6.86) and feeling protected against HIV infection (aOR 2.24, 95% CI: 1.07-4.7) were associated with willingness to participate in HIV vaccine studies.ConclusionThe majority of our study population in Mozambique expressed willingness to participate in a theoretical HIV vaccine trial. Participation in a HIV vaccine trial was seen as a way to contribute to the fight against HIV but was associated with some unrealistic expectations such as protection against HIV. This reinforces the need for continuous mobilization and awareness of potential participants to HIV vaccine trial.

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Genetic analysis and natural polymorphisms in HIV-1 gp41 isolates from Maputo City, Mozambique.

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Genetic analysis and natural polymorphisms in HIV-1 gp41 isolates from Maputo City, Mozambique.

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