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1.
Rev. chil. infectol ; 35(1): 49-61, 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-899777

ABSTRACT

Resumen Introducción Las recomendaciones internacionales de tratamiento anti-retroviral incluyen pruebas de resistencia para orientar el régimen de tratamiento en cada paciente, lo que no está disponible de forma estable en Ecuador. Objetivo Describir las mutaciones que confieren resistencia a anti-retrovirales en una población de pacientes ecuatorianos. Metodología A partir de muestras de plasma de 101 pacientes con VIH-1 con fallo a la terapia anti-retroviral, 15 niños y 86 adultos, se realizó pirosecuenciación con el GS Junior (Roche) y se analizaron las secuencias con el programa DeepChek. Resultados Las mutaciones más frecuentes fueron M184V/I, K101E/P/H, K103N/S, D30N, M46L/I, I54L/M, V82T/F/A/S/L y L90M en adultos, y F77L, K103N/S, M46L/I, V82T/F/A/S/L y L90M en niños. Se encontró una elevada resistencia a los inhibidores de la transcriptasa reversa (TR) no análogos de nucleósidos en poblaciones minoritarias virales de adultos y niños (34,9 y 70%, respectivamente), en los niños, tanto las poblaciones virales mayoritarias como minoritarias, fueron resistente a inhibidores de proteasa (> 45%). Los pacientes que tuvieron un mayor número de esquemas terapéuticos presentaron mayores niveles de resistencia a los anti-retrovirales. La mayoría de las muestras fueron del subtipo B en la región de la TR y proteasa, y CRF25_cpx en integrasa. Conclusiones Se muestran las mutaciones y la resistencia a antiretrovirales en una población de pacientes ecuatorianos con infección por VIH-1, que permitirán realizar un llamado de alerta a las autoridades de salud sobre la necesidad de realizar estudios de resistencia.


Background The international recommendations of antiretroviral treatment include resistance tests to guide the treatment regimen in each patient, which is not available on a regular basis in Ecuador. Aim To describe mutations that confer resistance to antiretrovirals in a population of Ecuadorian patients. Methods Plasma samples from 101 HIV-1 patients with failure to antiretroviral therapy, divided into 15 children and 86 adults, were studied with the GS Junior (Roche) and the sequences were analyzed with the DeepChek program. Results The most frequent mutations were M184V/I, K101E/P/H, K103N/S, D30N, M46L/I, I54L/M, V82T/F/A/S/L and L90M in adults and F77L, K103N/S, M46L/I, V82T/F/A/S/L and L90M in children. High resistance to non-nucleoside reverse transcriptase (RT) inhibitors in minority viral populations of adults and children (34.9% and 70%) was detected; in children both viral populations (majority and minority viral populations) (> 45%) were protease inhibitor resistant. Patients who had a greater number of therapeutic regimens had higher levels of resistance to antiretrovirals. Most of the samples were subtype B in the TR and protease region, and CRF25_cpx in integrase. Conclusions Mutations and resistance to antiretrovirals are shown in a population of Ecuadorian patients with HIV-1. These results will make it possible to issue a warning to health authorities about the need for resistance studies.


Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adult , HIV Infections/genetics , HIV Infections/drug therapy , HIV-1/drug effects , HIV-1/genetics , Drug Resistance, Multiple, Viral/genetics , Anti-Retroviral Agents/pharmacology , Mutation/drug effects , HIV Infections/blood , Logistic Models , Polymerase Chain Reaction , Cross-Sectional Studies , Age Factors , CD4 Lymphocyte Count , Viral Load , Antiretroviral Therapy, Highly Active/methods , Anti-Retroviral Agents/therapeutic use , Ecuador , HIV Reverse Transcriptase/drug effects
2.
Braz. j. infect. dis ; 21(3): 234-239, May-June 2017. tab, graf
Article in English | LILACS | ID: biblio-839219

ABSTRACT

ABSTRACT Background: Geographical distribution of HIV variants is an important way to understand the circulation and spread of such viral strains. Objectives: To evaluate the spatial distribution of HIV-1 variants in patients failing antiretroviral therapy, in Salvador, Brazil. Methods: We performed a cross-sectional evaluation of HIV resistance test reports of patients who underwent genotyping tests in a referral center in Salvador, Brazil, for the years 2008-2014. The laboratory database contains around 2500 resistance reports of patients failing antiretroviral therapy. Genotypic tests were performed by sequencing of HIV-1 POL region (TrueGene, Siemens). We assessed HIV-1 resistance mutations and subtype, as well as residential address, age, and gender of patients. Results: We evaluated 1300 reports, 772 (59.4%) of them from male patients. As expected, subtype B predominated (79%) followed by subtypes F1 (6.7%) and BF (6.5%). The most frequent mutations in HIV-1 reverse transcriptase were 184V (79.1%), 41L (33.5%), 67N (30.4%), 103N (42.4%), and 108I (11.1%). Most frequent mutations in HIV-1 protease were 63P (52.4%), 36I (47.9%), 15 V (33.0%), 62 V (28.1%) and 13 V (25.8%). Some mutations (41L, 215Y, 210W) were significantly more frequent among men. We detected a significantly higher accumulation of 103N mutation in specific areas of Salvador. We identified a more restricted circulation pattern for subtype FB (more frequent in some regions), and F1 (almost absent in a specific region). Conclusion: Our results suggest that specific subtypes/resistance mutations present a distinct frequency rate in specific areas of Salvador, probably due to a restricted circulation pattern. This trend to clustering was observed in regions covered by AIDS referral centers, suggesting that pattern of care for such patients can interfere in virological outcomes.


Subject(s)
Humans , Male , Female , Adult , HIV Infections/drug therapy , HIV-1/genetics , Anti-HIV Agents/therapeutic use , HIV Reverse Transcriptase/genetics , Mutation , RNA, Viral/genetics , HIV Infections/virology , Cross-Sectional Studies , HIV-1/drug effects , Treatment Failure , Viral Load , Spatial Analysis , Genotype
3.
Mem. Inst. Oswaldo Cruz ; 110(7): 847-864, Nov. 2015. graf
Article in English | LILACS | ID: lil-764593

ABSTRACT

Reverse transcriptase (RT) is a multifunctional enzyme in the human immunodeficiency virus (HIV)-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs) and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted.


Subject(s)
Humans , Anti-HIV Agents/chemistry , Computer-Aided Design , Drug Design , HIV Reverse Transcriptase/antagonists & inhibitors , HIV-1 , Reverse Transcriptase Inhibitors/pharmacology , HIV Infections/drug therapy , HIV Reverse Transcriptase/chemistry , HIV-1 , Models, Biological , Molecular Structure , Quantitative Structure-Activity Relationship , Reverse Transcriptase Inhibitors/chemistry
4.
Rev. med. Rosario ; 81(1): 19-23, ene.-abr. 2015. tab
Article in Spanish | LILACS | ID: lil-758454

ABSTRACT

Objetivo. Describir la función sexual de un grupo de mujeres con VIH bajo tratamiento antirretroviral. Evaluar si existe diferencia entre las tratadas con un esquema que contiene Inhibidores No Nucleósidos de la Transcriptasa Inversa (INNTI) y aquéllas que reciben Inhibidores de la Proteasa (IP). Material y métodos. Estudio descriptivo, transversal. Muestra: 92 pacientes mujeres con VIH bajo tratamiento antirretroviral, que son asistidas en el Instituto Centralizado de Asistencia e Investigación Clínica Integral (CAICI). Instrumento: Se les realizó una encuesta que consta de características demográficas, preguntas referidas al VIH y al The Female Sexual Function Index (FSFI). Análisis estadístico: se utilizó ANOVA, Kruskall-Wallis, Chi cuadrado, regresión logística y alpha de Cronbach. Resultados. Edad media: 42±10 años; 65% tenían pareja estable, siendo el 73% de estas sero-discordantes. La mayoría (45,7%) estaban en tratamiento antirretroviral por más de dos años, con una media de CD4 mayor a 500 cél/ml y el 90% con carga viral plasmática indetectable. El 64,1% presentaba otra enfermedad asociada, por lo que el 55,4% tomaba medicación concomitante. El 27,2% continuó con su actividad sexual luego del diagnóstico de VIH, pero el 26,1% nunca la retomó. La puntuación total alcanzada por medio del FSFI fue de 20,4±10,1 para las tratadas con IP y 20±10,6 para las tratadas con INNTI (p <0,005). Conclusiones. La muestra analizada presentó un puntaje compatible con disfunción sexual. No hubo diferencia estadísticamente significativa en la función sexual de las mujeres tratadas con IP y las tratadas con INNTI


Summary Objective: To describe the sexual function in a group of women with HIV on antiretroviral treatment. To assess whether there is a difference between those treated with Non-nucleoside Inhibitors of he Reverse Transcriptase (NNRTI) and those receiving protease inhibitors (PIs). Material and methods: Descriptive, transversal study. Study sample: 92 women with HIV on antiretroviral therapy who are assisted in the Central Institute of Integral Assistance and Clinical Research (CAICI). Instrument: They completed a survey consisting of questions about demographic characteristics, HIV, and The Female Sexual Function Index (FSFI). Statistical analysis: ANOVA, Kruskal-Wallis, Chi-square, logistic regression and Cronbach’s alpha. Results: Average age was 42±10 years; 65% had a steady partner, of which 73% were sero-discordant. Most patients (45.7%) had been on antiretroviral treatment for more than two years, with a mean CD4 greater than 500 cells/ml and 90% with undetectable plasma viral load. Other illnesses were present in 64.1%, and 55.4% were taking concomitant medication. Sexual activity after HIV diagnosis was continued by 27.2%, while 26.1% never resumed it. The total score achieved by the FSFI was 20.4±10.1 among those treated with IP and 20.0±10.6 among those treated with NNRTI(p<0.005). Conclusions: The score in the present sample supports the existence of sexual dysfunction. There was no statistically significant difference in the sexual function of women treated with either PI or NNRTI


Subject(s)
Humans , Female , HIV , Sexuality , Treatment Outcome , Autoimmune Diseases/prevention & control , HIV Protease Inhibitors , Reverse Transcriptase Inhibitors/therapeutic use , HIV Reverse Transcriptase/therapeutic use
5.
DST j. bras. doenças sex. transm ; 27(3-4): 73-78, 2015.
Article in English | LILACS | ID: biblio-979

ABSTRACT

The worldwide distribution of herpes simplex virus type 1 (HSV-1) allied to the emergence of resistant strains makes necessary and urgent the search and development of new substances capable of preventing and treating HSV-1 infections. Studies demonstrate synergy between genital herpes and human immunodeficiency virus type 1 (HIV-1), which represents a major concern for global public health. Objective: The objective of this study was to evaluate the activity of crude extracts and isolated substances from C. fluminensis in the in vitro replication of the HSV-1 virus and HIV-1-RT activity. Methods: This study evaluated the activity of extracts and isolated compounds from Clusia fluminensis Planch. & Triana against HSV-1 using Vero cells in culture and against HIV-1 using a recombinant reverse transcriptase enzyme (HIV -1 RT). The percentage of inhibition against HSV-1 was determined from viral lysis plaque reduction assay, and the anti-HIV-1-RT test was performed by a fluorimetric assay. It was also evaluated the cytotoxic activity of the samples using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]. Results: The crude extracts showed high percentage of inhibition against HSV-1, reaching 81.4 to 100.0% inhibition in non-cytotoxic concentration (50 µg/mL). The isolated compounds, lanosterol and clusianone, demonstrated 100% inhibition in non-cytotoxic concentration (50 µg/mL). We also examined the effects of the extracts and isolates on the activity of the HIV-1-RT. Among the crude extracts, only the methanolic extract of leaves and methanolic extract of stems showed inhibitory activity against HIV-1-RT. Regarding the isolated compounds, lanosterol showed a moderate activity. Conclusion: Our data demonstrate that extracts and isolates compounds Clusia fluminensis Planch. & Triana have promising antiviral activity inhibiting HSV-1 replication and HIV-1 by inhibiting the anti-RT activity.


A distribuição mundial do vírus herpes simplex tipo 1 (HSV-1) aliada ao surgimento de cepas resistentes torna necessária e urgente a busca e o desenvolvimento de novas substâncias capazes de prevenir e tratar infecções HSV-1. Estudos demonstram sinergia entre herpes genital e vírus da imunodeficiência humana tipo 1 (HIV-1), o que representa uma grande preocupação para a saúde pública global. Objetivo: O objetivo deste estudo foi avaliar a atividade de extratos brutos e substâncias isoladas de Clusia fluminensis Planch. & Triana na replicação in vitro do vírus HSV-1 e na atividade anti HIV-1-RT. Métodos: Este estudo avaliou a atividade de extratos e substâncias isoladas de Clusia fluminensis Planch. & Triana contra o HSV-1 utilizando células Vero em cultura e contra o HIV-1 utilizando a enzima transcriptase reversa recombinante (HIV-1 RT). A porcentagem de inibição contra o HSV-1 foi determinada a partir do ensaio de redução de placas de lise viral, e o ensaio anti-HIV-1 RT foi realizado por um ensaio fluorimétrico. Também foi avaliada a atividade citotóxica das amostras utilizando MTT [brometo de 3- (4,5-dimetiltiazol-2-il) -2,5-difeniltetrazólio]. Resultados: Os extratos demonstraram elevada percentagem de inibição contra o HSV-1, atingindo 81,4 a 100,0% de inibição em concentração não citotóxica (50 µg/mL). Os compostos isolados, lanosterol e clusianona, demonstraram 100% de inibição em concentração não citotóxica (50 µg/mL). Examinamos também os efeitos dos extratos e isolados sobre a atividade anti-HIV-1 RT. Entre os extratos brutos, apenas o extrato metanólico das folhas e caules apresentaram atividade anti-HIV-1 RT. Em relação aos compostos isolados, lanosterol mostrou uma atividade moderada. Conclusão: Nossos dados demonstram que os extratos e compostos isolados de Clusia fluminensis Planch. & Triana possuem atividade antiviral promissora inibindo a replicação do HSV-1 e HIV-1 através da inibição da atividade anti-RT.


Subject(s)
Clusiaceae , Herpesvirus 1, Human , HIV-1 , Lanosterol , HIV Reverse Transcriptase
6.
Botucatu; s.n; 2014. 60 p. ilus, tab.
Thesis in Portuguese | LILACS | ID: lil-772881

ABSTRACT

Apesar dos grandes avanços que conduziram a um declínio da infecção pelo HIV em crianças, a terapêutica antirretroviral vem sendo limitada pela emergência de resistência. Neste contexto, a finalidade deste estudo foi avaliar o perfil de mutações e resistência aos inibidores de transcriptase reversa análogos de nucleosídeos (ITRN) e não análogos de nucleosídeos (ITRNN) protease (IP) das variantes virais circulantes em pacientes pediátricos atendidos no Ambulatório de Imunologia Pediátrica da Faculdade de Medicina de Botucatu, UNESP. Foram avaliados dezenove pacientes, sendo dezesseis com falha terapêutica e, três virgens de tratamento. RNA viral plasmático foi utilizado como fonte para genotipagem das regiões genômicas da transcriptase reversa (TR) e protease (PR) do HIV. Os resultados demonstraram prevalência do subtipo B (78,95%). As mutações de resistência aos ITRNs encontradas em maior frequência foram L214F (73,7%), M184V (42,1%), R211K (42,1%), M41L (31,5%), T215Y (31,5%), L210W (21%), V118I (21%). As mutações K103N e Y188L encontradas em 26,3% e 10,5% dos pacientes foram as mais freqüentes entre as mutações associadas ao uso dos ITRNNs. Quanto aos IPs as mutações mais frequentes foram M36I (63,1%), L63P (52,6%), E35D (47,3%), R41K (31,5%), I13V (31,5%), M46V (26,3%), L90M (26,3%), I93L (26,3%), V77I (26,3%), V82A (21,1%), I54V (21,1%). No que se relaciona ao perfil de resistência, 3TC, AZT, EFV e NVP foram os ITR com menor potencial de uso devido à resistência. Já os IPs apresentam grande potencial de utilização na população estudada, o que se justifica pela alta barreira genética destes medicamentos. Dos três pacientes não tratados, um apresentava resistência a EFV e NVP, sugerindo ocorrência de resistência transmitida...


Although great progresses lead a decline of the HIV infection in children, the antiretroviral therapy has found obstacles as the resistance emergency. In this context the goal of this study was evaluate to the profile of mutations and genotypic resistance to the Nucleoside Reverse Transcriptase Inhibitors (NRTI), Nonnucleoside Reverse Transcriptase Inhibitors (NNRTI) and Protease Inhibitors (PI) in children assisted in the Pediatric Immunology Ambulatory, Botucatu School of Medicine. Patients (19) were evaluated (16 with therapeutic failure and 3 naïve). Viral RNA was used as source to RT and PR genomic regions genotyping. Subtype B was the most frequent (78.95%) in thi study. The NRTI resistance mutations found were L214F (73.7%), M184V (42.1%), R211K (42.1%), M41L (31.5%), T215Y (31.5%), L210W (21%), V118I (21%). K103N and Y188L were found in 26.3% e 10.5% and we are associated with NNRTI use. About the PI the mutations most frequent were M36I (63.1%), L63P (52.6%), E35D (47.3%), R41K (31.5%), I13V (31.5%), M46V (26.3%), L90M (26.3%), I93L (26.3%), V77I (26.3%), V82A (21.1%), I54V (21.1%). The ARVs resistance analysis showed that 3TC, AZT, EFV and NVP have the lower potential for use due to resistance. PI presented great potential for use due to high genetic barrier. From three naïve patients one presented resistant viral variants to EFV and NVP, suggesting transmitted resistance...


Subject(s)
Humans , Male , Female , Child , Anti-Retroviral Agents , HIV Reverse Transcriptase , HIV-1
7.
Botucatu; s.n; 2014. 60 p. ilus, tab.
Thesis in Portuguese | LILACS | ID: lil-772890

ABSTRACT

Apesar dos grandes avanços que conduziram a um declínio da infecção pelo HIV em crianças, a terapêutica antirretroviral vem sendo limitada pela emergência de resistência. Neste contexto, a finalidade deste estudo foi avaliar o perfil de mutações e resistência aos inibidores de transcriptase reversa análogos de nucleosídeos (ITRN) e não análogos de nucleosídeos (ITRNN) protease (IP) das variantes virais circulantes em pacientes pediátricos atendidos no Ambulatório de Imunologia Pediátrica da Faculdade de Medicina de Botucatu, UNESP. Foram avaliados dezenove pacientes, sendo dezesseis com falha terapêutica e, três virgens de tratamento. RNA viral plasmático foi utilizado como fonte para genotipagem das regiões genômicas da transcriptase reversa (TR) e protease (PR) do HIV. Os resultados demonstraram prevalência do subtipo B (78,95%). As mutações de resistência aos ITRNs encontradas em maior frequência foram L214F (73,7%), M184V (42,1%), R211K (42,1%), M41L (31,5%), T215Y (31,5%), L210W (21%), V118I (21%). As mutações K103N e Y188L encontradas em 26,3% e 10,5% dos pacientes foram as mais freqüentes entre as mutações associadas ao uso dos ITRNNs. Quanto aos IPs as mutações mais frequentes foram M36I (63,1%), L63P (52,6%), E35D (47,3%), R41K (31,5%), I13V (31,5%), M46V (26,3%), L90M (26,3%), I93L (26,3%), V77I (26,3%), V82A (21,1%), I54V (21,1%). No que se relaciona ao perfil de resistência, 3TC, AZT, EFV e NVP foram os ITR com menor potencial de uso devido à resistência. Já os IPs apresentam grande potencial de utilização na população estudada, o que se justifica pela alta barreira genética destes medicamentos. Dos três pacientes não tratados, um apresentava resistência a EFV e NVP, sugerindo ocorrência de resistência transmitida...


Although great progresses lead a decline of the HIV infection in children, the antiretroviral therapy has found obstacles as the resistance emergency. In this context the goal of this study was evaluate to the profile of mutations and genotypic resistance to the Nucleoside Reverse Transcriptase Inhibitors (NRTI), Nonnucleoside Reverse Transcriptase Inhibitors (NNRTI) and Protease Inhibitors (PI) in children assisted in the Pediatric Immunology Ambulatory, Botucatu School of Medicine. Patients (19) were evaluated (16 with therapeutic failure and 3 naïve). Viral RNA was used as source to RT and PR genomic regions genotyping. Subtype B was the most frequent (78.95%) in thi study. The NRTI resistance mutations found were L214F (73.7%), M184V (42.1%), R211K (42.1%), M41L (31.5%), T215Y (31.5%), L210W (21%), V118I (21%). K103N and Y188L were found in 26.3% e 10.5% and we are associated with NNRTI use. About the PI the mutations most frequent were M36I (63.1%), L63P (52.6%), E35D (47.3%), R41K (31.5%), I13V (31.5%), M46V (26.3%), L90M (26.3%), I93L (26.3%), V77I (26.3%), V82A (21.1%), I54V (21.1%). The ARVs resistance analysis showed that 3TC, AZT, EFV and NVP have the lower potential for use due to resistance. PI presented great potential for use due to high genetic barrier. From three naïve patients one presented resistant viral variants to EFV and NVP, suggesting transmitted resistance...


Subject(s)
Humans , Male , Female , Child , Anti-Retroviral Agents , HIV Reverse Transcriptase , HIV-1
8.
Article in English | WPRIM | ID: wpr-812288

ABSTRACT

AIM@#To evaluate the anti-HIV activity and mechanism of action of wikstroelide M, a daphnane diterpene from Daphne acutiloba Rehder (Thymelaeaceae).@*METHODS@#The anti-HIV activities of wikstroelide M against different HIV strains were evaluated by cytopathic effect assay and p24 quantification assay with ELISA. The inhibitory effect of wikstroelide M on HIV reverse transcription was analyzed by real-time PCR and ELISA. The effect of wikstroelide M on HIV-1 integrase nuclear translocation was observed with a cell-based imaging assay. The effect of wikstroelide M on LEDGF/p75-IN interaction was assayed by molecular docking.@*RESULTS@#Wikstroelide M potently inhibited different HIV-1 strains, including HIV-1IIIB, HIV-1A17, and HIV-19495, induced a cytopathic effect, with EC50 values ranging from 3.81 to 15.65 ng·mL⁻¹. Wikstroelide M also had high inhibitory activities against HIV-2ROD and HIV-2CBL-20-induced cytopathic effects with EC50 values of 18.88 and 31.90 ng·mL⁻¹. The inhibitory activities of wikstroelide M on the three HIV-1 strains were further confirmed by p24 quantification assay, with EC50 values ranging from 15.16 to 35.57 ng·mL⁻¹. Wikstroelide M also potently inhibited HIV-1IIIB induced cytolysis in MT-4 cells, with an EC50 value of 9.60 ng·mL⁻¹. The mechanistic assay showed that wikstroelide M targeted HIV-1 reverse transcriptase and nuclear translocation of integrase through disrupting the interaction between integrase and LEDGF/p75.@*CONCLUSION@#Wikstroelide M may be a potent HIV-1 and HIV-2 inhibitor, the mechanisms of action may include inhibition of reverse trascriptase activity and inhibition of integrase nuclear translocation through disrupting the interaction between integrase and LEDGF/p75.


Subject(s)
Anti-HIV Agents , Pharmacology , Therapeutic Uses , Cell Line , Daphne , Chemistry , Diterpenes , Pharmacology , HIV Infections , Drug Therapy , Virology , HIV Integrase , Metabolism , HIV Integrase Inhibitors , Pharmacology , Therapeutic Uses , HIV Reverse Transcriptase , HIV-1 , HIV-2 , Humans , Intercellular Signaling Peptides and Proteins , Metabolism , Phytotherapy , Plant Extracts , Pharmacology , Therapeutic Uses , Virus Integration , Virus Replication
9.
Article in Korean | WPRIM | ID: wpr-162996

ABSTRACT

Cyclic guanosine monophosphate adenosine monophosphate (cGAMP) synthase (cGAS) detects human immunodeficiency virus (HIV) and produces cGAMP to induce cytokines. Reverse transcribed DNA of HIV is critical for triggering innate immune responses as inhibitor of HIV reverse transcriptase blocked the induction of interferon-beta by the virus. Furthermore, knockout of cGAS in human or mouse cell lines abrogated the production of cytokines by HIV infection highlighting the essential role of cGAS in detection of HIV and other retroviruses.


Subject(s)
Adenosine Monophosphate , Animals , Cell Line , Cytokines , DNA , Guanosine Monophosphate , HIV Infections , HIV Reverse Transcriptase , HIV , Humans , Immunity, Innate , Interferon-beta , Mice , Retroviridae
10.
Mem. Inst. Oswaldo Cruz ; 108(4): 470-475, jun. 2013. tab
Article in English | LILACS | ID: lil-678287

ABSTRACT

The presence of transmitted human immunodeficiency virus (HIV)-1 drug-resistance (TDR) at the time of antiretroviral therapy initiation is associated with failure to achieve viral load (VL) suppression. Here, we report TDR surveillance in a specific population of men who have sex with men (MSM) in Belo Horizonte, Brazil. In this study, the rate of TDR was evaluated in 64 HIV-infected individuals from a cohort of MSM between 1996-June 2012. Fifty-four percent had a documented recent HIV infection, with a seroconversion time of less than 12 months. The median CD4+T lymphocyte count and VL were 531 cells/mm3and 17,746 copies/mL, respectively. Considering the surveillance drug resistance mutation criteria, nine (14.1%) patients presented TDR, of which three (4.7%), five (7.8%) and four (6.2%) had protease inhibitors, resistant against nucleos(t)ide transcriptase inhibitors and against non-nucleoside reverse-transcriptase inhibitors mutations, respectively. Two of the patients had multi-drug-resistant HIV-1. The most prevalent viral subtype was B (44, 68.8%), followed by subtype F (11, 17.2%). This study shows that TDR may vary according to the population studied and it may be higher in clusters of MSM.


Subject(s)
Adult , Humans , Male , Middle Aged , Young Adult , Anti-HIV Agents/therapeutic use , Drug Resistance, Viral , HIV Infections/virology , HIV-1 , Homosexuality, Male , Brazil , Genotype , HIV Infections/drug therapy , HIV Reverse Transcriptase/genetics , HIV-1 , Mutation , Prevalence , RNA, Viral , Viral Load
11.
Acta Pharmaceutica Sinica ; (12): 447-456, 2013.
Article in Chinese | WPRIM | ID: wpr-235644

ABSTRACT

Aptamers are capable of binding a wide range of biomolecular targets with high affinity and specificity. It has been widely developed for diagnostic and therapeutic purposes. Because of unique three dimensional structures and cell-membrane penetration, aptamers inhibit virus infection not only through binding specific target, such as the viral envelope, genomic site, enzyme, or other viral components, but also can be connected to each other or with siRNA jointly achieve antiviral activity. Taking human immunodeficiency virus and hepatitis C virus as examples, this paper reviewed the effects and mechanisms of aptamers on disturbing viral infection and replication steps. It may provide an insight to the development of aptamer-based new antiviral drugs.


Subject(s)
Antiviral Agents , Pharmacology , Aptamers, Nucleotide , Pharmacology , Therapeutic Uses , Genome, Viral , HIV , HIV Reverse Transcriptase , Metabolism , Hepacivirus , Genetics , Humans , Macular Degeneration , Drug Therapy , Neoplasms , Drug Therapy , Oligodeoxyribonucleotides , Therapeutic Uses , RNA, Small Interfering , Pharmacology , SELEX Aptamer Technique , Viral Envelope Proteins , Metabolism , Virus Replication
12.
Acta Pharmaceutica Sinica ; (12): 466-476, 2013.
Article in Chinese | WPRIM | ID: wpr-235642

ABSTRACT

Both reverse transcriptase (RT) and integrase (IN) play crucial roles in the life cycle of HIV-1, which are also key targets in the area of anti-HIV drug research. Reverse transcriptase inhibitors are involved in the most employed drugs used to treat AIDS patients and HIV-infected people, while one of the integrase inhibitors has already been approved by US FDA to appear on the market. Great achievement has been made in the research on both, separately. Recently, much more attention of medicinal chemistry researchers has been attracted to the strategies of multi-target drugs. Compounds with excellent potency against both HIV RT and IN, evidently defined as dual inhibitors targeting both enzymes, have been obtained through considerable significant exploration, which can be classified into two categories according to different strategies. Combinatorial chemistry approach together with high throughput screening methods and multi-target-based virtual screening strategy have been useful tools for identifying selective anti-HIV compounds for long times; Rational drug design based on pharmacophore combination has also led to remarkable results. In this paper, latest progress of both categories in the discovery and structural modification will be covered, with a view to contribute to the career of anti-HIV research.


Subject(s)
Drug Design , HIV Integrase Inhibitors , Chemistry , Pharmacology , HIV Reverse Transcriptase , HIV-1 , Humans , Molecular Structure , Reverse Transcriptase Inhibitors , Chemistry , Pharmacology , Structure-Activity Relationship
13.
Article in Chinese | WPRIM | ID: wpr-315009

ABSTRACT

<p><b>OBJECTIVE</b>To study the relationship between ultra-performance liquid chromatography (UPLC) fingerprints of Rheum species and their anti-HIV 1 activities.</p><p><b>METHOD</b>Twenty two samples of 16 species belonging to genus Rheum from various sources were collected and analyzed in this study. Firstly they were assayed for the HIV-1 reverse transcriptase (RT) associated ribonuclease H (RNase H) activity. Secondly the fingerprints were established by an optimized UPLC method. Sample was analyzed by UPLC-TOF-MS/MS to identify major peaks. The possible relationship between UPLC fingerprints and anti-HIV 1 activities of Rheum species were deduced by mathematical statistics method.</p><p><b>RESULT</b>Samples of R. austral, R. austral, R. hotaoense exhibited good anti-HIV 1 activities with IC50 < or = 0.2 mg x L(-1). The correlation of anti-HIV 1 activities and fingerprints showed that three compounds were the main bioactive components, and their retention times were 4.74, 7.99, 21.18 min, respectively.</p><p><b>CONCLUSION</b>Compounds in Rheum species with possible anti-HIV 1 activities were deduced by spectrum-effect relationship study. This study supported for study of medicinal plants in Rheum.</p>


Subject(s)
Anti-HIV Agents , Chemistry , Pharmacology , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Chemistry , Pharmacology , HIV Reverse Transcriptase , Metabolism , HIV-1 , Inhibitory Concentration 50 , Rheum , Chemistry , Ribonuclease H, Human Immunodeficiency Virus , Metabolism , Structure-Activity Relationship
14.
Rev. Inst. Med. Trop. Säo Paulo ; 54(4): 207-213, July-Aug. 2012. ilus, graf, tab
Article in English | LILACS | ID: lil-643952

ABSTRACT

The objective of this study is to identify subtypes of Human Immunodeficiency Virus type 1 (HIV-1) and to analyze the presence of mutations associated to antiretroviral resistance in the protease (PR) and reverse transcriptase (RT) regions from 48 HIV-1 positive treatment naïve patients from an outpatient clinic in Maringá, Paraná, Brazil. Sequencing was conducted using PR, partial RT and group-specific antigen gene (gag) nested PCR products from retrotranscribed RNA. Transmitted resistance was determined according to the Surveillance Drug Resistance Mutation List (SDRM) algorithm. Phylogenetic and SimPlot analysis of concatenated genetic segments classified sequences as subtype B 19/48 (39.6%), subtype C 12/48 (25%), subtype F 4/48 (8.3%), with 13/48 (27.1%) recombinant forms. Most recombinant forms were B mosaics (B/F 12.5%, B/C 10.4%), with one C/F (2.1%) and one complex B/C/F mosaic (2.1%). Low levels of transmitted resistance were found in this study, 2/48 (2.1% to NRTIs and 2.1% for PI). This preliminary data may subsidize the monitoring of the HIV evolution in the region.


O objetivo foi identificar subtipos do Vírus da Imunodeficiência Humana tipo-1 (HIV-1) e analisar a presença de mutações/polimorfismos nas regiões da protease (PR) e transcriptase reversa (TR) de 48 pacientes virgens de tratamento atendidos no município de Maringá, Paraná, Brasil. O sequenciamento foi conduzido usando produtos de nested PCR dos genes da PR, TR parcial e group-specific antigen gene (gag) de RNA retrotranscrito. A interpretação da resistência transmitida foi realizada segundo o algoritmo Surveillance Drug Resistance Mutation List (SDRM). As análises filogenética e SimPlot dos segmentos concatenados classificaram as sequências como subtipo B 19/48 (39,6%), subtipo C 12/48 (25%), subtipo F 4/48 (8,3%), com 13/48 (27,1%) formas recombinantes. A maioria das formas recombinantes era mosaicos B (B/F 12,5%, B/C 10,4%), com um C/F (2,1%) e um mosaico complexo B/C/F (2,1%). A prevalência de resistência transmitida foi de 4,2% (2,1% para ITRN e 2,1% para IP). Baixos níveis de resistência transmitida foram encontrados nesse estudo, 2/48 (2,1% para INTR e 2,1% para IP). Esses achados, embora preliminares, podem contribuir no monitoramento da epidemia de HIV na região.


Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Drug Resistance, Viral/genetics , HIV Infections/virology , HIV Protease/genetics , HIV Reverse Transcriptase/genetics , HIV-1 , Mutation/genetics , Base Sequence , Genotype , HIV-1 , Molecular Sequence Data , Phylogeny
15.
Mem. Inst. Oswaldo Cruz ; 107(4): 450-457, June 2012.
Article in English | LILACS | ID: lil-626436

ABSTRACT

Determining the prevalence and type of antiretroviral (ARV) resistance among ARV-naïve individuals is important to assess the potential responses of these individuals to first-line regimens. The prevalence of primary resistance and the occurrence of recent infections among individuals with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) were identified among recently diagnosed patients at five sexually transmitted disease/AIDS testing and counselling centres in the metropolitan region of Recife (RMR), Pernambuco, Brazil, between 2007-2009. One-hundred and eight samples were analysed using the Calypte® BED assay. Males predominated (56%), as did patients aged 31-50 years. Twenty-three percent presented evidence of a recent HIV infection. The median CD4+ T lymphocyte count was 408 cells/mm³ and the median viral load was 3.683 copies/mL. The prevalence of primary resistance was 4.6% (confidence interval 95% = 1-8.2%) based on criteria that excluded common polymorphisms in accordance with the surveillance drug resistance mutation criteria. The prevalence of resistance to non-nucleoside reverse transcriptase, nucleoside/nucleotide reverse transcriptase and protease inhibitors were 3.8%, 1.5% and 0.8%, respectively. Fifty-seven percent of strains were from clade B, 37.7% were clade F and 3.1% were clade C; there were no statistically significant differences with respect to resistance between clades. Recent infection tended to be more common in men (p = 0.06) and in municipalities in the south of the RMR (Jaboatão dos Guararapes and Cabo de Santo Agostinho) (p = 0.046). The high prevalence of recent infection and the high prevalence of non-B strains in this poor Brazilian region merit further attention.


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Drug Resistance, Viral/genetics , HIV Infections/virology , HIV Protease/genetics , HIV Reverse Transcriptase/genetics , HIV-1 , Mutation/genetics , Anti-HIV Agents/therapeutic use , Genotype , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV-1 , Prevalence , Protease Inhibitors/therapeutic use , RNA, Viral/genetics , Reverse Transcriptase Inhibitors/therapeutic use , Socioeconomic Factors , Urban Population , Viral Load
16.
Chinese Journal of Virology ; (6): 291-296, 2012.
Article in Chinese | WPRIM | ID: wpr-354733

ABSTRACT

Nucleoside reverse transcriptase inhibitors which act as a major component of highly active antiretroviral therapy regimens are widely used in treatment of Acquired Immune Deficiency Syndrome. However, the emergence of drug-resistant variants of HIV-1 severely limits the effectiveness of these drugs. Many drug resistance mutations confer a fitness cost, which can be partially overcome by compensatory mutations or other molecular mechanisms. This review focuses on the impacts of resistance mutations emerging during treatment with nucleoside reverse transcriptase inhibitors on viral fitness, and inter actions between these mutations.


Subject(s)
Animals , Drug Resistance, Viral , HIV Infections , Drug Therapy , Virology , HIV Reverse Transcriptase , Genetics , Metabolism , HIV-1 , Genetics , Physiology , Humans , Mutation , Nucleosides , Therapeutic Uses , Reverse Transcriptase Inhibitors , Therapeutic Uses
17.
Acta Pharmaceutica Sinica ; (12): 1011-1016, 2012.
Article in Chinese | WPRIM | ID: wpr-276207

ABSTRACT

This study is to investigate the mechanism of action of lindenane disesquiterpenoid shizukaol F on HIV-1 replication. Real time quantity PCR, ELISA assay and fluorescence methods were used to test HIV-1 reverse transcription process, RNA-dependent DNA polymerase activity, and RNase H activity, respectively. It showed that shizukaol F inhibited LTR/Gag production of HIV-1 reverse transcription with an IC50 of 9.11 micromol x L(-1). This result is consistent with its inhibitory effect on HIV-1 replication (IC50 of 6.12 micromol x L(-1)). Mechanism studies showed that compound shizukaol F inhibited HIV-1 RT-RNase H with IC50 of 26.4 micromol x L(-1), but had no effect on HIV-1 RT RNA-dependent DNA polymerase activity. In conclusion, shizukaol F is a new structural type HIV-1 RNase H inhibitor. This discovery will provide a clue for new type of reverse transcriptase inhibitors development.


Subject(s)
Cell Line, Tumor , Drugs, Chinese Herbal , Chemistry , Pharmacology , HEK293 Cells , HIV Reverse Transcriptase , Metabolism , HIV-1 , Physiology , Humans , Inhibitory Concentration 50 , Magnoliopsida , Chemistry , Molecular Structure , Plants, Medicinal , Chemistry , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Pathology , Reverse Transcriptase Inhibitors , Chemistry , Pharmacology , Ribonuclease H , Metabolism , Sesquiterpenes , Chemistry , Pharmacology , Virus Replication
18.
Acta Pharmaceutica Sinica ; (12): 1409-1422, 2012.
Article in Chinese | WPRIM | ID: wpr-274645

ABSTRACT

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) play an important roles in the prevention and treatment of AIDS. NNRTIs can specifically target at HIV reverse transcriptase (RT) and have the advantages of high potency and low toxicity, which make them a research focus for a long time. In the guidance of structural optimization strategies (bioisosterism, molecular hybridization and scaffold hopping) in medicinal chemistry, structural modification to lead compounds can be carried out to design new compounds with different levels, which will improve the efficiency of drug discovery and decrease the cost of drug development. It is an effective way to find new NNRTIs. In this review, we will expatiate on the application of different levels of structural optimization strategies in the NNRTIs structural modification with concrete examples.


Subject(s)
Anti-HIV Agents , Chemistry , Drug Design , HIV Reverse Transcriptase , Chemistry , Molecular Structure , Reverse Transcriptase Inhibitors , Chemistry
19.
Rev. panam. salud pública ; 30(6): 641-648, Dec. 2011.
Article in English | LILACS | ID: lil-612963

ABSTRACT

Objective. To assess human immunodeficiency virus (HIV) diversity and the prevalence of transmitted drug resistance (TDR) in Guatemala. Methods. One hundred forty-five antiretroviral treatment-naïve patients referred to the Roosevelt Hospital in Guatemala City were enrolled from October 2010 to March 2011. Plasma HIV pol sequences were obtained and TDR was assessed with the Stanford algorithm and the World Health Organization (WHO) TDR surveillance mutation list. Results. HIV subtype B was highly prevalent in Guatemala (96.6%, 140/145), and a 2.8% (4/145) prevalence of BF1 recombinants and 0.7% (1/145) prevalence of subtype C viruses were found. TDR prevalence for the study period was 8.3% (12/145) with the Stanford database algorithm (score > 15) and the WHO TDR surveillance mutation list. Most TDR cases were associated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) (83.3%, 10/12); a low prevalence of nucleoside reverse transcriptase inhibitors and protease inhibitors was observed in the cohort (< 1% for both families). Low selection of antiretroviral drug resistance mutations was found, except for NNRTI-associated mutations. Major NNRTI mutations such as K101E, K103N, and E138K showed higher frequencies than expected in ART-naïve populations. Higher literacy was associated with a greater risk of TDR (odds ratio 4.14, P = 0.0264). Conclusions. This study represents one of the first efforts to describe HIV diversity and TDR prevalence and trends in Guatemala. TDR prevalence in Guatemala was at the intermediate level. Most TDR cases were associated with NNRTIs. Further and continuous TDR surveillance is necessary to gain more in-depth knowledge about TDR spread and trends in Guatemala and to optimize treatment outcomes in the country.


Objetivo. Evaluar la diversidad del virus de la inmunodeficiencia humana (VIH) y la prevalencia de la farmacorresistencia transmitida en Guatemala. Métodos. Entre octubre del 2010 y marzo del 2011 se incluyeron en el estudio 145 pacientes no tratados anteriormente con antirretrovirales, derivados al Hospital Roosevelt en la Ciudad de Guatemala. Se obtuvieron las secuencias pol a partir del VIH plasmático y se evaluó la farmacorresistencia transmitida con el algoritmo de Stanford y la lista de mutaciones para la vigilancia de la farmacorresistencia transmitida de la Organización Mundial de la Salud (OMS). Resultados. El subtipo B del VIH fue sumamente prevalente en Guatemala (96,6%, 140/145), y se encontró una prevalencia de formas recombinantes BF1 de 2,8% (4/145) y una prevalencia del subtipo C del virus de 0,7% (1/145). La prevalencia de la farmacorresistencia transmitida durante el período de estudio fue de 8,3% (12/145) según el algoritmo de la base de datos de Stanford (puntuación > 15) y la lista de mutaciones para la vigilancia de la farmacorresistencia transmitida de la OMS. En la mayoría de los casos, la farmacorresistencia transmitida se asoció con los inhibidores de la transcriptasa inversa no análogos de nucleósidos (ITINN) (83,3%, 10/12); en la cohorte se observó una baja prevalencia asociada con los inhibidores de la transcriptasa inversa análogos de nucleósidos y con los inhibidores de la proteasa (< 1% para ambas familias de fármacos). Se encontró una baja selección de mutaciones causantes de farmacorresistencia debidas a los antirretrovirales, excepto en las mutaciones asociadas a los ITINN. Las mutaciones importantes relacionadas con los ITINN, como K101E, K103N y E138K, mostraron frecuencias más elevadas que las esperadas en las poblaciones vírgenes de tratamiento antirretroviral. En las personas con un nivel de escolaridad más elevado se encontró un mayor riesgo de farmacorresistencia transmitida (razón de posibilidades 4,14; P = 0,0264). Conclusiones. Este estudio representa uno de los primeros intentos de describir la diversidad del VIH, y la prevalencia de la farmacorresistencia transmitida y sus tendencias en Guatemala. La prevalencia de la farmacorresistencia transmitida en Guatemala presentó un nivel intermedio y en la mayoría de los casos se asoció con los ITINN. Se necesita una vigilancia más intensa y sostenida de la farmacorresistencia transmitida para conocer más exhaustivamente su grado de diseminación y sus tendencias en Guatemala, al igual que para optimizar los resultados del tratamiento antirretroviral en el país.


Subject(s)
Adult , Female , Humans , Male , Anti-HIV Agents/pharmacology , Drug Resistance, Viral , HIV-1 , Anti-HIV Agents/therapeutic use , Drug Resistance, Viral/genetics , Educational Status , Genes, pol , Genotype , Guatemala/epidemiology , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/virology , HIV Protease Inhibitors/pharmacology , HIV Protease Inhibitors/therapeutic use , HIV Reverse Transcriptase/genetics , HIV-1 , Molecular Epidemiology , Mutation, Missense , Point Mutation , Population Surveillance , Prevalence , Reverse Transcriptase Inhibitors/pharmacology , Reverse Transcriptase Inhibitors/therapeutic use
20.
Rev. panam. salud pública ; 30(6)Dec. 2011. tab
Article in English | LILACS | ID: lil-612968

ABSTRACT

Objetivo. Investigar la prevalencia de farmacorresistencia transmitida del VIH en adultos en Panamá mediante un estudio del umbral modificado de la Organización Mundial de la Salud (OMS) e investigar las tasas de resistencia inicial en lactantesseropositivos para el VIH en Panamá.Métodos. En el Instituto Conmemorativo Gorgas, en 47 adultos seropositivos al VIH se efectuó la genotipificación de las mutaciones asociadas con la farmacorresistencia transmitida en los genes de la transcriptasa inversa y la proteasa del VIH-1, según las directrices del estudio umbral de la OMS, modificadas para incluir a las personas ≤ 26 años de edad. Las tasas de prevalencia de las mutaciones farmacorresistentes contra tres clases de fármacos antirretroviral —inhibidores de la transcriptasa inversaanálogos de nucleósidos, inhibidores de la transcriptasa inversa no análogos de nucleósidos e inhibidores de la proteasa— se clasificaron en bajas (< 5,0%), moderadas (5,0%–15,0%) o altas (> 15,0%). También se llevó a cabo genotipificación y se calcularonlas tasas de prevalencia de las mutaciones causantes de farmacorresistencia en 25 lactantes.Resultados. En los adultos de Panamá la farmacorresistencia transmitida fue moderada: 6 de 47 adultos seropositivos para el VIH presentaron una o más mutacionesasociadas con farmacorresistencia transmitida. Las mutaciones farmacorresitentes de transmisión horizontal fueron moderadas para los inhibidores de la transcriptasainversa análogos de nucleósidos y los inhibidores de la transcriptasa inversa no análogos de nucleósidos, y bajas para los inhibidores de la proteasa. En Panamá la transmisiónvertical del VIH ha disminuido en el período 2002–2007, pero la prevalenciade la farmacorresistencia del VIH transmitida por vía vertical es moderada (12,0%) y está surgiendo como un problema debido a la cobertura antirretroviral incompletadurante el embarazo...


Objective. To investigate the prevalence of transmitted drug-resistant HIV among adults in Panama by using a modified World Health Organization Threshold Survey (WHO-TS) and to investigate rates of initial resistance among HIV-positive infants in Panama.Methods. At the Gorgas Memorial Institute, 47 HIV-positive adults were genotyped for mutations associated with transmitted drug resistance (TDR) in the reverse transcriptase andprotease genes of HIV-1, according to WHO-TS guidelines, modified to include patients ≤ 26 years old. Prevalence rates for drug-resistance mutations against three classes of antiretroviraldrugs—nucleoside analog reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors—were calculated as low (< 5.0%), moderate (5.0%–15.0%), and high (> 15.0%). Twenty-five infant patients were also genotyped and prevalence rates for drug-resistance mutations were calculated. Results. TDR among Panamanian adults was moderate: 6 of 47 HIV-positive adultsshowed one or more mutations associated with TDR. Horizontal TDR mutations were moderate for NRTIs and NNRTIs and low for protease inhibitors. Vertical transmission of HIV inPanama has decreased for 2002–2007, but vertical HIV TDR prevalence is moderate (12.0%) and is emerging as a problem due to incomplete antiretroviral coverage in pregnancy. Conclusions. The prevalence of HIV TDR indicated by this study, combined with knownrates of HIV infection in Panama, suggests more extensive surveys are needed to identify risk factors associated with transmission of HIV drug resistance. Specific WHO-TS guidelines for monitoring vertical transmission of drug-resistant HIV should be established.


Subject(s)
Adolescent , Adult , Female , Humans , Infant , Infant, Newborn , Male , Pregnancy , Young Adult , Anti-HIV Agents/pharmacology , Drug Resistance, Viral , HIV-1 , Anti-HIV Agents/therapeutic use , Drug Resistance, Viral/genetics , Genes, pol , Genotype , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/transmission , HIV Infections/virology , HIV Protease Inhibitors/pharmacology , HIV Protease Inhibitors/therapeutic use , HIV Protease/genetics , HIV Reverse Transcriptase/genetics , HIV-1 , Infectious Disease Transmission, Vertical , Prevalence , Panama/epidemiology , Pregnancy Complications, Infectious/virology , Reverse Transcriptase Inhibitors/pharmacology , Reverse Transcriptase Inhibitors/therapeutic use
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