Evaluación del impacto de la pandemia de COVID-19 en el seguimiento y tratamiento de gestantes con sífilis y sus parejas: análisis comparativo con un período prepandémico / Evaluation of the impact of the COVID-19 pandemic onthe follow-up and treatment of pregnant women with syphilis and their partners: comparative analysis with a pre-pandemic period

Se realizó un estudio observacional descriptivo transver-sal retrospectivo de las gestantes con nuevo diagnóstico de sífilis atendidas en el Hospital Materno Infantil de San Isidro "Dr. Carlos Gianantonio" durante los años pandé-micos 2020-2021. Se asistieron 108 gestantes con sífilis: 69 en 2020 y 39 en 2021. El tratamiento de aquellas que finalizaron el embarazo al momento de realizar este estu-dio (n=95) fue adecuado en el 78% (74) de los casos, en el 16,8% (16) fue inadecuado y el 5,2 % (5) perdió el segui-miento. El 11% presentó reinfección durante el embarazo. Con respecto a las parejas (n=103), el 84,6% (88) tenía una relación estable; se testeó al 70% (73) de las parejas, de las cuales el 45% (33) tenía VDRL positiva y se trató al 88% (29). Los resultados del estudio no muestran diferencias significativas en los indicadores evaluados (tratamiento adecuado y reinfección de la gestante y testeo/tratamien-to de la pareja) al comparar los períodos prepandémico (2018-2019) vs. pandémico (2020-2021)

A retrospective cross-sectional descriptive observational study of pregnant women with a new diagnosis of syphilis treated at the San Isidro Maternity Hospital during the 2020-2021 pandemic years was carried out. 108 pregnant women with syphilis were assisted: 69 in 2020 and 39 in 2021. The treatment of those who ended their pregnancy at the time of this study (n=95) was adequate in 78% (74) of the cases, 16,8% (16) were inadequate and 5.2% (5) lost follow-up. 11% presented reinfection during pregnancy. Regarding the couples (n=103), 84.6% (88) had a stable relationship, 70% (73) of the couples were tested, of which 45% (33) had positive vdrl and were treated 88% (29). The results of the study do not show significant differences in the indicators evaluated (adequate treatment and reinfection of the pregnant woman and testing/treatment of the partner) when comparing the pre-pandemic (2018-2019) vs. pandemic (2020-2021) periods

[Cohort of pregnant and postpartum women with COVID-19. Comparative analysis between two pandemic waves]. / Cohorte de gestantes y puérperas con COVID-19. Análisis comparativo entre dos olas pandémicas.

INTRODUCTION: The clinical presentation of pregnant women with COVID-19 varied according to the time of the pandemic. OBJECTIVE: The clinic, complications and lethality were described, as well as a comparative analysis of the clinical presentation during the first two pandemic waves of pregnant and postpartum women with COVID-19. METHODS: An observational prospective cohort study of pregnant women assisted in the Municipal Maternity of San Isidro was carried out between 04/01/2020 and 07/31/21. RESULTS: The infection was confirmed in 103 pregnant women, 76.7% had a mild condition, 18.4% moderate and 4.8% severe. 59% were assisted by telemedicine, 41% were admitted and 2.9% required mechanical ventilation. Most had a good evolution and the case fatality rate was < 1% (n = 1). At the time of this analysis, 78% of the women had completed pregnancy. 41% of them presented some type of complication, the most frequent being: premature rupture of the membrane 42%, arterial hypertension and other associated pathologies (including a patient with preeclampsia) 27% and preterm delivery 18%. In the comparative analysis between the first two pandemic waves, there was a higher proportion of moderate/severe cases (p = 0.016) and the indication for mechanical ventilation was significantly higher (p = 0.048) in 2021. DISCUSSION: These findings support the need for prioritize this group of patients to implement preventive strategies.

Introducción: La presentación clínica de las gestantes con COVID-19 fue variando según el momento de la pandemia. Objetivo: Se describió la clínica, complicaciones y letalidad, así como un análisis comparativo de la presentación clínica durante las dos primeras olas pandémicas de las gestantes y puérperas con COVID-19. Métodos: Se realizó un estudio de cohorte prospectivo observacional de las gestantes asistidas en la Maternidad Municipal de San Isidro entre el 01/04/2020 al 31/07/21. Resultados: Se confirmó la infección de 103 gestantes, de las cuales el 76.7% cursó un cuadro leve, 18.4% moderado y 4.8% grave. El 59% fueron asistidas por telemedicina, el 41% se internó, de las cuales el 2.9% requirieron asistencia respiratoria mecánica (ARM). La mayoría tuvo buena evolución y la tasa de letalidad fue < 1% (n = 1). Al momento del presente análisis el 78% de las mujeres habían finalizado la gestación. El 41% de ellas, presentó algún tipo de complicación, siendo lo más frecuente: ruptura prematura de membrana 42%, hipertensión arterial y otras patologías asociadas (incluyendo una paciente con preeclampsia) el 27% y parto pretérmino el 18%. En el análisis comparativo entre las dos primeras olas pandémicas, hubo una mayor proporción de casos moderados/graves (p=0.016) y fue significativamente mayor la indicación de ARM (p=0.048) en el 2021. Discusión: Estos hallazgos avalan la necesidad de priorizar a este grupo de pacientes para implementar estrategias preventivas.

Cohorte de gestantes y puérperas con COVID-19. Análisis comparativo entre dos olas pandémicas / Cohort of pregnant and postpartum women with COVID-19. Comparative analysis between two pandemic waves

Resumen Introducción: La presentación clínica de las gestantes con COVID-19 fue variando según el momento de la pandemia. Objetivo: Se describió la clínica, complicaciones y letalidad, así como un análisis comparativo de la presentación clínica durante las dos primeras olas pandémicas de las gestantes y puérperas con COVID-19. Métodos: Se realizó un estudio de cohorte prospectivo observacional de las gestantes asistidas en la Maternidad Municipal de San Isidro entre el 01/04/2020 al 31/07/21. Resultados: Se confirmó la infección de 103 gestantes, de las cuales el 76.7% cursó un cuadro leve, 18.4% moderado y 4.8% grave. El 59% fueron asistidas por telemedicina, el 41% se internó, de las cuales el 2.9% requirieron asistencia respira toria mecánica (ARM). La mayoría tuvo buena evolución y la tasa de letalidad fue <1% (n = 1). Al momento del presente análisis el 78% de las mujeres habían finalizado la gestación. El 41% de ellas, presentó algún tipo de complicación, siendo lo más frecuente: ruptura prematura de membrana 42%, hipertensión arterial y otras pato logías asociadas (incluyendo una paciente con preeclampsia) el 27% y parto pretérmino el 18%. En el análisis comparativo entre las dos primeras olas pandémicas, hubo una mayor proporción de casos moderados/graves (p=0.016) y fue significativamente mayor la indicación de ARM (p=0.048) en el 2021. Discusión: Estos hallazgos avalan la necesidad de priorizar a este grupo de pacientes para implementar estrategias preventivas.

Abstract Introduction: The clinical presentation of pregnant women with COVID-19 varied according to the time of the pandemic. Objective: The clinic, complications and lethality were described, as well as a comparative analy sis of the clinical presentation during the first two pandemic waves of pregnant and postpartum women with COVID-19. Methods: An observational prospective cohort study of pregnant women assisted in the Municipal Maternity of San Isidro was carried out between 04/01/2020 and 07/31/21. Results: The infection was confirmed in 103 pregnant women, 76.7% had a mild condition, 18.4% moderate and 4.8% severe. 59% were assisted by telemedicine, 41% were admitted and 2.9% required mechanical ventilation. Most had a good evolution and the case fatality rate was < 1% (n = 1). At the time of this analysis, 78% of the women had completed pregnancy. 41% of them presented some type of complication, the most frequent being: premature rupture of the membrane 42%, arterial hypertension and other associated pathologies (including a patient with preeclampsia) 27% and preterm delivery 18%. In the comparative analysis between the first two pandemic waves, there was a higher proportion of moderate/severe cases (p = 0.016) and the indication for mechanical ventilation was significantly higher (p = 0.048) in 2021. Discussion: These findings support the need for prioritize this group of patients to implement preventive strategies

Omicron Breakthrough Infection After Heterologous Prime-Boost Vaccination Induces a Vigorous Antibody Response.

Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is usually asymptomatic or mild and appears to be poorly immunogenic at least in unvaccinated individuals. Here, we found that health care workers vaccinated with 2 doses of Sputnik V and a booster dose of ChAdOx1 mount a vigorous neutralizing-antibody response after Omicron breakthrough infection.

Safety and efficacy of GSK2248761, a next-generation nonnucleoside reverse transcriptase inhibitor, in treatment-naive HIV-1-infected subjects.

GSK2248761 is a novel, once-daily (QD), next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) with activity against efavirenz-resistant strains. Two phase I/IIa, double-blind, randomized, placebo-controlled studies investigated the antiviral activity, safety, and pharmacokinetics (PK) of several doses of GSK2248761 monotherapy in treatment-naive HIV-infected subjects. In the initial study, 10 subjects (8 active and 2 placebo) per dose received sequentially descending GSK2248761 monotherapy regimens of 800, 400, 200, and 100 mg QD for 7 days. Because a dose-response relationship was not identified, a second study examined a lower, 30-mg QD dose in 8 subjects (6 active and 2 placebo). Adverse events, viral load (VL), PK, and reverse transcriptase mutations were assessed and combined for analysis. Treatment with GSK2248761 for 7 days was well tolerated with no serious adverse events or discontinuations. The mean VL reductions from baseline on day 8 were 0.97, 1.87, 1.84, 1.81, and 1.78 log(10) copies/ml for GSK2248761 doses of 30, 100, 200, 400, and 800 mg QD, respectively. GSK2248761 PK (maximum drug concentration in serum [C(max)], area under the plasma concentration-time curve from 0 h to the end of the dosing interval [AUC(0-τ)], and concentration at the end of the dosing interval [C(τ)]) increased proportionally over the dose range of 30 to 800 mg QD. The relationship between short-term VL change and GSK2248761 PK was best described by a maximum-effect (E(max)) model using C(τ) (E(max) = 2.0; 50% effective concentration [EC(50)] = 36.9 ng/ml). No NNRTI resistance mutations emerged during the study. GSK2248761 at 100 to 800 mg QD for 7 days was well tolerated, demonstrated potent antiviral activity in treatment-naive HIV-infected subjects, and had favorable PK and resistance profiles. GSK2248761 is no longer in clinical development.

A Canadian Critical Care Trials Group project in collaboration with the international forum for acute care trialists - Collaborative H1N1 Adjuvant Treatment pilot trial (CHAT): study protocol and design of a randomized controlled trial.

BACKGROUND: Swine origin influenza A/H1N1 infection (H1N1) emerged in early 2009 and rapidly spread to humans. For most infected individuals, symptoms were mild and self-limited; however, a small number developed a more severe clinical syndrome characterized by profound respiratory failure with hospital mortality ranging from 10 to 30%. While supportive care and neuraminidase inhibitors are the main treatment for influenza, data from observational and interventional studies suggest that the course of influenza can be favorably influenced by agents not classically considered as influenza treatments. Multiple observational studies have suggested that HMGCoA reductase inhibitors (statins) can exert a class effect in attenuating inflammation. The Collaborative H1N1 Adjuvant Treatment (CHAT) Pilot Trial sought to investigate the feasibility of conducting a trial during a global pandemic in critically ill patients with H1N1 with the goal of informing the design of a larger trial powered to determine impact of statins on important outcomes. METHODS/DESIGN: A multi-national, pilot randomized controlled trial (RCT) of once daily enteral rosuvastatin versus matched placebo administered for 14 days for the treatment of critically ill patients with suspected, probable or confirmed H1N1 infection. We propose to randomize 80 critically ill adults with a moderate to high index of suspicion for H1N1 infection who require mechanical ventilation and have received antiviral therapy for ≤ 72 hours. Site investigators, research coordinators and clinical pharmacists will be blinded to treatment assignment. Only research pharmacy staff will be aware of treatment assignment. We propose several approaches to informed consent including a priori consent from the substitute decision maker (SDM), waived and deferred consent. The primary outcome of the CHAT trial is the proportion of eligible patients enrolled in the study. Secondary outcomes will evaluate adherence to medication administration regimens, the proportion of primary and secondary endpoints collected, the number of patients receiving open-label statins, consent withdrawals and the effect of approved consent models on recruitment rates. DISCUSSION: Several aspects of study design including the need to include central randomization, preserve allocation concealment, ensure study blinding compare to a matched placebo and the use novel consent models pose challenges to investigators conducting pandemic research. Moreover, study implementation requires that trial design be pragmatic and initiated in a short time period amidst uncertainty regarding the scope and duration of the pandemic. TRIAL REGISTRATION NUMBER: ISRCTN45190901.

Lack of viral selection in human immunodeficiency virus type 1 mother-to-child transmission with primary infection during late pregnancy and/or breastfeeding.

Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) as described for women with an established infection is, in most cases, associated with the transmission of few maternal variants. This study analysed virus variability in four cases of maternal primary infection occurring during pregnancy and/or breastfeeding. Estimated time of seroconversion was at 4 months of pregnancy for one woman (early seroconversion) and during the last months of pregnancy and/or breastfeeding for the remaining three (late seroconversion). The C2V3 envelope region was analysed in samples of mother-child pairs by molecular cloning and sequencing. Comparisons of nucleotide and amino acid sequences as well as phylogenetic analysis were performed. The results showed low variability in the virus population of both mother and child. Maximum-likelihood analysis showed that, in the early pregnancy seroconversion case, a minor viral variant with further evolution in the child was transmitted, which could indicate a selection event in MTCT or a stochastic event, whereas in the late seroconversion cases, the mother's and child's sequences were intermingled, which is compatible with the transmission of multiple viral variants from the mother's major population. These results could be explained by the less pronounced selective pressure exerted by the immune system in the early stages of the mother's infection, which could play a role in MTCT of HIV-1.

Determinants of treatment access in a population-based cohort of HIV-positive men and women living in Argentina.

OBJECTIVE: To report emerging data on the use of highly active antiretroviral therapy (HAART) in Argentina by assessing patterns of HAART access and late vs early treatment initiation in a population-based cohort of adults infected with HIV type-1. DESIGN: The Prospective Study on the Use and Monitoring of Antiretroviral Therapy (PUMA) is a study of 883 HIV-positive individuals enrolled in the Argentinean drug treatment program. Individuals were 16 years of age and older and were recruited from 10 clinics across Argentina. METHODS: Sociodemographic and clinical characteristics were examined using contingency tables (Pearson chi-square test and Fisher exact test) for categoric variables and Wilcoxon rank-sum test for continuous variables. To analyze time to initiation of HAART we used Kaplan-Meier methods and Cox regression. RESULTS: Patients who initiated HAART were more likely to be older, have an AIDS-defining illness, be an injection drug user (IDU), have a lower median CD4 cell count, have a higher median viral load, and be less likely to be men who have sex with men (MSM). In multivariate analysis, AIDS-defining illness and plasma viral load were significantly associated with time to starting therapy. Patients who received late access were more likely to be diagnosed with AIDS and have higher median plasma viral loads than those receiving early access. CONCLUSION: Our results indicate that despite free availability of treatment, monitoring, and care in Argentina, a significant proportion of men and women are accessing HAART late in the course of HIV disease. Further characterization of the HIV-positive population will allow for a more comprehensive evaluation of the impact of HAART within the Argentinean drug treatment program.

Determinants of Treatment Access in a Population-based Cohort of HIV-positive Men and Women Living in Argentina.

OBJECTIVE: To report emerging data on the use of highly active antiretroviral therapy (HAART) in Argentina by assessing patterns of HAART access and late vs early treatment initiation in a population-based cohort of adults infected with HIV type-1. DESIGN: The Prospective Study on the Use and Monitoring of Antiretroviral Therapy (PUMA) is a study of 883 HIV-positive individuals enrolled in the Argentinean drug treatment program. Individuals were 16 years of age and older and were recruited from 10 clinics across Argentina. METHODS: Sociodemographic and clinical characteristics were examined using contingency tables (Pearson chi-square test and Fisher exact test) for categoric variables and Wilcoxon rank-sum test for continuous variables. To analyze time to initiation of HAART we used Kaplan-Meier methods and Cox regression. RESULTS: Patients who initiated HAART were more likely to be older, have an AIDS-defining illness, be an injection drug user (IDU), have a lower median CD4 cell count, have a higher median viral load, and be less likely to be men who have sex with men (MSM). In multivariate analysis, AIDS-defining illness and plasma viral load were significantly associated with time to starting therapy. Patients who received late access were more likely to be diagnosed with AIDS and have higher median plasma viral loads than those receiving early access. CONCLUSION: Our results indicate that despite free availability of treatment, monitoring, and care in Argentina, a significant proportion of men and women are accessing HAART late in the course of HIV disease. Further characterization of the HIV-positive population will allow for a more comprehensive evaluation of the impact of HAART within the Argentinean drug treatment program.

Safe treatment interruptions in patients with nadir CD4 counts of more than 350 cells/microL: a randomized trial.

OBJECTIVE: To evaluate clinical, immunologic, and virologic performance of patients with nadir CD4 counts of >350 cells/microL upon treatment interruption. DESIGN: Randomized, open-label clinical trial of 48 weeks' duration. METHODS: Patients on effective highly active antiretroviral therapy, with nadir CD4 counts of >350 cells/microL and peak viral loads of <50,000 copies/mL were randomized to continue therapy or to interrupt antiretroviral medication. End points for patients with treatment interruption were CD4 counts of <350 cells/microL, viral loads of >1 log above the pretherapy values, or clinical symptoms attributable to HIV, at which point treatment was restarted. In the continuation group, the end points were virologic failure, opportunistic infections, and treatment discontinuation due to toxicities. RESULTS: Twenty patients were randomized to stop therapy and 16 patients to continue. Median CD4 counts at baseline were 643 cells/microL for the interruption group and 633 cells/microL for the continuation group. No end points were reached in the interruption group. By week 8, viral load returned to values comparable to those of pretherapy in all patients in the interruption group and remained stable until week 48. CD4 counts dropped in the interruption group (median loss of 156 cells/microL) at week 48. Significant decreases in venous lactate were observed in the interruption group. CONCLUSIONS: Treatment interruptions in patients with nadir CD4 counts of >350 cells/microL seem safe for at least 48 weeks. Pretherapy viral load appears as a valuable tool to predict its level at week 48.

Cytomegalovirus UL97 mutations associated with ganciclovir resistance in immunocompromised patients from Argentina.

BACKGROUND: Prolonged therapy with ganciclovir (GCV) can result in the development of GCV-resistant strains due to mutations in the viral phosphotransferase (UL97 gene) and/or in the viral DNA polymerase (UL54 gene). OBJECTIVES: The purpose of this study was to detect by molecular methods the most prevalent UL97 mutants which confer ganciclovir-resistance in immunocompromised populations. STUDY DESIGN: Patients from two populations were selected: (a) renal transplant patients with active cytomegalovirus (CMV) infection and more than one cycle of GCV; (b) HIV-infected patients with retinitis due to CMV, who were under GCV induction, maintenance therapy or withdrawal. Patients were followed up by pp65 antigenemia and by viral isolation from blood or/and urine samples. Two fragments (133 and 255pb) of the UL97 gene were amplified by polymerase chain reaction (PCR) from CMV isolates. RESULTS: Nine from 12 isolates obtained were sequenced, three from two renal transplant patients and six from five HIV-infected patients. A UL97 mutation, known to confer GCV resistance, was found in two isolates from a renal transplant patient. A methionine to valine mutation at codon 460 (M460V) was detected. These isolates exhibited another mutation at codon 605, whose amino acid changed from aspartic acid (D) to glutamic acid (E). These findings were observed after treatment with IV-GCV/ O-GCV/ IV-GCV for 151 days. The 605 mutation was also detected in leukocytes from the same patient previous to the beginning of the treatment with GCV. CONCLUSIONS: Although a known resistant mutation appeared in a renal transplant patient, it was not associated with CMV disease. We suggest that the D605E mutation could "partially or totally compensate" for the effect of GCV resistance conferred by the 460 mutation. Further studies should be performed to confirm this hypothesis.

Origin of human immunodeficiency virus type 1 quasispecies emerging after antiretroviral treatment interruption in patients with therapeutic failure.

The emergence of antiretroviral (ARV) drug-resistant human immunodeficiency virus type 1 (HIV-1) quasispecies is a major cause of treatment failure. These variants are usually replaced by drug-sensitive ones when the selective pressure of the drugs is removed, as the former have reduced fitness in a drug-free environment. This was the rationale for the design of structured ARV treatment interruption (STI) studies for the management of HIV-1 patients with treatment failure. We have studied the origin of drug-sensitive HIV-1 quasispecies emerging after STI in patients with treatment failure due to ARV drug resistance. Plasma and peripheral blood mononuclear cell samples were obtained the day of treatment interruption (day 0) and 30 and 60 days afterwards. HIV-1 pol and env were partially amplified, cloned, and sequenced. At day 60 drug-resistant variants were replaced by completely or partially sensitive quasispecies. Phylogenetic analyses of pol revealed that drug-sensitive variants emerging after STI were not related to their immediate temporal ancestors but formed a separate cluster, demonstrating that STI leads to the recrudescence and reemergence of a sequestrated viral population rather than leading to the back mutation of drug-resistant forms. No evidence for concomitant changes in viral tropism was seen, as deduced from env sequences. This study demonstrates the important role that the reemergence of quasispecies plays in HIV-1 population dynamics and points out the difficulties that may be found when recycling ARV therapies with patients with treatment failure.

Higher rate of toxicity with no increased efficacy when hydroxyurea is added to a regimen of stavudine plus didanosine and nevirapine in primary HIV infection.

Twenty-four subjects presenting at a single treatment center with primary HIV infection were enrolled in a pilot study aimed to establish the possible role of hydroxyurea in this setting. Study participants were randomly assigned to receive or not to receive hydroxyurea in addition to stavudine (d4T) plus didanosine (ddI) and nevirapine (NVP). Seventy-five percent of patients without hydroxyurea had plasma HIV RNA below 50 copies/mL at 48 weeks by both intention-to-treat (ITT) and on-treatment (OT) analysis in comparison with 50% (ITT) and 67% (OT) of patients with hydroxyurea (p >.1). A median increase of >200 cells/mm3 was observed from baseline to week 48 whether or not hydroxyurea was included in the regimen. Overall, in 12 patients treated with hydroxyurea, 33 adverse events were reported versus 19 reported for 12 patients who did not receive hydroxyurea (p <.05). Our results suggest that that adding hydroxyurea to a regimen of d4T plus ddI and NVP increases toxicity without improving the antiviral effect.

Estudio de la presencia de variantes del HIV-1 resistentes a drogas antirretrovirales en Argentina: período 1997-2001 / Study of the presence of variants of the HIV-1 resistant to antiretroviral drugs in Argentina: period 1997-2001

La instauración de tratamientos antirretrovirales de alta eficacia (HAARTs) ha llevado a la disminución de la morbimortalidad asociada a HIV-1/SIDA en países industrializados. Sin embargo, uno de los principales factores asociados a la falla terapéutica es la selección de variantes de HIV-1 resistentes a las drogas antirretrovirales (ARVs). Dichas variantes virales se caracterizan por presentar mutaciones en las enzimas virales que son los blancos de la acción de los fármacos: la proteasa viral (PR) y la transcriptasa reversa (RT). Las variantes del HIV-1 resitente a ARVs seleccionadas en pacientes tratados no sólo se asocian al fracaso terapéutico en dichos individuos, sino que también pueden ser transmitidas a la población no infectada. De esta forma, individuos infectados con HIV-1 que nunca han sido expuestos a drogas ARVs (naïve) pueden albergar virus resistentes, lo que llevaría a la falla terapéutica al iniciarse el tratamiento. El objetivo del presente trabajo fue el de caracterizar los perfiles de resistencia en pacientes HIV-1 seropositivos con falla terapéutica. Asimismo, con el fin de estimar la tasa de transmisión de variantes resistentes a ARVs, se estudiaron los perfiles de resistencia en individuos infectados con HIV-1 que no habían recibido tratamiento. Se estudiaron 399 pacientes HIV-1 seropositivos con falla terapéutica y 94 individuos naive infectados con HIV-1. Las muestras de plasma fueron recolectadas entre 1997 y 2001 de individuos de la Cdad. de Buenos Aires y sus alrededores. Se amplificaron las regiones de la PR y RT del HIV-1 mediante la reacción en cadena de la polimerasa (PCR) y se procedió a la secuenciación nucleotídica, luego de lo cual se analizó la presencia de mutaciones asociadas a resistencia a ARVS previamente reportadas. En la población tratada con ARVs, se encontraron mutaciones asociadas a resistencia en el 90,3 por ciento de las muestras. La prevalencia de mutaciones asociadas a resistencia a AZT, 3TC, los inhibidores no nucleosídicos de la RT (NNRTIs), indinavir, ritonavir y nelfinavir superó el 40 por ciento, siendo las sustituciones más prevalentes: M46I/L, V82A/F/S/T y L90M en la PR; y M41L, D67N, K70R, K103N, Y181C/I, M184I/V, G190A/S y T215F/Y en la RT. La presencia de variantes resistentes a miembros de múltiples familiars de drogas fue superior al 20 por ciento... (TRUNCADO)

Estudio de la presencia de variantes del HIV-1 resistentes a drogas antirretrovirales en Argentina: período 1997-2001 / Study of the presence of variants of the HIV-1 resistant to antiretroviral drugs in Argentina: period 1997-2001

La instauración de tratamientos antirretrovirales de alta eficacia (HAARTs) ha llevado a la disminución de la morbimortalidad asociada a HIV-1/SIDA en países industrializados. Sin embargo, uno de los principales factores asociados a la falla terapéutica es la selección de variantes de HIV-1 resistentes a las drogas antirretrovirales (ARVs). Dichas variantes virales se caracterizan por presentar mutaciones en las enzimas virales que son los blancos de la acción de los fármacos: la proteasa viral (PR) y la transcriptasa reversa (RT). Las variantes del HIV-1 resitente a ARVs seleccionadas en pacientes tratados no sólo se asocian al fracaso terapéutico en dichos individuos, sino que también pueden ser transmitidas a la población no infectada. De esta forma, individuos infectados con HIV-1 que nunca han sido expuestos a drogas ARVs (naïve) pueden albergar virus resistentes, lo que llevaría a la falla terapéutica al iniciarse el tratamiento. El objetivo del presente trabajo fue el de caracterizar los perfiles de resistencia en pacientes HIV-1 seropositivos con falla terapéutica. Asimismo, con el fin de estimar la tasa de transmisión de variantes resistentes a ARVs, se estudiaron los perfiles de resistencia en individuos infectados con HIV-1 que no habían recibido tratamiento. Se estudiaron 399 pacientes HIV-1 seropositivos con falla terapéutica y 94 individuos naive infectados con HIV-1. Las muestras de plasma fueron recolectadas entre 1997 y 2001 de individuos de la Cdad. de Buenos Aires y sus alrededores. Se amplificaron las regiones de la PR y RT del HIV-1 mediante la reacción en cadena de la polimerasa (PCR) y se procedió a la secuenciación nucleotídica, luego de lo cual se analizó la presencia de mutaciones asociadas a resistencia a ARVS previamente reportadas. En la población tratada con ARVs, se encontraron mutaciones asociadas a resistencia en el 90,3 por ciento de las muestras. La prevalencia de mutaciones asociadas a resistencia a AZT, 3TC, los inhibidores no nucleosídicos de la RT (NNRTIs), indinavir, ritonavir y nelfinavir superó el 40 por ciento, siendo las sustituciones más prevalentes: M46I/L, V82A/F/S/T y L90M en la PR; y M41L, D67N, K70R, K103N, Y181C/I, M184I/V, G190A/S y T215F/Y en la RT. La presencia de variantes resistentes a miembros de múltiples familiars de drogas fue superior al 20 por ciento... (TRUNCADO) (AU)