Telemedicine in HIV health care during the COVID-19 pandemic: An implementation research study in Buenos Aires, Argentina.

BACKGROUND: From October 2020 to October 2022, we conducted an implementation study to offer telemedicine (TM) across four HIV units of general public hospitals in Buenos Aires. The intervention used TM to provide a continuum of care to patients with HIV. METHODS AND SETTING: We used the RE-AIM framework to evaluate the strategy. The study started during a COVID-19 outbreak with strict lockdown policies and continued until return to normal practices. Implementation facilitation served as the core implementation strategy. RESULTS: We reached 4118 patients (58% of eligible individuals), and the main perceived benefits were the ability to avoid exposure to infectious diseases and reduced travel time and cost. After a median of 515 days of follow-up, 95.7% of participants with HIV were receiving antiretroviral therapy, and 87.8% were virally suppressed, with a median CD4+ count of 648 cells/µL. In total, 36.6% reported clinical events, and 20.4% presented with COVID-19 infection. The proportion of physicians adopting TM was 69.37%. After enrolment, 2406 of 5640 (43%) follow-up visits were conducted via TM. By the end of the study, 26.29% of appointments offered in the four centres were through TM, whereas 73.71% were in-person appointments. CONCLUSION: It was feasible to implement TM in the four centres in the public health sector in Buenos Aires, Argentina. It was acceptable for both patients and healthcare workers, and effectively reached a large proportion of the population served in these clinics. Both healthcare workers and patients consider it a model of care that will continue to be offered in the future.

Resistencia antibiótica y aspectos clínicos de Neisseria gonorrhoeae anorrectal en un hospital de CABA, Argentina / Antimicrobial resistance and clinical aspects in anorectal Neisseria gonorrhoeae in a hospital in CABA, Argentina

La infección por Neisseria gonorrhoeae (NG) es considerada de alta prioridad en salud pública, por su capacidad para desarrollar resistencia a la mayoría de los antibióticos empleados para tratarla. La presentación anorrectal suele ser asintomática y frecuente en hombres que tienen sexo con hombres (HSH). En Argentina, se recomienda terapia antibiótica dual (ceftriaxona+azitromicina/doxiciclina) como primera línea empírica. Este estudio observacional y retrospectivo se realizó para evaluar el porcentaje de positividad de NG anorrectal, el perfil de sensibilidad a penicilina, tetraciclina, ciprofloxacina, ceftriaxona, cefixima y azitromicina, así como los aspectos clínicos-epidemiológicos de los pacientes atendidos entre 20/10/2015 y 20/03/2020 en consultorios coloproctológicos de un hospital público. Se detectaron 55/436 hisopados rectales positivos para NG (13%). El 95% era HSH y 71%, VIH+. En 18/55 NG fue la única infección. Las co-infecciones más frecuentes: HPV (38%) y C. trachomatis (35%). La sensibilidad a cefalosporinas de espectro extendido (CEE) y a azitromicina fueron 100% y 98%, respectivamente. Se observó la emergencia local de los primeros cinco aislamientos de NG anorrectal con sensibilidad reducida (SR) a CEE, el primer aislamiento con categoría no-sensible a azitromicina y otro con SR a azitromicina concomitantemente con SR a CEE. Aunque el uso de terapia empírica dual sigue siendo adecuado para nuestra institución, se observó la emergencia de aislamientos con SR y NS a las drogas de primera línea, evidenciando la importancia de la vigilancia epidemiológica a nivel local para definir los tratamientos empíricos.

Neisseria gonorrhoeae (NG) infection is considered a high public health priority because of its ability to develop resistance to most of the antibiotics used to treat it.The anorectal presentation is generally asymptomatic and frequent in men who have sex with men (MSM). In Argentina, dual therapy (ceftriaxone+azithromycin/doxycycline) is recommended as first line empiric therapy.This observational and retrospective study was conducted to evaluate the percentage of anorectal NG positivity, the susceptibility profile to penicillin, tetracycline, ciprofloxacin, ceftriaxone, cefixime and azithromycin, as well as the clinical-epidemiological aspects of patients attended between 20/10/2015 and 20/03/2020 in coloproctology of a public hospital.We detected 55/436 positive rectal swabs for NG (13%). 95% were MSM and 71% were PLHIV. In 18/55 NG was the only infection. The most frequent co-infections: HPV (38%) and C. trachomatis (35%).Susceptibility to extended-spectrum cephalosporins (ESCs) and azithromycin was 100% and 98%, respectively. Local emergence of the first five anorectal NG isolates with decreased susceptibility (DS) to ESCs, the first isolate with nonsusceptible category to azithromycin and another with DS to azithromycin concomitantly with DS to ESCs were observed.Although the use of dual empirical therapy continues to be adequate for our institution, the emergence of isolates with DS and NS to first-line drugs was observed, evidencing the importance of epidemiological surveillance at the local level to define empirical treatments

A small cluster randomised clinical trial to improve health outcomes among Argentine patients disengaged from HIV care.

Background: Patients disengaged from HIV care, e.g., missed medication pick-ups, not attending physician visits, account for ≥70% of new HIV infections. Re-engaging and sustaining engagement is essential to controlling the HIV pandemic. This study tested a physician-delivered evidence-based intervention, Motivational Interviewing (MI), to improve health outcomes, adherence to antiretroviral therapy (ART), HIV virologic suppression, CD4+ count, retention in HIV care, and self-efficacy among patients disengaged from care in Argentina. Methods: Regional clinics (n = 6) were randomised to condition, MI Intervention or Enhanced Standard of Care (ESOC), and recruited N = 360 patients disengaged from HIV care. ART adherence, HIV RNA viral load, CD4+ count retention, and self-efficacy were assessed at baseline, 6, 12, 18, and 24-months. Indirect effects from condition to main outcomes were examined using patient-provider relationship as a mediator. The study was a cluster-randomised clinical trial entitled Conexiones y Opciones Positivas en la Argentina 2 (COPA2) and was registered at clinicaltrials.gov, NCT02846350. Findings: Participants were an average age of 39·15 (SD = 10·96), 51% were women; intervention participants were older (p = ·019), and more ESOC participants were women (60% vs. 42%, p = 0·001). Using mixed models, the intervention had no effect on ART adherence over time by condition on HIV RNA viral load, CD4+ count retention, or self-efficacy. However, analysing mediated paths, there was an indirect effect of condition on ART adherence (B = 0·188, p = 0·009), HIV viral load (B = -0·095, P = 0·027), and self-efficacy (B = 0·063, P = 0·001), suggesting the intervention was associated with improved patient-provider relationships, which was in turn associated with increased ART adherence, lower HIV viral load, and higher self-efficacy. Interpretation: These findings suggest that physician-delivered MI may enhance the patient-provider relationship, self-efficacy, and ART adherence, and reduced HIV viral load in patients disengaged from HIV care. However, these findings are preliminary due to the small number of clusters randomised, and replication is warranted. Funding: National Institutes of Health.

Score clínico simple para el uso racional de ecografía pulmonar en pacientes ambulatorios con COVID-19 / Simple clinical score for rational use of lung ultrasound in COVID-19 outpatient settings

INTRODUCCIÓN: Debido a la rápida expansión mundial del COVID-19, se crearon Unidades Febriles de Urgencia (UFU) para la atención ambulatoria y estratificación del riesgo clínico de los pacientes. La ecografía pulmonar ha cobrado un interés creciente como método sensible para la detección de neumonía. El objetivo fue desarrollar un score simple y sensible de riesgo clínico de neumonía durante la primera ola de COVID-19. MÉTODOS: Se realizó un estudio de corte transversal sobre una cohorte de adultos con diagnóstico confirmado de COVID-19 asistidos en la UFU de un hospital general de la ciudad de Buenos Aires entre mayo y agosto de 2020. Se efectuó el análisis bivariado y multivariado de variables sociodemográficas y clínicas para la construcción y validación interna de un score predictivo de neumonía. RESULTADOS: El análisis final incluyó a 936 pacientes; 17,6% presentaron ecografía compatible con neumonía. El score incluyó 5 variables estadísticamente significativas: edad ≥50 años (3 puntos), tos (2 puntos), ausencia de odinofagia (1 punto), disnea (2 puntos) y saturación de oxígeno ≤95% (3 puntos). Para un punto de corte ≥3 la sensibilidad fue 80,5% y el valor predictivo negativo 93,3%, con buen desempeño en cohorte de derivación y de validación (área bajo curva ROC 0,79 y 0,76, respectivamente). DISCUSIÓN: Este score podría ser una herramienta útil para estratificar el riesgo clínico de neumonía en el ámbito prehospitalario y evitar la realización de imágenes con <3 puntos.

Simple clinical score for rational use of lung ultrasound in COVID-19 outpatient settings / Score clínico simple para el uso racional de ecografía pulmonar en pacientes ambulatorios con covid-19

RESUMEN INTRODUCCIÓN: Debido a la rápida expansión mundial del COVID-19, se crearon Unidades Febriles de Urgencia (UFU) para la atención ambulatoria y estratificación del riesgo clínico de los pacientes. La ecografía pulmonar ha cobrado un interés creciente como método sensible para la detección de neumonía. El objetivo fue desarrollar un score simple y sensible de riesgo clínico de neumonía durante la primera ola de COVID-19. MÉTODOS: Se realizó un estudio de corte transversal sobre una cohorte de adultos con diagnóstico confirmado de COVID-19 asistidos en la UFU de un hospital general de la ciudad de Buenos Aires entre mayo y agosto de 2020. Se efectuó el análisis bivariado y multivariado de variables sociodemográficas y clínicas para la construcción y validación interna de un score predictivo de neumonía. RESULTADOS: El análisis final incluyó a 936 pacientes; 17,6% presentaron ecografía compatible con neumonía. El score incluyó 5 variables estadísticamente significativas: edad ≥50 años (3 puntos), tos (2 puntos), ausencia de odinofagia (1 punto), disnea (2 puntos) y saturación de oxígeno ≤95% (3 puntos). Para un punto de corte ≥3 la sensibilidad fue 80,5% y el valor predictivo negativo 93,3%, con buen desempeño en cohorte de derivación y de validación (área bajo curva ROC 0,79 y 0,76, respectivamente). DISCUSIÓN: Este score podría ser una herramienta útil para estratificar el riesgo clínico de neumonía en el ámbito prehospitalario y evitar la realización de imágenes con <3 puntos.

ABSTRACT INTRODUCTION: Due to the rapid global expansion of COVID-19, Febrile Emergency Units (FEU) were created in the outpatient setting to stratify the clinical risk of patients. Pulmonary ultrasound has gained a growing interest as a sensitive method for the detection of pneumonia. This study aimed to at developing a simple and sensitive score to assess the risk of pneumonia during the first COVID-19 wave. METHODS: A cross-sectional study was conducted in a cohort of adult patients with laboratory-confirmed COVID-19, who received care at the FEU of a general hospital in the city of Buenos Aires from May through August 2020. Bivariate and multivariate analyses of sociodemographic and clinical variables were performed to build and internally validate a pneumonia predictive score. RESULTS: The final analysis included 936 patients; 17.6% had ultrasound compatible with pneumonia. The score included 5 statistically significant variables: age ≥50 years (3 points), cough (2 points), absence of odynophagia (1 point), dyspnea (2 points) and oxygen saturation ≤95% (3 points). A cut-off point ≥3 showed a sensitivity of 80.5% and a negative predictive value of 93.3%, with good discriminatory capacity both in derivation and validation cohorts (area under ROC curve 0.79 and 0.76, respectively). DISCUSSION: This score could be a useful tool to stratify the clinical risk of pneumonia in the pre-hospital setting and avoid imaging studies with a score <3.

Cumulative Burden of Mental Health Factors and Engagement in HIV Care in Argentina.

BACKGROUND: Cumulative burden of multiple mental health conditions may worsen physical health outcomes in vulnerable populations. Accordingly, identifying cumulative burdens of mental health conditions that may affect HIV treatment and care can guide public health strategies to reduce their impact on HIV-related health outcomes. This study examined the relationship between the cumulative burden of mental health conditions and factors associated with engagement in HIV care in Argentina. METHOD: Data for this study was obtained at baseline from Conexiones y Opciones Positivas en la Argentina 2 (COPA2). Participants (N = 360) were cisgender patients living with HIV who were lost to care, recruited from seven clinics serving people living with HIV in four Argentine urban centers. Cumulative burden of mental health conditions (i.e., depressive symptoms, problematic substance use, unhealthy alcohol use, and psychotic symptoms) was assessed. RESULTS: Every one-point increase in the number of mental health conditions present was associated with a decrement in patient-provider communication (b = - 0.22, p < .001), self-efficacy (b = - 0.13, p = .012), and motivation for adherence (b = - 0.11, p = .039). CONCLUSION: This study found cumulative burden of depression, problematic substance use, unhealthy alcohol use, and psychotic symptoms to be negatively associated with factors related to engagement in HIV care. Results highlight the importance of identification and treatment of challenges to mental health, in order to ameliorate their influence on engagement in HIV care.

Evaluación del impacto de la cuarentena por la pandemia de COVID-19 en la transmisión perinatal del VIH en Buenos Aires, Argentina / Assessment of the impact of the COVID-19 pandemic lockdown on perinatal HIV transmission in Buenos Aires, Argentina

Objetivos: Describir variables epidemiológicas clave durante el año 2020 (pandemia de COVID-19) con respecto a la prevención de la transmisión perinatal (TP) del VIH en Ciudad de Buenos Aires (CABA), comparando con períodos previos.Métodos: Análisis retrospectivo de los datos agregados de TP de las principales maternidades de CABA. El año pandémico (2020) se comparó con los años no pandémicos 2018 y 2019.Resultados: Se observó una reducción del total de nacimientos en 2020 en comparación con 2019 y 2018 (11.640 vs. 14.031 y 15,978, respectivamente). La proporción de nacidos vivos en madres VIH+ (MEV) fue 0,88% en 2020, sin diferencia con 2019 y 2018 (0,94% y 0,93%), p> 0,05 para todas las comparaciones. Entre las MEV, el diagnóstico intraparto fue del 2,9% para 2020, sin diferencias con 2019 (2,25%) y 2018 (9,3%), p> 0,05 (todas las comparaciones); el 8,8% comenzó el tratamiento antirretroviral con > 28 semanas de edad gestacional en 2020 frente al 16% y el 18,05% en 2018 y 2019 (p> 0,05, todas las comparaciones). La prevalencia de la carga viral indetectable en el momento del parto fue del 67% en 2020 frente al 64% en 2018 y del 65,4% en 2019 (p> 0,05, todas las comparaciones). La transmisión perinatal fue 0% en 2020 vs. 1,33% en 2018 y 2,25% 2019 (p> 0,05, todas las comparaciones).Conclusiones: En la primera ola de la pandemia de COVID-19 no se observaron cambios en la proporción de MEV asistidas, diagnóstico intraparto de VIH, inicio tardío del TARV y TP en CABA

Background: To describe key epidemiological variables in 2020 (COVID-19 pandemic) regarding prevention of mother-to-child transmission (MTCT) in Buenos Aires city (CABA) in comparison with previous periods. Methods: Retrospective analysis of aggregated MTCT data was gathered from six principal maternity hospitals in Buenos Aires city. Pandemic year (2020) was compared to non-pandemic years 2018-19 individually considering key epidemiological variables. Results: A reduction of total births was observed in 2020 compared to 2019 and 2018 (11640 vs. 14031 and 15978, respectively). Proportion of live births in HIV-infected women (HPW) was 0.88% in 2020 without difference with 2019 and 2018 (0.94% and 0.93%), p> 0.05 for all comparisons. Among HPW, intrapartum diagnosis was 2.9% for 2020, with no difference between 2019 (2.25%) and 2018 (9.3%), p>0.05 (all comparisons); 8.8% had antiretroviral therapy (ART) started > 28 weeks of gestational age in 2020 vs. 16% and 18.05% in 2018 and 2019 (p> 0.05, all comparisons). Prevalence of undetectable viral load at delivery was 67% in 2020 vs 64% in 2018 and 65.4% in 2019 (p> 0.05, all comparisons). Perinatal transmission was 0% in 2020 vs 1.33% in 2018 and 2.25% 2019 (p> 0.05, all comparisons) Conclusions: In first wave of COVID 19 pandemic no changes in the proportion of HPW assisted, HIV intrapartum diagnosis, late ART initiation and MTCT-rate was observed in CABA

COVID-19 associated with AIDS-related disseminated histoplasmosis: a case report.

Limited information is available concerning the coexistence of COVID-19 and opportunistic infections in people living with HIV. The possible association of COVID-19 with AIDS-related respiratory diseases should be considered, particularly in patients with advance immunosuppression. We report the case of a male patient with AIDS-related disseminated histoplasmosis associated with COVID-19.

Raltegravir versus efavirenz in antiretroviral-naive pregnant women living with HIV (NICHD P1081): an open-label, randomised, controlled, phase 4 trial.

BACKGROUND: Although antiretroviral regimens containing integrase inhibitors rapidly suppress HIV viral load in non-pregnant adults, few published data from randomised controlled trials have compared the safety and efficacy of any integrase inhibitor to efavirenz when initiated during pregnancy. We compared safety and efficacy of antiretroviral therapy with either raltegravir or efavirenz in late pregnancy. METHODS: An open-label, randomised controlled trial was done at 19 hospitals and clinics in Argentina, Brazil, South Africa, Tanzania, Thailand, and the USA. Antiretroviral-naive pregnant women (20-<37 weeks gestation) living with HIV were assigned to antiretroviral regimens containing either raltegravir (400 mg twice daily) or efavirenz (600 mg each night) plus lamivudine 150 mg and zidovudine 300 mg twice daily (or approved alternative backbone regimen), using a web-based, permuted-block randomisation stratified by gestational age and backbone regimen. The primary efficacy outcome was plasma HIV viral load below 200 copies per mL at (or near) delivery. The primary efficacy analysis included all women with a viral load measurement at (or near) delivery who had viral load of at least 200 copies per mL before treatment and no genotypic resistance to any study drugs; secondary analyses eliminated these exclusion criteria. The primary safety analyses included all women who received study drug, and their infants. This trial is registered with Clinicaltrials.gov, number NCT01618305. FINDINGS: From Sep 5, 2013, to Dec 11, 2018, 408 women were enrolled (206 raltegravir, 202 efavirenz) and 394 delivered on-study (200 raltegravir, 194 efavirenz); 307 were included in the primary efficacy analysis (153 raltegravir, 154 efavirenz). 144 (94%) women in the raltegravir group and 129 (84%) in the efavirenz group met the primary efficacy outcome (absolute difference 10%, 95% CI 3-18; p=0·0015); the difference primarily occurred among women enrolling later in pregnancy (interaction p=0·040). Frequencies of severe or life-threatening adverse events were similar among mothers (30% in each group; 61 raltegravir, 59 efavirenz) and infants (25% in each group; 50 raltegravir, 48 efavirenz), with no treatment-related deaths. INTERPRETATION: Our findings support major guidelines. The integrase inhibitor dolutegravir is currently a preferred regimen for the prevention of perinatal HIV transmission with raltegravir recommended as a preferred or alternative integrase inhibitor for pregnant women living with HIV. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Institute of Allergy and Infectious Diseases.

Hepatitis C Virus (HCV) Clearance After Treatment With Direct-Acting Antivirals in Human Immunodeficiency Virus (HIV)-HCV Coinfection Modulates Systemic Immune Activation and HIV Transcription on Antiretroviral Therapy.

BACKGROUND: Hepatitis C virus (HCV) coinfection among people with human immunodeficiency virus (HIV) might perturb immune function and HIV persistence. We aimed to evaluate the impact of HCV clearance with direct-acting antivirals (DAAs) on immune activation and HIV persistence in HIV/HCV-coinfected individuals on antiretroviral therapy (ART). METHODS: In a prospective observational study, ART-treated participants with HIV/HCV coinfection received sofosbuvir/daclatasvir ±â€…ribavirin (n = 19). Blood samples were collected before DAA therapy, at the end of treatment, and 12 months after DAA termination (12MPT). T- and natural killer (NK)-cell phenotype, soluble plasma factors, cell-associated (CA)-HIV deoxyribonucleic acid (DNA) forms (total, integrated, 2LTR), CA-unspliced (US) and multiple-spliced ribonucleic acid (RNA), and plasma HIV RNA were evaluated. RESULTS: Hepatitis C virus clearance was associated with (1) a downmodulation of activation and exhaustion markers in CD4+, CD8+ T, and NK cells together with (2) decreased plasma levels of Interferon gamma-induced protein 10 (IP10), interleukin-8 (IL-8), soluble (s)CD163 and soluble intercellular adhesion molecule (sICAM). Cell-associated US HIV RNA was significantly higher at 12MPT compared to baseline, with no change in HIV DNA or plasma RNA. CONCLUSIONS: Elimination of HCV in HIV/HCV-coinfected individuals alters immune function and the transcriptional activity of latently infected cells. This report provides insights into the effects of HCV coinfection in HIV persistence and regards coinfected subjects as a population in which HIV remission might prove to be more challenging.

Chemsex y uso de sustancias durante las relaciones sexuales: resultados de una encuesta realizada en Argentina / Chemsex and use of substances during sexual intercourse: results of a survey conducted in Argentina

Introducción: Chemsex está relacionado con el uso de ciertas drogas que facilitan la excitación y el prolongar la duración de los encuentros sexuales.Objetivo: Describir el perfil de consumo de los usuarios de sustancias durante las relaciones sexuales (SRS) y su relación con variables demográficas, de estilo de vida y de salud.Métodos: Estudio descriptivo y transversal realizado a través de una encuesta autoadministrada y anónima en el marco de la plataforma Google Forms® que se transmitió en diferentes redes sociales. Objetivo: describir los aspectos demográficos y de estilo de vida de los encuestados y del subgrupo de usuarios de SRS y chemsex.Resultados: Se recibieron 2924 encuestas; 421 personas (16,9%) refirieron haber consumido al menos una vez uno o más de los siguientes: mefedrona, metanfetamina, crystal meth, GHB/GBL, cocaína, LSD, poppers, ketamina y éxtasis. Chemsex se definió como el consumo de los tres primeros y su prevalencia fue del 1,1%. El perfil de usuario de SRS y chemsex en nuestro estudio fue un hombre de entre 26 y 35 años, HSH y habitante de la Ciudad de Buenos Aires. Hubo mayor proporción de personas con VIH y diagnósticos de ITS en el último año dentro de los usuarios de SRS y chemsex.Conclusiones: Esta es la primera encuesta que trata este tema en nuestro país y en América Latina. Teniendo en cuenta la tendencia a un menor uso de los condones RESUMENARTÍCULO ORIGINALISSN 2314-3193. Actualizaciones en sida e infectología. Buenos Aires. noviembre 2020. volumen 28. número 103: 40-50y a presentar más diagnósticos de ITS y VIH en la población de usuarios de SRS, consideramos de interés conocer la epidemiología en nuestra población

Introduction: Chemsex is related to the use of certain drugs to facilitate sustained arousal and induce a feeling of instant rapport with sexual partners.Aim: To describe the consumption profile of users of substances during sexual intercourse (SSI) and its relationship with demographic, lifestyle and health variables.Methods: Descriptive and cross-sectional study conducted through a self-administered and anonymous survey under the Google Forms platform ® which was broadcasted on different social networks. Main outcome measures: Description on demographic and lifestyle aspects of the respondents and in the subgroup of SSI and chemsex users.Results: 2924 surveys were received; 421 people (16.9%) referred to having consumed at least once one or more of the following: mephedrone, crystal meth, GHB/GBL, cocaine, LSD, poppers, ketamine and ecstasy. Chemsex was defined as the consumption of the first three and its prevalence was 1.1%. A SSI and chemsex user profile in our study was a man between 26 and 35 years, MSM and inhabitant of the city of Buenos Aires. SSI and chemsex users were more likely to and STI in the last year and to have HIV diagnosis.Conclusions: This is the first survey that deals with this issue in our country and in Latin America. Accounting for the tendency to less use of condoms and to present more diagnoses of STIs and HIV in the population of SSI users, we consider it necessary to study this subject in our country as the rising reports in world literature show a boost in substance use.Keywords: Chemsex, Drugs, HIV, VIH, STI, ITS.Chemsex and use of substances during sexual intercourse: results of a survey conducted in Argentina

Inflammatory biomarker levels over 48 weeks with dual vs triple lopinavir/ritonavir-based therapy: Substudy of a randomized trial.

BACKGROUND: Inflammation has been associated with increased morbidity and mortality in HIV-positive patients. We compared inflammatory biomarkers with dual therapy using lopinavir/ritonavir plus lamivudine (LPV/r+3TC) versus triple therapy using LPV/r plus two nucleoside reverse transcriptase inhibitors (LPV/r+2NRTIs) in treatment-naïve HIV-positive adults. METHODS: This was a substudy among Argentinian participants in the randomized trial GARDEL. We measured hsCRP, IL-6, MCP-1, TNF, D-dimer and sCD14 from plasma collected at baseline, week 24 and week 48. Generalized estimating equations with an identity/logit link were used to model the average impact of dual versus triple therapy on each biomarker over time, controlling for baseline levels. Additional models estimated the average effect of virologic suppression on biomarker levels over time, adjusting for age, sex, and baseline CD4 count. RESULTS: Of 191 trial participants enrolled in Argentina, 172 had baseline and follow-up measurements and were included. Median (IQR) age was 35.5 (28.5, 45) years and CD4 cell count was 310 (219, 414) cells/mm3. Dual therapy was not associated with significantly different biomarker levels over 48 weeks relative to triple therapy. Virologic suppression was associated with statistically significant decreases in MCP-1, TNF and D-dimer levels and an unexpected increase in sCD14 levels. No change was observed in hsCRP or the proportion of participants with undetectable IL-6 levels. CONCLUSIONS: In addition to having virologic non-inferiority, LPV/r+3TC dual therapy is generally associated with similar inflammatory biomarker levels over 48 weeks compared to LPV/r+2NRTIs triple therapy in treatment-naïve adults. Further study of dual treatment regimens is warranted.

Dolutegravir-lamivudine as initial therapy in HIV-1 infected, ARV-naive patients, 48-week results of the PADDLE (Pilot Antiretroviral Design with Dolutegravir LamivudinE) study.

INTRODUCTION: A proof-of-concept study was designed to evaluate the antiviral efficacy, safety and tolerability of a two-drug regimen with dolutegravir 50 mg once daily (QD) plus lamivudine 300 mg once daily as initial highly active antiretroviral therapy (HAART) among antiretroviral (ARV)-naive patients. METHODS: PADDLE is a pilot study including 20 treatment-naive adults. To be selected, participants had no IAS-USA-defined resistance, HIV-1 RNA ≤100,000 copies/mL at screening and negative HBsAg. Plasma viral load (pVL) was measured at baseline; days 2, 4, 7, 10, 14, 21 and 28; weeks 6, 8 and 12; and thereafter every 12 weeks up to 96 weeks. Primary endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL in an intention to treat (ITT)-exposed analysis at 48 weeks (the FDA snapshot algorithm). RESULTS: Median HIV-1 RNA at entry was 24,128 copies/mL (interquartile range (IQR): 11,686-36,794). Albeit as per protocol, all patients had pVL ≤100,000 copies/mL at screening as required by inclusion criteria, four patients had ≥100,000 copies/mL at baseline. Median baseline CD4+ T-cell count was 507 per cubic millimetre (IQR: 296-517). A rapid decline in pVL was observed (median VL decay from baseline to week 12 was 2.74 logs). All patients were suppressed at week 8 onwards up to week 24. At week 48, 90% (18/20) reached the primary endpoint of a pVL <50 copies/mL. Median change in CD4 cell count between baseline and week 48 was 267 cells/mm3 (IQR: 180-462). No major tolerability/toxicity issues were observed. Nineteen patients completed 48 weeks of the study, and one patient (with undetectable VL at last visit) committed suicide. One patient presented a low-level protocol-defined confirmed virological failure at week 36, being the only observed failure. This patient had pVL <50 copies/mL at the end-of-study visit without having changed the two-drug regimen. Observed failure rate was 5%. This is the first report of integrase strand transfer inhibitor/lamivudine dual regimen in ARV-naive patients. CONCLUSIONS: This novel dual regimen of dolutegravir and lamivudine warrants further clinical research and consideration as a potential therapeutic option for ARV-therapy-naive patients. CLINICALTRIALS.GOV IDENTIFIER: NCT02211482.

Pancitopenia en paciente con infección por VIH

Se expone el caso de una mujer joven con diagnóstico de infección por el virus de inmunodeficiencia humana (VIH) y abandono de tratamiento antiretroviral, ingresada por cuadro febril y tos, con sospecha de tuberculosis miliar. Evoluciona durante su internación con pancitopenia y esplenomegalia, iniciándose investigación y diagnóstico precoz de síndrome hemofagocítico (SHF). Presenta evolución desfavorable y óbito debido a múltiples comorbilidades.

This is the case of a young woman who was diagnosed with a human immunodeficiency virus (HIV) infection and had stopped the antiretroviral therapy. She was admitted for fever and cough with suspicion of miliary tuberculosis. The patient evolved during her hospitalization to splenomegalic pancytopenia. An investigation started and there was an early diagnosis of hemophagocytic syndrome (HPS). The patients evolved unfavorably and died due to multiple co-morbilities.

[Lopinavir/ritonavir in new initial antiretroviral treatment strategies]. / Lopinavir/ritonavir en nuevas estrategias de tratamiento antirretroviral de inicio.

According to evidence from randomized controlled trials and epidemiological data, the antiretroviral treatment (ART) of choice has consisted of the combination of 2 nucleoside analog reverse-transcriptase inhibitors (NRTI) plus 1 non-nucleoside analog reverse-transcriptase inhibitor (NNRTI) or a protease inhibitor (PI) for more than 17 years. There are several unresolved issues, notably the toxocity associated with NRTI, especially thymidine analogs, and the possibility of cross resistance, which may affect subsequent treatment. The development of new antiretroviral drugs with simpler dosing regimens and lower toxicity has led to evaluation of innovative strategies such as dual therapy for initial ART in treatment-naive, with the aim of preventing long-term toxicity and increasing treatment adherence. Despite encouraging results, some combinations have proven unsatisfactory. The strategies with favorable results to date consist of twice-daily lopinavir/ritonavir (LPV/r)-based regimens, those in the PROGRESS (LPV/r + raltegravir) and GARDEL (LPV/r + lamivudine) trials, and the combination of darunavir and raltegravir (NEAT 001 trial), although the latter observed a higher tendency (statistically nonsignificant) to virological failure in the dual combination arm. These trials were based on the use of NRTI-sparing regimens consisting of 2-3 fully- active agents for highly-active ART in treatment-naïve HIV-positive patients. Recent studies provide evidence supporting the use of NRTI-sparing regimens in HIV-infected patients with failure to an initial NNRTI-based ART regimen. The present review will discuss only LPV/r-based innovative strategies in initial ART regimens.

Changes in lipid levels after 48 weeks of dual versus triple therapy observed in the GARDEL study.

INTRODUCTION: Treatment with ritonavir-boosted protease inhibitors and nucleoside analogues frequently leads to rises in lipids, which might increase the cardiovascular risk. The aim of this study was to describe changes in lipid levels among HIV positive patients participating in the GARDEL study. MATERIALS AND METHODS: The GARDEL study compared the efficacy and safety of a dual therapy (DT) combination of LPV/r 400/100 mg BID+3TC 150 mg BID to a triple therapy (TT) with LPV/r 400/100 mg BID+3TC or FTC and a third investigator-selected NRTI in fixed-dose combination among HIV+ treatment naïve patients. We compared changes in lipid levels from baseline to week 48 in both arms. RESULTS: Patient's characteristics were well balanced regarding mean baseline total cholesterol (157 mg/dL DT, 154 mg/dL TT), triglycerides (142 mg/dL DT, 139 mg/Dl TT), LDL-C (94 mg/dL DT, 91 mg/dL TT) and HDL-C (36 mg/dL DT, 35 mg/dL TT). Changes in total cholesterol, LDL-C and HDL-C were higher in DT arm, compared to TT (32% DT vs 26% TT for cholesterol; 25% DT vs 16% TT for LDL and 33% DT vs 28% TT for HDL). Increase in triglycerides was higher in TT compared to DT (55% DT vs 92% TT) (Table 1). In TT arm LDL-C and total cholesterol elevations were lower among patients receiving TDF compared to those treated with ZDV or ABC. CONCLUSION: Changes in lipid parameters were observed in both arms. Albeit the increase was numerically higher for cholesterol (total and LDL-C) in DT arm while TT arm had higher increases in TG; no difference was observed when week 48 values were compared with the NCEP ATP III goals for cardiovascular risk reduction (1). So, the DT strategy, even missing the lipid-lowering effect observed with tenofovir, does not seem to add significant risk to patients treated with this novel strategy.

Lopinavir/ritonavir en nuevas estrategias de tratamiento antirretroviral de inicio / Lopinavir/ritonavir in new initial antiretroviral treatment strategies

La combinación de 2 inhibidores de la transcriptasa inversa análogos de nucleósidos (ITIAN) con 1 inhibidor de la transcriptasa inversa no análogo de nucleósidos (ITINAN) o con un inhibidor de la proteasa (IP) ha sido el tratamiento antirretroviral (TAR) de elección por más de 17 años, según la evidencia derivada de estudios aleatorizados controlados y de datos epidemiológicos. Entre los temas sin resolver se destacan la toxicidad causada por los ITIAN, particularmente los análogos timidínicos, y la posibilidad de resistencia cruzada que puede afectar a tratamientos subsiguientes. Con la aparición de nuevos fármacos antirretrovirales, de mayor comodidad posológica y menor toxicidad, se han comenzado a evaluar estrategias innovadoras como la biterapia para el TAR de inicio en pacientes vírgenes de tratamiento ARV, con el objetivo de prevenir la toxicidad a largo plazo y favorecer la adherencia al tratamiento. Si bien hay resultados alentadores, algunas combinaciones no han mostrado resultados satisfactorios. Las estrategias con resultados favorables hasta la fecha se observaron con regímenes basados en lopinavir/ritonavir (LPV/r) 2 veces al día, los estudios PROGRESS (LPV/r + raltegravir) y GARDEL (LPV/r + lamivudina) y con la combinación de darunavir y raltegravir (estudio NEAT 001), aunque en este último estudio se observó una mayor tendencia (estadísticamente no significativa) de fallo virológico en la rama dual. Los mismos fundamentan el uso de regímenes ahorradores de ITIAN con 2-3 agentes totalmente activos para los pacientes VIH+ vírgenes de TAR de gran actividad. Estudios recientes aportaron evidencias para el uso de regímenes ahorradores de ITIAN en pacientes infectados por VIH con fracaso a su primer TAR basado en ITINAN. Esta revisión se limitará a las estrategias innovadoras basadas en LPV/r en TAR de inicio (AU)

According to evidence from randomized controlled trials and epidemiological data, the antiretroviral treatment (ART) of choice has consisted of the combination of 2 nucleoside analog reverse-transcriptase inhibitors (NRTI) plus 1 non-nucleoside analog reverse-transcriptase inhibitor (NNRTI) or a protease inhibitor (PI) for more than 17 years. There are several unresolved issues, notably the toxocity associated with NRTI, especially thymidine analogs, and the possibility of cross resistance, which may affect subsequent treatment. The development of new antiretroviral drugs with simpler dosing regimens and lower toxicity has led to evaluation of innovative strategies such as dual therapy for initial ART in treatment-naive, with the aim of preventing long-term toxicity and increasing treatment adherence. Despite encouraging results, some combinations have proven unsatisfactory. The strategies with favorable results to date consist of twice-daily lopinavir/ritonavir (LPV/r)-based regimens, those in the PROGRESS (LPV/r + raltegravir) and GARDEL (LPV/r + lamivudine) trials, and the combination of darunavir and raltegravir (NEAT 001 trial), although the latter observed a higher tendency (statistically nonsignificant) to virological failure in the dual combination arm. These trials were based on the use of NRTI-sparing regimens consisting of 2-3 fully- active agents for highly-active ART in treatment-naïve HIV-positive patients. Recent studies provide evidence supporting the use of NRTI-sparing regimens in HIV-infected patients with failure to an initial NNRTI-based ART regimen. The present review will discuss only LPV/rbased innovative strategies in initial ART regimens (AU)

Dual therapy with lopinavir and ritonavir plus lamivudine versus triple therapy with lopinavir and ritonavir plus two nucleoside reverse transcriptase inhibitors in antiretroviral-therapy-naive adults with HIV-1 infection: 48 week results of the randomised, open label, non-inferiority GARDEL trial.

BACKGROUND: Daily oral triple therapy is effective at halting HIV disease progression, but can have toxic effects and is costly. We investigated whether dual therapy with lopinavir and ritonavir plus lamivudine is non-inferior to standard triple therapy. METHODS: The GARDEL study (Global AntiRetroviral Design Encompassing Lopinavir/r and Lamivudine vs LPV/r based standard therapy) is a 48 week, phase 3, randomised, controlled, open-label, non-inferiority trial in antiretroviral-therapy-naive adults (age ≥18 years) with documented HIV-1 RNA viral load of at least 1000 copies per mL. The study was done at 19 centres in six countries. Patients were randomly assigned (1:1) to dual therapy or triple therapy by sealed envelopes, in blocks of four, stratified by baseline viral load (<100,000 vs ≥100,000 copies per mL). Dual therapy consisted of lopinavir 400 mg and ritonavir 100 mg plus lamivudine 150 mg, both twice daily. Triple therapy consisted of lopinavir 400 mg and ritonavir 100 mg twice daily and lamivudine or emtricitabine plus another nucleoside reverse transcriptase inhibitor (NRTI) in fixed-dose combination. Efficacy was analysed in all participants who received at least one dose of study drug. The primary endpoint was virological response rate, defined as the proportion of patients with HIV RNA less than 50 copies per mL at 48 weeks. Dual therapy was classed as non-inferior to triple therapy if the lower bound of the 95% CI for the difference between groups was no lower than -12%. Patients and investigators were unmasked to treatment allocation. This study is registered with ClinicalTrials.gov, number NCT01237444. FINDINGS: Between Dec 10, 2010, and May 15, 2012, 217 patients were randomly assigned to the dual-therapy group and 209 to the triple-therapy group. 198 patients in the dual-therapy group and 175 in the triple-therapy group completed 48 weeks of treatment. At week 48, 189 patients (88·3%) in the dual-therapy group and 169 (83·7%) in the triple-therapy group had viral response (difference 4·6%, 95% CI -2·2 to 11·8; p=0·171). Patients with baseline viral load of at least 100,000 copies per mL showed similar results (87·2% vs 77·9%, respectively; difference 9·3%, 95% CI -2·8 to 21·5; p=0·145). Toxicity-related or tolerability-related discontinuations were more common in the triple-therapy group (n=10 [4·9%]) than in the dual-therapy group (n=1 [0·4%]; difference 4·5%, 95% CI -8·1 to -0·9; p=0·011). 65 adverse events in the dual-therapy group and 88 in the triple-therapy group were possibly or probably drug related (p=0·007). Two serious adverse events occurred, both in the dual-therapy arm, one of which (a case of gastritis) was reported as possibly or probably related to drug treatment. INTERPRETATION: Dual therapy with lopinavir and ritonavir plus lamivudine regimen warrants further clinical research and consideration as a potential therapeutic option for antiretroviral-therapy-naive patients. FUNDING: Fundación Huésped and AbbVie.