Cost-effectiveness of the addition of CDK4/6 inhibitors to standard endocrine therapy in first-line treatment of women with advanced HR+/HER2- breast cancer in Mexico.

PURPOSE: To estimate the cost-effectiveness of adding a CDK4/6 inhibitor to standard endocrine therapy in the first-line setting for advanced HR+/HER2- breast cancer in postmenopausal and premenopausal women, from the perspective of the Mexican public healthcare system. METHODS: We used a partitioned survival model to simulate relevant health outcomes in a synthetic cohort of patients with breast cancer derived from the PALOMA-2, MONALEESA-2, MONARCH-3 trials for postmenopausal patients, and from the MONALEESA-7 study for premenopausal patients. Effectiveness was measured in life years gained. Cost-effectiveness is reported through incremental cost-effectiveness ratios (ICER). RESULTS: In postmenopausal patients, palbociclib led to an increase of 1.51 life years, ribociclib of 1.58 years, and abemaciclib of 1.75 years, compared to letrozole alone. The ICER was 36,648 USD, 32,422 USD, and 26,888 USD, respectively. In premenopausal patients, ribociclib led to an increase of 1.82 life years when added to goserelin and endocrine therapy, with an ICER of 44,579 USD. In the cost minimization analysis, for postmenopausal patients, ribociclib was the treatment with the highest costs due to follow-up requirements. CONCLUSION: Palbociclib, ribociclib, and abemaciclib demonstrated a significant increase in effectiveness in postmenopausal patients, and ribociclib in premenopausal patients, when added to standard endocrine therapy for patients with advanced HR+/HER2- breast cancer. At the national stablished willingness to pay, only the addition of abemaciclib to standard endocrine therapy in postmenopausal women would be considered cost-effective. However, differences on results between therapies for postmenopausal patients were not statistically significant.

Simultaneous monitoring of HIV viral load and screening of SARS-CoV-2 employing a low-cost RT-qPCR test workflow.

The COVID-19 pandemic interrupted routine care for individuals living with HIV, putting them at risk of virologic failure and HIV-associated illness. Often this population is at high risk for exposure to SARS-CoV-2 infection, and once infected, for severe disease. Therefore, close monitoring of HIV plasma viral load (VL) and screening for SARS-CoV-2 infection are needed. We developed a non-proprietary method to isolate RNA from plasma, nasal secretions (NS), or both. The extracted RNA is then submitted to RT-qPCR to estimate the VL and classify HIV/SARS-CoV-2 status (i.e., HIV virologic failure or suppressed; SARS-CoV-2 as positive, presumptive positive, negative, or indeterminate). In contrived samples, the in-house RNA extraction workflow achieved a detection limit of 200-copies per mL for HIV RNA in plasma and 100-copies per mL for SARS-CoV-2 RNA in NS. Similar detection limits were observed for HIV and SARS-CoV-2 in pooled plasma/NS contrived samples. When comparing in-house with standard extraction methods, we found high agreement (>0.91) between input and measured RNA copies for HIV LTR in contrived plasma; SARS-CoV-2 N1/N2 in contrived NS; and LTR, N1, and N2 in pooled plasma/NS samples. We further evaluated this workflow on 133 clinical specimens: 40 plasma specimens (30 HIV-positive), 67 NS specimens (31 SARS-CoV-2-positive), and 26 combined plasma/NS specimens (26 HIV-positive with 10 SARS-CoV-2-positive), and compared the results obtained using the in-house RNA extraction to those using a commercial kit (standard extraction method). The in-house extraction and standard extraction of clinical specimens were positively correlated: plasma HIV VL (R2 of 0.81) and NS SARS-CoV-2 VL (R2 of 0.95 and 0.99 for N1 and N2 genes, respectively); and pooled plasma/NS HIV VL (R2 of 0.71) and SARS-CoV-2 VL (R2 of 1 both for N1 and N2 genes). Our low-cost molecular test workflow ($1.85 per pooled sample extraction) for HIV RNA and SARS-CoV-2 RNA could serve as an alternative to current standard assays ($12 per pooled sample extraction) for laboratories in low-resource settings.

Resting energy expenditure in HIV/AIDS patients: Development and validation of a predictive equation.

BACKGROUND: Accurate measurements of resting energy expenditure (REE) are important for determining nutritional needs in HIV patients. Indirect calorimetry (IC) is a noninvasive method that reflects REE but can be costly and is frequently calculated with predictive equations. Research suggests that REE obtained by predictive equations in people living with HIV/AIDS (PLWH) is inaccurate. The aim of the study is to develop and validate a new predictive equation of REE based on a population of PLWH. METHODS: Cross-sectional study including 164 PLWH (82 to develop and 82 to validate the equation). Multiple linear regression was used to determine the relationship between variables and to develop the new predictive equation. Intraclass correlation coefficient (ICC) and Bland-Altman methods were used to evaluate agreement between the new predictive equation and indirect calorimetry. RESULTS: A new predictive equation with an accuracy of 67% when compared with IC was developed. This equation included as covariates: fat free mass, antiretroviral therapy status and age. CONCLUSION: A new equation to predict energy expenditure in PLWH was developed and validated. This formula can be used to estimate REE if IC is not available.

Assessment of HIV-1 integration in tissues and subsets across infection stages.

The integration of HIV DNA into the host genome contributes to lifelong infection in most individuals. Few studies have examined integration in lymphoid tissue, where HIV predominantly persists before and after antiretroviral treatment (ART). Of particular interest is whether integration site distributions differ between infection stages with paired blood and tissue comparisons. Here, we profiled HIV integration site distributions in sorted memory, tissue-resident, and/or follicular helper CD4+ T cell subsets from paired blood and lymphoid tissue samples from acute, chronic, and ART-treated individuals. We observed minor differences in the frequency of nonintronic and nondistal intergenic sites, varying with tissue and residency phenotypes during ART. Genomic and epigenetic annotations were generally similar. Clonal expansion of cells marked by identical integration sites was detected, with increased detection in chronic and ART-treated individuals. However, overlap between or within CD4+ T cell subsets or tissue compartments was only observed in 8 unique sites of the 3540 sites studied. Together, these findings suggest that shared integration sites between blood and tissue may, depending on the tissue site, be the exception rather than the rule and indicate that additional studies are necessary to fully understand the heterogeneity of tissue-sequestered HIV reservoirs.

Accuracy of Predictive Equations for Energy Expenditure in Mexicans Living With HIV/AIDS With and Without Antiretroviral Therapy.

INTRODUCTION: Determination of the resting energy expenditure (REE) is essential for planning nutrition therapy in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) to help to improve their nutrition status. We aim to evaluate the agreement and accuracy of prediction equations that estimate the REE in a Mexican population with a diagnosis of HIV/AIDS with and without antiretroviral therapy (ART). METHODS: A cross-sectional study in Mexican patients with HIV/AIDS with and without ART. Weight, height, and body composition measured with dual-energy x-ray absorptiometry were evaluated. The REE was determined with indirect calorimetry and estimated using the Mifflin-St Jeor (MSJ), Harris-Benedict (HB), Schofield 1 and 2, Cunningham, Melchior 91, Melchior 93, and Batterham equations. The Bland-Altman method assessed agreement between the real and estimated values, and the percent difference between these values was used to assess the prediction accuracy. RESULTS: Sixty-five adults without ART and 102 adults with ART were included. The mean REE (kcal/kg) was 24.8 ± 2.4 and 23.8 ± 3.6 in patients without and with ART, respectively. Good agreement and reliability were observed in the HB (intraclass correlation coefficient [ICC], 0.75; P < .05), Batterham (ICC, 0.79; P < .05), Schofield 1 (ICC, 0.74; P < .05), and Schofield 2 (ICC, 0.78; P < .05) results in individuals without ART. In individuals with ART, good agreement and reliability were observed with the HB equation (ICC, 0.76; P < .05). The MSJ equation showed good agreement with poor reliability (ICC, 0.05; P < .05). CONCLUSION: The equations with the best agreement and accuracy were Schofield 2, Batterham, and HB in individuals without ART and HB and MSJ in the population with ART.

Assessment of depression, anxiety, hopelessness and suicidal risk in HIV+ inpatients / Evaluación de depresión, ansiedad, desesperanza y riesgo suicida en pacientes con VIH hospitalizados

Abstract Introduction. People living with HIV frequently experience anxiety, depression, hopelessness and suicide risk, particularly if they are hospitalized due to HIV complications. Objective. The aim of this study was to evaluate the presence of anxiety, depression, hopelessness and suicide risk in HIV+ inpatients at admission and discharge. Method. A comparative study was conducted with the HIV+ inpatient population of the National Institute for Respiratory Diseases in Mexico City, from February to November 2013. The Hospital Anxiety and Depression Scale, the Beck Hopelessness Scale and the Plutchik Suicide Risk Scale were applied at hospital admission and discharge. Results. One hundred and fifteen patients completed all three assessments. Upon admission, 10.4% of the patients scored above the cut-off point for suicide risk; 1.7% presented high levels of hopelessness; 5.2% had clinical depression, and 7% had clinical anxiety. The comparison of scores at admission and discharge showed significant decreases in all symptom levels. Discussion and conclusion. Most of the patients presented low levels of all symptoms assessed at admission and these decreased at discharge. Further research is necessary with the hospitalized HIV population.

Resumen Introducción. Las personas que viven con VIH experimentan con frecuencia ansiedad, depresión, desesperanza y riesgo suicida, particularmente si son hospitalizadas debido a complicaciones por el VIH. Objetivo. El propósito del presente estudio fue evaluar y comparar la presencia de ansiedad, depresión, desesperanza y riesgo suicida en pacientes hospitalizados con VIH, a su ingreso y su egreso. Método. Se llevó a cabo un estudio comparativo con pacientes de VIH+ hospitalizados en el Instituto Nacional de Enfermedades Respiratorias en la Ciudad de México de febrero a noviembre de 2013. Se aplicaron la Escala de Ansiedad y Depresión Hospitalaria, la Escala de Desesperanza de Beck y la Escala de Riesgo Suicida de Plutchik. Resultados. Ciento quince pacientes completaron las tres escalas. A su ingreso, 10.4% de los pacientes obtuvieron puntajes por encima del punto de corte en la Escala de Riesgo Suicida; 1.7% presentaron niveles altos de desesperanza; 5.2% puntuaron con depresión clínica; y 7% puntuaron para ansiedad clínica. La comparación entre los resultados obtenidos al ingreso y el egreso hospitalario mostró una disminución significativa en todos los síntomas al egreso. Discusión y conclusión. La mayoría de los pacientes presentaron niveles bajos de los síntomas evaluados y éstos disminuyeron al egreso. Son necesarias investigaciones adicionales de salud mental en población hospitalizada con VIH.

In vitro functional assessment of natural HIV-1 group M Vpu sequences using a universal priming approach.

The HIV-1 accessory protein Vpu exhibits high inter- and intra- subtype genetic diversity that may influence Vpu function and possibly contribute to HIV-1 pathogenesis. However, scalable methods to evaluate genotype/phenotype relationships in natural Vpu sequences are limited, particularly those expressing the protein in CD4+ T-cells, the natural target of HIV-1 infection. A major impediment to assay scalability is the extensive genetic diversity within, and immediately upstream of, Vpu's initial 5' coding region, which has necessitated the design of oligonucleotide primers specific for each individual HIV-1 isolate (or subtype). To address this, we developed two universal forward primers, located in relatively conserved regions 38 and 90 bases upstream of Vpu, and a single universal reverse primer downstream of Vpu, which are predicted to cover the vast majority of global HIV-1 group M sequence diversity. We show that inclusion of up to 90 upstream bases of HIV-1 genomic sequence does not significantly influence in vitro Vpu expression or function when a Rev/Rev Response Element (RRE)-dependent expression system is used. We further assess the function of four diverse HIV-1 Vpu sequences, revealing reproducible and significant differences between them. Our approach represents a scalable option to measure the in vitro function of genetically diverse natural Vpu isolates in a CD4+ T-cell line.

Endoscopic assessment of adenoid size is an indicator of tissue virologic response to highly active antiretroviral therapy.

OBJECTIVE: To compare human immunodeficiency virus viral load (HIVVL) in plasma versus the adenoid HIVVL during highly active antiretroviral therapy (HAART). DESIGN: Adenoid biopsies were taken basally and after 3 and 6 months of treatment. Also, the adenoid diameter by simple endoscopy was measured, and its correlation with adenoid HIVVL was calculated. SETTING AND PATIENTS: A public tertiary care human immunodeficiency virus (HIV) hospital research centre. Twenty-seven antiretroviral-naive HIV-infected patients, with a mean age of 34.7 years, were included in the study. MAIN OUTCOME MEASURE: Correlation between adenoid diameter and plasma and tissue HIVVL. RESULTS: At 3 months, although plasma HIVVL reduced by almost 5 log to a level below 1 log, adenoid HIVVL only decreased 2.36 log, remaining well over 4 log. At 6 months, plasma HIVVL further decreased to 0.205 log, but adenoid HIVVL remained at 2.424 log. Adenoid diameter also decreased over time, with means at 8.52, 5.61, and 4 mm, respectively. It significantly correlated with plasma and adenoid viral load, but the correlation was higher with the biopsies. CONCLUSION: HIVVL in adenoid tissue is more resilient to HAART than plasma VL and may need more than 6 months to reach asymptomatic levels. Nevertheless, simple endoscopic measurement of the adenoid diameter is a good indicator of viral load decrease in this tissue.