Thirty to fifty percent of hepatocellular carcinomas (HCC) display an immune class genetic signature. In this type of tumor, HCC-specific CD8 T cells carry out a key role in HCC control. Those potential reactive HCC-specific CD8 T cells recognize either HCC immunogenic neoantigens or aberrantly expressed host’s antigens, but they become progressively exhausted or deleted. These cells express the negative immunoregulatory checkpoint programmed cell death protein 1 (PD-1) which impairs T cell receptor signaling by blocking the CD28 positive co-stimulatory signal. The pool of CD8 cells sensitive to anti-PD-1/PD-L1 treatment is the PD-1dim memory-like precursor pool that gives rise to the effector subset involved in HCC control. Due to the epigenetic imprints that are transmitted to the next generation, the effect of PD-1 blockade is transient, and repeated treatments lead to tumor resistance. During long-lasting disease, besides the TCR signaling impairment, T cells develop other failures that should be also set-up to increase T cell reactivity. Therefore, several PD-1 blockade-based combinatory therapies are currently under investigation such as adding antiangiogenics, anti-TGFβ1, blockade of other negative immune checkpoints, or increasing HCC antigen presentation. The effect of these combinations on CD8⁺ T cells is discussed in this review.

To compare the clinical, immunologic, and virologic outcomes of efavirenz (EFV)-based versus protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) in severely immunosuppressed HIV-1-infected patients. Retrospective observational cohort study. Responses were analyzed according to the intent-to-treat principle among antiretroviral-naive patients with < 100 CD4 cells/muL who started EFV (n = 92) or a PI (n = 218) plus 2 nucleoside reverse transcriptase inhibitors. The primary end point was time to treatment failure. Secondary end points were percentage of patients with a viral load < 400 copies/mL, time to virologic failure, time to CD4 lymphocyte count > 200 cells/microL, and incidence of opportunistic events or death. The median baseline CD4 cell count and viral load were 34 cells/microL and 5.54 log10 copies/mL (EFV group) and 38 cells/microL and 5.40 log10 copies/mL (PI group). Time to treatment failure was shorter with a PI-based regimen than with an EFV-based regimen (adjusted relative hazard [RH] = 2.19, 95% confidence interval [CI]: 1.23-3.89). After 12 months of therapy, a significantly higher proportion of patients receiving EFV reached a viral load < 400 copies/mL (69.4 vs. 45.1%; P < 0.05). The probability of virologic failure was higher with a PI than with EFV (adjusted HR = 2.52, 95% CI: 1.14-5.61; P = 0.024). There was no difference in time to CD4 cell count > 200 cells/microL or in incidence of opportunistic events or death. : In severely immunosuppressed, antiretroviral-naive, HIV-1-infected patients, treatment with an EFV-based regimen compared with a nonboosted PI-based regimen resulted in a superior virologic response with no difference in immunologic or clinical effectiveness.

Background: People in their fifties with HIV are considered older adults, but they appear not to be a homogeneous group.Objective: To evaluate the differences among older adults with HIV according to their chronological age and the year of HIV diagnosis.Methods: Cross-sectional study of the FUNCFRAIL cohort. Patients 50 or over with HIV were included and were stratified by both chronological age and the year of HIV diagnosis: before 1996 (long-term HIV survivors [LTHS]) and after 1996. We recorded sociodemographic data, HIV-related factors, comorbidities, frailty, physical function, other geriatric syndromes, and quality of life (QOL).Results: We evaluated 801 patients. Of these, 24.7% were women, 47.0% were LTHS, and 14.7% were 65 or over. Of the 65 or over patients, 73% were diagnosed after 1996. Higher rates of comorbidities among LTHS were found, being the more prevalent: COPD, history of cancer, osteoarthritis, depression, and other psychiatric disorders while the more prevalent among the 65 or over patients were: hypertension, diabetes, dyslipidemia, cancer, and osteoarthritis. LTHS showed a significantly worse QOL. There were no differences by the year of HIV diagnosis regarding frailty and functional impairment (SPPB <10) but they were more than twice as prevalent in the 65 or over patients compared to the other chronological age groups.Conclusions: A LTHS and a 65 or over person are both “older adults with HIV,” but their characteristics and requirements differ markedly. It is mandatory to design specific approaches focused on the real needs of the different profiles.

We evaluated the therapeutic outcomes of all antiretroviral-naive HIV-1-infected patients with fewer than 100 CD4 cells/microl, who received efavirenz-based highly active antiretroviral therapy (HAART). Sixty-one percent suffered AIDS-defining diseases, and after a median follow-up of 45 weeks there were three deaths and five AIDS-related conditions (two relapses, three new). Efavirenz-based HAART was found to be effective in profoundly immunosuppressed HIV-1-infected patients.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with an incidence that is exponentially increasing. Hepatocellular carcinoma (HCC) is the most frequent primary tumor. There is an increasing relationship between these entities due to the potential risk of developing NAFLD-related HCC and the prevalence of NAFLD. There is limited evidence regarding prognostic factors at the diagnosis of HCC. This study compares the prognosis of HCC in patients with NAFLD against other etiologies. It also evaluates the prognostic factors at the diagnosis of these patients. For this purpose, a multicenter retrospective study was conducted involving a total of 191 patients. Out of the total, 29 presented NAFLD-related HCC. The extreme gradient boosting (XGB) method was employed to develop the reference predictive model. Patients with NAFLD-related HCC showed a worse prognosis compared to other potential etiologies of HCC. Among the variables with the worst prognosis, alcohol consumption in NAFLD patients had the greatest weight within the developed predictive model. In comparison with other studied methods, XGB obtained the highest values for the analyzed metrics. In conclusion, patients with NAFLD-related HCC and alcohol consumption, obesity, cirrhosis, and clinically significant portal hypertension (CSPH) exhibited a worse prognosis than other patients. XGB developed a highly efficient predictive model for the assessment of these patients.