CD4 and CD8 Lymphocyte Counts as Surrogate Early Markers for Progression in SARS-CoV-2 Pneumonia: A Prospective Study.

BACKGROUND: COVID-19 pathophysiology and the predictive factors involved are not fully understood, but lymphocytes dysregulation appears to play a role. This paper aims to evaluate lymphocyte subsets in the pathophysiology of COVID-19 and as predictive factors for severe disease. PATIENT AND METHODS: A prospective cohort study of patients with SARS-CoV-2 bilateral pneumonia recruited at hospital admission. Demographics, medical history, and data regarding SARS-CoV-2 infection were recorded. Patients systematically underwent complete laboratory tests, including parameters related to COVID-19 as well as lymphocyte subsets study at the time of admission. Severe disease criteria were established at admission, and patients were classified on remote follow-up according to disease evolution. Linear regression models were used to assess associations with disease evolution, and Receiver Operating Characteristic (ROC) and the corresponding Area Under the Curve (AUC) were used to evaluate predictive values. RESULTS: Patients with critical COVID-19 showed a decrease in CD3+CD4+ T cells count compared to non-critical (278 (485 IQR) vs. 545 (322 IQR)), a decrease in median CD4+/CD8+ ratio (1.7, (1.7 IQR) vs. 3.1 (2.4 IQR)), and a decrease in median CD4+MFI (21,820 (4491 IQR) vs. 26,259 (3256 IQR)), which persisted after adjustment. CD3+CD8+ T cells count had a high correlation with time to hospital discharge (PC = -0.700 (-0.931, -0.066)). ROC curves for predictive value showed lymphocyte subsets achieving the best performances, specifically CD3+CD4+ T cells (AUC = 0.756), CD4+/CD8+ ratio (AUC = 0.767), and CD4+MFI (AUC = 0.848). CONCLUSIONS: A predictive value and treatment considerations for lymphocyte subsets are suggested, especially for CD3CD4+ T cells. Lymphocyte subsets determination at hospital admission is recommended.

[Spanish recommendations for proper use of enfuvirtide]. / Recomendaciones españolas sobre el uso adecuado de enfuvirtida.

Enfuvirtide is a high-cost, parenterally administered drug commonly used in late phases of HIV infection, when its efficacy may be compromised. To optimize enfuvirtide use, consensus recommendations for this purpose have been formulated by 247 physicians attending patients with HIV infection in Spain. A literature review was performed in which grades of evidence and recommendations were defined according to the origin of the data (randomized clinical trials, non-randomized studies, expert opinion). Twenty-eight local consensus meetings were held between May and September 2005 to discuss the most important aspects related to the use of enfuvirtide, following a pre-established system used in all the meetings. The main conclusions were as follows: a) enfuvirtide use is often excessively delayed and is given to patients with little chance of treatment success; b) enfuvirtide is indicated in patients who require antiretroviral treatment and for whom an optimum treatment with three other fully effective drugs cannot be designed; c) the most important prognostic factor is the availability of at least one other completely active drug; d) there is no infallible method to avoid the development of local reactions, but measures are available to decrease their incidence and severity; and e) patient counseling and training for correct administration of the drug are essential to improve adherence, the repercussions of local reactions and, of course, the efficacy of the treatment.

Epidemiological and clinical features, response to HAART, and survival in HIV-infected patients diagnosed at the age of 50 or more.

BACKGROUND: Over the last years, the mean age of subjects with HIV infection and AIDS is increasing. Moreover, some epidemiological and clinical differences between younger and older HIV-infected individuals have been observed. However, since introduction of HAART therapy, there are controversial results regarding their response to HAART. The aim of the present study is to evaluate epidemiological and clinical features, response to HAART, and survival in elderly HIV-infected patients with regard to younger HIV-infected patients. METHODS: A prospective cohort study (1998-2003) was performed on patients from Sabadell Hospital, in Northeast of Spain. The cohort includes newly attended HIV-infected patients since January 1, 1998. For the purpose of this analysis, data was censured at December 31, 2003. Taking into account age at time of diagnosis, it was considered 36 HIV-positive people aged 50 years or more (Group 1, G1) and 419 HIV-positive people aged 13-40 years (Group 2, G2). Epidemiological, clinical, biological and therapy data are recorded. Statistical analysis was performed using Chi-squared test and Fisher exact test, Mann-Whitney U test, Kaplan-Meier, Log Rank test, and Two-Way ANOVA from random factors. RESULTS: G1 showed higher proportion of men than G2. The most common risk factors in G1 were heterosexual transmission (P = 0.01) and having sex with men or women (P < 0.001). G1 and G2 show parallel profiles through the time regarding immunological response (P = 0.989) and virological response (P = 0.074). However, older people showed lower CD4 cell counts at first clinic visit (P < 0.001) and, eventually, they did not achieve the same counts as G2. G1 presented faster progression to AIDS (P < 0.001) and shorter survival (P < 0.001). CONCLUSION: Older patients have different epidemiological features. Their immunological and virological responses are good. However, older patients do not achieve the same CD4 cell counts likely due to they have lower counts at first clinic visit. Thus, it is essential physicians know older HIV-infected patients features to consider the possibility of HIV infection in these patients with the aim of treatment would not be delayed.

Results of a study of prolonging treatment with pegylated interferon-alpha2a plus ribavirin in HIV/HCV-coinfected patients with no early virological response.

OBJECTIVE: To assess the efficacy and safety of an extended treatment period in HIV/hepatitis C virus (HCV)-coinfected patients without early virological response (EVR). METHODS: Patients received pegylated interferon (peg-INF)-alpha2a 180 microg/week plus ribavirin 800 mg/d for 12 weeks. Patients achieving EVR at week 12 continued under therapy for an additional 12 or 36 weeks depending on genotype. Patients without EVR were randomized to complete the standard treatment or treatment lasting 72 weeks (extension arm). RESULTS: One hundred and ten patients were included (mean age 38.7 years, mean weight 68 kg, 74% males, 74% on highly active antiretroviral therapy, mean CD4+ T-cell count 564 cells/mm3). Fifty-one patients harboured genotype 1, 44 genotype 2/3, and 15 genotype 4. Fifty-three had an HCV load >800,000 IU/ml. Premature interruptions occurred in 32.7%. EVR was achieved in 63.6% (51% in genotype 1, 88.6% in genotype 2/3, 33.3% in genotype 4). End-of-treatment response was 52.7% (47.2% in genotype 1, 68.2% in genotype 2/3, 26.7% in genotype 4). Sustained virological response (SVR) was achieved in 41.8% (37.3% in genotype 1, 54.6% in genotype 2/3, 20% in genotype 4). Only one patient allocated to the extended arm achieved SVR. The rate of drop-outs in the extension arm was 68%. The negative predictive value of EVR was 97.5%. CONCLUSIONS: This study shows no benefit of extending therapy in patients without EVR at week 12. Measures to improve adherence to HCV antiviral therapy should be considered when new approaches based on extended periods of treatment are investigated.

Long-term safety and efficacy of nevirapine-based approaches in HIV type 1-infected patients.

Using a multicenter, cross-sectional, observation study, the long-term safety, metabolic profile, and viral efficacy of nevirapine (NVP)-based approaches in HIV-1-infected patients treated for at least 2 years were assessed. For 4 months, all consecutive HIV-1-infected patients who had been receiving an NVP-containing regimen for at least 2 years were recruited. A total of 613 patients were included with a median follow-up period of 43 months (IQR: 31-51). At baseline, 24.5% (150 patients) were treatment naive, 41.5% (254 patients) switched for simplification purposes, and 34% (209 patients) were failing HAART. Increases by five times or more in AST/ALT values were observed in fewer than 2% of patients. Only 5.7% of all adverse events reported during the investigation were attributable to NVP. The percentage of patients with normal HDL cholesterol levels rose from 17.7% at baseline to 35.4% at the last visit. At the latest time point available for analysis, 76% of naive and 74% of those who had switched had HIV-1 RNA loads of <50 copies/ml, while 59% of salvage patients achieved this level of viral suppression. Factors associated with viral suppression at the latest visit were adequate adherence (OR: 2.58, 95% CI: 0.85-7.78, p < 0.001), first-line treatment (OR: 3.02, 95% CI: 1.52-6.00, p = 0.002), and baseline CD4 cells >400 cells/microl (OR: 2.34, 95% CI: 1.22-4.47, p = 0.010). Exposure to nevirapine for up to 4 years is safe. Liver toxicity is infrequent and generally mild. HDL cholesterol levels consistently increase over time and viral suppression is maintained.