Does Haptoglobin Phenotype Impact Infection Mortality?

Introduction: The physiological status of a subject and the pathophysiology in some diseases might be under the influence of haptoglobin phenotype. The objective of this work was to determine the relationship between mortality from HIV/AIDS infection and haptoglobin phenotype in a black population in Côte d’Ivoire. Methods: The study was conducted from a retrospective panel of 933 sera/plasma from the previous workup of the ANRS 12136 TEMPRANO trial at month 0 of patients in deferred-ART arms. For each subject, we determined the serum haptoglobin concentration, haptoglobin phenotype, and other variables from patient files from the TEMPRANO trial database. Statistical tests used were Chi-2, Fischer, and Kruskal-Wallis tests for non-gaussian distribution. We used the Kaplan-Meier method for survival analysis. Results: The distributions of the haptoglobin phenotypes were 32.3% for Hp 1-1, 39.5% for Hp 2-1 and 27.2% for Hp 2-2. The blood haptoglobin concentration seemed to be associated with haptoglobin phenotypes (p-value > 5%). The survival rate at M30 and for an extended follow-up up to 6 years was independent of haptoglobin phenotype (p-value > 5%). Besides, the haptoglobin phenotypes do not appear to be associated with CD4+ T-cell count and with hemoglobin concentration. Conclusion: Haptoglobin phenotype seems to not impact the mortality of HIV/AIDS infection. However, given the antioxidant and immunomodulatory properties of some haptoglobin phenotypes, it would be relevant to seek out possible confounding factors indirectly associated with haptoglobin phenotypes and clinical or biological infection variables.

Effect of ABCB1 C3435T Polymorphism on Clinical Outcomes in Kenyan HIV Patients on Lopinavir-Based Regimens

ATP Binding Cassette sub-family B member 1 （ABCB1） affects disposition of many drugs and thus affects the pharmacokinetics of drugs and ultimately treatment response. Polymorphisms of ABCB 1 especially ABCB 1 C3435T polymorphism may thus affect pharmacokinetics of antiretroviral drugs and hence CD4 treatment response and other clinical outcomes of HIV patients. Methods： The study design was a historical cohort study and entailed collection of patient data. PureLink genomic DNA extraction mini kit was used for the extraction and purification of genomic DNA. TaqMan drug genotyping assay and protocol was used in the DNA amplification and genotyping. Data analysis was done using STATA software version 10. Results： Study participants with the CT genotype had lower creatinine levels after 6 months on lopinavir-based regimens compared with those with the CC genotype （p = 0.001）. In addition, the study participants with the CT genotype had consistently higher CD4 cell counts compared with those with the CC genotype from the time of ART switch but this was not statistically significant. However, there was no significant association between the ABCB 1 C3435T genotypes and haemoglobin and ALT levels. Conclusion： There was a significant association between ABCB1 C3435T polymorphism and creatinine levels 6 months after therapy on lopinavir-based regimens.

Factors Associated with Sample Rejection for CD4+/CD8+ T Cell Count Analyses at the Kenyatta National Hospital Comprehensive Care Center Laboratory, Kenya

Background: The appropriate time to initiate antiretroviral therapy (ART) in HIV/AIDS patients is determined by measurement of CD4+/CD8+ T cell count. The CD4/CD8+ T cell count is also useful, together with viral load, in monitoring disease progression and effectiveness treatment regimens. Several factors may contribute to sample rejection during the CD4+/CD8+ T cells count, resulting in negative effects on patient management. Objective: Evaluate the causes for CD4+CD8+ T cell count sample rejection at the Kenyatta National Hospital Comprehensive Care Center Laboratory. Method: A retrospective cross-sectional study was conducted between 2018 and 2020. Data was obtained from the “rejected samples” for PartecR FlowCyp flow cytometry file. Designed data collection sheet was used for data capture. A total of 3972 samples were submitted for CD4+/CD8+ T cell count during the study period. Causes for sample rejection were numbered 1 to 12, each representing a reason for sample rejection. Number 1 was sub-categorized into clotted, hemolyzed, short-draw and lipemic. Data was analyzed using excel, and presented using tables, graphs and pie charts. Approval to conduct the study was obtained from KNH/UoN ERC. Results: In the study period, 81/3972 (2.0%) samples were rejected. Samples submitted more than 48 hours after collection were mostly rejected. Other factors included improper collection technique, delayed testing, patient identification error and incorrect use of vacutainer. A combination of clotted samples, specimen submission more than 48 hours caused the most frequent sample rejection, followed with combination of specimen submission more than 48 hours, delayed testing and delayed specimen processing. Together, clotted samples, incorrect vacutainer and poor specimen label caused the least sample rejection. Conclusion: Sample rejection rate for CD4/CD8+ T cell count was relatively low, and multiple factors contributed to rejection. However, improved quality assurance will enable more benefit to patients who seek this test in the laboratory.

Impact of baseline CD4^＋ T cell counts on the efficacy of nevirapinebased highly active antiretroviral therapy in Chinese HIV/AIDS patients： a prospective, multicentric study

Background CD4^＋T cell counts have been used as the indicator of human immunodeficiency virus type 1 （HIV-1） disease progression and thereby to determine when to start highly active antiretroviral therapy （HAART）. Whether and how the baseline CD4^＋T cell count affects the immunological and viral responses or adverse reactions to nevirapine （NVP）-containing HAART in Chinese HIV-1 infected adults remain to be characterized. Methods One hundred and ninety-eight HIV-seropositive antiretroviral therapy （ART）-naive subjects were enrolled into a prospective study from 2005 to 2007. Data were analyzed by groups based on baseline CD4^＋T cell counts either between 100-200 cells/μl or 201-350 cells/μl. Viral responses, immunologic responses and adverse events were monitored at baseline and at weeks 4, 12, 24, 36, 52, 68, 84, 100. Results Eighty-six and 112 subjects ranged their CD4^＋T cell counts 100-200 cells/μl and 201-350 cells/μl, respectively. The pre-HAART viral load in CD4 201-350 cells/μl group was significantly lower than that in CD4 100-200 cells/μl group （P=0.000）. After treatment, no significant differences were observed between these two groups either in the plasma viral load （pVL） or in the viral response rate calculated as the percentage of pVL less than 50 copies/ml or less than 400 copies/ml. The CD4^＋T cell counts were statistically higher in the 201-350 group during the entire follow-ups （P 〈0.01） though CD4^＋ T cell count increases were similar in these two groups. After 100-week treatment, the median of CD4^＋ T cell counts were increased to 331 cells/μl for CD4 100-200 cells/μl group and to 462 cells/μl for CD4 201-350 cells/μl group. Only a slightly higher incidence of nausea was observed in CD4 201-350 cells/μl group （P=0.05） among all adverse reactions, including rash and liver function abnormality. Conclusions The pVLs and viral response rates are unlikely to be associated with the baseline CD4^＋T cell counts. Initiating HAART in Chinese HIV-1 infected patients with higher baseline CD4^＋T cell counts could result in higher total CD4^＋T cell counts thereby achieve a better immune recovery. These results support current guidelines to start HAART at a threshold of 350 cells/μl.

Persistently low CD4 cell counts are associated with hepatic events in HCV/HIV coinfected patients: data from the national free antiretroviral treatment program of China

Background: Chronic liver disease has emerged as a leading cause of non-acquired immune deficiency syndrome (AIDS)-related mortality in hepatitis C virus (HCV)/human immunodeficiency virus (HIV)-coinfected patients. The relationship between CD4 cell count and HIV-related opportunistic infections and tumors has been well characterized;however, it is unclear whether CD4 cell count is associated with HCV-related hepatic events.Methods: This observational cohort study enrolled HCV/HIV-coinfected patients from the National Free Antiretroviral Treatment Program of China from 2004 to 2019 in Guangzhou. The primary outcome was a composite of hepatic events, including cirrhosis complications, hepatocellular carcinoma (HCC), and liver-related mortality. Kaplan-Meier survival and multivariate logistic regression analyses were performed.Results: Among the 793 patients, 43 developed hepatic events during a median follow-up of 6.7 years, including 35 cirrhosis complications, 13 HCC cases, and 14 cases of liver-related mortality. The 5-year and 10-year cumulative incidences of hepatic events were 4.2% and 9.3%, respectively. Patients who developed hepatic events had a less satisfactory increase in CD4 cell count, lower peak CD4 (354.5 cells/μLvs. 560.0 cells/μL,P < 0.001), and lower percentage of peak CD4 > 500 cells/μL (30.2%vs. 60.7%,P < 0.001) after the initiation of antiretroviral therapy (ART) than those who did not. The cumulative incidences of hepatic events were higher in patients with lower peak CD4 levels with adjusted odds ratios of 3.96 (95% confidence interval [CI]: 1.51-10.40), 2.25 (95% CI: 0.87-5.86), and 0.98 (95% CI: 0.35-2.74) for patients with peak CD4 at <200 cells/μL, 200-350 cells/μL, and 351 to 500 cells/μL, respectively, relative to those with peak CD4 > 500 cells/μL. Peak CD4 was negatively associated with the risk of hepatic events in a dose-response manner (P-value for trend = 0.004).Conclusion: Persistently low CD4 cell counts after ART are independently associated with a high risk of hepatic events in HCV/HIV-coinfected patients, highlighting the important role of immune reconstitution in improving liver outcomes.

Engaging HIV-infected patients in antiretroviral therapy services： CD4 cell count testing after HIV diagnosis from 2005 to 2009 in Yunnan and Guangxi, China

Background The initiation and expansion of China＇s national free antiretroviral therapy program has led to significant improvement of survival among its participants. Success of further scaling up treatment coverage rests upon intensifying HIV screening and efficient linkage of care. Timely CD4 cell count testing after HIV diagnosis is necessary to determine whether a patient meets criteria for antiretroviral treatment, and represents a crucial link to engage HIV-infected patients in appropriate care, which has not been evaluated in China.Methods We evaluated all patients ≥16 years who tested HIV positive from 2005 to 2009 in Yunnan and Guangxi.Multivariate Logistic regression models were applied to identify factors associated with lack of CD4 cell count testing within 6 months after HIV diagnosis.Results A total of 83 556 patients were included. Over the study period, 30 635 （37%） of subjects received a CD4 cell count within 6 months of receiving the HIV diagnosis. The rate of CD4 cell count testing within 6 months of HIV diagnosis increased significantly from 7% in 2005 to 62% in 2009. Besides the earlier years of HIV diagnosis, negative predictors for CD4 cell count testing in multivariate analyses included older age, not married or unclear marriage status,incarceration, diagnosis at sexual transmitted disease clinics, mode of HIV transmission classified as men who have sex with men, intravenous drug users or transmission route unclear, while minority ethnicity, receipt of high school or higher education, diagnosis at voluntary counseling and testing clinics, and having HIV positive parents were protective.Conclusions Significant progress has been made in increasing CD4 testing among newly diagnosed HIV positive patients in Yunnan and Guangxi from 2005-2009. However, a sizable proportion of HIV positive patients still lack CD4testing within 6 months of diagnosis. Improving CD4 testing, particularly among patients with identified risk factors, is essential to link patients with ART services and optimize treatment coverage

Virological and immunological outcomes in HIV-1-infected Chinese patients treated with a combination of Efavirenz and Indinavir for 48 weeks

Background The incidence of HIV-1-related infection d iseases and the mortality of AIDS have dramatically decreased since highly activ e antiretroviral therapy began to be used clinically in China in 1999. And we in itiated a second clinical trial using a combination of Efavirenz and Indinavir to observe the effects of the immunoreaction.Methods Twenty patients with laboratory-confirmed chronic HIV-1 infection were recruited. Blood samples were collected initially and during the weeks after initiation of treatment. Within 48 hours of blood sampling, peripheral blood plasma and mononuclear cells were separated using routine methods. HIV-1 viral load was measured in thawed plasma samples. Within 48 hours of peripheral blood sampling, CD4 + and CD8 + T cell subsets were enumerated.Results The drug regimen was efficient in reducing HIV-1 plasma viral load and increasing total CD4 + T cell counts. The percentage of CD4 + and CD8 + T cel l subsets expressing CD38 and HLA-DR activation markers was positively correlated with plasma viral load and tended to normalize.Conclusions The combination of Efavirenz and Indinavir was generally well tolerated and efficient at reducing HIV-1 RNA. Furthermore, the treatment improved the immunological function.