Mean CD4 Cell Research Articles

Reconstitution of Lymphocyte Subsets and Outcomes After Matched and Mismatched Hematopoietic Stem-Cell Transplantation

Abstract 4485 Allogeneic stem-cell transplantation (ASCT) is curative for many malignant and nonmalignant hematological disorders. Limitations of expanding this form of treatment are related primarily to non-relapse mortality (NRM) associated with reconstituting the recipient's immune system. We aimed to study reconstitution of lymphocyte subsets after matched and mismatched transplantation. Lymphocyte subsets (absolute numbers of CD3, CD4, CD8, CD19, CD56, CD25, CD45RA, CD45RO) were evaluated by flow cytometry at 1,3,6 and 12 months (mo) post-ASCT. Lymphocyte recovery was determined using means at each time point and group differences were assessed using analysis of variance. Kaplan-Meier survival curves were used to estimate time-to-event outcome measures and the log-rank test was used to evaluate differences between groups. 100 patients (pts) were included in the study. 25 pts received a matched sibling donor transplant (MSD), 20 pts a 10/10 MUD, 18 pts a 9/10 MUD, 9 pts a T cell depleted haploidentical (TCD haplo), and 28 a T cell replete haploidentical donor (TCR haplo). 53 pts received bone marrow and 47 had peripheral blood stem cells. Most patients were treated for acute leukemia (AML 41, ALL 23), 16 MDS, 6 CML, 4 CLL, 5 lymphoma. Median age was 43 years (range: 20–71). The median follow-up was 13.6 mo. 60 pts were alive and disease-free at last follow-up and 28 pts died 75% due to relapse. Non-relapse mortality (NRM) was 6% for the entire cohort. Overall, alive pts (vs who died) had higher mean CD3 (615 vs 349, p=0.03 on day 90), CD8 (427 vs 187, p=0.03 on day 90), CD4 (391 vs 54, p=0.01, on day 365) cells, and lower mean CD56 cells (178 vs 300, p=0.01, on day 30) post ASCT. Pts who progressed (vs did not), had lower 1 year mean CD4 cells (123 vs 394, p=0.02), lower mean CD3 cells (359 vs 1147, p=0.06), with no differences in CD8, NK, and CD45RA. NRM was associated with higher mean NK numbers at 6 months (499 vs 188, p=0.01) and with lower mean CD3 at day 90 (184 vs 557, p=0.07). T-cell recovery occurred most rapidly in MSD transplants ([Figure1][1]C), and compared with 10/10 MUD had higher mean CD3 cells in the first mo (1085 vs 510, p=0.01), CD4 in the first 6 mo (310 vs 147, p<0.01 day 180) and CD4CD45RA in the first 6 mo (105 vs 31, p=0.02 on day 180). Interestingly, we have found that higher CD4CD25 cell numbers recovered early and most rapidly in the MSD transplants, which may partly explain a lower incidence of GVHD in this group. Overall, TCR haplos had a similar pattern of T-cell recovery and outcomes as 10/10 MUDs ([Figure1][1]C-E). There was a significant delay in CD3 recovery between MSD and TCR haplos in the first 3 mo (mean 779 vs 483, p=0.04 on day 90), CD4 (mean 270 vs 170, p=0.03 day 90) and in the first 6 months for CD45RA (mean 105 vs 28, p=0.01 on day 180), while these differences were significant only at day 30 for CD8 cells (mean 703 vs 88, p<0.01). No significant differences in T cell subsets were found between 10/10 MUD and TCR HaploSCT for CD3, CD4, CD8, CD45RA and CD4CD25 for any time points. Of all types of transplant, TCD haplos had most impaired T-cell reconstitution and worst outcomes ([Figure 1][1]A and [1][1]B). As previously reported it was characterized by rapid early NK cell recovery and delayed CD3, CD4, CD8 reconstitution. Interestingly, pts surviving 6–9 months post-transplant recovered CD3, C4, CD8 cells; however, naive T-cell recovery remained impaired for more than 1 year post-transplant, suggesting that T cell recovery comes predominantly from the memory T cell compartment. In conclusion, these results suggest that recovery of lymphocyte subsets may vary widely with the type of transplant, may correlate with outcomes, and it is important to be further explored in this setting. ![Figure][2] Disclosures: No relevant conflicts of interest to declare. [1]: #F1 [2]: pending:yes

Reconstitution of Lymphocyte Subsets and Outcomes After Matched and Mismatched Hematopoietic Stem-Cell Transplantation

Abstract 4485Allogeneic stem-cell transplantation (ASCT) is curative for many malignant and nonmalignant hematological disorders. Limitations of expanding this form of treatment are related primarily to non-relapse mortality (NRM) associated with reconstituting the recipient's immune system. We aimed to study reconstitution of lymphocyte subsets after matched and mismatched transplantation.Lymphocyte subsets (absolute numbers of CD3, CD4, CD8, CD19, CD56, CD25, CD45RA, CD45RO) were evaluated by flow cytometry at 1,3,6 and 12 months (mo) post-ASCT. Lymphocyte recovery was determined using means at each time point and group differences were assessed using analysis of variance. Kaplan-Meier survival curves were used to estimate time-to-event outcome measures and the log-rank test was used to evaluate differences between groups. 100 patients (pts) were included in the study. 25 pts received a matched sibling donor transplant (MSD), 20 pts a 10/10 MUD, 18 pts a 9/10 MUD, 9 pts a T cell depleted haploidentical (TCD haplo), and 28 a T cell replete haploidentical donor (TCR haplo). 53 pts received bone marrow and 47 had peripheral blood stem cells. Most patients were treated for acute leukemia (AML 41, ALL 23), 16 MDS, 6 CML, 4 CLL, 5 lymphoma. Median age was 43 years (range: 20–71). The median follow-up was 13.6 mo. 60 pts were alive and disease-free at last follow-up and 28 pts died 75% due to relapse. Non-relapse mortality (NRM) was 6% for the entire cohort.Overall, alive pts (vs who died) had higher mean CD3 (615 vs 349, p=0.03 on day 90), CD8 (427 vs 187, p=0.03 on day 90), CD4 (391 vs 54, p=0.01, on day 365) cells, and lower mean CD56 cells (178 vs 300, p=0.01, on day 30) post ASCT. Pts who progressed (vs did not), had lower 1 year mean CD4 cells (123 vs 394, p=0.02), lower mean CD3 cells (359 vs 1147, p=0.06), with no differences in CD8, NK, and CD45RA. NRM was associated with higher mean NK numbers at 6 months (499 vs 188, p=0.01) and with lower mean CD3 at day 90 (184 vs 557, p=0.07). T-cell recovery occurred most rapidly in MSD transplants (Figure1C), and compared with 10/10 MUD had higher mean CD3 cells in the first mo (1085 vs 510, p=0.01), CD4 in the first 6 mo (310 vs 147, p<0.01 day 180) and CD4CD45RA in the first 6 mo (105 vs 31, p=0.02 on day 180). Interestingly, we have found that higher CD4CD25 cell numbers recovered early and most rapidly in the MSD transplants, which may partly explain a lower incidence of GVHD in this group. Overall, TCR haplos had a similar pattern of T-cell recovery and outcomes as 10/10 MUDs (Figure1C-E). There was a significant delay in CD3 recovery between MSD and TCR haplos in the first 3 mo (mean 779 vs 483, p=0.04 on day 90), CD4 (mean 270 vs 170, p=0.03 day 90) and in the first 6 months for CD45RA (mean 105 vs 28, p=0.01 on day 180), while these differences were significant only at day 30 for CD8 cells (mean 703 vs 88, p<0.01). No significant differences in T cell subsets were found between 10/10 MUD and TCR HaploSCT for CD3, CD4, CD8, CD45RA and CD4CD25 for any time points. Of all types of transplant, TCD haplos had most impaired T-cell reconstitution and worst outcomes (Figure 1A and 1B). As previously reported it was characterized by rapid early NK cell recovery and delayed CD3, CD4, CD8 reconstitution. Interestingly, pts surviving 6–9 months post-transplant recovered CD3, C4, CD8 cells; however, naïve T-cell recovery remained impaired for more than 1 year post-transplant, suggesting that T cell recovery comes predominantly from the memory T cell compartment.In conclusion, these results suggest that recovery of lymphocyte subsets may vary widely with the type of transplant, may correlate with outcomes, and it is important to be further explored in this setting. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Prevalence of drug resistance mutations in HIV-1 protease gene from North India

Results Among 35 patients, there were 17 drug naive and 18 first line drugs experienced HIV-1 infected patients (22 males & 13 females; mean age: 35.95 years; mean CD4 cells: 216.4cells/mm). Majority of our patients showed mutations at T12S/T (82.85%), K14R (40%), I15V (71.42%), L19I/T/V/M (97.14%), M36I (71.42%), R41K (88.57%), L63P (65.71%), H63K (100%) and L89M (74.28%) positions in both group of patients while other mutations were at positions 35, 37, 45, 60, 62, 77, and 82 in few cases. Interestingly, one first line drug experienced patient showed major DR mutations at D30N and M46I positions. Majority (94.28%) was belonging to subtype C and 2 patients were belonging to subtypes A (A1).

The outcome and choice of initial combination anti-retroviral therapy in treatment-naïve HIV-infected individuals

Background : Optimization of initial highly active antiretroviral therapy (HAART) for complete viral suppression and better tolerability is paramount for the prognosis of HIV-infected patients. Durable suppression of HIV therefore depends on the use of potent, well-tolerated antiretroviral regimens to which patients can easily adhere. The aim is to determine the outcome and factors influencing the choice of initial combination antiretroviral drugs in the treatment-naive HIV patients. Methods : The outcome and factors influencing the choice of initial antiretroviral drugs were investigated in HIV-infected treatment-naive individuals in a large HIV treatment clinic in south-western Nigeria using a cross-sectional design between January to December 2010. Results : 432 patients were analyzed (mean age 38 years ± 9.010), 67.6% females, 50.1% prior AIDS. Mean CD4 cells and HIV RNA were 146 cells/mm 3 and 194312 copies/ml respectively. Zidovudine-lamivudine-nevirapine regimen (ZDV-3TC-NVP) was prescribed in 34.3%, followed by tenofovir-emtricitabine-efavirenz (TDF-FTC-EFV) 26.9%, TDF-FTC-NVP (17.6%), TDF-3TC-NVP (8%), ZDV-3TC-EFV (4.6%), abacavir (ABC)-3TC-EFV (3.7%), ABC-3TC-NVP (2.8%). Difference in prescription was noted among the doctors. Compared with TDF-3TC-NVP, starting TDF-FTC-EFV was mainly associated in multivariate analysis with reduced pill burden (P 200,000 copies/ml (P=0.0015). TDF-3TC-NVP and TDF-3TC-ZDV-atazanavir (ATV)-ritonavir (RTV) were more likely in patients with drug substitution and switch programs respectively (P<0.001; P<0.001). ABC-3TC-EFV was more likely in patients with deranged creatinine levels (P=0.002). At 6 months and 12 months, 364 (84.3%) and 392 (90.7%) achieved virologic suppression respectively (HIV RNA copies <200 copies/ml). CD4 cells increased by 138 cells/mm 3 and 198 cells/mm 3 at 6 months and 12 months respectively. Virologic suppression was more likely with TDF-FTC-EFV (93.7%) while CD4 cells increase was higher with ZDV-3TC-NVP. The 2 most common often prescribed regimens, TDF-FTC-EFV and ZDV-3TC-NVP, had virologic response rates of 93.7% and 84.2% (P<0.001). Conclusion : Factors such as physician preference and patient-reported features play a role in the choice of initial HAART regimen. Identification of these features and simplification of treatment regimens will be necessary in order to maximize the effectiveness of HAART regimens.

Fractionated Neem Leaf Extract is Safe and Increases CD4+ Cell Levels in HIV/AIDS Patients

The safety and effect of an acetone-water neem leaf extract (IRAB) on CD4 cells was investigated in 60 HIV/AIDS patients as part of an ongoing study to determine the influence of neem on immunity and viral load in HIV/AIDS. Patients were confirmed as HIV I or II positive, as having CD4 cell count, less than 300 cells/microL, and as antiretrovirally naïve. They were given oral IRAB (1.0 g daily for 12 weeks). Clinical and laboratory tests were carried out at baseline and at 4 weekly intervals. Thus, the patients served as their own controls. Sixty patients completed treatment. Fifty (83.33%) were completely compliant with respect to laboratory tests. Increase in mean CD4 cells, 266 cells/microL (159%), for the 50 patients was significant (P < 0.001) between baseline and week 12. Erythrocyte sedimentation rate (64 mm/hr at baseline) was 16 mm/hr at week 12, whereas total number of incidences of HIV/AIDS-related pathologies decreased from 120 at baseline to 5. Mean bodyweight, hemoglobin concentration, and lymphocyte differential count increased significantly by 12% (P < 0.05), 24% (P < 0.0001), and 20% (P < 0.0001), respectively. There were no adverse effects and no abnormalities in kidney and liver function parameters. The results support the safety of IRAB in HIV/AIDS, and its significant influence on CD4 cells may be useful in the formulation of multidrug combination therapies for HIV/AIDS. However, its antiretroviral activity is being evaluated in our laboratory.