Treatment of Thrombocytopenia in Chimpanzees Infected With Human Immunodeficiency Virus by Pegylated Recombinant Human Megakaryocyte Growth and Development Factor

Blood ◽  
1998 ◽  
Vol 91 (12) ◽  
pp. 4427-4433 ◽  
Author(s):  
Laurence A. Harker ◽  
Ulla M. Marzec ◽  
Francis Novembre ◽  
I. Birgitta Sundell ◽  
Edmund K. Waller ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Growth And Development ◽  
Serum Levels ◽  
Platelet Production ◽  
Platelet Counts ◽  
Viral Loads ◽  
Development Factor ◽  
Immunodeficiency Virus ◽  
Baseline Values ◽  
Normal Controls

Three chimpanzees experimentally infected with human immunodeficiency virus (HIV) developed significant chronic thrombocytopenia after 5, 4, and 2 years, with peripheral platelet counts averaging 64 ± 19 × 103/μL (P = .004 compared with 228 ± 92 × 103/μL in 44 normal control animals), mean platelet volumes of 11.2 ± 1.8 fL (P > .5 compared with 10.9 ± 0.7 fL in normal controls), endogenous thrombopoietin (TPO) levels of 926 ± 364 pg/mL (P < .001 compared with 324 ± 256 pg/mL in normal controls), uniformly elevated platelet anti-glycoprotein (GP) IIIa49-66 antibodies, and corresponding viral loads of 534, 260, and 15 × 103 RNA viral copies/mL. Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) was administered subcutaneously (25 μg/kg twice weekly for 3 doses) to determine the effects of stimulating platelet production on peripheral platelet concentrations in this cohort of thrombocytopenic HIV-infected chimpanzees. PEG-rHuMGDF therapy increased (1) peripheral platelet counts 10-fold (from 64 ± 19 to 599 ± 260 × 103 platelets/μL;P = .02); (2) marrow megakaryocyte numbers 30-fold (from 11.7 ± 6.5 × 106/kg to 353 ± 255 × 106/kg;P = .04); (3) marrow megakaryocyte progenitor cells fourfold (from a mean of 3.6 ± 0.6 to 14.1 × 103 CFU-Meg/1,000 CD34+ marrow cells); and (4) serum levels of Mpl ligand from 926 ± 364 pg/mL (endogenous TPO) to predosing trough levels of 1,840 ± 353 pg/mL PEG-rHuMGDF (P = .02). The peripheral neutrophil counts were also transiently increased from 5.2 ± 2.6 × 103/μL to 9.9 ± 5.0 × 103/μL (P= .01), but neither the erythrocyte counts nor the reticulocyte counts were altered significantly (P > .1). The serum levels of antiplatelet GPIIIa49-66 antibodies exhibited reciprocal reductions during periods of thrombocytosis (P < .07). PEG-rHuMGDF therapy did not increase viral loads significantly (395, 189, and 53 × 103 RNA viral copies/mL; P > .5 compared with baseline values). The striking increase in peripheral platelet counts produced by PEG-rHuMGDF therapy implies that thrombocytopenia in HIV-infected chimpanzees is attributable to insufficient compensatory expansion in platelet production resulting from HIV-impaired delivery of platelets despite stimulated megakaryocytopoiesis. These data suggest that PEG-rHuMGDF therapy may similarly correct peripheral platelet counts in thrombocytopenic HIV-infected patients.

Treatment of Thrombocytopenia in Chimpanzees Infected With Human Immunodeficiency Virus by Pegylated Recombinant Human Megakaryocyte Growth and Development Factor

Blood ◽  
1998 ◽  
Vol 91 (12) ◽  
pp. 4427-4433 ◽  
Author(s):  
Laurence A. Harker ◽  
Ulla M. Marzec ◽  
Francis Novembre ◽  
I. Birgitta Sundell ◽  
Edmund K. Waller ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Growth And Development ◽  
Serum Levels ◽  
Platelet Production ◽  
Platelet Counts ◽  
Viral Loads ◽  
Development Factor ◽  
Immunodeficiency Virus ◽  
Baseline Values ◽  
Normal Controls

Abstract Three chimpanzees experimentally infected with human immunodeficiency virus (HIV) developed significant chronic thrombocytopenia after 5, 4, and 2 years, with peripheral platelet counts averaging 64 ± 19 × 103/μL (P = .004 compared with 228 ± 92 × 103/μL in 44 normal control animals), mean platelet volumes of 11.2 ± 1.8 fL (P &gt; .5 compared with 10.9 ± 0.7 fL in normal controls), endogenous thrombopoietin (TPO) levels of 926 ± 364 pg/mL (P &lt; .001 compared with 324 ± 256 pg/mL in normal controls), uniformly elevated platelet anti-glycoprotein (GP) IIIa49-66 antibodies, and corresponding viral loads of 534, 260, and 15 × 103 RNA viral copies/mL. Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) was administered subcutaneously (25 μg/kg twice weekly for 3 doses) to determine the effects of stimulating platelet production on peripheral platelet concentrations in this cohort of thrombocytopenic HIV-infected chimpanzees. PEG-rHuMGDF therapy increased (1) peripheral platelet counts 10-fold (from 64 ± 19 to 599 ± 260 × 103 platelets/μL;P = .02); (2) marrow megakaryocyte numbers 30-fold (from 11.7 ± 6.5 × 106/kg to 353 ± 255 × 106/kg;P = .04); (3) marrow megakaryocyte progenitor cells fourfold (from a mean of 3.6 ± 0.6 to 14.1 × 103 CFU-Meg/1,000 CD34+ marrow cells); and (4) serum levels of Mpl ligand from 926 ± 364 pg/mL (endogenous TPO) to predosing trough levels of 1,840 ± 353 pg/mL PEG-rHuMGDF (P = .02). The peripheral neutrophil counts were also transiently increased from 5.2 ± 2.6 × 103/μL to 9.9 ± 5.0 × 103/μL (P= .01), but neither the erythrocyte counts nor the reticulocyte counts were altered significantly (P &gt; .1). The serum levels of antiplatelet GPIIIa49-66 antibodies exhibited reciprocal reductions during periods of thrombocytosis (P &lt; .07). PEG-rHuMGDF therapy did not increase viral loads significantly (395, 189, and 53 × 103 RNA viral copies/mL; P &gt; .5 compared with baseline values). The striking increase in peripheral platelet counts produced by PEG-rHuMGDF therapy implies that thrombocytopenia in HIV-infected chimpanzees is attributable to insufficient compensatory expansion in platelet production resulting from HIV-impaired delivery of platelets despite stimulated megakaryocytopoiesis. These data suggest that PEG-rHuMGDF therapy may similarly correct peripheral platelet counts in thrombocytopenic HIV-infected patients.

Effects of megakaryocyte growth and development factor on platelet production, platelet life span, and platelet function in healthy human volunteers

Blood ◽  
2000 ◽  
Vol 95 (8) ◽  
pp. 2514-2522 ◽  
Author(s):  
Laurence A. Harker ◽  
Lorin K. Roskos ◽  
Ulla M. Marzec ◽  
Richard A. Carter ◽  
Judith K. Cherry ◽  
...  
Keyword(s):  
Life Span ◽  
Binding Sites ◽  
Growth And Development ◽  
Annexin V ◽  
Normal Function ◽  
Healthy Human ◽  
Platelet Production ◽  
Platelet Counts ◽  
Development Factor ◽  
Human Volunteers

The effects of thrombopoietic stimulation on megakaryocytopoiesis, platelet production, and platelet viability and function were examined in normal volunteers randomized to receive single bolus subcutaneous injections of 3 μg/kg pegylated recombinant megakaryocyte growth and development factor (PEG-rHuMGDF) or placebo in a 3:1 ratio. PEG-rHuMGDF transiently doubled circulating platelet counts, from 237 ± 41 × 103/μL to 522 ± 90 × 103/μL (P< .0001), peaking on day 12. Baseline and day-12 samples showed no differences in responsiveness of platelets to adenosine diphosphate or thrombin receptor agonist peptide (P > .4 in all cases); expression of platelet ligand-induced binding sites or annexin V binding sites (P > .6 in both cases); or density of platelet TPO-receptors (P > .5). Platelet counts normalized by day 28. The life span of autologous 111In-labeled platelets increased from 205 ± 18 hours (baseline) to 226 ± 22 hours (P < .01) on day 8. Platelet life span decreased from 226 ± 22 hours (day 8) to 178 ± 53 hours (P < .05) on day 18. The theoretical basis for senescent changes in mean platelet life span was illustrated by biomathematical modeling. Platelet turnover increased from 43.9 ± 11.9 × 103 platelets/μL/d (baseline) to 101 ± 27.6 × 103 platelets/μL/d (P = .0009), and marrow megakaryocyte mass expanded from 37.4 ± 18.5 fL/kg to 62 ± 17 × 1010 fL/kg (P = .015). Although PEG-rHuMGDF initially increased megakaryocyte volume and ploidy, subsequently ploidy showed a transient reciprocal decrease when the platelet counts exceeded placebo values. In healthy human volunteers PEG-rHuMGDF transiently increases megakaryocytopoiesis 2-fold. Additionally, peripheral platelets expand correspondingly and exhibit normal function and viability during the ensuing 10 days. The induced perturbation in steady state thrombopoiesis resolves by 4 weeks.

Effects of megakaryocyte growth and development factor on platelet production, platelet life span, and platelet function in healthy human volunteers

Blood ◽  
2000 ◽  
Vol 95 (8) ◽  
pp. 2514-2522 ◽  
Author(s):  
Laurence A. Harker ◽  
Lorin K. Roskos ◽  
Ulla M. Marzec ◽  
Richard A. Carter ◽  
Judith K. Cherry ◽  
...  
Keyword(s):  
Life Span ◽  
Binding Sites ◽  
Growth And Development ◽  
Annexin V ◽  
Normal Function ◽  
Healthy Human ◽  
Platelet Production ◽  
Platelet Counts ◽  
Development Factor ◽  
Human Volunteers

Abstract The effects of thrombopoietic stimulation on megakaryocytopoiesis, platelet production, and platelet viability and function were examined in normal volunteers randomized to receive single bolus subcutaneous injections of 3 μg/kg pegylated recombinant megakaryocyte growth and development factor (PEG-rHuMGDF) or placebo in a 3:1 ratio. PEG-rHuMGDF transiently doubled circulating platelet counts, from 237 ± 41 × 103/μL to 522 ± 90 × 103/μL (P&lt; .0001), peaking on day 12. Baseline and day-12 samples showed no differences in responsiveness of platelets to adenosine diphosphate or thrombin receptor agonist peptide (P &gt; .4 in all cases); expression of platelet ligand-induced binding sites or annexin V binding sites (P &gt; .6 in both cases); or density of platelet TPO-receptors (P &gt; .5). Platelet counts normalized by day 28. The life span of autologous 111In-labeled platelets increased from 205 ± 18 hours (baseline) to 226 ± 22 hours (P &lt; .01) on day 8. Platelet life span decreased from 226 ± 22 hours (day 8) to 178 ± 53 hours (P &lt; .05) on day 18. The theoretical basis for senescent changes in mean platelet life span was illustrated by biomathematical modeling. Platelet turnover increased from 43.9 ± 11.9 × 103 platelets/μL/d (baseline) to 101 ± 27.6 × 103 platelets/μL/d (P = .0009), and marrow megakaryocyte mass expanded from 37.4 ± 18.5 fL/kg to 62 ± 17 × 1010 fL/kg (P = .015). Although PEG-rHuMGDF initially increased megakaryocyte volume and ploidy, subsequently ploidy showed a transient reciprocal decrease when the platelet counts exceeded placebo values. In healthy human volunteers PEG-rHuMGDF transiently increases megakaryocytopoiesis 2-fold. Additionally, peripheral platelets expand correspondingly and exhibit normal function and viability during the ensuing 10 days. The induced perturbation in steady state thrombopoiesis resolves by 4 weeks.

Prevalence of and Risk Factors for Low Free Testosterone Levels in Japanese Men with Well-controlled Human Immunodeficiency Virus Infection

2020 ◽  
Vol 18 (5) ◽  
pp. 381-386
Author(s):  
Yusuke Yoshino ◽  
Ichiro Koga ◽  
Yoshitaka Wakabayashi ◽  
Takatoshi Kitazawa ◽  
Yasuo Ota
Keyword(s):  
Risk Factors ◽  
Human Immunodeficiency Virus ◽  
Standard Deviation ◽  
Hiv Infection ◽  
Free Testosterone ◽  
Serum Levels ◽  
University Hospital ◽  
Rapid Decline ◽  
Total Testosterone ◽  
Immunodeficiency Virus

Background: The change in the prevalence of hypogonadism with age in men with human immunodeficiency virus (HIV) infection is subject to debate. Objective: To address this issue, we diagnosed hypogonadism based on serum levels of free testosterone (fTST) rather than total testosterone which is thought to be an inaccurate indicator. We also determined the relationship between age and fTST levels and identified risk factors for hypogonadism in men with HIV infection. Method: We retrospectively reviewed fTST levels and associated clinical factors in 71 wellcontrolled HIV-infected men who were treated at Teikyo University Hospital between April 2015 and March 2016 and who had data available on serum fTST levels, measured >6 months after starting antiretroviral therapy. fTST was measured using radioimmunoassay on blood samples collected in the morning. Risk factors for hypogonadism were identified using Welch’s t-test and multiple regression analysis. Results: The men had a mean (± standard deviation) age of 47.4 ± 13.6 years, and mean (± standard deviation) serum fTST level of 13.0 ± 6.1 pg/mL. Fifteen (21.1%) men had hypogonadism based on a fTST <8.5 pg/mL. Serum fTST levels significantly decreased with age (−0.216 pg/mL/year). Older age and low hemoglobin levels were identified as risk factors for hypogonadism. Conclusion: The men in the study experienced a more rapid decline in fTST levels with age than men in the general population (−0.161 pg/mL/year). Serum fTST levels in men with HIV infection should be monitored, especially in older men and those with low hemoglobin levels.

scholarly journals Epidemiological, Virological and Serological Features of Coronavirus Disease 2019 (COVID-19) Cases in People Living With Human Immunodeficiency Virus in Wuhan: A Population-based Cohort Study

2020 ◽  
Author(s):  
Jiao Huang ◽  
Nianhua Xie ◽  
Xuejiao Hu ◽  
Han Yan ◽  
Jie Ding ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cohort Study ◽  
Demographic Data ◽  
Case Fatality ◽  
Population Based ◽  
Severe Illness ◽  
Viral Loads ◽  
Viral Shedding ◽  
Signal Value ◽  
Immunodeficiency Virus

Abstract Background We aimed to describe the epidemiological, virological, and serological features of coronavirus disease 2019 (COVID-19) cases in people living with human immunodeficiency virus (HIV; PLWH). Methods This population-based cohort study identified all COVID-19 cases among all PLWH in Wuhan, China, by 16 April 2020. The epidemiological, virological, and serological features were analyzed based on the demographic data, temporal profile of nucleic acid test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the disease, and SARS-CoV-2–specific immunoglobin (Ig) M and G after recovery. Results From 1 January to 16 April 2020, 35 of 6001 PLWH experienced COVID-19, with a cumulative incidence of COVID-19 of 0.58% (95% confidence interval [CI], .42–.81%). Among the COVID-19 cases, 15 (42.86) had severe illness, with 2 deaths. The incidence, case-severity, and case-fatality rates of COVID-19 in PLWH were comparable to those in the entire population in Wuhan. There were 197 PLWH who had discontinued combination antiretroviral therapy (cART), 4 of whom experienced COVID-19. Risk factors for COVID-19 were age ≥50 years old and cART discontinuation. The median duration of SARS-CoV-2 viral shedding among confirmed COVID-19 cases in PLWH was 30 days (interquartile range, 20–46). Cases with high HIV viral loads (≥20 copies/mL) had lower IgM and IgG levels than those with low HIV viral loads (&lt;20 copies/ml; median signal value divided by the cutoff value [S/CO] for IgM, 0.03 vs 0.11, respectively [P &lt; .001]; median S/CO for IgG, 10.16 vs 17.04, respectively [P = .069]). Conclusions Efforts are needed to maintain the persistent supply of antiretroviral treatment to elderly PLWH aged 50 years or above during the COVID-19 epidemic. The coinfection of HIV and SARS-CoV-2 might change the progression and prognosis of COVID-19 patients in PLWH.

scholarly journals Prevention of Thrombocytopenia and Neutropenia in a Nonhuman Primate Model of Marrow Suppressive Chemotherapy by Combining Pegylated Recombinant Human Megakaryocyte Growth and Development Factor and Recombinant Human Granulocyte Colony-Stimulating Factor

Blood ◽  
1997 ◽  
Vol 89 (1) ◽  
pp. 155-165 ◽  
Author(s):  
Laurence A. Harker ◽  
Ulla M. Marzec ◽  
Andrew B. Kelly ◽  
Ellen Cheung ◽  
Aaron Tomer ◽  
...  
Keyword(s):  
Platelet Count ◽  
Neutrophil Count ◽  
Growth And Development ◽  
Granulocyte Colony Stimulating Factor ◽  
Serum Concentrations ◽  
Colony Stimulating Factor ◽  
Platelet Counts ◽  
Development Factor ◽  
Trough Serum ◽  
Stimulating Factor

Abstract This report examines the effects on hematopoietic regeneration of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF ) (2.5 μg/kg/d) alone and in combination with recombinant human granulocyte colony stimulating factor (rHu-GCSF ) (10 μg/kg/d) for 21 days in rhesus macaques receiving intense marrow suppression produced by single bolus injections of hepsulfam (1.5 g/m2). In six hepsulfam-only control animals thrombocytopenia (platelet count <100 × 109/L) was observed between days 12 and 25 (nadir 39 ± 20 × 109/L on day 17), and neutropenia (absolute neutrophil count <1 × 109/L) occurred between days 8 and 30 (nadir 0.167 ± 0.120 × 109/L on day 15). PEG-rHuMGDF (2.5 μg/kg/d) injected subcutaneously into four animals from day 1 to day 22 following hepsulfam administration produced trough serum concentrations of 1.9 ± 0.2 ng/mL and increased the platelet count twofold over basal prechemotherapy levels (856 ± 594 × 109/L v baseline of 416 ± 88 × 109/L; P = .01). PEG-rHuMGDF alone also shortened the period of posthepsulfam neutropenia from 22 days to 12 days (P = .01), although the neutropenic nadir was not significantly altered (neutrophil count 0.224 ± 0.112 × 109/L v 0.167 ± 0.120 × 109/L; P < .3). rHu-GCSF (10 μg/kg/d) injected subcutaneously into four animals from day 1 to day 22 following hepsulfam administration produced trough serum concentrations of 1.4 ± 1.1 ng/mL, and reduced the time for the postchemotherapy neutrophil count to attain 1 × 109/L from 22 days to 4 days (P = .005). The postchemotherapy neutropenic nadir was 0.554 ± 0.490 × 109neutrophils/L (P = .3 v hepsulfam-only control of 0.167 ± 0.120 × 109/L). However, thrombocytopenia of <100 × 109 platelets/L was not shortened (persisted from day 12 to day 25), or less severe (nadir of 56 ± 32 × 109 platelets/L on day 14; P = .7 compared with untreated hepsulfam animals). The concurrent administration of rHu-GCSF (10 μg/kg/d) and PEG-rHuMGDF (2.5 μg/kg/d) in four animals resulted in postchemotherapy peripheral platelet counts of 127 ± 85 × 109/L (P = .03 compared with 39 ± 20 × 109/L for untreated hepsulfam alone, and P = .02 compared with 856 ± 594 × 109/L for PEG-rHuMGDF alone), and shortened the period of neutropenia <1 × 109/L from 22 days to 4 days (P = .8 compared with rHu-GCSF alone). Increasing PEG-rHuMGDF to 10 μg/kg/d and maintaining the 21-day schedule of coadministration with rHu-GCSF (10 μg/kg/d) in another four animals produced postchemotherapy platelet counts of 509 ± 459 × 109/L (P < 10−4compared with untreated hepsulfam alone, and P = .04 compared with 2.5 μg/kg/d PEG-rHuMGDF alone), and 4 days of neutropenia. Coadministration of rHu-GCSF and PEG-rHuMGDF did not significantly alter the pharmacokinetics of either agent. The administration of PEG-rHuMGDF (2.5 μg/kg/d) from day 1 through day 22 and rHu-GCSF (10 μg/kg/d) from day 8 through day 22 in six animals produced peak postchemotherapy platelet counts of 747 ± 317 × 109/L (P < 10−4 compared with untreated hepsulfam alone, and P = .7 compared with PEG-rHuMGDF alone), and maintained the neutrophil count < 3.5 × 109/L (P = .008 v rHu-GCSF therapy alone). Thus, both thrombocytopenia and neutropenia are eliminated by initiating daily PEG-rHuMGDF therapy on day 1 and subsequently adding daily rHu-GCSF after 1 week in the rhesus model of hepsulfam marrow suppression. This improvement in platelet and neutrophil responses by delaying the addition of rHu-GCSF to PEG-rHuMGDF therapy demonstrates the importance of optimizing the dose and schedule of cytokine combinations after severe myelosuppressive chemotherapy.

scholarly journals High-Potency Human Immunodeficiency Virus Vaccination Leads to Delayed and Reduced CD8+ T-Cell Expansion but Improved Virus Control

2005 ◽  
Vol 79 (15) ◽  
pp. 10059-10062 ◽  
Author(s):  
Miles P. Davenport ◽  
Lei Zhang ◽  
Ansuman Bagchi ◽  
Arthur Fridman ◽  
Tong-Ming Fu ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Cell Expansion ◽  
Virus Infections ◽  
Significant Delay ◽  
Viral Kinetics ◽  
Cell Numbers ◽  
Viral Loads ◽  
Immunodeficiency Virus ◽  
T Cell Expansion

ABSTRACT CD8+ T lymphocytes are thought to play an important role in the control of acute and chronic human immunodeficiency virus infections. However, there is a significant delay between infection and the first observed increase in virus-specific CD8+ T-cell numbers. Prior to this time, viral kinetics are not significantly different between controls and vaccinees. Surprisingly, higher initial virus-specific CD8+ T-cell numbers lead to a longer delay prior to initial CD8+ T-cell expansion, and slower CD8+ T-cell increases. Nevertheless, higher initial CD8+ T-cell numbers were associated with reduced peak and chronic viral loads and reduced CD4+ T-cell depletion.

scholarly journals Recombinant human megakaryocyte growth and development factor stimulates thrombocytopoiesis in normal nonhuman primates

Blood ◽  
1995 ◽  
Vol 86 (1) ◽  
pp. 54-59 ◽  
Author(s):  
AM Farese ◽  
P Hunt ◽  
T Boone ◽  
TJ MacVittie
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Growth And Development ◽  
Nonhuman Primates ◽  
Normal Male ◽  
Platelet Counts ◽  
Development Factor ◽  
Development In Vitro

Megakaryocyte growth and development factor (MGDF) is a novel cytokine that binds to the c-mpl receptor and stimulates megakaryocyte development in vitro and in vivo. This report describes the ability of recombinant human (r-Hu) MGDF to affect megakaryocytopoiesis in normal nonhuman primates. r-HuMGDF was administered subcutaneously to normal, male rhesus monkeys once per day for 10 consecutive days at dosages of 2.5, 25, or 250 micrograms/kg of body weight. Bone marrow and peripheral blood were assayed for clonogenic activity and peripheral blood counts were monitored. Circulating platelet counts increased significantly (P < .05) for all doses within 6 days of r-HuMGDF administration and reached maximal levels between day 12 and day 14 postcytokine administration. The 2.5, 25.0, and 250.0 micrograms/kg/d doses elicited peak mean platelet counts that were 592%, 670%, and 449% of baseline, respectively. Bone marrow-derived clonogenic data showed significant increases in the concentration of megakaryocyte (MEG)- colony-forming unit (CFU) and granulocyte-erythroid-macrophage- megakaryocyte (GEMM)-CFU, whereas that of granulocyte-macrophage (GM)- CFU and burst-forming unit-erythroid (BFU-e) remained unchanged during the administration of r-HuMGDF. These data show that r-HuMGDF is a potent stimulator of thrombocytopoiesis in the normal nonhuman primate.

scholarly journals Cryptococcal Antigenemia in Human Immunodeficiency Virus Antiretroviral Therapy–Experienced Ugandans With Virologic Failure

2019 ◽  
Vol 71 (7) ◽  
pp. 1726-1731 ◽  
Author(s):  
Edward Mpoza ◽  
Radha Rajasingham ◽  
Lillian Tugume ◽  
Joshua Rhein ◽  
Maria Sarah Nabaggala ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
Antiretroviral Therapy ◽  
Cryptococcal Meningitis ◽  
Virologic Failure ◽  
Cost Effective ◽  
World Health ◽  
Load Testing ◽  
Viral Loads ◽  
Immunodeficiency Virus

Abstract Background Detectable serum or plasma cryptococcal antigen (CrAg) precedes symptomatic cryptococcal meningitis. The World Health Organization recommends CrAg screening for human immunodeficiency virus–positive persons with CD4 count &lt;100 cells/μL initiating antiretroviral therapy (ART). However, an increasing proportion of patients with cryptococcosis are now ART experienced. Whether CrAg screening is cost-effective in those with virologic failure is unknown. Methods We retrospectively performed nationwide plasma CrAg testing among ART-experienced Ugandan adults with virologic failure (≥1000 copies/mL) using leftover plasma after viral load testing during September 2017–January 2018. For those who were CrAg positive, we obtained ART history, meningitis occurrence, and 6-month survival via medical records review. Results Among 1186 subjects with virologic failure, 35 (3.0%) were CrAg positive with median ART duration of 41 months (interquartile range, 10–84 months). Among 25 subjects with 6-month outcomes, 16 (64%) survived, 7 (28%) died, and 2 (8%) were lost. One survivor had suffered cryptococcal meningitis 2 years prior. Two others developed cryptococcal meningitis and survived. Five survivors were known to have received fluconazole. Thus, meningitis-free survival at 6 months was 61% (14/23). Overall, 91% (32/35) of CrAg-positive persons had viral load ≥5000 copies/mL compared with 64% (735/1151) of CrAg-negative persons (odds ratio, 6.0 [95% confidence interval, 1.8–19.8]; P = .001). CrAg prevalence was 4.2% (32/768) among those with viral loads ≥5000 copies/mL and 0.7% (3/419) among those with viral loads &lt;5000 copies/mL. Conclusions In addition to the CD4 threshold of &lt;100 cells/μL, reflexive CrAg screening should be considered in persons failing ART in Uganda with viral loads ≥5000 copies/mL.

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