500?10 6/L), case 6～10 as sub-group2(SG2, CD4 at 499～200?10 6/L), case 11～12 (CD4

Objective.To determine whether malariotherapy (an old therapy for treatment of neurosyphilis)improves some clinical and laboratory parameters of HIV-positive patients without iatrogenic complications.Methods.Total 8 asymptomatic HIV-1 positive subjects whose CD4 cell counts were over 250×106 cells/L were selected for the phase-1 studies of malariotherapy and were intravenously injected Plasmodia vivax to induce artificial malaria.Malaria was terminated with chloroquine after 10～20 malarial fever episodes.Cell-bound CD4 levels were measured by APAAP (a solid-phase enzyme essay)and levels of neopterin (NPT),beta-2-microglobulin (B2M),soluble tumor necrosis factor receptor-2(sTNF-RII),interleukin-2(IL-2)and HIV P24 antigen were measured by ELISA. Patients were followed up to 24～30 months.Results.CD4 levels increased in 5,NPT decreased in 7 of 8 patients;IL-2 increased in 5 of 6 patients after malariotherapy.The total trends of B2M and sTNF-RII basically remained stable.HIV P24 antigen remained undetectable in 6, remained detectably low level in 1 and experienced increase in 1 of 8 patients after malariotherapy.No any severe complications occurred in all 8 patients.Conclusions.The results indicate that malariotherapy basically is safe for HIV infection and it seems that the therapy improves some immunological parameters of HIV patients.

OBJECTIVETo demonstrate the side effects of malariotherapy and to explore safe procedures in conduct of malariotherapy for human immunodeficiency virus (HIV) infected patients.

METHODSTwenty HIV/acquired immunodeficiency syndrome (AIDS) patients were selected for the study of malariotherapy and were intravenously infected with Plasmodia vivax to induce therapeutic malaria. Malaria was terminated with chloroquine after 10 - 20 malarial febrile episodes. Clinical assessments were made before (baseline), during (malarial phase) and after (post) termination of malaria. The density of Plasmodia in peripheral blood from the HIV/AIDS patients were compared to that from HIV-negative naturally infected malarial patients who donated the blood for the therapeutically induced malaria. CD(4) cell baseline levels were correlated to the severity of malarial symptoms and parasitemia.

RESULTSThere were no significant differences of Plasmodium density between the HIV/AIDS patients injected with P. vivax and the HIV-negative blood donors. However, it was found that the HIV-positive patients had milder malarial symptoms and parasitemia with progressively lower CD(4) cell baseline levels. All patients developed every day or every other day fever episodes with headache and shaking chill. These symptoms were well tolerated with the aid of anti-pyretic medications. Spleen and liver enlargement were seen in 15 of 20 and 4 of 20 patients respectively. Transitory liver effects with increase of serum glutamic-pyruvic transaminase were seen in 2 of 20 during malarial phase. Most patients experienced mild to medium anemia and 6 of 20 patients developed thrombocytopenia during malarial phase. All these side effects disappeared after termination of malaria or within one month thereafter. No complications occurred in these patients.

CONCLUSIONSTherapeutically induced acute vivax malaria was well tolerated in 20 HIV-positive subjects who represented a range of CD(4) cell levels from 1868/ micro l to 15/ micro l. Malariotherapy did not induce complications while increasing CD(4) cell levels in most treated HIV/AIDS patients (results published elsewhere).

Adult ; Animals ; CD4-Positive T-Lymphocytes ; Female ; HIV Infections ; therapy ; Humans ; Immunotherapy ; adverse effects ; methods ; Lymphocyte Count ; Malaria, Vivax ; immunology ; Male ; Plasmodium vivax ; immunology

OBJECTIVETo explore the mechanisms of malariotherapy for human immunodeficiency virus (HIV)-infected patients and to identify which stage(s) of HIV infection is suitable for the treatment of malariotherapy.

METHODSTherapeutic acute vivax malaria was induced and terminated after 10 fever episodes in 12 HIV-1-infected subjects: Group 1 (G1) had 5 patients with CD(4) T-cell counts >or=500/ micro l at baseline, Group 2 (G2) had 5 patients with CD4 at 499 - 200/ micro l and Group 3 had 2 patients with CD(4) < 200/ micro l (not included in statistical analysis). Enzyme-Linked-Immuno-Sorbent Assay (ELISA) was used to measure plasma levels of cytokines and soluble activation markers. Flow cytometry was used to measure levels of lymphocyte subsets and phenotypes and CD(4) cell apoptosis. Bayer bDNA assay was used to test plasma levels of HIV-1 RNA (viral load). Samples were taken and tested twice before malaria (baselines), three times during malaria and seven times after termination of malaria (at day 10 and 1, 3, 6, 12, 18 and 24 months).

RESULTSLevels of plasma tumor necrosis factor-alpha (TNF-alpha), soluble TNF-alpha receptor-2 (sTNF-RII), neopterin (NPT) and soluble IL-2 receptor (sIL-2R) significantly increased during malaria and sharply reduced to baselines post malaria in all groups. Stronger responses of the aforementioned factors were seen in G2 than in G1 during malaria (P = 0.081, 0.001, 0.013, 0.020). CD4 count and percentage; CD(4)/CD(8) ratio and CD(25)(+) and CD(4)(+)CD(25)(+) percentages increased but HLA-DR+ percentage decreased either during or post malaria in G2. Most G2 patients experienced sustained increase but most G1 patients underwent natural history decline of CD(4) counts and percentages during 2-year follow-up. Percentage of apoptotic CD(4) cells decreased post malaria in all groups. G3 patients had weaker immune responses, however, one advanced AIDS patient in this group experienced clinical improvement after malariotherapy. Most of the 12 patients experienced increase of HIV viral load during malaria but the viral load returned to baseline levels 1 - 3 months after cure of malaria and remained near baseline levels for up to two years.

CONCLUSIONSPart of the mechanisms of malariotherapy is to induce high levels of cytokine activities and subsequently the changes of T-lymphocyte subsets and phenotypes in HIV-infected patients. These findings suggest that malariotherapy may treat HIV-1-infected patients whose CD4 baselines are in the range of 500 - 200/ micro l.

Acute Disease ; Adult ; CD4 Lymphocyte Count ; Cytokines ; blood ; Female ; HIV Seropositivity ; immunology ; therapy ; virology ; HIV-1 ; isolation & purification ; Humans ; Malaria, Vivax ; immunology ; Male ; Viral Load