Impact of acute vivax malaria on the immune system and viral load of HIV-positive subjects.
OBJECTIVE
To 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.


METHODS
Therapeutic 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).


RESULTS
Levels 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.


CONCLUSIONS
Part 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.
Chen
Xiaoping
X
Department of AIDS Control and Prevention, Guangzhou Center for Disease Control and Prevention, Guangzhou 510080, China. xpingchen@163.com
Xiao
Binquan
B
Shi
Wenjun
W
Xu
Huifang
H
Gao
Kai
K
Rao
Jili
J
Zhang
Zhoubin
Z
D000208:Acute Disease; D000328:Adult; D018791:CD4 Lymphocyte Count; D016207:Cytokines / Q000097:blood; D005260:Female; D006679:HIV Seropositivity / Q000276:immunology* / Q000628:therapy / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D016780:Malaria, Vivax / Q000276:immunology*; D008297:Male; D019562:Viral Load
D016207:Cytokines