A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

BACKGROUND: In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. METHODS: We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies. RESULTS: A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies. CONCLUSIONS: In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.)

Uptake and kinetic properties of choline and ethanolamine in Plasmodium falciparum

Purpose: The asexual proliferation of Plasmodium, inside the erythrocyte, is accompanied by the synthesis of huge quantities of phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn). These needful phospholipids for the cytoplasmic membrane of the merozoites are provided by the precursors choline and ethanolamine. PtdCho and PtdEtn are synthesized by the parasite because the erythrocyte is unable to do it. In order to assess the dynamism of the phospholipid pathways, we aimed to investigate the respective shape of the uptake of choline and ethanolamine by Plasmodium falciparum Method: Time-course experiments and kinetic assays were performed respectively with fixed and ranged concentrations of radioactively-labelled choline and ethanolamine. The labelled-precursors were added in the culture of P. falciparum infected-erythrocytes and the incorporated molecules in phospholipids were measured with a scintigraph counter. Result: The results showed that the incorporation of precursors in the infected-erythrocyte occurred with a Michaelis-Menten’s kinetic shape. According to the maximum rate (V max ), the pathway of ethanolamine incorporation was faster than that of choline. Similarly, affinity for ethanolamine was greater than that of choline. Conclusion: Although PtdCho is the major phospholipid in the membrane, this study rules out that the influx of ethanolamine in the infected-erythrocyte, in vivo conditions, is more dynamic than choline

Immunomodulatory Effect of the Aqueous Extract of Erigeron floribundus (Kunth) Sch Beep (Asteraceae) Leaf in Rabbits

Purpose: The leaves of Erigeron floribundus (Kunth) Sch. Beep. or (syn: Conyza sumatrensis (Retz) E.K. Walker) (Asteraceae) are used by some traditional healers in West Africa in HIV/AIDS therapy. The purpose of this study was to assess the immune-boosting properties of the aqueous leaf extract of Erigeron floribundus (Ef) by monitoring blood markers of cellular immunity in rabbit. Methods: Two sets each of five groups (six rabbits per group) were used in this study. The groups in the first set each received intraperitoneally a single dose of Ef (25, 50, 75 or 100 mg/kg) or 0.9 % NaCl (control). The groups in the second set received methylprednisolone (15 mg/kg, MP15) and mixtures of MP15 with Ef (50, 75 or 100 mg/kg), MP15 or isoprinosine 50 mg/kg (Ip50, reference standard). Whole blood was collected in EDTA tubes from the marginal vein of the rabbit ear on Days 0, 3, 9, 15 and 21 after administration for the determination of CD4+ count by flow cytometry, and also of neutrophils and total lymphocytes in the blood. Results : Each plant extract dose tested (50, 75 and 100 mg/kg) induced a significant increase in neutrophils (p < 0.001), total lymphocytes and TCD4+ (p < 0.0001) from the 3rd to 15th day after administration, compared to control (0.9 % NaCl). Furthermore, the same test extract doses significantly reversed the immunosuppressive effect of methylprednisolone (p < 0.001) to the same extent as isoprinosine. Conclusion: The aqueous extract of the leaves of Erigeron floribundus stimulated the increase of neutrophils, total lymphocytes and TCD4+ in rabbit blood and thus provides some justification for its use in the traditional treatment of AIDS