Effect of Plasmodium falciparum malaria on concentration of HIV-1-RNA in the blood of adults in rural Malawi: a prospective cohort study.

BACKGROUND: Raised HIV viral load in blood has been associated with accelerated disease progression and increased transmission of infection. To assess the effect of Plasmodium falciparum malaria on concentrations of HIV in blood, we did a prospective cohort study in Malawi. METHODS: We recruited 367 HIV-1-infected adults. Among 334 people aparasitaemic at baseline, 148 had at least one malaria episode during follow-up and received antimalarial treatment. Of these, 77 had HIV-1-RNA measurements at baseline, during malaria, and post-malaria. We used linear regression with generalised estimating equations to assess effect of four definitions of malaria (any parasitaemia, parasite density > or =2000/microL, febrile parasitaemia, and febrile parasitaemia with parasite density > or =2000/microl) on changes in log HIV-1 RNA, overall and by baseline CD4 count. FINDINGS: With malaria defined as any parasitaemia, HIV-1-RNA concentration almost doubled between baseline (median 96215 copies per mL) and malaria (168901 copies per mL), a 0.25 (95% CI 0.11-0.39) log increase in mean RNA concentration. HIV-1-RNA concentration fell to median 82058 copies per mL by about 8-9 weeks post-malaria. Increases in HIV-1-RNA were greatest for people with fever, parasite density 2000/microL or greater, and CD4 count more than 300 cells per muL, in whom concentrations rose from median 38483 copies per mL at baseline to 196098 copies per mL during malaria, a mean log increase of 0.82 (95% CI 0.55-1.10, p<0.0001), and fell to median 75331 copies per mL post-malaria. People who remained aparasitaemic showed no changes in HIV-1-RNA concentration. INTERPRETATION: HIV-infected individuals with malaria have a significantly increased viral load, which might enhance HIV transmission and accelerate disease progression.

Immune activation and induction of HIV-1 replication within CD14 macrophages during acute Plasmodium falciparum malaria coinfection.

OBJECTIVES: To determine the impact of Plasmodium falciparum malaria coinfection and its treatment on cellular reservoirs of viral replication in HIV-1-infected persons and to relate this to changes in systemic immune activation. METHODS: Plasma samples were obtained from HIV-1-infected individuals (n = 10) at diagnosis of acute malaria, 4 weeks after parasite clearance and from HIV-infected aparasitemic controls (n = 10). Immunomagnetic HIV-1 capture analysis was used to determine the cellular origin of cell-free virus particles present in all 30 plasma samples and indices of immune activation were measured using enzyme-linked immunosorbent assays. RESULTS: Compared with controls, the detectable proportion of HIV-1 particles derived from CD14 macrophages and CD26 lymphocytes was increased in persons with acute malaria coinfection and correlated with markedly increased plasma concentrations of both proinflammatory cytokines and soluble markers of macrophage and lymphocyte activation. Parasite clearance following treatment with antimalarial drugs resulted in decreased detection of HIV-1 particles derived from the CD14 macrophage cell subset and correlated with a marked diminution in systemic immune activation. CONCLUSIONS: Acute P. falciparum malaria coinfection impacts virus-host dynamics in HIV-1-infected persons at the cellular level, notably showing a reversible induction of HIV-1 replication in CD14 macrophages that is associated with changes in immune activation.

Effects of HIV-1 serostatus, HIV-1 RNA concentration, and CD4 cell count on the incidence of malaria infection in a cohort of adults in rural Malawi.

BACKGROUND: To assess the effects of human immunodeficiency virus (HIV) infection on susceptibility to malaria, we compared the incidence rates of malaria by HIV type 1 (HIV-1) serostatus, baseline blood HIV-1 RNA concentration, and baseline CD4 cell count, over the course of a malaria season. METHODS: We followed a cohort of 349 adults in Malawi. For the 224 HIV-1-seropositive adults (64% of the cohort), we measured HIV-1 RNA concentration (n=187) and CD4 cell count (n=184) at baseline. Parasitemia was defined as presence of asexual parasites on a thick film of blood and was treated with sulfadoxine/pyrimethamine (SP), in accordance with national policy. Hazard ratios (HRs) of parasitemia were estimated using Cox regression. Demographics were adjusted for. RESULTS: HIV-1 seropositivity was associated with parasitemia (adjusted HR, 1.8 [95% confidence interval {CI}, 1.2-2.7] for a first parasitemia episode; adjusted HR, 2.5 [95% CI, 1.5-4.2] for a second parasitemia episode [> 14 days after the first episode]; adjusted HR, 1.9 [95% CI, 1.4-2.6] for parasitemia overall). Treatment failure (parasitemia < or = 14 days after SP treatment) did not differ by HIV-1 serostatus (risk ratio, 1.3 [95% CI, 0.5-3.2]). HIV-1 RNA concentrations and CD4 cell counts were moderately but inconsistently associated with parasitemia. A high parasite density with fever was associated with HIV-1 seropositivity and low CD4 cell count. CONCLUSION: HIV-infected adults in malaria-endemic areas are at increased risk for malaria. Where possible, additional malaria prevention efforts should be targeted at this population.