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Aims In limited resource settings monitoring antiretroviral ( ARV) treatment efficacy is restrained by the lack of access to technological equipment. The aim of the study was to assess the use of dried plasma ( DPS) and blood spots ( DBS) to facilitate ARV monitoring in remote settings where clinical monitoring is the primary strategy. Methods A cross-sectional study in HIV-positive ARV-treated patients in Kiremba, Burundi was performed. DBS were used for HIV-1 viral load (limit of the assay 250 copies ml−1) and genotypic drug resistance tests and dried plasma spots were used for concentration measurements. Results Three hundred and seven patients [201 female (88.6%), 14 children (4.5%)] were enrolled. HIV-1 viral load was <250, 250-1000 and >1000 copies ml−1 in 250 (81.7%), 33 (10.8%) and 23 patients (7.5%). Eleven samples out of 23 were successfully amplified revealing nucleoside reverse transcriptase inhibitor ( NRTI) and non-nucleoside reverse transcriptase inhibitor ( NNRTI)-resistance associated mutations [in seven (58.3%) and six patients (50%)]. Nevirapine trough concentrations were <3000 ng ml−1 in 28/189 patients (14.8%) and efavirenz 12 h concentrations were <1000 ng ml−1 in 2/16 patients (12.5%). Children and patients with nevirapine exposure <3000 ng ml−1 presented a higher risk of viral replication. Conclusions Viral loads <250 copies ml−1 were observed in 81.7% of patients (83.6% adults and 42.9% children). Children and patients with low nevirapine concentrations had higher risk of viral replication. Dried blood and plasma spots may be useful for monitoring HIV-positive patients including viral load and drug level measurement as part of treatment management in remote areas. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Nevirapine pharmacokinetics are affected by several factors including CYP2B6 single nucleotide polymorphisms (SNPs). These genetic profiles are more common in African patients and they affect the drug clearance being associated with higher trough concentrations. Pharmacokinetic/pharmacogenetic (PK/PG) studies are difficult to perform in remote areas where refrigeration is not available, although dried plasma and dried blood methods have been validated. WHAT THIS STUDY ADDS • Dried plasma spots are useful tools for studying nevirapine PK with a good association to plasma concentrations and they can be used in rural areas since a cold chain is not necessary. Dried blood spots can be used to store and analyze patients' DNA for PG polymorphisms. Nevirapine trough concentrations in Burundese patients, not studied so far, are above the target concentration (3000 ng ml−1) in 84% of patients. CYP2B6 (both at position 516 and 983) but not ABCB1 (3435 and 1236) SNPs as well as age correlate with higher nevirapine exposure. AIMS The pharmacokinetics (PK) and pharmacogenetics (PG) of nevirapine have been studied in rich and limited-resource countries. CYP2B6 single nucleotide polymorphisms (SNPs) have been associated with decreased drug clearance. We evaluated the PG determinants of nevirapine trough concentrations in a rural cohort in Burundi using easy to store and transport dried sample spot devices. METHODS A cross-sectional analysis in HIV-positive nevirapine-treated patients in Kiremba, north of Burundi, was performed in 2009. After blood withdrawal whole blood was stored on dried blood spots and plasma (after centrifugation) was placed on dried plasma spot devices and stored at room temperature. Nevirapine plasma and dried sample spot concentrations were compared to test the clinical usefulness of this method. SNPs in CYP2B6 and ABCB1 (using a real time PCR technique) were analyzed and associated with nevirapine plasma trough concentrations. RESULTS Nevirapine concentrations measured on dried plasma spot devices were highly related to plasma concentrations in 60 patients, although a negative bias was observed (−18%). Nevirapine trough concentrations were above the target concentration (3000 ng ml−1) in 84% of patients and they were associated with CYP2B6 SNPs (both at position 516 and 983). No effect of ABCB1 SNPs was noted. CONCLUSIONS Dried plasma spot devices are accurate tools for measuring nevirapine concentrations in rural settings where refrigeration is not available, despite a moderate underestimation bias. They allowed the evaluation of nevirapine concentrations in a cohort of HIV-infected people in rural Burundi, confirming very good exposure and correlation with PG polymorphisms in the CYP2B6 encoding gene. [ABSTRACT FROM AUTHOR]

The in vivo response of falciparum malaria to oral chloroquine and quinine was evaluated in two identical hospital-based, comparative open trials carried out 2 years apart in the same seasonal period at a hospital located in the highlands of Northern Burundi. Children aged 0-14 with uncomplicated falciparum malaria were administered either chloroquine, at 25 mg/kg over 3 days, or quinine, at 10 mg/kg per 8 hourly for 5 days (alternate allocation) and treatment response was evaluated by the WHO 7-day test. In the first study (1992/1993) 472 patients qualified for analyses (211 in the chloroquine and 261 in the quinine group), as compared to 249 subjects in the second study (1994/1995). In each study, the response to quinine was significantly higher than that to chloroquine (P = 0.004 and < 0.001, respectively). While the response to quinine showed insignificant changes over time (95.8 vs. 92.9%), chloroquine was found to be significantly less effective in the second study as compared to the first (77.8 vs. 63.1%; OR (95% CI) 2.04 (1.21-3.43)). Such decline in chloroquine efficacy was attributable to the age group < 5 years of age, where response to chloroquine decreased from 72.9% in 1992/93 to 56% in 1994/1995. Uncontrolled chloroquine use, which spread after the onset in late 1993 of the still ongoing ethnic fighting, appears to be the most likely reason for such a decrease in chloroquine efficacy. Chloroquine resistance has long been known to be present in the hyperendemic lowlands of Burundi, but no data have so far been reported on the response to antimalarials in the highlands of the country. These findings should be considered when deciding on drug policies for the treatment of falciparum malaria in Burundi.

In an open, randomized, controlled therapeutic trial, 56 children with cerebral malaria (CM) were randomly assigned to receive standard quinine regimen with or without pentoxifylline (10 mg/kg/day by continuous intravenous infusion). Pentoxifylline exerted an inhibitory effect on the synthesis of tumor necrosis factor (TNF), a possible mediator of CM. The 26 children who received pentoxifylline had significantly shorter comas than controls (median, 6 vs. 46 h; P < .001) Pentoxifylline recipients showed a trend toward a lower mortality, with a borderline significant difference (P = .055). The better outcome in the pentoxifylline group was associated with a decline in TNF serum levels on the third day of treatment in a few subjects that was not seen in controls. While alternative or concurrent mechanisms of action may be of some relevance, larger double-blind trials are needed to determine whether pentoxifylline has a therapeutic role in CM.