Adequacy of WHO weight-band dosing and fixed-dose combinations for the treatment of TB in children.

BACKGROUND: We examined whether the updated WHO weight-band dosing recommendations and fixed-dose combination tablets for the treatment of TB in children achieves recommended calculated dosages and adequate drug plasma exposure.DESIGN/METHODS: Children on first-line TB treatment per WHO guidelines were enrolled. Blood sampling at pre-dose, 1, 2, 4, 8, and 12 h post-dose after at least 4 weeks of treatment was performed. Drugs concentrations were measured using validated liquid chromatography tandem with mass spectrometry and pharmacokinetic parameters calculated using noncompartmental analysis. Plasma drug exposure below the lower limit of the 95% confidence interval of the mean for children was considered low and above the upper limit was high.RESULTS: Of 71 participants, 34 (47.9%) had HIV coinfection. The median calculated dose for isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB) was 10.0 (range 4.3-13.3), 15.0 (range 8.6-20.0), 30.0 (range 21.0-40.0), and 20.4 (range 14.3-26.7) mg/kg, respectively. Overall, most patients had under-exposure for RIF and PZA and over-exposure for INH and EMB. Drug dose and weight-for-age Z-score were associated with area under the curve from time 0-24 h for all drugs.CONCLUSIONS: Despite adherence to WHO dosing guidelines, low PZA and RIF plasma exposures were frequent in our study population. Higher than currently recommended dosages of RIF and PZA may be needed in children.

Effect of HIV infection on plasma exposure to first-line TB drugs and target attainment in children.

BACKGROUND: Whether HIV infection adversely affects exposure to first-line TB drugs in children is debatable. It is also not known whether HIV infection increases the risk of plasma underexposure or overexposure to TB drugs. This study sought to address these questions.DESIGN/METHODS: Children on TB treatment were enrolled. After 4 weeks on therapy, blood samples were collected at pre-dose, 1, 2, 4, 8, and 12 h post-dose for pharmacokinetic analysis. Plasma drug exposure below and above the lower and upper bounds of the 95% confidence intervals of the reference mean for children were considered underexposure and overexposure, respectively. The effect of HIV infection on drugs exposure and risk of underexposure were examined using multivariate analysis.RESULTS: Of 86 participants (median age: 4.9 years), 45 had HIV coinfection. HIV coinfection was associated with lower pyrazinamide (PZA) and ethambutol exposures in adjusted analysis. Patients with TB-HIV coinfection were three times more likely to have PZA underexposure than those with TB only. Underexposure of rifampin was common irrespective of HIV coinfection status.CONCLUSIONS: HIV coinfection was associated with a higher risk for PZA underexposure in children. This effect should be accounted for in models and simulations to determine optimal PZA dose for children.

Effect of malnutrition on the pharmacokinetics of anti-TB drugs in Ghanaian children.

BACKGROUND: Anti-TB drugs dosing based on weight alone may contribute to suboptimal drug concentrations and poor treatment outcomes in malnourished children. We examined the effect of malnutrition on the pharmacokinetics (PK) of first-line anti-TB drugs in children.METHODS: Drug concentrations were measured in Ghanaian children during the intensive phase of TB treatment. Weight-for-age (WFA), height-for-age (HFA), weight-for-height (WFH) and body mass index-for-age (BFA) were calculated and children with Z-scores < -2 SD (standard deviations) were considered as having malnutrition. PK differences of anti-TB drugs were compared by nutritional status.RESULTS: Of 100 participants, 24/48 (50.0%) of those younger than 5 years had wasting, 58/86 (67.4%) were underweight, and 56/99 (56.6%) had stunting; 22/51 (43.1%) children aged ≥5 years had low BFA. Children with stunting were more likely than controls to have lower mean peak concentration (Cmax) and area under the curve (AUC0-8h) of rifampin (RIF) and pyrazinamide (PZA), as well as a higher frequency of Cmax below the normal range. Wasting and underweight were associated with lower mean ethambutol (EMB) Cmax and AUC0-8h.CONCLUSIONS: The current WHO-recommended dosages were associated with lower plasma exposure of RIF, PZA and EMB in children with stunting, wasting and underweight. Anti-TB drugs dosing models for children may need to include height.

The immunological response of HIV-positive patients initiating HAART at the Komfo Anokye Teaching Hospital, Kumasi, Ghana.

OBJECTIVE: The study sought to document the experience of immunological improvement among Ghanaian PLHIV on HAART comparing different categories of patients. SETTING: Serology Unit, Komfo Anokye Teaching Hospital, Kumasi, Ghana. PARTICIPANTS: The study comprised a convenient sample of 303 treatment naïve HIV patients due to start HAART. METHODS: Questionnaires were used to collect patient demographic and clinical data. Four CD4 counts were measured at six-monthly intervals to determine rates of CD4 change. These were pre-therapy, 1(st) post-therapy, 2(nd) post-therapy, and 3(rd) post-therapy counts. The rates of CD4 change among the different categories of patients were also compared. RESULTS: At baseline, women had higher CD4 count (mean of 77.4 cells/µl), and mean age of participants was 40 years. The CD4 count increased from a mean baseline of 70.2 cells/µl to 229.2, 270.0, and 297.6 cells/µl at 6, 12, and 18 months of treatment respectively (P < 0.0001 at each time point). There were no gender (P=0.46) and age (P=0.96) differences in treatment response. There was no difference (P=0.18) in treatment response comparing those with CD4 <250 cells/µl and those whose CD4 count was between 250 and 350 cells/µl at baseline although patients with baseline CD4 count <250 cells/µl showed larger increases after 12 months of treatment. Out of 282 patients with pre-therapy CD4 count ≤250 cells/µl, 241 (85.5%) and 41 (14.5%) were adherents and nonadherents respectively. Mean rate of increase was 15.2 and 8.4 cells/µl/month in adherent and non-adherent patients respectively (p=0.2). CONCLUSION: The study suggests that a sustained CD4 increase could be achieved in adherent patients commencing therapy with baseline CD4 count ≤250 cells/µl, and that these patients have greater ability for immunological recovery during 12 months of treatment The study, therefore, concludes that significant immunological improvement is possible among Ghanaian PLHIV on HAART as long as a high level of treatment adherence is observed.

Ear, nose and throat lesions in hiv/aids patients in komfo anokye teaching hospital, kumasi, ghana.

BACKGROUND: HIV/AIDS is one of the devastating endemic diseases within the subregion. This condition may be associated with certain specific presentations of which may be confined to the ear, nose, throat and the neck region. OBJECTIVE: The main objective of this study was to evaluate ear, nose and throat (ENT) lesions which may be more associated with the HIV/AIDS infection. MATERIALS AND METHOD: Ninety-three patients who reported to the ENT Clinic of Komfo Anokye Teaching Hospital with certain ENT presentations were screened for HIV/AIDS infection. This was a five-year prospective study conducted at the ENT Clinic and the Microbiology laboratory (KATH). Ethical clearance was approved by the Joint Ethical Committee (KATH/KNUST). Those with other co-morbid pathologies were excluded. RESULT: In all 67.2% were found to be sero-positive. Among the common ENT manifestations include Herpes zoster oticus (Ramsay-Hunt syndrome) 33.9%, Cervical lymphadenopathy 21.0%, Fungal sinusitis 6.5%, Oropharyngeal candidiasis 17.7% etc. CONCLUSION: This study collaborates the knowledge that ENT lesions are more associated with the HIV/AIDS infection presence of which should always prompt the ENT surgeon to screen the patients for the HIV/AIDS.