Rifabutin pharmacokinetics and safety among TB/HIV-coinfected children receiving lopinavir/ritonavir-containing second-line ART.

BACKGROUND: Treatment options are limited for TB/HIV-coinfected children who require PI-based ART. Rifabutin is the preferred rifamycin for adults on PIs, but the one study evaluating rifabutin with PIs among children was stopped early due to severe neutropenia. METHODS: We evaluated rifabutin safety and plasma pharmacokinetics among coinfected children 3-15 years of age receiving rifabutin 2.5 mg/kg daily with standard doses of lopinavir/ritonavir. The AUC0-24 at 2, 4 and 8 weeks after rifabutin initiation was described using intensive sampling and non-compartmental analysis. Clinical and laboratory toxicities were intensively monitored at 12 visits throughout the study. RESULTS: Among 15 children with median (IQR) age 13.1 (10.9-14.0) years and weight 25.5 (22.3-30.5) kg, the median (IQR) rifabutin AUC0-24 was 5.21 (4.38-6.60) µg·h/mL. Four participants had AUC0-24 below 3.8 µg·h/mL (a target for the population average exposure) at week 2 and all had AUC0-24 higher than 3.8 µg·h/mL at the 4 and 8 week visits. Of 506 laboratory evaluations during rifabutin, grade 3 and grade 4 abnormalities occurred in 16 (3%) and 2 (0.4%) instances, respectively, involving 9 (60%) children. Specifically, grade 3 (n = 4) and grade 4 (n = 1) neutropenia resolved without treatment interruption or clinical sequelae in all patients. One child died at week 4 of HIV-related complications. CONCLUSIONS: In children, rifabutin 2.5 mg/kg daily achieved AUC0-24 comparable to adults and favourable HIV and TB treatment outcomes were observed. Severe neutropenia was relatively uncommon and improved with ongoing rifabutin therapy. These data support the use of rifabutin for TB/HIV-coinfected children who require lopinavir/ritonavir.

Longitudinal evaluation of adherence, retention, and transition patterns of adolescents living with HIV in Nigeria.

INTRODUCTION: Adherence to antiretroviral therapy (ART) and retention in treatment programs are required for successful virologic suppression and treatment outcomes. As the number of adolescents living with HIV continues to increase globally, more information about adherence and retention patterns during and through transition from child- to adult-centered care is needed to ensure provision of a high level of care and inform development of targeted interventions to improve patient outcomes in this vulnerable population. In this analysis, we sought to describe long-term trends in adherence, retention, and virologic suppression in adolescents receiving ART at a pediatric HIV clinic in Nigeria through transition to the adult clinic. SETTING: The Jos University Teaching Hospital, United States President's Emergency Plan for AIDS Relief (PEPFAR)-funded HIV clinic in Jos, Plateau State, Nigeria. METHODS: We conducted a retrospective observational longitudinal evaluation of data that had been collected during the course of care in a large pediatric ART program in Nigeria. We used descriptive statistics to define our patient population and quantify retention from ART initiation through adolescence and transition to adult-centered care. Logistic regression was used to evaluate predictors of loss to follow-up. We used medication possession ratio (MPR) to quantify adherence for each year a patient was on ART. To evaluate adherence and virologic suppression, we measured the proportion of patients with ≥95% MPR and the proportion with virologic suppression (viral load ≤400 copies/mL) within each age cohort, and used bivariate analyses to examine any association between MPR and VL suppression for all person-years observed. RESULTS: A total of 476 patients received at least one dose of ART as an adolescent (ages 10-19 years). The proportions of patients lost to follow-up were: 11.9% (71/597) prior to adolescence, 19.1% (31/162) during adolescence, and 13.7% (10/73) during transition to adult-centered care. While over 80% of patients had ≥95% medication adherence in all age groups, their viral load suppression rates through adolescence and post-transition were only 55.6%-64.0%. For patients that successfully transitioned to adult-centered care, we observed 87.7% (50/57) retention at month 12 post-transition, but only 34.6% (9/26) viral load suppression. CONCLUSIONS: Our evaluation found considerable proportions of adolescents lost to follow-up throughout the ART program cascade. We also found discrepancies between the proportions of patients with ≥95% MPR and the proportions with VL suppression, suggesting that true medication adherence in this population may be poor. Significant attention and targeted interventions to improve retention and adherence focused on adolescents are needed in order for global programs to achieve 90-90-90 goals.

Prevalence of and risk factors for pulmonary tuberculosis among newly diagnosed HIV-1 infected Nigerian children.

INTRODUCTION: Studies on the prevalence of and risk factors for tuberculosis (TB) among newly diagnosed human immunodeficiency virus (HIV)-infected children in sub-Saharan Africa are scarce and in Nigeria there is paucity of reported data. We determined the prevalence of and risk factors for pulmonary TB (PTB) in newly diagnosed (treatment-naïve) HIV-1 infected children at the pediatric HIV clinic of the Jos University Teaching Hospital (JUTH) in Nigeria. METHODS: We performed a retrospective analysis of 876 children, aged 2 months - 13 years, diagnosed with HIV-1 infection between July 2005 and December 2012, of which 286 were diagnosed with PTB at presentation after TB screening. The study site was the AIDS Prevention Initiative in Nigeria (APIN)-supported Pediatric HIV clinic at JUTH, Jos. A multivariate forward logistic regression modelling was used to identify risk factors for PTB-HIV co-infection. RESULTS: The prevalence of PTB-HIV co-infection was 32% (286/876). Severe immunosuppression (SI) and World Health Organization (WHO) HIV clinical stage 3/4 were identified as independent risk factors for PTB-HIV co-infection in HIV infected children. The odds of PTB-HIV co-infection was increased two-fold in HIV-infected children with WHO clinical stage 3/4 compared to those with stage 1/2 (adjusted odds ratio (AOR) 1.76 [1.31-2.37], p<0.001) and 1.5-fold in children with SI compared to those without SI (AOR 1.52 [1.12-2.06], p=0.007). CONCLUSION: In our setting, the burden of PTB was high among newly diagnosed HIV-infected children, and late WHO HIV clinical stage and severe immunosuppression were associated with PTB-HIV co-infection. Therefore there is a clear need to improve strategies for early diagnosis of both HIV and PTB to optimize clinical outcomes.

Molecular characterization of cryptosporidium in children aged 0- 5 years with diarrhea in Jos, Nigeria.

INTRODUCTION: Cryptosporidium is an important cause of diarrhea in children and immune-compromised individuals. Recent advances in molecular diagnostics have led to the discovery of subtype families that are thought to be more commonly associated with diarrhea. We aimed to isolate and characterize Cryptosporidium spp among children with diarrhea in Jos, Nigeria. METHODS: Stool samples were collected from165 children aged 0-5 years with diarrhea. Cryptosporidium oocysts were examined by wet mount preparation, using formalin ether and a modified acid fast staining method. DNA was extracted from positive samples using QIAamp DNA stool mini kit and PCR-RFLP assay was carried out after quantification. Genotyping and phylogenetic analysis were done to determine the subtype families and their relatedness. RESULTS: From the 165 children studied, 8 (4.8%) were infected with Cryptosporidium. PCR-RFLP assay and genotype characterization found the following Cryptosporidium species: C. hominis 6 (75%) and C. parvum 2 (25.0%), with family subtypes Id-5, Ie-1 and IIa-1, IId-1 respectively.The most common species was C. hominis and the frequent subtype was C. hominis-Id 5 (62.5%). CONCLUSION: Cryptosporidium is not an uncommon cause of diarrhea in children, with C. hominis being the dominant species. Also C. hominis Id is the commonest sub-family subtype. Put together, zoonotic species may be an important cause of diarrhea in children aged 0-5 years in Jos, Nigeria.

Mother-to-Child Transmission Outcomes of HIV-Exposed Infants Followed Up in Jos North-Central Nigeria.

OBJECTIVE: Since 2010, Nigeria has adopted World Health Organization (WHO) 'Option B' which requires administration of triple antiretroviral prophylaxis or treatment (ART) to all HIVinfected pregnant women. We studied the transmission outcomes of HIV-exposed children up to 18 months of age. DESIGN: This was a retrospective, observational study of HIV-infected pregnant women and their exposed infants who accessed prevention of mother to child transmission (PMTCT) services at Jos University Teaching Hospital, Jos, North-central Nigeria. METHODS: HIV-infected women were enrolled during antenatal care or at labor/delivery between January 1, 2010 and December 31, 2012. Antiretroviral (ARV) prophylaxis/therapy was provided according to the 2010 Nigerian PMTCT guidelines (adapted WHO 2010 guidelines); Infant HIV diagnosis was performed at 6 weeks and at 6 months. HIV antibody diagnosis was used for exposed children at 18 months. RESULTS: A total of 996 HIV-exposed children were followed up. Of those children, 140 (14.1%) were lost to follow up by 18 months of age. Twelve children (1.4%) died (all HIV negative) before 18 months of age and six infants (0.7%) were confirmed to be HIV-infected (4 by the age of 6 months and 2 thereafter) and were referred for treatment. A total of 838 (84.1%) children tested HIV negative at 18 months and were discharged. Mother-to-child transmission (MTCT) of HIV by 18 months was lower among women on ART before pregnancy compared to those women who started ART/Triple ARV prophylaxis during pregnancy/delivery. (0.4%; 3/700 vs 2.0%; 3/150 P=0.05). Home delivery was associated with higher transmission than facility delivery (p=0.03). Mode of delivery or method of infant feeding had no significant impact on vertical transmission by 18 months. CONCLUSION: In North-central Nigeria where HIV is prevalent, ART started before pregnancy is enormously effective in preventing mother-to-child transmission. Adoption of WHO 'Option B+' deserves serious consideration in such settings.

Factors associated with antiretroviral treatment interruption in human immunodeficiency virus (HIV)-1-infected children attending the Jos University Teaching Hospital, Jos, Nigeria.

BACKGROUND: Interrupting anti-retroviral therapy (ART) for any number of reasons is an indication of a compromised adherence to ART. Several factors, including the pill burden from other drugs used in treating co-infections in children with human immunodeficiency virus (HIV), may influence ART adherence. The aim of this study was to identify the factors associated with ART interruption in HIV-1-infected children. MATERIALS AND METHODS: A retrospective cohort study analysing data on 580 children consecutively enrolled on ART between February 2006 and December 2010 at the paediatric HIV clinic of Jos University Teaching Hospital (JUTH), Jos. Subjects were children aged 2 months - 15 years diagnosed with HIV-1 infection and on first-line ART. Cotrimoxazole prophylaxis was usually commenced at diagnosis while awaiting ART commencement. Children diagnosed with tuberculosis (TB) were also placed on multiple individual anti-TB drugs. STATISTICAL ANALYSIS USED: A comparison of the data on children with and without ART interruption was made. Variables associated with ART interruption in a univariate analysis were fit in a multivariate logistic model to determine the factors that were associated with ART interruption. RESULTS: Children on anti-TB drugs were twice more likely to interrupt ART compared to those who were not, (adjusted odds ratio, AOR = 1.84 (1.03-3.28); P = 0.04). But children on cotrimoxazole prophylaxis had a 57% reduction in the odds of interrupting ART compared to those who were not, (AOR = 0.43 (0.20-0.93); P = 0.03). CONCLUSION: Children on ART and also taking multiple individual anti-TB drugs should be monitored closely for ART adherence. Cotrimoxazole prophylaxis should be encouraged in children diagnosed with HIV while awaiting ART commencement as this may prime them for a better ART adherence.

Nonadherence to First-Line Antiretroviral Therapy among Human Immunodeficiency Virus-1 Infected Children at the Jos University Teaching Hospital; Jos; Nigeria

Background: Nonadherence to antiretroviral therapy (ART) may encourage the development of resistance to antiretroviral drugs (ARVs). Poor adherence is known to be associated with ART failure which could compromise the benefits of ART in children. Therefore; it is important to identify the reasons why children on ART may fail to take their ARVs. In this study; we described the characteristics of human immunodeficiency virus-1 (HIV-1) infected children with ART nonadherence as well as the reasons for their nonadherence. Methodology: A retrospective cohort study in which data on 580 HIV-1 infected children enrolled on ART between February 2006 and December 2010 at the pediatric HIV clinic of the Jos University Teaching Hospital; Jos; was analyzed. Subjects were aged 2 months to 15 years. Information on adherence was obtained by child or caregiver self-report. They also had repeated adherence counseling during each clinic follow-up visit and were taught the use of alarm clocks daily for reminding them of when the next ARV dose will be due. Results: There were 30 (5.2) children with non-adherence to ART. Among children with nonadherence; majority were: Children aged 1-10 years (76.7); males (53.3) and did not know their diagnosis of HIV (90.9). The odds of nonadherence was two times higher among children who failed first-line ART compared with those who did not (odds ratio [95 confidence interval]; 2.28 [1.03-5.02]; P = 0.04). The most common reason for nonadherence was: Forgot to take medications (46.7). Conclusion: The low rate of nonadherence to ART in this study could be attributed to repeated adherence counseling during each clinic follow-up visit and the use of alarm clocks daily for reminders on when the next ARV dose will be due