Safety and efficacy of rifabutin among HIV/TB-coinfected children on lopinavir/ritonavir-based ART.

BACKGROUND: TB is the leading cause of death among HIV-infected children, yet treatment options for those who require PI-based ART are suboptimal. Rifabutin is the preferred rifamycin for adults on PI-based ART; only one study has evaluated its use among children on PIs and two of six children developed treatment-limiting neutropenia. METHODS: Since 2009, rifabutin has been available for HIV/TB-coinfected children requiring PI-based ART in the Harvard/APIN programme in Nigeria. We retrospectively analysed laboratory and clinical toxicities at baseline and during rifabutin therapy, and examined HIV/TB outcomes. RESULTS: Between 2009 and 2015, 48 children received rifabutin-containing TB therapy with PI (lopinavir/ritonavir)-based ART: 50% were female with a median (IQR) baseline age of 1.7 (0.9-5.0) years and a median (IQR) CD4+ cell percentage of 15% (9%-25%); 52% were ART experienced. Eighty-five percent completed the 6 month rifabutin course with resolution of TB symptoms and 79% were retained in care at 12 months. Adverse events (grade 1-4) were more common at baseline (27%) than during rifabutin treatment (15%) (P = 0.006). Absolute neutrophil count was lower during rifabutin compared with baseline (median = 1762 versus 2976 cells/mm3, respectively), but only one instance (2%) of grade 3 neutropenia occurred during rifabutin treatment. CONCLUSIONS: With clinical and laboratory monitoring, our data suggest that rifabutin is a safe option for TB therapy among children on PI-based ART. By contrast with the only other study of this combination in children, severe neutropenia was rare. Furthermore, outcomes from this cohort suggest that rifabutin is effective, and a novel option for children who require PI-based ART. Additional study of rifabutin plus PIs in children is urgently needed.

Patterns and Predictors of First-Line Antiretroviral Therapy Modification in HIV-1-Infected Adults in a Large Urban Outpatient Cohort in Nigeria.

OBJECTIVE: We described the magnitude, type, and factors associated with first-line antiretroviral therapy (ART) modification in HIV-1-infected adults on ART in Jos, Nigeria. METHOD: Data on 6309 patients initiated on first-line ART between January 2004 and December 2006 were analyzed retrospectively. Factors predictive of modification to initial ART were assessed by chi-square and multivariable logistic regression analysis. RESULTS: Overall, 5212 (83%) included patients incurred a modification (73.3% drug substitution and 9.7% drug switch) to their initial first-line ARV regimen during a median (interquartile range) follow-up period of 7 (3-8) years. Drug substitutions of zidovudine (ZDV) were less likely than of tenofovir (TDF; adjusted odd ratio [AOR] 0.6; 95% confidence interval [CI]: 0.51-0.71), and Drug substitutions of efavirenz (EFV) were more likely than of nevirapine (NVP)-containing (AOR 1.82; 95% CI: 1.42-2.33) regimens. Predictors of switch to second-line regimen include older age (AOR 2.05; 95% CI: 1.68-2.51), CD4 count≤100 cells/mm3 (AOR 1.89; 95% CI: 1.49-2.37), EFV compared to NVP (AOR 1.38; 95% CI: 1.02-1.88), and drug toxicity (AOR 1.90; 95% CI: 1.48-2.43). CONCLUSION: Modification to initial ART was common in this study. Further evaluation of the contribution of guideline changes on regimen modification and treatment outcomes is recommended.

Pharmaceutical care outcomes in an outpatient human immunodeficiency virus treatment center in Jos, Nigeria.

RATIONALE: Pharmacotherapy for patients infected with human immunodeficiency virus (HIV) is complex and increases the potential for drug therapy problems (DTPs). We described the frequency and type of DTPs in a Nigerian cohort of HIV infected patients on antiretroviral therapy (ART), as well as the changes in HIV clinical outcomes after pharmacists' intervention. METHODS: A prospective 1-year descriptive study was conducted from July 2010 to June 2011, at the adult HIV clinic of Jos University Teaching Hospital, Nigeria. DTPs and the associated pharmacist-initiated interventions were documented. Chi-square and Wilcoxon signed ranks test was used as appropriate, to compare the main outcome measures of pre- and post-intervention levels of viral load and CD+ cell count. RESULTS: A total of 64,839 prescriptions were dispensed to 9320 patients. Interventions were documented for 85 unique patients (incidence of 1.31 interventions/1000 prescriptions), of which 62 (73%) and 3 (3.5%) were on first- and second-line ART, respectively, while 20 (23.5%) were yet to commence ART. Reasons for pharmacist intervention included failure to initiate therapy for HIV or hepatitis B infection; therapeutic failure (25.9%); and drug toxicity (24.7%). After intervention, the percentage of patients with HIV ribonucleic acid level <400 copies/mL rose from 29.4% to 67.1% (P < 0.001), while median (interquartile range) CD4+ cell count increased from 200 (123-351) to 361 (221-470) cells/mm(3) (P < 0.001). CONCLUSION: Pharmacist intervention resulted in clinically significant improvements in patients HIV virological and immunological outcomes. This highlights an important role for the pharmacist in the treatment and care of HIV-infected patients, in a multidisciplinary team.

Accumulation of protease mutations among patients failing second-line antiretroviral therapy and response to salvage therapy in Nigeria.

BACKGROUND: To date, antiretroviral therapy (ART) guidelines and programs in resource-limited settings (RLS) have focused on 1(st)- and 2(nd)-line (2 L) therapy. As programs approach a decade of implementation, policy regarding access to 3(rd)-line (3 L) ART is needed. We aimed to examine the impact of maintaining patients on failing 2 L ART on the accumulation of protease (PR) mutations. METHODS AND FINDINGS: From 2004-2011, the Harvard/APIN PEPFAR Program provided ART to >100,000 people in Nigeria. Genotypic resistance testing was performed on a subset of patients experiencing 2 L failure, defined as 2 consecutive viral loads (VL)>1000 copies/mL after ≥6 months on 2 L. Of 6714 patients who received protease inhibitor (PI)-based ART, 673 (10.0%) met virologic failure criteria. Genotypes were performed on 61 samples. Patients on non-suppressive 2 L therapy for <12 months prior to genotyping had a median of 2 (IQR: 0-5) International AIDS Society (IAS) PR mutations compared with 5 (IQR: 0-6) among patients failing for >24 months. Patients developed a median of 0.6 (IQR: 0-1.4) IAS PR mutations per 6 months on failing 2 L therapy. In 38% of failing patients no PR mutations were present. For patients failing >24 months, high- or intermediate-level resistance to lopinavir and atazanavir was present in 63%, with 5% to darunavir. CONCLUSIONS: This is the first report assessing the impact of duration of non-suppressive 2 L therapy on the accumulation of PR resistance in a RLS. This information provides insight into the resistance cost of failing to switch non-suppressive 2 L regimens and highlights the issue of 3 L access.