Sub therapeutic drug levels among HIV/TB co-infected patients receiving Rifampicin in northwestern Tanzania: A cross sectional clinic based study

Background: Tuberculosis/Human Immunodeficiency Virus (TB/HIV) is a very common co-infection which carries a high mortality rate. Though World Health Organization recommends co-treatment of TB/HIV to improve its outcome, Rifampicin potentially induces metabolism and sub-therapeutic antiretroviral plasma levels of non nucleoside reverse transcriptase inhibitors and protease inhibitors which may cause inadequate virological suppression if corrections are not timely done. In Tanzania Therapeutic drug monitoring is not done; so the proportion of sub-therapeutic ARV plasma levels among TB/HIV patients co-treated with anti-tuberculous drugs is not known. The aim of this study was therefore to determine the magnitude and risk factors of sub-therapeutic ARV plasma levels among adult HIV patients co-treated with anti tuberculous Medications.Materials and methods: A cross sectional hospital based study was conducted among adult HIV patients on ARV and TB co-treatment for at least one month. Patients were serially enrolled through routine HIV care and treatment services until the sample size was reached. The information about demographic, clinical and adherence level, Anti-TB duration, viral load, baseline and enrollment CD4 counts, Hepatitis B co-infection and ARV plasma levels was collected and analyzed using STATA 12 software.Results: In total 118 patients were included in this study; of whom 26 (22%) had sub-therapeutic ARV plasma levels. The sub-therapeutic ARV levels were independently associated with adherence <95% (OR =6.8, p= 0.001), female gender (OR = 3.4, p= 0.028) and virological failure (OR= 3.8, p= 0.016). NVP based regimen was associated with sub-therapeutic drug levels on univariate model (OR = 2.1, p= 0.010).Conclusion: The magnitude of sub-therapeutic ARV plasma levels is high among adult HIV/TB coinfected patients on anti-TB co-treatment in Tanzania. These patients stand a high risk of inadequate virological suppression with a potential resistance development and a long term poor clinical outcome. Identifying at risk patients and adherence enhancement could potentially improve the overall outcome of this subgroup of patients in resource restricted setting like ours where TDM is not available.Keywords: HIV; HIV/TB co-infection; HIV/TB co-treatment Rifampicin; Antiretroviral therapy; Plasma ARV drug levels; Therapeutic drug monitorin

Minimal essential data to document contact tracing and single dose rifampicin (SDR) for leprosy control in routine settings

In leprosy control there is a renewed interest in active case finding, which is increasingly being combined with chemoprophylactic interventions to try and reduce M. leprae transmission. The Leprosy Post-Exposure Prophylaxis (LPEP) programme, currently ongoing in eight endemic countries, pilots the provision of single-dose rifampicin (SDR) to eligible contacts of leprosy patients. LPEP has developed a surveillance system including data collection, reporting and regular monitoring for every participating country. This system is still largely programmespecific to LPEP. To facilitate continuity after completion of the project phase and start-up in other interested countries, we aim at identifying the minimal set of data required to appropriately document contact tracing activities and SDR administration for leprosy control in a routine setting. We describe four indicators for the index case (plus four already routinely collected) and seven indicators for household/neighbour screening, and community surveys. We propose two generic forms to capture all relevant information required at field and district level to follow-up on individuals or data if needed, provide gu

HIV patients treated with low-dose prednisolone exhibit lower immune activation than untreated patients

HIV-associated general immune activation is a strong predictor for HIV disease progression, suggesting that chronic immune activation may drive HIV pathogenesis. Consequently, immunomodulating agents may decelerate HIV disease progression. In an observational study, we determined immune activation in HIV patients receiving low-dose (5 mg/day) prednisolone with or without highly-active antiretroviral therapy (HAART) compared to patients without prednisolone treatment. Lymphocyte activation was determined by flow cytometry detecting expression of CD38 on CD8(+) T cells. The monocyte activation markers sCD14 and LPS binding protein (LBP) as well as inflammation markers soluble urokinase plasminogen activated receptor (suPAR) and sCD40L were determined from plasma by ELISA. CD38-expression on CD8+ T lymphocytes was significantly lower in prednisolone-treated patients compared to untreated patients (median 55.40% [percentile range 48.76-67.70] versus 73.34% [65.21-78.92], p = 0.0011, Mann-Whitney test). Similarly, we detected lower levels of sCD14 (3.6 μg/ml [2.78-5.12] vs. 6.11 μg/ml [4.58-7.70]; p = 0.0048), LBP (2.18 ng/ml [1.59-2.87] vs. 3.45 ng/ml [1.84-5.03]; p = 0.0386), suPAR antigen (2.17 μg/ml [1.65-2.81] vs. 2.56 μg/ml [2.24-4.26]; p = 0.0351) and a trend towards lower levels of sCD40L (2.70 pg/ml [1.90-4.00] vs. 3.60 pg/ml [2.95-5.30]; p = 0.0782). Viral load in both groups was similar (0.8 × 105 ng/ml [0.2-42.4 × 105] vs. 1.1 × 105 [0.5-12.2 × 105]; p = 0.3806). No effects attributable to prednisolone were observed when patients receiving HAART in combination with prednisolone were compared to patients who received HAART alone.\ud Patients treated with low-dose prednisolone display significantly lower general immune activation than untreated patients. Further longitudinal studies are required to assess whether treatment with low-dose prednisolone translates into differences in HIV disease progression

Leprosy post-exposure prophylaxis with single-dose rifampicin

_Objective:_ Leprosy post-exposure prophylaxis with single-dose rifampicin (SDRPEP) has proven effective and feasible, and is recommended by WHO since 2018. This SDR-PEP toolkit was developed through the experience of the leprosy postexposure prophylaxis (LPEP) programme. It has been designed to facilitate and standardise the implementation of contact tracing and SDR-PEP administration in regions and countries that start the intervention. _Results:_ Four tools were developed, incorporating the current evidence for SDRPEP and the methods and learnings from the LPEP project in eight countries. (1) th

Plasma Concentrations of Efavirenz and Nevirapine among HIV-Infected Patients with Immunological Failure Attending a Tertiary Hospital in North-Western Tanzania

Background: Sub-therapeutic and supra-therapeutic plasma concentrations of antriretrovirals are the significant causes of treatment failure and toxicity respectively among HIV-infected patients. We conducted this study to determine the pattern of efavirenz and nevirapine plasma drug concentrations among adult HIV-infected patients with immunological failure attending at a tertiary hospital in North-western Tanzania. Materials and Methods: A cross-sectional study was conducted among adult HIV-infected patients with immunological failure who have been on either efavirenz or nevirapine based antiretroviral regimen for more than 6 months. Patients were serially enrolled through routine Care and Treatment Clinic (CTC) activities. Plasma drug concentrations for efavirenz and nevirapine were determined by high performance liquid chromatography (HPLC) and Gas Chromatography (GC) respectively. Demographic, clinical and laboratory data such as viral load and CD4 counts were collected. Data analysis was done using STATA 12. Results: Of the 152 patients with immunological failure enrolled, the sub-therapeutic, therapeutic and supra-therapeutic plasma antiretroviral drug concentrations were found in 43/152 (28.3%), 76/152 (50.0%) and 33/152 (21.7%) respectively. Half of the patients were outside therapeutic window with either sub-therapeutic or supra-therapeutic plasma ARV drug concentrations. There was a significant difference in distribution of ARV adherence (p-value<0.001), NRTI backbone (p-value = 0.039), HIV stage (p-value = 0.026) and viral load (p-value = 0.007) within sub-therapeutic, therapeutic and supratherapeutic ARV plasma drug concentrations. Conclusion: There is a wide inter-individual variability of plasma ARV concentrations among HIV patients with immunological failure, with a large proportion of patients being outside therapeutic window. This variability is significant based on ARV adherence, NRTI backbone, viral load and HIV stage. Routine therapeutic drug monitoring (TDM) could assist identifying these patients early and making timely correction to avoid virological failure, poor immunological outcome and prevent associated drug toxicities. Nonetheless, ARV adherence should be strictly emphasized on HIV patients with immunological failure