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

Abstract

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 monitoring