Susan Clarke

Pharmacokinetic Interactions of Nevirapine and Methadone and Guidelines for Use of Nevirapine to Treat Injection Drug Users

Administration of nevirapine to HIV-infected injection drug users who also receive methadone results in a significant reduction in methadone exposure after 7-10 days of therapy. Many patients require an increase in methadone dose to counteract this effect.

Absence of opioid withdrawal symptoms in patients receiving methadone and the protease inhibitor lopinavir-ritonavir.

A study was designed to determine the interactions, both clinical and pharmacokinetic, between methadone and lopinavir-ritonavir. Results demonstrated a 36% reduction in the methadone area under the plasma concentration-time curve after the introduction of lopinavir-ritonavir, with no coincident symptoms of opioid withdrawal and no requirement for methadone dose adjustment.

Assessing limiting factors to the acceptance of antiretroviral therapy in a large cohort of injecting drug users.

A comprehensive questionnaire was designed to assess the knowledge and understanding of injecting drug users (IDUs) regarding their HIV disease, and to determine any factors that may increase the acceptance of antiretroviral therapy (ART) by this group.

Late onset hepatitis and prolonged deterioration in hepatic function associated with nevirapine therapy.

The aetiology of hepatic dysfunction in patients with HIV infection is multifactorial. Re-activation of hepatitis C infection, drug toxicity, and opportunistic infections are all potential causes. Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor used as part of combination antiretroviral therapy for the treatment of HIV infection. It is associated with a significant incidence of hepatotoxicity, usually occurring in the initial month of therapy. We report the case of a 49-year-old man who developed NVP-induced prolonged hepatotoxicity 5 months after commencing antiretroviral therapy.

Role of individualization of hepatitis C virus (HCV) therapy duration in HIV/HCV-coinfected individuals*

The aim of this study was to assess the efficacy, safety and tolerability of pegylated interferon and ribavirin in HIV/hepatitis C virus (HCV)‐coinfected patients, prescribed for the same duration and at the same dosage as that used in HCV monoinfection studies.

Antiretroviral therapy for drug users

Injection drug use represents the primary risk factor for up to 40% of patients with HIV infection. Physicians are generally reluctant to prescribe antiretroviral therapy (ART) for these patients due to possible poor adherence, and the potential for complex drug interactions to occur. Providing daily observed ART in conjunction with methadone maintenance therapy (MMT) has significantly improved accessibility of ART for many drug users. Knowledge of potential drug interactions between methadone, ART, and both legally and illegally prescribed drugs has permitted such interactions to be anticipated and either avoided or treated appropriately. Optimizing ART for drug users therefore demands a multidisciplinary approach from medical, clinical pharmacology and psychiatric services.

The Tolerability of Efavirenz after Nevirapine-Related Adverse Events

Eight patients who were infected with human immunodeficiency virus, and who had each sustained an adverse drug reaction while following a regimen including nevirapine, were switched to a regimen including efavirenz. None of the patients experienced adverse events identical to that which necessitated discontinuation of nevirapine. This study demonstrates that adverse events related to nevirapine are not a class-specific effect.

The changing epidemiology of HIV infection in injecting drug users in Dublin, Ireland.

Introduction Injecting drug users (IDUs) represent 41.6% of the total cohort of HIV‐infected patients in Ireland. Between January 1999 and December 2000, referrals to the largest tertiary centre for HIV infection in Dublin have increased dramatically. This has occurred on a background of a reduction in the overall incidence of HIV infection in Ireland between 1990 and 1998. Here we describe the changing epidemiology of HIV disease in IDUs and explore potential aetiological factors.

Interferon gamma release assays for the diagnosis of latent TB infection in HIV-infected individuals in a low TB burden country.

Background Interferon gamma release assays (IGRAs) are used to diagnose latent tuberculosis infection. Two IGRAs are commercially available: the Quantiferon TB Gold In Tube (QFT-IT) and the T-SPOT.TB. There is debate as to which test to use in HIV+ individuals. Previous publications from high TB burden countries have raised concerns that the sensitivity of the QFT-IT assay, but not the T-SPOT.TB, may be impaired in HIV+ individuals with low CD4+ T-cell counts. We sought to compare the tests in a low TB burden setting. Methodology/Principal Findings T-SPOT.TB, QFT-IT, and tuberculin skin tests (TST) were performed in HIV infected individuals. Results were related to patient characteristics. McNemar’s test, multivariate regression and correlation analysis were carried out using SPSS (SPSS Inc). 256 HIV infected patients were enrolled in the study. The median CD4+ T-cell count was 338 cells/µL (range 1–1328). 37 (14%) patients had a CD4+ T-cell count of <100 cells/µL. 46/256 (18% ) of QFT-IT results and 28/256 (11%) of T-SPOT.TB results were positive. 6 (2%) of QFT-IT and 18 (7%) of T-SPOT.TB results were indeterminate. An additional 9 (4%) of T-SPOT.TB results were unavailable as tests were not performed due to insufficient cells or clotting of the sample. We found a statistically significant association between lower CD4+ T-cell count and negative QFT-IT results (OR 1.055, p = 0.03), and indeterminate/unavailable T-SPOT.TB results (OR 1.079, p = 0.02). Conclusions/Significance In low TB prevalence settings, the QFT-IT yields more positive and fewer indeterminate results than T-SPOT.TB. Negative results on the QFT-IT and indeterminate/unavailable results on the T-SPOT.TB were more common in individuals with low CD4+ T-cell counts.

Long-term neurological follow-up of HIV-positive patients diagnosed with syphilis

No cerebrospinal fluid (CSF) abnormalities are found in HIV-positive patients in long-term follow-up after standard syphilis treatment. Syphilis has been reported to have immunological effects on HIV infection and HIV is known to modulate both the manifestations of syphilis and the serological response to therapy. HIV-positive patients who had been diagnosed with and treated for syphilis prior to 2007 were identified. Patients were consented for lumbar puncture. Serum HIV viral load, CD4 count and CSF were recorded. Thirty-five patients with previously diagnosed and treated syphilis underwent lumbar puncture. Thirty-four patients had a normal neurological exam. Only one patient had an abnormal mean white cell count (10.7 cells per high-power field). The finding that those with previously diagnosed syphilis had normal CSF and clinical findings is reassuring and supports the practice of using standard syphilis therapy in HIV-positive patients.