Predictors of Antiretroviral Pharmacokinetics in HIV-infected Women With Virologic Suppression on Combination Antiretroviral Therapy
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 88
- 试验地点
- 15
研究概览
简要总结
Women represent an increasing proportion of HIV cases globally and in Canada, yet are underrepresented in clinic trials. It is therefore critical to conduct this study on antiretroviral (ARV) pharmacokinetics (PK) in women to obtain additional information on ARV drug levels in women and their relation to adverse events (AEs).
The hypothesis for this study is three-fold:
- that the mean drug levels (Cmin and Cmax) of ARVs will be significantly higher in our female population as compared to the mean drug levels in the historical HIV population (which is primarily men)
- that ARV drug levels, particularly Cmin, are associated with body weight in women
- that higher ARV drug levels, particularly Cmax, are associated with higher frequency and severity of AEs.
The objectives of this study are as follows:
Primary objectives:
- To demonstrate that levels of Protease Inhibitors (PIs) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) are significantly higher in our female population as compared to the mean drug levels in the historical general population (which is primarily men).
- To determine the association between PI and NNRTI minimum concentration (Cmin) and body weight in our female population.
Secondary objectives
- To determine the association between maximum concentration (Cmax) and the frequency and severity of AEs as measured by the proportion of patients with grade 2 or higher laboratory or clinical AEs and the Symptom Index Score in women.
- To determine the association between ARV drug levels and age, race, height, body mass index, adherence, hormonal levels and therapy, menstruation history, duration of HIV infection, duration on ARV therapy, baseline viral load, baseline CD4 count, present CD4 count, hepatitis B or C infection, class of ARVs, presence of ritonavir and other medications.
详细描述
Predictors of antiretroviral pharmacokinetics in HIV-infected women with virologic suppression on combination antiretroviral therapy
Background
Women in Canada constitute the fastest growing population groups at risk for infection with HIV and AIDS. Women now represent approximately 40% of all AIDS cases worldwide and approximately 20% of cases in Canada. Although the AIDS epidemic has been ongoing for more than 20 years, surprisingly little is known about the differential efficacy and toxicity of various antiretroviral (ARV) drugs in women as compared to men. This gap in knowledge is a result of the initial exclusion of and continued underrepresentation of women in ARV clinical trials. Many studies suggest that HIV-infected women taking ARV treatment (ART) have more adverse events (AEs) than men, especially in relationship to systemic symptoms like diarrhea, as well as organ toxicity, including hepatotoxicity, lactic acidosis, peripheral neuropathy and, notably, lipodystrophy. Currently, the occurrence and management of AEs is the most important issue in the treatment of HIV. Understanding the reasons for the differences of AEs in HIV-infected women is critical and has yet to be evaluated within a large cohort. It is unknown whether these differences relate to hormonal influences, drug metabolism, adherence, fat distribution, body size or other factors. Some small studies have found that drug levels (e.g. Cmin, Cmax, AUC) are higher in women and are associated with increased toxicity. Ultimately, we plan to conduct a randomized clinical trial (RCT) to assess the utility of therapeutic drug monitoring (TDM) and ARV drug dose adjustment on the frequency of AEs in women. Prior to conducting this RCT, it is critical to conduct this study on ARV pharmacokinetics (PK) in women to obtain additional information on ARV drug levels in women and their relation to AEs.
Hypothesis
The hypothesis for this study is three-fold:
研究设计
- 研究类型
- Observational
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patient must be HIV infected
- •Patient must be 18 years old or older
- •Patient must be a biologic woman
- •Patient must be taking her first combination ARV regimen that includes a PI or an NNRTI for the past three months with no changes in any agent of the combination in that period (first combination ARV regimen is defined as a regimen started when the patient was ARV-naïve; however switches are allowed as long as the switches are not for virologic failure)
- •Patient must be taking either a PI or an NNRTI but not both
- •If taking a PI, patient must be taking only one PI excluding low dose ritonavir used as boosting
- •Patient must have a viral load < 50 copies/mL on two occasions at least 1 month apart including a value within three months before the baseline visit
- •Patient has to have signed and dated a full informed consent
排除标准
- •Patient who would have difficulty participating in a trial due to non-adherence or substance abuse
- •Patient who is pregnant or breast-feeding
- •Patient with a malignancy receiving systemic chemotherapy
- •Patient with end stage organ disease
- •Patient with other significant non-HIV underlying disease that might impinge upon disease progression or death
- •Patient who is not taking standard dosing of a PI or NNRTI as listed in Appendix G