Pharmacokinetics of Antiretroviral Agents in HIV-1 Infected Pregnant Women

Highly active antiretroviral therapy is currently recommended for HIV-1 infected pregnant women for the management of maternal HIV infection and for prevention of perinatal HIV transmission. Many physiological changes occur during pregnancy may lead to changes in pharmacokinetics of drugs. Some of these pharmacokinetic changes may include increases in volume of distribution and total body clearance as well as decreases in oral absorption, area under the concentration time curve, peak and trough concentrations. All of these changes may result in decrease in drug exposure. Other than zidovudine, little is known about the pharmacokinetics of other antiretroviral agents during pregnancy. A number of studies have suggested a correlation between trough concentration: IC50 ratio and virological responses. The objective of the study is to examine the pharmacokinetics of antiretroviral agents during different stages of pregnancy in comparison with the non-pregnant state (post-partum and historical control). HIV infected pregnant women in general good health who are on at least three antiretroviral drug combination will be enrolled in the study. Pharmacokinetic profiles of the antiretroviral agents taken by the subjects will be obtained two to four times during pregnancy and again at around one month post-partum. These data will be used to assess the need for dosage adjustment or therapeutic drug monitoring of antiretroviral agents during pregnancy.

Inclusion criteria

HIV-1 positive as documented by ELISA and confirmed by Western Blot test

Positive urine pregnancy test or positive serum Beta-HCG

Age greater than or equal to 18 years

At least 14-week gestation at the time of screening as estimated by the subject's obstetrician

Having a normal pregnancy per the subject's obstetrician's assessment

Maintained on or to be started on a HAART regimen containing at least three antiretroviral agents

Hgb greater than or equal to 10 gm/dL, platelet greater than or equal to 100,000/mL, PT less than or equal to 14.0 sec

S.Cr. less than 2.0 mg/dL, ALT and AST less than or equal to 2 times the upper limit of normal

Exclusion criteria

Receiving treatment for an active HIV-related opportunistic infection

Significant medical conditions such as diabetes (including gestational diabetes), hypertension, coronary artery disease, seizure disorder, asthma, or other medical conditions that in the investigators' opinion will not be safe for the subject to participate in this study

History of significant obstetric complications during prior pregnancy(ies)

Concurrent illicit drug or alcohol abuse

Not receiving ongoing medical care for HIV infection and pregnancy

Efavirenz as part of HAART regimen

Combination of didanosine and stavudine as part of HAART regimen

Presence of persistent diarrhea or history of malabsorption that will interfere with the subject's ability to absorb the antiretroviral drugs

Refusal to allow the investigators to obtain medical records from her HIV care provider and her obstetricians during the course of the study

Unable to obtain venous access for blood draw

Refusal to agree to allow the specimen to be stored for future research