Biomedical subjects

Donna Mildvan

Publications and source records attributed to Donna Mildvan.

At least 19 recordsLinked to original sources

PubMed2006

A randomized, partially blinded phase 2 trial of antiretroviral therapy, HIV-specific immunizations, and interleukin-2 cycles to promote efficient control of viral replication (ACTG A5024).

Strategies to limit life-long dependence on antiretroviral therapy (ART) are needed. We randomized 81 human immunodeficiency virus (HIV)-infected subjects to 4 interventional arms involving continued ART plus ALVAC vCP1452 (or placebo) with or without interleukin (IL)-2 infusions. Viral load rebound 12 weeks after ART interruption was then analyzed to assess immune control. Fifty-two subjects reached the study end point. ALVAC recipients had 0.5 log(10) lower virologic rebounds (P=.033). IL-2 plus vaccine boosted CD4(+) T cell counts (P<.001) but did not diminish viral rebound. Significant changes were not detected for HIV-specific lymphoproliferative responses in any arm. This exploratory protocol provides useful clinical data for future therapeutic immunization trial design.

AIDS Vaccines↗

PubMed2006

Evidence that intermittent structured treatment interruption, but not immunization with ALVAC-HIV vCP1452, promotes host control of HIV replication: the results of AIDS Clinical Trials Group 5068.

BACKGROUND: The ability to control human immunodeficiency virus (HIV) replication in vivo in the absence of antiretroviral therapy (ART) is a measure of the efficiency of antiviral immunity. In a study of patients with chronic, ART-suppressed HIV infection, AIDS Clinical Trials Group 5068 investigated the effects of immunization with an exogenous HIV vaccine and pulse exposure to the subject's unique viral epitopes, by means of structured treatment interruptions (STIs), on the dynamics of viral rebound during a subsequent analytical treatment interruption (ATI). METHODS: Ninety-seven subjects receiving stable ART with an HIV-1 RNA load <50 copies/mL and CD4(+) T lymphocyte count >400 cells/mm(3) were randomized to undergo continued ART, STIs, ALVAC-HIV vCP1452 immunization, or STIs and ALVAC-HIV vCP1452 immunization. RESULTS: Subjects in the 2 STI arms had a significantly longer median doubling time in the period of the initial rise of viral load, a significantly lower median peak viral load, a significantly lower median end-of-ATI viral load set point, and a greater proportion of subjects with an end-of-ATI viral load set point <1,000 copies/mL, compared with the subjects in the 2 arms without STIs. With an immunization schedule of 3 sets of 3 weekly injections, ALVAC-HIV vCP1452 did not affect viral load measures. CONCLUSIONS: In this randomized, controlled study of intermittent STI as a therapeutic autoimmunization strategy, evidence of enhanced immunologic control of HIV replication was demonstrated.

AIDS Vaccines↗

PubMed2006

HIV and aging.

Approximately one in five individuals living with HIV infection in the United States is 50 years of age or older. This proportion continues to increase as HIV incidence remains stable and potent antiretroviral therapy has reduced the morbidity and mortality associated with HIV infection. Newly identified HIV-seropositive older individuals are proportionately more likely than younger persons to have AIDS at the time of diagnosis. Clinicians have to think about the possibility of HIV infection in older persons to avoid delays in diagnosis and treatment. Immunologic recovery in older individuals initiated on combination antiretroviral therapy is less robust in some studies compared with younger individuals. However, virologic suppression on treatment in young versus old antiretroviral naïve patients is comparable. Co-morbid conditions and their treatment pose a special challenge to health care providers with regard to drug metabolism and interactions with HIV medications. HIV prevention should be discussed with all at risk individuals. The HIV epidemic will only worsen if medical practitioners neglect to discuss sexual risk behavior with their older patients.

Journal Article↗

PubMed2005

HIV incidence among injection drug users in New York City, 1990 to 2002: use of serologic test algorithm to assess expansion of HIV prevention services.

OBJECTIVES: We sought to estimate HIV incidence among injection drug users (IDUs) in New York City from 1990 to 2002 to assess the impact of an expansion of syringe exchange services. Syringe exchange increased greatly during this period, from 250,000 to 3,000,000 syringes exchanged annually. METHODS: Serum samples were obtained from serial cross-sectional surveys of 3,651 IDUs. HIV-positive samples were tested with the Serologic Test Algorithm for Recent HIV Seroconversion (STARHS) assay to identify recent HIV infections and to estimate HIV incidence. Consistency with other incidence studies was used to assess strengths and limitations of STARHS. RESULTS: HIV incidence declined from 3.55/100 person-years at risk (PYAR) from 1990-1992, to 2.63/100 PYAR from 1993-1995, to 1.05/100 PYAR from 1996-1998, and to 0.77/100 PYAR from 1999-2002 (P<.001). There was a very strong negative linear relationship (r= -.99, P<.005) between the annual numbers of syringes exchanged and estimated HIV incidence. These results were highly consistent with a large number of shorter incidence studies among IDUs conducted during the time period. CONCLUSIONS: STARHS testing of samples from large serial cross-sectional surveys can provide important data for the assessment of community-level HIV prevention.

AIDS Serodiagnosis↗

PubMed2005

Monitoring processed, mature Human Immunodeficiency Virus type 1 particles immediately following treatment with a protease inhibitor-containing treatment regimen.

Protease inhibitors (PIs) block HIV-1 maturation into an infectious virus particle by inhibiting the protease processing of gag and gag-pol precursor proteins. We have used a simple anti-HIV-1 p24 Western blot to monitor the processing of p55gag precursor into the mature p24 capsid immediately following the first dosage of a PI-containing treatment regimen. Evidence of PI activity was observed in plasma virus as early as 72 hours post treatment-initiation and was predictive of plasma viral RNA decrease at 4 weeks.

Journal Article↗

PubMed2005

Serum neopterin, an immune activation marker, independently predicts disease progression in advanced HIV-1 infection.

BACKGROUND: CD4+ T lymphocyte (CD4) counts and plasma human immunodeficiency virus (HIV) type 1 RNA concentrations predict clinical outcome in HIV-1 infection. Our objective was to assess the independent prognostic value for disease progression of soluble markers of immune system activation. METHODS: This retrospective marker-validation study utilized previously obtained clinical and laboratory data, including CD4+ cell counts, and made use of stored frozen serum samples to assay for levels of beta2-microglobulin, neopterin, endogenous interferon, triglycerides, interleukin-6, soluble tumor necrosis factor- alpha receptor II, and HIV-1 RNA, and to determine HIV genotypic reverse-transcriptase inhibitor resistance. The 152 patients who participated in this study represented a subsample of participants in AIDS Clinical Trials Group (ACTG) 116B/117, a randomized trial that demonstrated the clinical benefit of didanosine over zidovudine monotherapy in persons with advanced HIV-1 infection. Marker data were analyzed in relation to protocol-defined clinical disease progression, using Cox proportional hazards models. RESULTS: The median duration of follow-up was 344 days. Elevated baseline values for neopterin (P=.0009), endogenous interferon (P=.00039) and interleukin-6 (P=.0007) were each associated with greater subsequent risk of clinical disease progression. In a head-to-head comparison that was adjusted for CD4+ cell count (P=.0165) and HIV-1 RNA level (P=.1220), we found that elevated values for neopterin (P=.0002) and, to a lesser extent, endogenous interferon (P=.0053) were the strongest predictors of increased risk of clinical disease progression 6 months later. CONCLUSIONS: Soluble markers of immune activation add prognostic information to CD4 counts and viral load for risk of disease progression in advanced HIV-1 infection. The robust performance of neopterin, an inexpensive and reliably measured serum marker, supports its potential suitability for patient monitoring, particularly in resource-limited settings.

Anti-HIV Agents↗

PubMed2005

Lower CD4+ T lymphocyte nadirs may indicate limited immune reconstitution in HIV-1 infected individuals on potent antiretroviral therapy: analysis of immunophenotypic marker results of AACTG 5067.

BACKGROUND: Although initiation of potent antiretroviral therapy (ART) has significantly improved immune perturbations in individuals with AIDS, it is unclear which factors are most important in determining the degree of immune reconstitution. METHODS: Whole blood was analyzed at baseline and week 12 in six groups of subjects (n = 81): those with acute or following immune reconstitution after Pneumocystis jirovecii (previously known as Pneumocystis carinii) pneumonia (PcP) (two groups) and cytomegalovirus (CMV) retinitis (two groups), HIV-infection without AIDS (one group), and healthy volunteers (one group). Absolute CD4+ and CD8+ T lymphocytes, naive (CD45RA+) and memory (CD45RO+) CD4+ T lymphocytes and percentages of activated CD8+ T lymphocytes (CD8+/CD38+/HLA-DR), and CD28 expression on CD4+ and CD8+ T lymphocytes were enumerated. RESULTS: The reconstituted CMV group, which had a history of a lower CD4+ T lymphocyte nadir compared to the reconstituted PcP group (15 cells/mm(3) versus 48 cells/mm(3); p = .013), had significantly lower absolute CD4+, CD8+ and naive CD4+ T lymphocytes and a trend toward lower memory CD4+ T lymphocytes compared to the reconstituted PcP group. Moreover, no difference was noted between the reconstituted groups in the proportion of subjects with undetected HIV-1 RNA. The reconstituted subjects had significantly lower absolute CD4+, memory CD4+ and naive CD4+ T lymphocytes than the HIV-positive controls and a significantly higher percentage of activated CD8+ T lymphocytes with a lower percentage of CD8+CD28 expression than the HIV-negative controls. CONCLUSION: The association of CD4+ T lymphocyte nadir with the extent of immune reconstitution in HIV-infected individuals suggests that HIV-1 may cause irreparable immune system damage despite potent ART.

Adult↗

PubMed2005

Reductions in hepatitis C virus and HIV infections among injecting drug users in New York City, 1990-2001.

OBJECTIVE: To assess trends in HIV, hepatitis C virus (HCV) and HIV/HCV infection among injecting drug users (IDU) from 1990 to 2001 in New York City. The 1990-2001 time period included a very large expansion of syringe exchange in New York City, from 250,000 to 3,000,000 syringes exchanged annually. METHODS: Cross-sectional seroprevalence surveys of IDU entering drug abuse treatment in New York City, with sample sizes for HCV of 72 in 1990-1991 and 412 in 2000-2001. A structured risk behavior questionnaire was administered, and HIV and HCV testing were conducted. HCV testing was performed on de-linked stored serum samples. RESULTS: Over the 1990-2001 period, HIV prevalence declined from 54 to 13%. HCV prevalence declined from 80 to 59% among HIV-seronegative individuals, and from 90 to 63% overall. The estimated HCV incidence in 2000-2001 among new injectors was 18 per 100 person-years at risk. CONCLUSIONS: The large-scale expansion of syringe exchange was temporally associated with large reductions in both HIV and HCV prevalence. The prevalence and incidence of HCV, however, still remain at high levels among IDU in New York City.

Adult↗

PubMed2004

Daily low-dose subcutaneous interleukin-2 added to single- or dual-nucleoside therapy in HIV infection does not protect against CD4+ T-cell decline or improve other indices of immune function: results of a randomized controlled clinical trial (ACTG 248).

CONTEXT: Approaches to preserve or enhance immune function in HIV-1 infection are needed. OBJECTIVES: To examine the ability of daily low-dose interleukin-2 (IL-2) in combination with antiretroviral therapy to preserve circulating CD4+ T-cell counts, the clinical safety and tolerability of this treatment, and safety with respect to changes in plasma HIV-1 RNA levels. DESIGN: Twenty-four-week, phase 2, multicenter, randomized, open-label trial conducted at 12 AIDS Clinical Trials Units between September 1995 and May 1997. PARTICIPANTS: A total of 115 HIV-infected persons with screening CD4+ T-cell counts between 300 and 700 cells/mm who were on stable single- or dual-nucleoside therapy for at least 2 months, 11% of whom were also on a protease inhibitor at study entry. INTERVENTIONS: Patients were randomly assigned to receive IL-2 at a dose of 1 million IU subcutaneously once daily plus continued anti-retroviral therapy (ART + IL-2, n = 57) vs. continued ART alone (ART alone, n = 58). IL-2 dose reductions were made for objective or subjective toxicities. All subjects randomly assigned to the IL-2 arm who interrupted ART were also required to discontinue IL-2 for the same period. MAIN OUTCOME MEASURES: The primary endpoint was a decrease in CD4 T-cell count from baseline; the safety analysis was based on change in plasma HIV RNA by bDNA; and clinical safety and tolerability were analyzed by standard clinical criteria. RESULTS: Of the patients with a baseline CD4 T-cell count recorded, 15 (27%) of 55 patients randomly assigned to ART alone had a drop of > or =25% in their CD4 T-cell count and 23 (41%) of 56 patients randomly assigned to ART + IL-2 had a drop of > or =25% in their CD4 T-cell count at some time over the 24 weeks of the study. This difference was not statistically significant. There was a statistically significant greater variance in CD4 T-cell counts in the IL-2-treated group. More patients in the IL-2 group had at least a 25% increase in CD4 T-cell counts over baseline (34 vs. 13%, P = 0.007). A comparison of grade 3 or worse toxicity showed no differences between the arms, but IL-2 was associated with significantly more grade 2 or worse general body symptoms, primarily discomfort and fatigue. There was no significant difference between the groups with regard to changes in plasma HIV RNA, lymphocyte proliferation, natural killer cell activity, skin test responses to recall antigens, or antibody responses to immunization. Plasma markers of immune activation all increased significantly in IL-2 recipients. CONCLUSIONS: In patients with baseline CD4 T-cell counts > or =300 cells/mm primarily treated with single- or dual-nucleoside ART, subcutaneously administered IL-2 at a dose of 1 million IU daily for up to 24 weeks had low toxicity but showed no consistent benefit in preventing decline in CD4 T-cell counts and minimal evidence of immunologic improvement vs. continued ART alone.

AIDS Vaccines↗

PubMed2004

Immunophenotypic markers and antiretroviral therapy (IMART): T cell activation and maturation help predict treatment response.

To determine whether markers of T cell activation and maturation are independently predictive of the response to potent antiretroviral therapy, the Immunophenotypic Markers and Antiretroviral Therapy study applied a novel data-sharing strategy across 5 Adult AIDS Clinical Trial Group trials that counted naive and activated CD4(+) and CD8(+) T cells in 324 subjects. Regression models--adjustment for baseline CD4 cell count, human immunodeficiency virus (HIV) RNA, and study--revealed that high pretreatment CD8(+) T cell activation predicted virologic failure (P=.046). Additional models showed the greatest increase in CD4(+) T cell counts in subjects with highest pretreatment naive CD4(+) T cell counts (P<.0001), which was enhanced by high CD4(+) and low CD8(+) T cell activation. Total lymphocyte count also predicted a subsequent CD4(+) T cell change. These results document the utility of T cell markers in predicting treatment outcome and their potential value for the study and management of HIV-1 infection.

Adult↗

PubMed2004

Anemia in HIV infection: clinical impact and evidence-based management strategies.

Anemia in human immunodeficiency virus (HIV)-infected patients can have serious implications, which vary from functional and quality-of-life decrements to an association with disease progression and decreased survival. In 2002, 16 members of the Anemia in HIV Working Group, an expert panel of physicians involved in the care of HIV-infected patients that met first in 1998, reconvened to assess new data and to translate these data into evidence-based treatment guidelines. The group reached consensus on the prevalence of anemia in the highly active antiretroviral therapy era; the risk factors that are independently associated with the development of anemia; the impact of anemia on quality of life, physical functioning, and survival; the impact of the treatment of hepatitis C virus coinfection on anemia in HIV-infected patients; evidence-based guidelines for treatment of anemia in HIV-infected patients, including the therapeutic role of epoetin alfa; and directions for future research.

Anemia↗

PubMed2004

"Informed altruism" and "partner restriction" in the reduction of HIV infection in injecting drug users entering detoxification treatment in New York City, 1990-2001.

OBJECTIVE: To assess recent developments in the HIV epidemic in injecting drug users (IDUs) in New York City. With >50,000 cases of AIDS in IDUs, New York has experienced the largest HIV/AIDS epidemic in IDUs of any city in the world. METHODS: Serial cross-sectional surveys conducted continuously from 1990 to 2001 of IDUs entering the Beth Israel Medical Center (BIMC) drug detoxification program in New York City. HIV serostatus, use of prevention services, and risk behaviors were measured. Individuals were permitted to participate multiple times in the surveys but not more than once in any year. RESULTS: Two thousand eight hundred eighty-seven individuals contributed 3100 observations from 1990 to 2001. There was a substantial and consistent decline in the prevalence of HIV infection among IDUs entering the BIMC detoxification program, from 54% (165/304) in 1991 to 13% (39/303) in 2001 (P < 0.0001). The decline was highly linear, with r2 = 0.92 and a slope of -3.7% in seroprevalence per year. The decline occurred for both males and females, both short and long-term IDUs, and the three largest racial/ethnic subgroups (all P < 0.001 by Cochran-Armitage testing). Use of HIV prevention services increased substantially, particularly syringe exchange and voluntary HIV counseling and testing. General reductions in injection risk behaviors occurred, but substantial numbers of IDUs continued to engage in both receptive and distributive syringe sharing. Two conditional types of risk reduction not currently recommended by health authorities were reported: "informed altruism," in which persons who knew that they were HIV seropositive reduced transmission behavior, and "partner restriction," in which persons who shared needles and syringes primarily confined this sharing within small social networks. CONCLUSIONS: HIV infection continues to decline in this population of IDUs in New York City, suggesting the possibility of bringing very high prevalence epidemics under control. Risk elimination may not be required; rather, multiple forms of risk reduction may be effective in reducing HIV transmission within a local population of IDUs.

Adult↗

PubMed2004

Once-daily versus twice-daily lopinavir/ritonavir in antiretroviral-naive HIV-positive patients: a 48-week randomized clinical trial.

The safety, pharmacokinetics, and antiviral activity of lopinavir, a human immunodeficiency virus (HIV) protease inhibitor, coformulated with ritonavir as a pharmacokinetic enhancer were evaluated in 38 antiretroviral-naive patients randomized 1:1 to receive open-label lopinavir/ritonavir at a dose of 800/200 mg once daily or 400/100 mg twice daily, each in combination with stavudine and lamivudine twice daily, for 48 weeks. Over the course of 48 weeks, median predose concentrations of lopinavir exceeded the protein-binding corrected concentration required to inhibit replication of wild-type HIV by 50% in vitro by 40- and 84-fold in the once- and twice-daily groups, respectively. Predose concentrations of lopinavir were more variable in the once-daily group (mean +/- SD, 3.62+/-3.38 microg/mL for the once-daily group and 7.13+/-2.93 microg/mL for the twice-daily group). At week 48, in an intent-to-treat (missing = failure) analysis, 74% of patients in the once-daily group and 79% of patients in the twice-daily group had HIV RNA levels of <50 copies/mL (P=.70). Study drug-related discontinuations occurred in 1 patient in each treatment group. Genotypic resistance testing of 4 patients with HIV RNA levels >400 copies/mL between weeks 24 and 48 demonstrated no protease inhibitor-resistance mutations.

Adult↗

PubMed2003

Immune reconstitution is comparable in antiretroviral-naive subjects after 1 year of successful therapy with a nucleoside reverse-transcriptase inhibitor- or protease inhibitor-containing antiretroviral regimen.

We compared immune restoration in patients who suppressed human immunodeficiency virus type 1 replication after treatment with a protease inhibitor (PI) plus nevirapine or with 3 nucleoside reverse-transcriptase inhibitors (NRTIs) plus nevirapine. Changes in total and memory CD4 and CD8 cells were similar in the groups, as were decreases in immune activation (e.g., CD38 and HLA-DR) and increases in CD28 expression. Increases in naive CD4 and CD8 cells tended to be greater in the NRTI-treated group, with differences in naive CD4 cells significant at weeks 8 and 12 (P<.05) but not at week 48. Lymphocyte apoptosis decreased in both groups, but the week-1 decrease was greater in the PI-treated group (P<.02). Lymphocyte proliferation and skin-test responses were comparable. We find little evidence for differences in the major direct immunologic effect of PI versus NRTI regimens and propose that effects observed elsewhere were indirect, mediated through antiviral activity or adaptation of the virus to selection pressure.

Adult↗

PubMed2003

Can immune markers predict subsequent discordance between immunologic and virologic responses to antiretroviral therapy? Adult AIDS Clinical Trials Group.

It is unclear why discordant immunologic and virologic responses occur during therapy for human immunodeficiency virus (HIV) infection. This study examined whether markers of immune activation and naive/memory lymphocyte subsets at study baseline could predict discordance between HIV type 1 (HIV-1) RNA and CD4+ lymphocyte responses at week 24 of antiretroviral therapy. Ten diverse, prospective antiretroviral studies with 1007 evaluable subjects were included. Subsets of subjects at increased risk for discordance were identified by recursive partitioning. The strongest predictor of more-favorable immunologic than virologic responses was a lower baseline CD4+ lymphocyte count. Weaker predictors in small subsets of subjects were fewer activated CD4+ lymphocytes and fewer CD8+ lymphocytes. Conversely, the strongest predictors of more-favorable virologic than immunologic responses were higher baseline CD4+ lymphocyte count and percentage. Additional predictors in some analyses were higher CD8+ lymphocyte count or percentage and lower HIV-1 RNA concentrations. Baseline markers of immune activation and naive/memory lymphocyte subsets had limited ability to predict subsequent discordance.

Acquired Immunodeficiency Syndrome↗

PubMed2003

Implications of anemia in human immunodeficiency virus, cancer, and hepatitis C virus.

Anemia is a multifactorial problem in patients with human immunodeficiency virus (HIV) infection, cancer, and hepatitis C virus (HCV) infection. New insights regarding anemia symptoms and quality of life (QOL) have prompted reassessment of traditional triggers for anemia treatment to increase hemoglobin (Hb) and improve QOL. In HIV-positive patients, anemia is independently associated with disease progression and survival. Many HIV-positive patients receiving highly active antiretroviral therapy (HAART) still develop mild to moderate anemia and associated QOL impairment. Epoetin alfa effectively increases Hb and improves QOL in these patients. Many HIV-positive patients are coinfected with HCV. Standard HCV therapy (interferon alfa/ribavirin) can cause anemia that may result in treatment alterations and compromised virologic outcome. Epoetin alfa therapy in anemic HCV patients increases Hb levels and may provide other benefits. Neuroprotective effects of epoetin alfa in preclinical models of central nervous system disorders have recently been demonstrated, implying a new therapeutic role for this cytokine.

Anemia↗

PubMed2002

Effect of etanercept (Enbrel) on interleukin 6, tumor necrosis factor alpha, and markers of immune activation in HIV-infected subjects receiving interleukin 2.

The effect of etanercept, a soluble p75 tumor necrosis factor (TNF) receptor:Fc fusion protein (Enbrel; Immunex, Seattle, WA) on plasma cytokines was evaluated in 11 HIV-infected subjects receiving highly active antiretroviral therapy (HAART) for 28 weeks with or without subcutaneous or intravenous recombinant human interleukin 2 (rhIL-2). Plasma IL-6 and C-reactive protein (CRP) levels increased after rhIL-2 treatment. Etanercept pretreatment attenuated these increases. Median plasma IL-6 levels were 20.29 pg/ml 4 days after rhIL-2 and 7.87 pg/ml 4 days after etanercept and rhIL-2 (p = 0.22); median CRP levels were 78.73 and 46.16 microg/ml, respectively (p = 0.03). An effect on TNF bioactivity could not be assessed as all measurements were below limits of detection. No significant changes were seen in temperature or plasma levels of IL-4, IL-10, IL-12, interferon gamma, or HIV-1 RNA levels. All subjects had undetectable or low-level HIV-1 RNA levels before etanercept dosing. One subject died; however, her death was thought to be unrelated to etanercept. Pretreatment with etanercept may blunt activation of IL-6 and CRP expression induced by rhIL-2. The safety and utility of etanercept in HIV-infected persons should be explored further.

Antiretroviral Therapy, Highly Active↗

PubMed2002

Pharmacokinetic interaction between nevirapine and ethinyl estradiol/norethindrone when administered concurrently to HIV-infected women.

OBJECTIVE: To determine the effects of nevirapine (NVP), a nonnucleoside reverse-transcriptase inhibitor of HIV-1 and P450 inducer, on the pharmacokinetics (PK) of ethinyl estradiol (EE)/norethindrone (NET), a widely used oral contraceptive, and to assess the effects of EE/NET on the steady-state PK of NVP. METHODS: Ten HIV-1-infected women underwent intensive PK sampling after single-dose administration of EE/NET (days 0-1). Oral NVP 200 mg once daily (days 2-15), followed by 200 mg twice daily (days 16-29), was added to background potent antiretroviral therapy. On day 30, intensive PK sampling was performed after concurrent administration of NVP 200 mg and a single dose of EE/NET. RESULTS: Concomitant administration of NVP at steady state with EE/NET resulted in a significant (29%) median reduction in the area under the plasma concentration time curve (AUC(infinity)) and a significant reduction in mean residence time (MRT) and half-life (t(1/2)) of EE. There was a significant (18%) median reduction in the AUC(infinity) for NET that was not associated with a detectable change in NET C(max), MRT, or t(1/2). CONCLUSION: Oral contraceptives should not be the primary method of birth control in women of child-bearing potential who are treated with NVP.

Adult↗