scholarly journals Pharmacokinetic Profiles of Nevirapine and Indinavir in Various Fractions of Seminal Plasma

2001 ◽  
Vol 45 (10) ◽  
pp. 2902-2907 ◽  
Author(s):  
Rieneke M. E. van Praag ◽  
Sjoerd Repping ◽  
Jan W. A. de Vries ◽  
Joep M. A. Lange ◽  
Richard M. W. Hoetelmans ◽  
...  
Keyword(s):  
Seminal Plasma ◽  
Seminal Vesicles ◽  
Sexual Abstinence ◽  
Limited Data ◽  
Dosing Interval ◽  
Drug Ingestion ◽  
Drug Concentrations ◽  
Antiretroviral Drug ◽  
Immunodeficiency Virus

ABSTRACT Limited data are available on antiretroviral drug concentrations in seminal plasma during a dosing interval. Further, since human ejaculate is composed of fluids originating from the testes, the seminal vesicles, and the prostate, all having different physiological characteristics, drug concentrations in total seminal plasma do not necessarily reflect concentrations in the separate compartments. Five human immunodeficiency virus type 1-infected patients on nevirapine (NVP; 200 mg twice a day [b.i.d.]) and/or indinavir (IDV; 800 mg b.i.d. with ritonavir, 100 mg b.i.d.) regimens used a split ejaculate technique to separate seminal plasma in two fractions, representing fluids from the testes and prostate (first fraction) and fluids from the seminal vesicles (second fraction). Split-ejaculate samples were provided at 0, 2, 5, and 8 h after drug ingestion, on separate days after 3 days of sexual abstinence. NVP and IDV showed time-dependent concentrations in seminal plasma, with peak concentrations in both fractions at 2 and 2 to 5 h, respectively, after drug ingestion. The NVP concentrations were not significantly different between the first and second fractions of the ejaculate at all time points measured and were in the therapeutic range, except for the predose concentration in two patients. The median (range) predose IDV concentrations in the first and second fractions of the ejaculate were 448 (353 to 1,015) ng/ml and 527 (240 to 849) ng/ml, respectively (P = 0.7). In conclusion, NVP and IDV concentrations in seminal plasma are dependent on the time after drug ingestion. Furthermore, our data suggest that NVP and IDV achieve therapeutic concentrations in both the testes and prostate and the seminal vesicles throughout the dosing interval.

scholarly journals Effects of Formulation and Dosing Strategy on Amprenavir Concentrations in the Seminal Plasma of Human Immunodeficiency Virus Type 1–Infected Men

2002 ◽  
Vol 35 (6) ◽  
pp. 760-762 ◽  
Author(s):  
Naumann I. Chaudry ◽  
Joseph J. Eron ◽  
Odin J. Naderer ◽  
Arlene S. Pereira ◽  
M. B. Wire ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Seminal Plasma ◽  
Immunodeficiency Virus ◽  
Dosing Strategy

scholarly journals Human Seminal Plasma Abrogates the Capture and Transmission of Human Immunodeficiency Virus Type 1 to CD4+ T Cells Mediated by DC-SIGN

2007 ◽  
Vol 81 (24) ◽  
pp. 13723-13734 ◽  
Author(s):  
Juan Sabatté ◽  
Ana Ceballos ◽  
Silvina Raiden ◽  
Mónica Vermeulen ◽  
Karen Nahmod ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Seminal Plasma ◽  
Intercellular Adhesion Molecule ◽  
Target Cells ◽  
Human Seminal Plasma ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) is expressed by dendritic cells (DCs) at mucosal surfaces and appears to play an important role in the dissemination of human immunodeficiency virus type 1 (HIV-1) infection. DC-SIGN binds HIV-1 gp120 and efficiently transmits the virus to T CD4+ cells, which become the center of viral replication. Semen represents the main vector for HIV-1 dissemination worldwide. In the present study we show that human seminal plasma (SP), even when used at very high dilutions (1:104 to 1:105), markedly inhibits the capture and transmission of HIV-1 to T CD4+ cells mediated by both DCs and B-THP-1-DC-SIGN cells. In contrast, SP does not inhibit the capture of HIV-1 by DC-SIGN-negative target cells, such as the T-cell line SupT-1, monocytes, and activated peripheral blood mononuclear cells. The SP inhibitor has a high molecular mass (>100 kDa) and directly interacts with DC-SIGN-positive target cells but not with HIV-1. Moreover, the inhibitor binds to concanavalin A, suggesting that it contains high-mannose N-linked carbohydrates. Of note, using biotin-labeled SP we found that the binding of SP components to DCs was abrogated by mannan, while their interaction with B-THP-1 cells was almost completely dependent on the expression of DC-SIGN. Since epithelium integrity is often compromised after vaginal or anal intercourse, as well as in the presence of ulcerative-sexually transmitted diseases, our results support the notion that components of the SP might be able to access to the subepithelium, inhibiting the recognition of HIV-1 gp120 by DC-SIGN-positive DCs.

scholarly journals High Concentrations of Nelfinavir as an Independent Risk Factor for Lipodystrophy in Human Immunodeficiency Virus-Infected Patients

2002 ◽  
Vol 46 (12) ◽  
pp. 4009-4012 ◽  
Author(s):  
Jean-Marc Tréluyer ◽  
Jean-Pierre Morini ◽  
Jérome Dimet ◽  
Isabelle Gorin ◽  
Elisabeth Rey ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Risk Factor ◽  
Independent Risk Factor ◽  
Drug Exposure ◽  
Self Report ◽  
Antiretroviral Drug ◽  
Immunodeficiency Virus ◽  
Trough Concentrations ◽  
High Concentrations

ABSTRACT To assess the relationship between antiretroviral drug exposure and lipodystrophy, 69 human immunodeficiency virus type 1-infected patients receiving nelfinavir were investigated cross-sectionally. Lipodystrophy was defined by patients' self-report. Nelfinavir trough concentrations in plasma were significantly related to overall lipodystrophy and peripheral fat wasting scores and appeared to be an independent risk factor for lipodystrophy

scholarly journals Dynamics of Human Immunodeficiency Virus Type 1 Replication in Vertically Infected Infants

1999 ◽  
Vol 73 (1) ◽  
pp. 362-367 ◽  
Author(s):  
Katherine Luzuriaga ◽  
Hulin Wu ◽  
Margaret McManus ◽  
Paula Britto ◽  
William Borkowsky ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Drug Regimen ◽  
Turnover Rates ◽  
Antiretroviral Drug ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Plasma human immunodeficiency virus type 1 (HIV-1) turnover and kinetics were studied in children aged 15 days to 2 years following the initiation of a triple antiretroviral drug regimen consisting of zidovudine, lamivudine, and nevirapine. HIV-1 turnover was at least as rapid as that previously described in adults; turnover rates were more rapid in infants and children aged 3 months to 2 years than in infants less than 3 months of age. These data confirm the central role of HIV-1 replication in the pathogenesis of vertical HIV-1 infection and reinforce the importance of early, potent combination therapies for the long-term control of HIV-1 replication.

scholarly journals In Vitro Antiviral Interaction of Lopinavir with Other Protease Inhibitors

2002 ◽  
Vol 46 (7) ◽  
pp. 2249-2253 ◽  
Author(s):  
Akhteruzzaman Molla ◽  
Hongmei Mo ◽  
Sudthida Vasavanonda ◽  
Lixin Han ◽  
C. Thomas Lin ◽  
...  
Keyword(s):  
Protease Inhibitors ◽  
Drug Combination ◽  
Wild Type ◽  
Synergistic Inhibition ◽  
Drug Concentrations ◽  
Immunodeficiency Virus ◽  
Hiv Type 1

ABSTRACT The in vitro inhibition of wild-type human immunodeficiency virus (HIV) by combinations of lopinavir and six other protease inhibitors over a range of two-drug combination ratios was evaluated. Combinations of lopinavir with indinavir, nelfinavir, amprenavir, tipranavir, and BMS-232632 generally displayed an additive relationship. In contrast, a consistent, statistically significant synergistic inhibition of HIV type 1 replication with combinations of lopinavir and saquinavir was observed. Analysis of the combination indices indicated that lopinavir with saquinavir was synergistic over the entire range of drug combination ratios tested and at all levels of inhibition in excess of 40%. Cellular toxicity was not observed at the highest drug concentrations tested. These results suggest that administration of combinations of the appropriate dose of lopinavir with other protease inhibitors in vivo may result in enhanced antiviral activity with no associated increase in cellular cytotoxicity. More importantly, the observed in vitro synergy between lopinavir and saquinavir provides a theoretical basis for the clinical exploration of a novel regimen of lopinavir-ritonavir and saquinavir.

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