Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1998 May;72(5):4265-73.
doi: 10.1128/JVI.72.5.4265-4273.1998.

Effectiveness of postinoculation (R)-9-(2-phosphonylmethoxypropyl) adenine treatment for prevention of persistent simian immunodeficiency virus SIVmne infection depends critically on timing of initiation and duration of treatment

C C Tsai  1 , P Emau, K E Follis, T W Beck, R E Benveniste, N Bischofberger, J D Lifson, W R Morton
Affiliations

Effectiveness of postinoculation (R)-9-(2-phosphonylmethoxypropyl) adenine treatment for prevention of persistent simian immunodeficiency virus SIVmne infection depends critically on timing of initiation and duration of treatment

C C Tsai et al. J Virol. 1998 May.

Abstract

(R)-9-(2-Phosphonylmethoxypropyl)adenine (PMPA), an acyclic nucleoside phosphonate analog, is one of a new class of potent antiretroviral agents. Previously, we showed that PMPA treatment for 28 days prevented establishment of persistent simian immunodeficiency virus (SIV) infection in macaques even when therapy was initiated 24 h after intravenous virus inoculation. In the present study, we tested regimens involving different intervals between intravenous inoculation with SIV and initiation of PMPA treatment, as well as different durations of treatment, for the ability to prevent establishment of persistent infection. Twenty-four cynomolgus macaques (Macaca fascicularis) were studied for 46 weeks after inoculation with SIV. All mock-treated control macaques showed evidence of productive infection within 2 weeks postinoculation (p.i.). All macaques that were treated with PMPA for 28 days beginning 24 h p.i. showed no evidence of viral replication following discontinuation of PMPA treatment. However, extending the time to initiation of treatment from 24 to 48 or 72 h p.i. or decreasing the duration of treatment reduced effectiveness in preventing establishment of persistent infection. Only half of the macaques treated for 10 days, and none of those treated for 3 days, were completely protected when treatment was initiated at 24 h. Despite the reduced efficacy of delayed and shortened treatment, all PMPA-treated macaques that were not protected showed delays in the onset of cell-associated and plasma viremia and antibody responses compared with mock controls. These results clearly show that both the time between virus exposure and initiation of PMPA treatment as well as the duration of treatment are crucial factors for prevention of acute SIV infection in the macaque model.

PubMed Disclaimer

Figures

FIG. 1
FIG. 1
Plasma viral load levels in mock-treated and PMPA-treated macaques after intravenous inoculation with uncloned SIVmne. SIV RNA levels in plasma were measured by a sensitive quantitative competitive RT-PCR assay as described in the text. Threshold sensitivity for the assay was 300 copy eq/ml of plasma.
FIG. 2
FIG. 2
Frequencies of infectious cells in PBMC from macaques. The frequency of infectious cells was measured by cocultivation of serial dilutions of PBMC with target cells for detection of viral replication as described in the text.
FIG. 3
FIG. 3
Anti-SIV IgG antibody response in mock-treated and PMPA-treated macaques after intravenous inoculation with uncloned SIVmne. Titers were expressed as the reciprocal of the highest dilution that yielded positive immunofluorescent staining. The lowest titer of SIV-positive antibody in this assay was 1:40.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Balzarini J, Zhang H, Herdewijn P, Johns D G, De Clercq E. Intracellular metabolism and mechanism of anti-retrovirus action of 9-(2-phosphonylmethoxyethyl)adenine, a potent anti-human immunodeficiency virus compound. Proc Natl Acad Sci USA. 1991;88:1499–1503. - PMC - PubMed
    1. Balzarini J, Holy A, Jindrich J, Naesens L, Snoeck R, Schols D, DeClerq E. Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates: potent and selective in vitro and in vivo antiretrovirus activities of (R)-9-(-2-phosphonomethoxypropyl)-2,6-diaminopurine. Antimicrob Agents Chemother. 1993;37:332–338. - PMC - PubMed
    1. Benveniste R E, Arthur L O, Tsai C-C, Sowder R, Copeland T D, Henderson L E, Oroszlan S. Isolation of a lentivirus from a macaque with lymphoma: comparison to HTLV-III/LAV and other lentiviruses. J Virol. 1986;60:483–490. - PMC - PubMed
    1. Benveniste R E, Morton W R, Clark E A, Tsai C-C, Ochs H D, Ward J M, Kuller L, Knott W B, Hill R W, Gale M J, Thouless M E. Inoculation of baboons and macaques with simian immunodeficiency virus/mne, a primate lentivirus closely related to human immunodeficiency virus type 2. J Virol. 1988;62:2091–2101. - PMC - PubMed
    1. Bertolli J, St. Louis M E, Simonds R J, Nieburg P, Kamenga M, Brown C, Tarande M, Quinn T, Ou C Y. Estimating the timing of mother-to-child transmission of human immunodeficiency virus in a breast-feeding population in Kinshasa, Zaire. J Infect Dis. 1996;174:722–726. - PubMed

Publication types

MeSH terms

LinkOut - more resources