Prevention of SIV Infection in Macaques by ( R )-9-(2-Phosphonylmethoxypropyl)adenine

Abstract

The efficacy of pre- and postexposure treatment with the antiviral compound (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) was tested against simian immunodeficiency virus (SIV) in macaques as a model for human immunodeficiency virus (HIV). PMPA was administered subcutaneously once daily beginning either 48 hours before, 4 hours after, or 24 hours after virus inoculation. Treatment continued for 4 weeks and the virologic, immunologic, and clinical status of the macaques was monitored for up to 56 weeks. PMPA prevented SIV infection in all macaques without toxicity, whereas all control macaques became infected. These results suggest a potential role for PMPA prophylaxis against early HIV infection in cases of known exposure.

Enantiomeric radiochemical synthesis of R and S (1‐(6‐amino‐9H‐purin‐9‐yl)‐3‐fluoropropan‐2‐yloxy)methylphosphonic acid (FPMPA)

“…Our assay of R-PMPA inhibition of SIVmac239 provided an IC 50 of 2.32 μM (95% CI; 1.51-3.34] that was consistent with previously reported data 24 (Figure 7 (a)). Two separate assays with (RS)-FPMPA provided viral growth IC 50 s of 4.85 μM (95% CI; 3.8-6.67) and 6.66 μM (95% CI; 5.1-8.9) (Figure 7(b)), which were not statistically significantly different.…”

Knowledge, attitude and practice towards HIV post-exposure prophylaxis of health professionals of Gimbi town in Ethiopia: a cross-sectional study

“…[2][3][4][5] This is evidenced by data obtained from animal's studies 6,7 and a case control study of post exposure prophylaxis following needle stick injury in health care settings. 8 According to the centers for diseases control and prevention (CDC), individuals who took zidovudine monotherapy following occupational exposure were less likely to acquire HIV as compared to those who did not take medication.…”

Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4+ T cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV): Implications for HIV-1 infections of humans

“…Some potent RT inhibitors, whether administered alone or in combination with other antiretroviral agents, effectively reduce virus loads in vivo to undetectable levels. One of these inhibitors, PMPA, lowers SIV RNA levels by Ͼ97% in chronically infected animals and can even prevent the establishment of viral infections in macaque monkeys if given shortly after virus inoculation (19)(20)(21). To ascertain whether this drug could control the early T cell and͞or the late macrophage phases of SHIV DH12R infections in vivo, PMPA was administered intramuscularly (30 mg per kg) for 28 days to two animals, starting on day 5 or 21 postinfection.…”