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Prophylactic and therapeutic effect of AZT/3TC in RT-SHIV infected Chinese-origin rhesus macaques.

Wang W, Yao N, Cong Z, Jiang H, Qin C, Wei Q - AIDS Res Ther (2014)

Bottom Line: The precise efficacy of nucleoside analogue reverse-transcriptase inhibitors (NRTIs) in preventing and inhibiting virus replication remains unknown in RT-SHIV infected Chinese-origin rhesus macaques (Ch RM).Treatment with AZT/3TC inhibited transiently RT-SHIV replication during chronic infection, but did not significantly affect peripheral blood CD4+ T cells in macaques.Therefore, the Ch RM model with RT-SHIV infection can be used to evaluate the efficacy of new NRTIs.

View Article: PubMed Central - HTML - PubMed

Affiliation: Comparative Medicine Center, Peking Union Medical College (PUMC), Beijing 100021, China. qinchuan@pumc.edu.cn.

ABSTRACT

Background: The precise efficacy of nucleoside analogue reverse-transcriptase inhibitors (NRTIs) in preventing and inhibiting virus replication remains unknown in RT-SHIV infected Chinese-origin rhesus macaques (Ch RM).

Findings: Ch RM were inoculated intravenously with 200 TCID50 RT-SHIV and treated by gavage with NRTIs (20 mg AZT and 10 mg 3TC twice per day) for four consecutive weeks beginning at one hour, on day 217 or 297 post inoculation, respectively. Treatment with AZT/3TC inhibited transiently RT-SHIV replication during chronic infection, but did not significantly affect peripheral blood CD4+ T cells in macaques. Treatment with AZT/3TC at 1 hour post infection prevented RT-SHIV infection in two out of four animals during the 120-day observation period.

Conclusions: Therefore, the Ch RM model with RT-SHIV infection can be used to evaluate the efficacy of new NRTIs.

No MeSH data available.


Related in: MedlinePlus

The levels of plasma viral loads and peripheral blood CD4+ T cells in individual control macaques. Data are expressed as the mean number of copies of viral RNA (red line) and peripheral blood CD4+ T cells (blue line) of individual macaques through the observation period. The areas of pockmarks show the time periods with AZT/3TC or water gavage.
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Figure 1: The levels of plasma viral loads and peripheral blood CD4+ T cells in individual control macaques. Data are expressed as the mean number of copies of viral RNA (red line) and peripheral blood CD4+ T cells (blue line) of individual macaques through the observation period. The areas of pockmarks show the time periods with AZT/3TC or water gavage.

Mentions: As expected, plasma RT-SHIV-specific RNA was detected in the control group of macaques and reached a peak of 0.69 ~ 6.30 × 106 copies per ml at 1 or 3 weeks post inoculation (Figure 1), consistent with a previous report that RT-SHIV effectively infects Ch RM[11]. Eight to 12 weeks after infection, RT-SHIV viremia reached a plateau and maintained a high level of 1.0 to 3.5 × 104 copies per ml in the control group of macaques throughout the observation period. Furthermore, treatment with a combination of AZT with 3TC starting on day 297 or 217 post-infection significantly reduced the levels of plasma viral loads in these macaques (G1102V, G1104V, G1112V and G1114V), and the levels of viremia in those experimental monkeys were lower than that of the detection threshold (virus RNA load <100 copies/mL) at most time points post drug treatment (Figure 2). These data indicated that treatment with both AZT and 3TC inhibited RT-SHIV replication in macaques. More importantly, treatment with both AZT and 3TC one hour after inoculation dramatically prevented and inhibited RT-SHIV replication in macaques. Evidentially, there was no detectable viremia and viral RNA in three macaques throughout the drug treatment period, and only moderate levels of viremia were detected in another macaque (G1105V) at the phase of drug treatment. One (G1116V) out of three treated monkeys had viral rebound after the end of drug treatment. Similar patterns of provirus DNA were detected in the PBMC of the different groups of monkeys (data not shown). Interestingly, the numbers of peripheral blood CD4+ T cells at the end of the observation period were similar to that at the baseline, except for one macaque (G1102V) that received AZT/3TC on day 297 post inoculation with nearly 65% reduced numbers of peripheral blood CD4+ T cells (Figures 2 and3). Furthermore, there were no obvious clinical symptoms in the infected animals, including G1102V, and these animals remained healthy during the experimental period. Therefore, treatment with a combination of AZT and 3TC prevented and inhibited RT-SHIV replication, but had little effect on the numbers of peripheral blood CD4+ T cells in macaques.


Prophylactic and therapeutic effect of AZT/3TC in RT-SHIV infected Chinese-origin rhesus macaques.

Wang W, Yao N, Cong Z, Jiang H, Qin C, Wei Q - AIDS Res Ther (2014)

The levels of plasma viral loads and peripheral blood CD4+ T cells in individual control macaques. Data are expressed as the mean number of copies of viral RNA (red line) and peripheral blood CD4+ T cells (blue line) of individual macaques through the observation period. The areas of pockmarks show the time periods with AZT/3TC or water gavage.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4016570&req=5

Figure 1: The levels of plasma viral loads and peripheral blood CD4+ T cells in individual control macaques. Data are expressed as the mean number of copies of viral RNA (red line) and peripheral blood CD4+ T cells (blue line) of individual macaques through the observation period. The areas of pockmarks show the time periods with AZT/3TC or water gavage.
Mentions: As expected, plasma RT-SHIV-specific RNA was detected in the control group of macaques and reached a peak of 0.69 ~ 6.30 × 106 copies per ml at 1 or 3 weeks post inoculation (Figure 1), consistent with a previous report that RT-SHIV effectively infects Ch RM[11]. Eight to 12 weeks after infection, RT-SHIV viremia reached a plateau and maintained a high level of 1.0 to 3.5 × 104 copies per ml in the control group of macaques throughout the observation period. Furthermore, treatment with a combination of AZT with 3TC starting on day 297 or 217 post-infection significantly reduced the levels of plasma viral loads in these macaques (G1102V, G1104V, G1112V and G1114V), and the levels of viremia in those experimental monkeys were lower than that of the detection threshold (virus RNA load <100 copies/mL) at most time points post drug treatment (Figure 2). These data indicated that treatment with both AZT and 3TC inhibited RT-SHIV replication in macaques. More importantly, treatment with both AZT and 3TC one hour after inoculation dramatically prevented and inhibited RT-SHIV replication in macaques. Evidentially, there was no detectable viremia and viral RNA in three macaques throughout the drug treatment period, and only moderate levels of viremia were detected in another macaque (G1105V) at the phase of drug treatment. One (G1116V) out of three treated monkeys had viral rebound after the end of drug treatment. Similar patterns of provirus DNA were detected in the PBMC of the different groups of monkeys (data not shown). Interestingly, the numbers of peripheral blood CD4+ T cells at the end of the observation period were similar to that at the baseline, except for one macaque (G1102V) that received AZT/3TC on day 297 post inoculation with nearly 65% reduced numbers of peripheral blood CD4+ T cells (Figures 2 and3). Furthermore, there were no obvious clinical symptoms in the infected animals, including G1102V, and these animals remained healthy during the experimental period. Therefore, treatment with a combination of AZT and 3TC prevented and inhibited RT-SHIV replication, but had little effect on the numbers of peripheral blood CD4+ T cells in macaques.

Bottom Line: The precise efficacy of nucleoside analogue reverse-transcriptase inhibitors (NRTIs) in preventing and inhibiting virus replication remains unknown in RT-SHIV infected Chinese-origin rhesus macaques (Ch RM).Treatment with AZT/3TC inhibited transiently RT-SHIV replication during chronic infection, but did not significantly affect peripheral blood CD4+ T cells in macaques.Therefore, the Ch RM model with RT-SHIV infection can be used to evaluate the efficacy of new NRTIs.

View Article: PubMed Central - HTML - PubMed

Affiliation: Comparative Medicine Center, Peking Union Medical College (PUMC), Beijing 100021, China. qinchuan@pumc.edu.cn.

ABSTRACT

Background: The precise efficacy of nucleoside analogue reverse-transcriptase inhibitors (NRTIs) in preventing and inhibiting virus replication remains unknown in RT-SHIV infected Chinese-origin rhesus macaques (Ch RM).

Findings: Ch RM were inoculated intravenously with 200 TCID50 RT-SHIV and treated by gavage with NRTIs (20 mg AZT and 10 mg 3TC twice per day) for four consecutive weeks beginning at one hour, on day 217 or 297 post inoculation, respectively. Treatment with AZT/3TC inhibited transiently RT-SHIV replication during chronic infection, but did not significantly affect peripheral blood CD4+ T cells in macaques. Treatment with AZT/3TC at 1 hour post infection prevented RT-SHIV infection in two out of four animals during the 120-day observation period.

Conclusions: Therefore, the Ch RM model with RT-SHIV infection can be used to evaluate the efficacy of new NRTIs.

No MeSH data available.


Related in: MedlinePlus