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Cytomegalovirus viral load kinetics in patients with HIV/AIDS admitted to a medical intensive care unit: a case for pre-emptive therapy.

Mayaphi SH, Brauer M, Morobadi DM, Mazanderani AH, Mafuyeka RT, Olorunju SA, Tintinger GR, Stoltz A - PLoS ONE (2014)

Bottom Line: Patients who had VLs >1,000 copies/ml at baseline testing had significantly higher mortality compared to those who had <1,000 copies/ml {hazard ratio of 3.46, p = 0.003 [95% confidence interval (CI): 1.55-7.71]}.Analysis of the highest CMV VL per patient showed that patients who had VLs of >5,100 copies/ml and did not receive ganciclovir had 100% mortality compared to 58% mortality in those who received ganciclovir at VLs of >5,100 copies/ml, 50% mortality in those who were not treated and had low VLs of <5,100 copies/ml, and 44% mortality in those who had ganciclovir treatment at VLs of <5,100 copies/ml (p = 0.084, 0.046, 0.037, respectively).This study showed a significantly increased mortality in patients with HIV/AIDS who had high CMV VLs, and suggests that a threshold value of 1,000 copies/ml may be appropriate for pre-emptive treatment in this group.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Virology, University of Pretoria/National Health Laboratory Service - Tshwane Academic Division (NHLS-TAD), Pretoria, South Africa.

ABSTRACT

Background: Cytomegalovirus (CMV) infection is associated with severe diseases in immunosuppressed patients; however, there is a lack of data for pre-emptive therapy in patients with HIV/AIDS.

Method: This was a retrospective study, which enrolled patients diagnosed with HIV/AIDS (CD4<200 cells/μl), who had detectable CMV viral load (VL) during their stay in an adult medical intensive care unit between 2009-2012.

Results: After screening 82 patients' records, 41 patients met the enrolment criteria. Their median age was 37 (interquartile range [IQR]: 31-46), and median CD4 count was 29 cells/μl (IQR: 5-55). Sixteen patients (39%) had serial measurements of CMV VL before treatment with ganciclovir. Patients whose baseline CMV VL values were between 1,000-3,000 copies/ml had significantly higher values (median of 14,650 copies/ml) on follow-up testing done 4-12 days later. Those with undetectable VLs at baseline testing had detectable VLs (median of 1,590 copies/ml) mostly within 20 days of follow-up testing. Patients who had VLs >1,000 copies/ml at baseline testing had significantly higher mortality compared to those who had <1,000 copies/ml {hazard ratio of 3.46, p = 0.003 [95% confidence interval (CI): 1.55-7.71]}. Analysis of the highest CMV VL per patient showed that patients who had VLs of >5,100 copies/ml and did not receive ganciclovir had 100% mortality compared to 58% mortality in those who received ganciclovir at VLs of >5,100 copies/ml, 50% mortality in those who were not treated and had low VLs of <5,100 copies/ml, and 44% mortality in those who had ganciclovir treatment at VLs of <5,100 copies/ml (p = 0.084, 0.046, 0.037, respectively).

Conclusion: This study showed a significantly increased mortality in patients with HIV/AIDS who had high CMV VLs, and suggests that a threshold value of 1,000 copies/ml may be appropriate for pre-emptive treatment in this group.

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Kaplan-Meier curve analysis showing survival probalities between the groups of patients: (A) who had CMV viral loads <1000 copies/ml compared to those who had viral loads >1000 copies/ml at baseline testing, (B) who had CMV viral loads <5000 copies/ml compared to those who had viral loads >5000 copies/ml at baseline testing, (C) who had CMV viral loads <10000 copies/ml compared to those who had viral loads >10000 copies/ml at baseline testing. HR = hazard ratio, CI = confidence interval.
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pone-0093702-g002: Kaplan-Meier curve analysis showing survival probalities between the groups of patients: (A) who had CMV viral loads <1000 copies/ml compared to those who had viral loads >1000 copies/ml at baseline testing, (B) who had CMV viral loads <5000 copies/ml compared to those who had viral loads >5000 copies/ml at baseline testing, (C) who had CMV viral loads <10000 copies/ml compared to those who had viral loads >10000 copies/ml at baseline testing. HR = hazard ratio, CI = confidence interval.

Mentions: A large proportion of patients (71%, n = 29) had detectable viral loads at baseline testing with a median CMV VL of 3430 copies/ml (IQR:1380–16450), while others had undetectable viral loads. The latter eventually had detectable viral loads on subsequent testing. Sixteen patients (39%) had serial measurements of CMV VL before treatment with ganciclovir. Patients whose baseline CMV VL values were between 1000–3000 copies/ml had significantly higher values (median of 14650 copies/ml) on follow up testing done 4–12 days later (Table 1). Those with undetectable VLs at baseline testing had detectable VLs (median of 1590 copies/ml) mostly within 20 days of follow up testing (Table 2). Patients (n = 24) who had CMV VLs >1000 copies/ml at baseline testing had significantly higher mortality compared to those (n = 17) who had CMV VLs <1000 copies/ml (hazard ratio of 3.46, p = 0.003 [95% CI: 1.55–7.71]) (Fig. 2). The trend with higher mortality was also noticed when patients were stratified by a CMV VL of 5000 copies/ml at baseline testing, and no statistical significance noted with a CMV VL of 10000 copies/ml threshold (Fig. 2).


Cytomegalovirus viral load kinetics in patients with HIV/AIDS admitted to a medical intensive care unit: a case for pre-emptive therapy.

Mayaphi SH, Brauer M, Morobadi DM, Mazanderani AH, Mafuyeka RT, Olorunju SA, Tintinger GR, Stoltz A - PLoS ONE (2014)

Kaplan-Meier curve analysis showing survival probalities between the groups of patients: (A) who had CMV viral loads <1000 copies/ml compared to those who had viral loads >1000 copies/ml at baseline testing, (B) who had CMV viral loads <5000 copies/ml compared to those who had viral loads >5000 copies/ml at baseline testing, (C) who had CMV viral loads <10000 copies/ml compared to those who had viral loads >10000 copies/ml at baseline testing. HR = hazard ratio, CI = confidence interval.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3974798&req=5

pone-0093702-g002: Kaplan-Meier curve analysis showing survival probalities between the groups of patients: (A) who had CMV viral loads <1000 copies/ml compared to those who had viral loads >1000 copies/ml at baseline testing, (B) who had CMV viral loads <5000 copies/ml compared to those who had viral loads >5000 copies/ml at baseline testing, (C) who had CMV viral loads <10000 copies/ml compared to those who had viral loads >10000 copies/ml at baseline testing. HR = hazard ratio, CI = confidence interval.
Mentions: A large proportion of patients (71%, n = 29) had detectable viral loads at baseline testing with a median CMV VL of 3430 copies/ml (IQR:1380–16450), while others had undetectable viral loads. The latter eventually had detectable viral loads on subsequent testing. Sixteen patients (39%) had serial measurements of CMV VL before treatment with ganciclovir. Patients whose baseline CMV VL values were between 1000–3000 copies/ml had significantly higher values (median of 14650 copies/ml) on follow up testing done 4–12 days later (Table 1). Those with undetectable VLs at baseline testing had detectable VLs (median of 1590 copies/ml) mostly within 20 days of follow up testing (Table 2). Patients (n = 24) who had CMV VLs >1000 copies/ml at baseline testing had significantly higher mortality compared to those (n = 17) who had CMV VLs <1000 copies/ml (hazard ratio of 3.46, p = 0.003 [95% CI: 1.55–7.71]) (Fig. 2). The trend with higher mortality was also noticed when patients were stratified by a CMV VL of 5000 copies/ml at baseline testing, and no statistical significance noted with a CMV VL of 10000 copies/ml threshold (Fig. 2).

Bottom Line: Patients who had VLs >1,000 copies/ml at baseline testing had significantly higher mortality compared to those who had <1,000 copies/ml {hazard ratio of 3.46, p = 0.003 [95% confidence interval (CI): 1.55-7.71]}.Analysis of the highest CMV VL per patient showed that patients who had VLs of >5,100 copies/ml and did not receive ganciclovir had 100% mortality compared to 58% mortality in those who received ganciclovir at VLs of >5,100 copies/ml, 50% mortality in those who were not treated and had low VLs of <5,100 copies/ml, and 44% mortality in those who had ganciclovir treatment at VLs of <5,100 copies/ml (p = 0.084, 0.046, 0.037, respectively).This study showed a significantly increased mortality in patients with HIV/AIDS who had high CMV VLs, and suggests that a threshold value of 1,000 copies/ml may be appropriate for pre-emptive treatment in this group.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Virology, University of Pretoria/National Health Laboratory Service - Tshwane Academic Division (NHLS-TAD), Pretoria, South Africa.

ABSTRACT

Background: Cytomegalovirus (CMV) infection is associated with severe diseases in immunosuppressed patients; however, there is a lack of data for pre-emptive therapy in patients with HIV/AIDS.

Method: This was a retrospective study, which enrolled patients diagnosed with HIV/AIDS (CD4<200 cells/μl), who had detectable CMV viral load (VL) during their stay in an adult medical intensive care unit between 2009-2012.

Results: After screening 82 patients' records, 41 patients met the enrolment criteria. Their median age was 37 (interquartile range [IQR]: 31-46), and median CD4 count was 29 cells/μl (IQR: 5-55). Sixteen patients (39%) had serial measurements of CMV VL before treatment with ganciclovir. Patients whose baseline CMV VL values were between 1,000-3,000 copies/ml had significantly higher values (median of 14,650 copies/ml) on follow-up testing done 4-12 days later. Those with undetectable VLs at baseline testing had detectable VLs (median of 1,590 copies/ml) mostly within 20 days of follow-up testing. Patients who had VLs >1,000 copies/ml at baseline testing had significantly higher mortality compared to those who had <1,000 copies/ml {hazard ratio of 3.46, p = 0.003 [95% confidence interval (CI): 1.55-7.71]}. Analysis of the highest CMV VL per patient showed that patients who had VLs of >5,100 copies/ml and did not receive ganciclovir had 100% mortality compared to 58% mortality in those who received ganciclovir at VLs of >5,100 copies/ml, 50% mortality in those who were not treated and had low VLs of <5,100 copies/ml, and 44% mortality in those who had ganciclovir treatment at VLs of <5,100 copies/ml (p = 0.084, 0.046, 0.037, respectively).

Conclusion: This study showed a significantly increased mortality in patients with HIV/AIDS who had high CMV VLs, and suggests that a threshold value of 1,000 copies/ml may be appropriate for pre-emptive treatment in this group.

Show MeSH
Related in: MedlinePlus