The natural viral load profile of patients with pandemic 2009 influenza A(H1N1) and the effect of oseltamivir treatment

Abstract

Background: The natural history of viral shedding from the upper respiratory tract of the new pandemic 2009 influenza A(H1N1) and the effect of oseltamivir treatment were uncertain.

Methods: A retrospective cohort study involving 145 consecutive patients with specimens positive by reverse transcriptase-polymerase chain reaction for the matrix and new H1 genes was conducted.

Results: The nontreated and oseltamivir-treated patients were comparable in their viral load at presentation, demography, and the presenting symptoms. No correlation was observed between viral load with age and number of symptoms. Viral load of nasopharyngeal aspirate (NPA) was significantly lower in treated than in nontreated patients at day 5 after symptom onset. When oseltamivir was initiated </= 2 days after symptom onset, a greater rate of viral load reduction in NPA of treated patients than that of nontreated patients was observed (-0.638 [95% CI, -0.809 to -0.466] vs -0.409 [95% CI, -0.663 to -0.185] log(10) copies/mL/d post-symptom onset), and the viral load was undetectable at day 6 after oseltamivir initiation, which was 1 day earlier than that of those whose treatment was initiated > 2 days of symptom onset. The viral load was inversely correlated with concomitant absolute lymphocyte count in nontreated patients (Pearson correlation coefficient [r] = -0.687, P = .001) and treated patients (Pearson r = -0.365, P < .001). Resolution of fever was 1.4 days later in nontreated than treated patients (P = .012)

Conclusions: The natural viral load profile was described. Oral oseltamivir suppresses viral load more effectively when given early in mild cases of pandemic 2009 influenza A(H1N1) infections.

Figure 1

(A) The mean ± SD viral load (log₁₀ copies/mL) profile in different respiratory specimens of pandemic A(H1N1)-infected patients not treated with oseltamivir at different intervals (days) post symptom onset. The detection limit of the quantitative RT-PCR was 2.95 log₁₀ copies/mL. (B) The mean ± SD viral load (log₁₀ copies/mL) profile in different respiratory specimens of pandemic A(H1N1)-infected patients treated with oseltamivir at different intervals (days) post symptom onset. The detection limit of the quantitative RT-PCR was 2.95 log₁₀ copies/mL. NPA= nasopharyngeal aspirate; NPS= nasopharyngeal swab; NTS= naso-throat swab; pandemic A(H1N1)= pandemic 2009 influenza A(H1N1); RT-PCR= reverse transcriptase-polymerase chain reaction.

Figure 2

The mean ± SD viral load (log₁₀ copies/mL) profile in different respiratory specimens of pandemic A(H1N1)-infected patients at different days post oseltamivir initiation. The detection limit of the quantitative RT-PCR was 2.95 log₁₀ copies/mL. See Figure 1 legend for expansion of abbreviations.

Figure 3

(A) The mean ± SD viral load (log₁₀ copies/mL) profile in NPA at different days post symptom onset in pandemic A(H1N1)-infected patients not treated and treated with oseltamivir. The detection limit of the quantitative RT-PCR was 2.95 log₁₀ copies/mL. (B) The percentage of pandemic A(H1N1)-infected patients with detectable virus in respiratory specimens at different days post oseltamivir initiation in those with oseltamivir initiated ≤ 2 and > 2 days post symptom onset. See Figure 1 legend for expansion of abbreviations.

Figure 4

The mean ± SD viral load (log₁₀ copies/mL) profile of NPA at different intervals (days) post symptom onset in pandemic A(H1N1)-infected patients not treated and treated with oseltamivir ≤ 2 and > 2 days of symptom onset. The detection limit of the quantitative RT-PCR was 2.95 log10 copies/mL. See Figure 1 legend for expansion of abbreviations.