Extended high viremics: a substantial fraction of individuals maintain high plasma viral RNA levels after acute HIV-1 subtype C infection

Abstract

Objective: The present study addressed two questions: what fraction of individuals maintain a sustained high HIV-1 RNA load after the acute HIV-1C infection peak and how long is a high HIV-1 RNA load maintained after acute HIV-1C infection in this subpopulation?

Design/methods: Plasma HIV-1 RNA dynamics were studied in 77 participants with primary HIV-1C infection from African cohorts in Gaborone, Botswana, and Durban, South Africa. HIV-infected individuals who maintained mean viral load of at least 100,000 (5.0 log(10)) copies/ml after 100 days postseroconversion (p/s) were termed extended high viremics. Individuals were followed longitudinally for a median [interquartile range (IQR)] of 573 (226-986) days p/s.

Results: The proportion of extended high viremics was 34% [95% confidence interval (CI) 23-44%] during the period 100-300 days p/s and 19% (95% CI 9-29%) over the period of 200-400 days p/s. The median (IQR) duration of HIV-1 RNA load at least 100,000 copies/ml among extended high viremics was 271 (188-340) days p/s. For the subset with average viral load at least 100,000 copies/ml during 200-400 days p/s, the median (IQR) duration was 318 (282-459) days. The extended high viremics had a significantly shorter time to CD4 cell decline to 350 cells/μl (median: 88 vs. 691 days p/s for those not designated as extended high viremics; P < 0.0001, Gehan-Wilcoxon test).

Conclusion: A high proportion of extended high viremics - individuals maintaining high plasma HIV-1 RNA load after acute infection - have been identified during primary HIV-1 subtype C infection. These extended high viremics likely contribute disproportionately to HIV-1 incidence.

Figure 1

Dynamics of HIV-1 RNA load in primary HIV-1 subtype C infection, n=75, pre-HAART data. Time from estimated seroconversion is shown on the x axis. HIV-1 RNA load is shown on the y axis, and the 100,000 (5.0 log₁₀) copies/ml level highlighted by the dashed line. Individuals with mean HIV-1 RNA load ≥ 100,000 (5.0 log₁₀) copies/ml during the period 100–300 days p/s (shaded by gray) were termed Extended High Viremics. The HIV-1 RNA measurements of Extended High Viremics are denoted by shaded circles. The HIV-1 RNA measurements of others are denoted by open circles. Viral load dynamics in primary HIV-1 subtype C infection are indicated by the overall mean HIV-1 RNA load (solid curve) with 95% confidence intervals (dashed curves).

Figure 2

Distribution of HIV-1 RNA load in primary HIV-1 subtype C infection during time interval 100–300 days p/s.

Figure 3

Individual curves of HIV-1 RNA load during the period 0–400 days p/s in primary HIV-1 subtype C infection. Curves representing Extended High Viremics are denoted by black lines. Curves from others are shown by gray lines. Two time intervals, 100–300 days p/s and 200–400 days p/s, are denoted by dashed gray lines.

Figure 4

Kaplan-Meier survival analysis of time to CD4 decline below 250 and 350 cell counts in two groups, Extended High Viremics (mean VL_100–300 ≥ 5.0 log₁₀ copies/ml) vs. Others (mean VL_100–300 < 5.0 log₁₀ copies/ml). Data from both Durban and Botswana cohorts are presented. The significance was determined by the Gehan-Wilcoxon test. A: CD4 decline below 250 cell count. B: CD4 decline below 350 cell count.

Figure 5

Probability of high viral RNA load at the specified threshold during primary HIV-1 subtype C infection. Time from seroconversion (up to 800 days p/s) is shown on the x axis. Probability of HIV-infected individuals presenting with HIV-1 RNA load at or above specified threshold is denoted on the y axis. A: HIV-1 RNA threshold of 10,000 (4.0 log₁₀) copies/ml. B: HIV-1 RNA threshold of 50,000 (4.7 log₁₀) copies/ml. C: HIV-1 RNA threshold of 100,000 (5.0 log₁₀) copies/ml.