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

Harvard School of Public Health, Boston, Massachusetts 02115, USA.
AIDS (London, England) (Impact Factor: 6.56). 04/2011; 25(12):1515-22. DOI: 10.1097/QAD.0b013e3283471eb2
Source: PubMed

ABSTRACT 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?
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.
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).
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.

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    • "Different circulating virus sub-types are another potential biological cofactor. HIV-1 subtype C is found predominantly in areas of high HIV prevalence in SSA and appears to be linked to extended high viremia (Kaul et al., 2011; Novitsky et al., 2011). Other potential biological cofactors include STIs such as herpes simplex virus type 2 (Abu-Raddad et al., 2008; Korenromp et al., 2001), tropical co-infections increasing HIV viral load (Abu-Raddad et al., 2006, 2013), hormonal contraception (Heffron et al., 2012), and host genetics and immunology (Kaul et al., 2011). "
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    • "Rather, we hypothesize that a combination of sexual mixing in a high-prevalence setting, structural factors that put young people at increased risk of exposure and unique biological factors, such as the predominance of clade C HIV [8] [9], is driving the epidemic in sub- Saharan Africa over and above individual sexual behaviors. Kenyon et al assert that we dismiss the role of behavior, in particular concurrency, and also race in explaining differences in the epidemics observed in South Africa and the United States. "
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    • "Concurrency particularly enhances population spread of HIV because of the virus's long duration of infectiousness (Garnett & Johnson, 1997), and it increases the opportunities for transmission during acute HIV infection when the transmission probability is greatest (Pilcher et al., 2004; Pinkerton, 2008). Although acute infection is time limited, there is some evidence that a subset of HIV-1 subtype C-infected individuals maintains high plasma HIV-1 levels for an extended period of time (Novitsky et al., 2011). The estimates from several mathematical modeling studies suggest that from 9% to 50% of HIV transmissions in a sub-Saharan African setting were attributable to sexual contact with individuals with early infection (Abu-Raddad & Longini, 2008; Cohen & Pilcher, 2005; Hayes & White, 2006; Hollingsworth, Anderson, & Fraser, 2008; Powers et al., 2011). "
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