Differences in HIV Type 1 Neutralization Breadth in 2 Geographically Distinct Cohorts in Africa

Abstract

To investigate whether distinct populations have differing human immunodeficiency virus type 1 (HIV) neutralizing antibody responses, we compared 20 women from Tanzania's HIV Superinfection Study (HISIS) cohort, who were infected multiple HIV subtypes, and 22 women from the Centre for the AIDS Programme of Research in South Africa (CAPRISA) cohort, who were infected exclusively with HIV subtype C. By 2 years after infection, 35% of HISIS subjects developed neutralization breadth, compared with 9% of CAPRISA subjects (P = .0131). Cumulative viral loads between 3 and 12 months were higher in the HISIS group (P = .046) and strongly associated with breadth (P < .0001). While viral load was the strongest predictor, other factors may play a role, as the odds of developing breadth remained higher in HISIS even after correction for viral load.

Diversification in the HIV-1 Envelope Hyper-variable Domains V2, V4, and V5 and Higher Probability of Transmitted/Founder Envelope Glycosylation Favor the Development of Heterologous Neutralization Breadth

“…Indeed, in the parent IAVI cohort study, heterologous neutralization was detected in less than 2% of individuals at 24 months post-infection [36]. The ability to neutralize heterologous Env variants that the immune response has not encountered, loosely defined as neutralization breadth, has been shown to develop in plasma by around 2–4 years after HIV-1 infection, in anywhere from 10 to 80% of individuals, depending on the nature of the cohort, timing of sample collection, and the methods used to evaluate and quantify breadth [18,21,22,33,34,36,41,49,50]. In agreement with these findings, neutralization scores indicative of breadth in the IAVI study were generally first observed at a mean of 3.5 years [36].…”

“…Features of HIV-1 Env have been previously associated with the level and type of neutralization breadth that develops within an individual [9,33,38]. Indeed, in the IAVI study involving multiple HIV-1 suptypes, subtype C infection was a significant correlate of higher neutralization breadth score [36].…”

“…Viral replication capacity, Env diversity, super-infection, and high viral load may all contribute to the antigenic stimulation necessary to augment heterologous neutralization breadth [21,23,27,31,33–36]. Certain HIV-1 Env characteristics, often related to subtype or glycans, may also favor the development of neutralization breadth [9,19,33,36–38]. Host immunologic factors such as T follicular helper cell activity and activation within the B and T cell compartments could also modulate the development and maintenance of neutralization breadth [39–41].…”

HIV-1 Dual Infected LTNP-EC Patients Developed an Unexpected Antibody Cross-Neutralizing Activity

“…Several studies have demonstrated a positive correlation between plasma viral load and titers of neutralizing antibodies to heterologous virus proposing that the development of these antibodies was a consequence of viral replication [ 9 , 19 , 19 , 22 , 22 ]. Broadly cross-neutralizing activity has also been associated to partial B-cell restoration and it has been shown to be variable over time [ 17 ].…”

Lower Broadly Neutralizing Antibody Responses in Female Versus Male HIV-1 Infected Injecting Drug Users

“…Previous studies on clinical variables associated with the development of bNAb responses did not show a strong association with the gender of the infected individual [8,11,14,15,53,54,55,56]. A lower frequency of neutralization breadth was, however, detected amongst females in the Swiss 4.5k Screen [15,38].…”