Limits...
HIV-1 superinfection occurs less frequently than initial infection in a cohort of high-risk Kenyan women.

Ronen K, McCoy CO, Matsen FA, Boyd DF, Emery S, Odem-Davis K, Jaoko W, Mandaliya K, McClelland RS, Richardson BA, Overbaugh J - PLoS Pathog. (2013)

Bottom Line: Amplicons in three genome regions were sequenced and a median of 901 sequences obtained per gene per timepoint.These data were combined with published data from 17 additional women in the same cohort, totaling 146 women screened.Andersen-Gill proportional hazards models were used to compare incidences, adjusting for covariates known to influence HIV susceptibility in this cohort.

View Article: PubMed Central - PubMed

Affiliation: Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.

ABSTRACT
HIV superinfection (reinfection) has been reported in several settings, but no study has been designed and powered to rigorously compare its incidence to that of initial infection. Determining whether HIV infection reduces the risk of superinfection is critical to understanding whether an immune response to natural HIV infection is protective. This study compares the incidence of initial infection and superinfection in a prospective seroincident cohort of high-risk women in Mombasa, Kenya. A next-generation sequencing-based pipeline was developed to screen 129 women for superinfection. Longitudinal plasma samples at <6 months, >2 years and one intervening time after initial HIV infection were analyzed. Amplicons in three genome regions were sequenced and a median of 901 sequences obtained per gene per timepoint. Phylogenetic evidence of polyphyly, confirmed by pairwise distance analysis, defined superinfection. Superinfection timing was determined by sequencing virus from intervening timepoints. These data were combined with published data from 17 additional women in the same cohort, totaling 146 women screened. Twenty-one cases of superinfection were identified for an estimated incidence rate of 2.61 per 100 person-years (pys). The incidence rate of initial infection among 1910 women in the same cohort was 5.75 per 100 pys. Andersen-Gill proportional hazards models were used to compare incidences, adjusting for covariates known to influence HIV susceptibility in this cohort. Superinfection incidence was significantly lower than initial infection incidence, with a hazard ratio of 0.47 (CI 0.29-0.75, pā€Š=ā€Š0.0019). This lower incidence of superinfection was only observed >6 months after initial infection. This is the first adequately powered study to report that HIV infection reduces the risk of reinfection, raising the possibility that immune responses to natural infection are partially protective. The observation that superinfection risk changes with time implies a window of protection that coincides with the maturation of HIV-specific immunity.

Show MeSH

Related in: MedlinePlus

Summary of timing of superinfection events relative to initial infection events.Subject identifiers for the 21 cases of superinfection are listed with the 9 cases identified here listed first, followed by the 12 cases from prior studies [5], [12], [17]. Time since initial infection (years) is represented as blue bars. The red rectangles represent the interval between the last timepoint at which only the initial variant was detected and the first timepoint at which the superinfecting variant was detected. The blue line marks the interval midpoint. *QB045 was HIV RNA-positive at enrollment and was therefore excluded from the incidence analysis.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3757054&req=5

ppat-1003593-g004: Summary of timing of superinfection events relative to initial infection events.Subject identifiers for the 21 cases of superinfection are listed with the 9 cases identified here listed first, followed by the 12 cases from prior studies [5], [12], [17]. Time since initial infection (years) is represented as blue bars. The red rectangles represent the interval between the last timepoint at which only the initial variant was detected and the first timepoint at which the superinfecting variant was detected. The blue line marks the interval midpoint. *QB045 was HIV RNA-positive at enrollment and was therefore excluded from the incidence analysis.

Mentions: Combining the data here with those from previous studies in the Mombasa cohort [5], [12], [17], a total of 146 women were examined for superinfection: 90 were tested using NGS, 39 using both NGS and Sanger sequencing, and 17 using only Sanger sequencing. Among the 39 women previously identified as singly infected by Sanger sequencing and tested by NGS here, no new cases of superinfection were identified, suggesting older methods were sensitive enough to detect superinfection. Twenty-one cases of superinfection were confirmed based on detection of the superinfecting virus in two or more samples. The timing windows of all 21 superinfection events are summarized in Figure 4 and Table S2. The midpoint of the timing window of the 9 new cases ranged from 81 to 1041 dpi, with 6 occurring within the first year of infection. The window of superinfection events was defined to a median of within 127 days, with window sizes of 90 to 1253 days. Timing of all 21 cases ranged from 63 to 1895 dpi, defined to a median of within 146 days.


HIV-1 superinfection occurs less frequently than initial infection in a cohort of high-risk Kenyan women.

Ronen K, McCoy CO, Matsen FA, Boyd DF, Emery S, Odem-Davis K, Jaoko W, Mandaliya K, McClelland RS, Richardson BA, Overbaugh J - PLoS Pathog. (2013)

Summary of timing of superinfection events relative to initial infection events.Subject identifiers for the 21 cases of superinfection are listed with the 9 cases identified here listed first, followed by the 12 cases from prior studies [5], [12], [17]. Time since initial infection (years) is represented as blue bars. The red rectangles represent the interval between the last timepoint at which only the initial variant was detected and the first timepoint at which the superinfecting variant was detected. The blue line marks the interval midpoint. *QB045 was HIV RNA-positive at enrollment and was therefore excluded from the incidence analysis.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3757054&req=5

ppat-1003593-g004: Summary of timing of superinfection events relative to initial infection events.Subject identifiers for the 21 cases of superinfection are listed with the 9 cases identified here listed first, followed by the 12 cases from prior studies [5], [12], [17]. Time since initial infection (years) is represented as blue bars. The red rectangles represent the interval between the last timepoint at which only the initial variant was detected and the first timepoint at which the superinfecting variant was detected. The blue line marks the interval midpoint. *QB045 was HIV RNA-positive at enrollment and was therefore excluded from the incidence analysis.
Mentions: Combining the data here with those from previous studies in the Mombasa cohort [5], [12], [17], a total of 146 women were examined for superinfection: 90 were tested using NGS, 39 using both NGS and Sanger sequencing, and 17 using only Sanger sequencing. Among the 39 women previously identified as singly infected by Sanger sequencing and tested by NGS here, no new cases of superinfection were identified, suggesting older methods were sensitive enough to detect superinfection. Twenty-one cases of superinfection were confirmed based on detection of the superinfecting virus in two or more samples. The timing windows of all 21 superinfection events are summarized in Figure 4 and Table S2. The midpoint of the timing window of the 9 new cases ranged from 81 to 1041 dpi, with 6 occurring within the first year of infection. The window of superinfection events was defined to a median of within 127 days, with window sizes of 90 to 1253 days. Timing of all 21 cases ranged from 63 to 1895 dpi, defined to a median of within 146 days.

Bottom Line: Amplicons in three genome regions were sequenced and a median of 901 sequences obtained per gene per timepoint.These data were combined with published data from 17 additional women in the same cohort, totaling 146 women screened.Andersen-Gill proportional hazards models were used to compare incidences, adjusting for covariates known to influence HIV susceptibility in this cohort.

View Article: PubMed Central - PubMed

Affiliation: Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.

ABSTRACT
HIV superinfection (reinfection) has been reported in several settings, but no study has been designed and powered to rigorously compare its incidence to that of initial infection. Determining whether HIV infection reduces the risk of superinfection is critical to understanding whether an immune response to natural HIV infection is protective. This study compares the incidence of initial infection and superinfection in a prospective seroincident cohort of high-risk women in Mombasa, Kenya. A next-generation sequencing-based pipeline was developed to screen 129 women for superinfection. Longitudinal plasma samples at <6 months, >2 years and one intervening time after initial HIV infection were analyzed. Amplicons in three genome regions were sequenced and a median of 901 sequences obtained per gene per timepoint. Phylogenetic evidence of polyphyly, confirmed by pairwise distance analysis, defined superinfection. Superinfection timing was determined by sequencing virus from intervening timepoints. These data were combined with published data from 17 additional women in the same cohort, totaling 146 women screened. Twenty-one cases of superinfection were identified for an estimated incidence rate of 2.61 per 100 person-years (pys). The incidence rate of initial infection among 1910 women in the same cohort was 5.75 per 100 pys. Andersen-Gill proportional hazards models were used to compare incidences, adjusting for covariates known to influence HIV susceptibility in this cohort. Superinfection incidence was significantly lower than initial infection incidence, with a hazard ratio of 0.47 (CI 0.29-0.75, pā€Š=ā€Š0.0019). This lower incidence of superinfection was only observed >6 months after initial infection. This is the first adequately powered study to report that HIV infection reduces the risk of reinfection, raising the possibility that immune responses to natural infection are partially protective. The observation that superinfection risk changes with time implies a window of protection that coincides with the maturation of HIV-specific immunity.

Show MeSH
Related in: MedlinePlus