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HIV-1 transmitting couples have similar viral load set-points in Rakai, Uganda.

Hollingsworth TD, Laeyendecker O, Shirreff G, Donnelly CA, Serwadda D, Wawer MJ, Kiwanuka N, Nalugoda F, Collinson-Streng A, Ssempijja V, Hanage WP, Quinn TC, Gray RH, Fraser C - PLoS Pathog. (2010)

Bottom Line: In addition, sequence data was available to establish transmission by genetic linkage for 57 of these couples.Sex, age, viral subtype, index partner, and self-reported genital ulcer disease status (GUD) were known.The most parsimonious explanation is that this is due to shared characteristics of the transmitted virus, a finding which sheds light on both the role of viral factors in HIV-1 pathogenesis and on the evolution of the virus.

View Article: PubMed Central - PubMed

Affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.

ABSTRACT
It has been hypothesized that HIV-1 viral load set-point is a surrogate measure of HIV-1 viral virulence, and that it may be subject to natural selection in the human host population. A key test of this hypothesis is whether viral load set-points are correlated between transmitting individuals and those acquiring infection. We retrospectively identified 112 heterosexual HIV-discordant couples enrolled in a cohort in Rakai, Uganda, in which HIV transmission was suspected and viral load set-point was established. In addition, sequence data was available to establish transmission by genetic linkage for 57 of these couples. Sex, age, viral subtype, index partner, and self-reported genital ulcer disease status (GUD) were known. Using ANOVA, we estimated the proportion of variance in viral load set-points which was explained by the similarity within couples (the 'couple effect'). Individuals with suspected intra-couple transmission (97 couples) had similar viral load set-points (p = 0.054 single factor model, p = 0.0057 adjusted) and the couple effect explained 16% of variance in viral loads (23% adjusted). The analysis was repeated for a subset of 29 couples with strong genetic support for transmission. The couple effect was the major determinant of viral load set-point (p = 0.067 single factor, and p = 0.036 adjusted) and the size of the effect was 27% (37% adjusted). Individuals within epidemiologically linked couples with genetic support for transmission had similar viral load set-points. The most parsimonious explanation is that this is due to shared characteristics of the transmitted virus, a finding which sheds light on both the role of viral factors in HIV-1 pathogenesis and on the evolution of the virus.

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Related in: MedlinePlus

Clustering of sequences from the couples for whom sequence data was available.Sequences from the couples were analysed together with sequences from 511 other infected individuals in the cohort (‘filler sequences’) to prevent spurious linkage due to independent infections with similar circulating virus. For the sake of clarity, filler sequences are not shown in this figure (the full trees are shown in Figure S1, S2 and S3). Sequences from couples are categorised as polyphyletic (red), monophyletic with bootstrap <80% (blue) or monophyletic with bootstrap ≥80% (green). Additional couples who are monophyletic but for one invading sequence are indicated in orange. Black indicates a sequence from a couple which are monophyletic for sequences taken at another timepoint. A Concatenated sequences, B gp41 only C p24 only.
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ppat-1000876-g001: Clustering of sequences from the couples for whom sequence data was available.Sequences from the couples were analysed together with sequences from 511 other infected individuals in the cohort (‘filler sequences’) to prevent spurious linkage due to independent infections with similar circulating virus. For the sake of clarity, filler sequences are not shown in this figure (the full trees are shown in Figure S1, S2 and S3). Sequences from couples are categorised as polyphyletic (red), monophyletic with bootstrap <80% (blue) or monophyletic with bootstrap ≥80% (green). Additional couples who are monophyletic but for one invading sequence are indicated in orange. Black indicates a sequence from a couple which are monophyletic for sequences taken at another timepoint. A Concatenated sequences, B gp41 only C p24 only.

Mentions: The phylogenetic trees used to identify the level of linkage between couples are shown in Figure 1. The additional sequences included to prevent spurious linkage have been excluded from the figure for clarity (full trees are shown in Figure S1, S2 and S3). The outcome of the phylogenetic clustering analysis and resulting inclusion criteria for the ANOVA are summarised in a flow chart (Figure S4).


HIV-1 transmitting couples have similar viral load set-points in Rakai, Uganda.

Hollingsworth TD, Laeyendecker O, Shirreff G, Donnelly CA, Serwadda D, Wawer MJ, Kiwanuka N, Nalugoda F, Collinson-Streng A, Ssempijja V, Hanage WP, Quinn TC, Gray RH, Fraser C - PLoS Pathog. (2010)

Clustering of sequences from the couples for whom sequence data was available.Sequences from the couples were analysed together with sequences from 511 other infected individuals in the cohort (‘filler sequences’) to prevent spurious linkage due to independent infections with similar circulating virus. For the sake of clarity, filler sequences are not shown in this figure (the full trees are shown in Figure S1, S2 and S3). Sequences from couples are categorised as polyphyletic (red), monophyletic with bootstrap <80% (blue) or monophyletic with bootstrap ≥80% (green). Additional couples who are monophyletic but for one invading sequence are indicated in orange. Black indicates a sequence from a couple which are monophyletic for sequences taken at another timepoint. A Concatenated sequences, B gp41 only C p24 only.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2865511&req=5

ppat-1000876-g001: Clustering of sequences from the couples for whom sequence data was available.Sequences from the couples were analysed together with sequences from 511 other infected individuals in the cohort (‘filler sequences’) to prevent spurious linkage due to independent infections with similar circulating virus. For the sake of clarity, filler sequences are not shown in this figure (the full trees are shown in Figure S1, S2 and S3). Sequences from couples are categorised as polyphyletic (red), monophyletic with bootstrap <80% (blue) or monophyletic with bootstrap ≥80% (green). Additional couples who are monophyletic but for one invading sequence are indicated in orange. Black indicates a sequence from a couple which are monophyletic for sequences taken at another timepoint. A Concatenated sequences, B gp41 only C p24 only.
Mentions: The phylogenetic trees used to identify the level of linkage between couples are shown in Figure 1. The additional sequences included to prevent spurious linkage have been excluded from the figure for clarity (full trees are shown in Figure S1, S2 and S3). The outcome of the phylogenetic clustering analysis and resulting inclusion criteria for the ANOVA are summarised in a flow chart (Figure S4).

Bottom Line: In addition, sequence data was available to establish transmission by genetic linkage for 57 of these couples.Sex, age, viral subtype, index partner, and self-reported genital ulcer disease status (GUD) were known.The most parsimonious explanation is that this is due to shared characteristics of the transmitted virus, a finding which sheds light on both the role of viral factors in HIV-1 pathogenesis and on the evolution of the virus.

View Article: PubMed Central - PubMed

Affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.

ABSTRACT
It has been hypothesized that HIV-1 viral load set-point is a surrogate measure of HIV-1 viral virulence, and that it may be subject to natural selection in the human host population. A key test of this hypothesis is whether viral load set-points are correlated between transmitting individuals and those acquiring infection. We retrospectively identified 112 heterosexual HIV-discordant couples enrolled in a cohort in Rakai, Uganda, in which HIV transmission was suspected and viral load set-point was established. In addition, sequence data was available to establish transmission by genetic linkage for 57 of these couples. Sex, age, viral subtype, index partner, and self-reported genital ulcer disease status (GUD) were known. Using ANOVA, we estimated the proportion of variance in viral load set-points which was explained by the similarity within couples (the 'couple effect'). Individuals with suspected intra-couple transmission (97 couples) had similar viral load set-points (p = 0.054 single factor model, p = 0.0057 adjusted) and the couple effect explained 16% of variance in viral loads (23% adjusted). The analysis was repeated for a subset of 29 couples with strong genetic support for transmission. The couple effect was the major determinant of viral load set-point (p = 0.067 single factor, and p = 0.036 adjusted) and the size of the effect was 27% (37% adjusted). Individuals within epidemiologically linked couples with genetic support for transmission had similar viral load set-points. The most parsimonious explanation is that this is due to shared characteristics of the transmitted virus, a finding which sheds light on both the role of viral factors in HIV-1 pathogenesis and on the evolution of the virus.

Show MeSH
Related in: MedlinePlus