HIV-1 Transmitting Couples Have Similar Viral Load Set-Points in Rakai, Uganda

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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.

Vyšlo v časopise: HIV-1 Transmitting Couples Have Similar Viral Load Set-Points in Rakai, Uganda. PLoS Pathog 6(5): e32767. doi:10.1371/journal.ppat.1000876
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1000876

Souhrn

Zdroje

1. FellayJ

ShiannaKV

GeD

ColomboS

LedergerberB

2007 A whole-genome association study of major determinants for host control of HIV-1. Science 317 944 947

2. KankiPJ

HamelDJ

SankaleJL

HsiehC

ThiorI

1999 Human immunodeficiency virus type 1 subtypes differ in disease progression. J Infect Dis 179 68 73

3. KaleebuP

FrenchN

MaheC

YirrellD

WateraC

2002 Effect of human immunodeficiency virus (HIV) type 1 envelope subtypes A and D on disease progression in a large cohort of HIV-1-positive persons in Uganda. J Infect Dis 185 1244 1250

4. NeilsonJR

JohnGC

CarrJK

LewisP

KreissJK

1999 Subtypes of HIV-1 and disease stage among women in Nairobi, Kenya. Journal of Virology 73 4393 4403

5. SpiraS

WainbergMA

LoembaH

TurnerD

BrennerBG

2003 Impact of clade diversity on HIV-1 virulence, antiretroviral drug sensitivity and drug resistance. Journal of Antimicrobial Chemotherapy 51 229 240

6. KiwanukaN

LaeyendeckerO

RobbM

KigoziG

ArroyoM

2008 Effect of human immunodeficiency virus Type 1 (HIV-1) subtype on disease progression in persons from Rakai, Uganda, with incident HIV-1 infection. J Infect Dis 197 707 713

7. TaylorBS

SobieszczykME

McCutchanFE

HammerSM

2008 The challenge of HIV-1 subtype diversity. N Engl J Med 358 1590 1602

8. BaetenJM

ChohanB

LavreysL

ChohanV

McClellandRS

2007 HIV-1 subtype D infection is associated with faster disease progression than subtype A in spite of similar plasma HIV-1 loads. J Infect Dis 195 1177 1180

9. FraserC

HollingsworthTD

ChapmanR

de WolfF

HanageWP

2007 Variation in HIV-1 set-point viral load: epidemiological analysis and an evolutionary hypothesis. Proc Natl Acad Sci U S A 104 17441 17446

10. MellorsJW

RinaldoCRJr

GuptaP

WhiteRM

ToddJA

1996 Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science 272 1167 1170

11. KivelaPS

KrolA

SalminenMO

GeskusRB

SuniJI

2005 High plasma HIV load in the CRF01-AE outbreak among injecting drug users in Finland. Scand J Infect Dis 37 276 283

12. GoldsteinS

OurmanovI

BrownCR

PlishkaR

Buckler-WhiteA

2005 Plateau levels of viremia correlate with the degree of CD4+-T-cell loss in simian immunodeficiency virus SIVagm-infected pigtailed macaques: variable pathogenicity of natural SIVagm isolates. J Virol 79 5153 5162

13. BallSC

AbrahaA

CollinsKR

MarozsanAJ

BairdH

2003 Comparing the ex vivo fitness of CCR5-tropic human immunodeficiency virus type 1 isolates of subtypes B and C. J Virol 77 1021 1038

14. ArienKK

AbrahaA

Quinones-MateuME

KestensL

VanhamG

2005 The Replicative Fitness of Primary Human Immunodeficiency Virus Type 1 (HIV-1) Group M, HIV-1 Group O, and HIV-2 Isolates. J Virol 79 8979 8990

15. AshtonLJ

LearmontJ

LuoK

WylieB

StewartG

1994 HIV infection in recipients of blood products from donors with known duration of infection. Lancet 344 718 720

16. IoannidisJPA

TatsioniA

AbramsEJ

BulterysM

CoombsRW

2004 Maternal viral load and rate of disease progression among vertically HIV-1-infected children: an international meta- analysis. AIDS 18 99 108

17. TangJ

TangS

LobashevskyE

ZuluI

AldrovandiG

2004 HLA allele sharing and HIV type 1 viremia in seroconverting Zambians with known transmitting partners. AIDS Res Hum Retroviruses 20 19 25

18. WawerMJ

GrayRH

SewankamboNK

SerwaddaD

PaxtonL

1998 A randomized, community trial of intensive sexually transmitted disease control for AIDS prevention, Rakai, Uganda. AIDS 12 1211 1225

19. WawerMJ

SewankamboNK

SerwaddaD

QuinnTC

PaxtonLA

1999 Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. Rakai Project Study Group. Lancet 353 525 535

20. HoelscherM

DowlingWE

Sanders-BuellE

CarrJK

HarrisME

2002 Detection of HIV-1 subtypes, recombinants, and dual infections in east Africa by a multi-region hybridization assay. AIDS 16 2055 2064

21. LutaloT

GrayRH

WawerM

SewankamboN

SerwaddaD

2007 Survival of HIV-infected treatment-naive individuals with documented dates of seroconversion in Rakai, Uganda. AIDS 21 Suppl 6 S15 19

22. WawerMJ

GrayRH

SewankamboNK

SerwaddaD

LiX

2005 Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis 191 1403 1409

23. PosadaD

2008 jModelTest: phylogenetic model averaging. Mol Biol Evol 25 1253 1256

24. GuindonS

GascuelO

2003 A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol 52 696 704

25. StamatakisA

2006 RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. Bioinformatics 22 2688 2690

26. StamatakisA

HooverP

RougemontJ

2008 A rapid bootstrap algorithm for the RAxML Web servers. Syst Biol 57 758 771

27. StamatakisA

BlagojevicF

NikolopoulosDS

AntonopoulosCD

2007 Exploring new search algorithms and hardware for phylogenetics: RAxML meets the IBM cell. Journal of Vlsi Signal Processing Systems for Signal Image and Video Technology 48 271 286

28. GrayRH

LiX

WawerMJ

SerwaddaD

SewankamboNK

2004 Determinants of HIV-1 load in subjects with early and later HIV infections, in a general-population cohort of Rakai, Uganda. J Infect Dis 189 1209 1215

29. LynchM

WalshB

1998 Genetics and Analysis of Quantitative Traits. U.S.A. Sinauer Associates Inc

30. LegendreP

LegendreL

1998 Numerical Ecology: Elsevier, Amsterdam, The Netherlands

31. KeeleBF

GiorgiEE

Salazar-GonzalezJF

DeckerJM

PhamKT

2008 Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci U S A 105 7552 7557

32. AbrahamsMR

AndersonJA

GiorgiEE

SeoigheC

MlisanaK

2009 Quantitating the multiplicity of infection with human immunodeficiency virus type 1 subtype C reveals a non-poisson distribution of transmitted variants. J Virol 83 3556 3567

33. KeeleBF

LiH

LearnGH

HraberP

GiorgiEE

2009 Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1. J Exp Med 206 1117 1134

34. HaalandRE

HawkinsPA

Salazar-GonzalezJ

JohnsonA

TichacekA

2009 Inflammatory genital infections mitigate a severe genetic bottleneck in heterosexual transmission of subtype A and C HIV-1. PLoS Pathog 5 e1000274 doi :10.1371/journal.ppat.1000274

35. LeslieAJ

PfafferottKJ

ChettyP

DraenertR

AddoMM

2004 HIV evolution: CTL escape mutation and reversion after transmission. Nat Med 10 282 289

36. CoombsRW

ReichelderferPS

LandayAL

2003 Recent observations on HIV type-1 infection in the genital tract of men and women. AIDS 17 455 480

37. O'BrienSJ

NelsonGW