title: HIV-1 subtype distribution trends and evidence of transmission clusters among incident cases in a rural clinical cohort in southwest Uganda, 2004-2010.
abstract: The high diversity of HIV-1 has been shown to affect disease progression, transmission, and response to antiretroviral therapy and may influence HIV vaccine design. We describe the distribution trends of HIV-1 subtypes over a 7-year period among incident cases in a rural clinical cohort in Southwest Uganda and identify transmission clusters. Viral RNA was extracted from cryopreserved plasma samples from 94 participants who seroconverted and enrolled between 2004 and 2010. Partial gag (p24) and env (gp41) genes were directly sequenced to identify subtypes and transmission clusters with more than 95% bootstrap values. Direct sequencing of the partial pol gene and use of individual participant sexual life histories were also used to confirm these transmission clusters. The overall gag/env subtype distribution was A 28% (n=26), C 1% (n=1), and D 45% (n=42) and 27% (n=25) were intergene unique recombinant forms. The proportions of subtype A, D, or recombinants showed no significant increasing or decreasing trend over this time period (p=0.51). Phylogenetic analysis of the three genes confirmed 13 transmission clusters of which seven clusters were confirmed sexual partners using individual participants' sexual life histories. Subtype D has remained the predominant subtype in this population. From 2004 to 2010, there was no change in the proportions of these subtypes. Phylogenetic analysis and participants' sexual life histories revealed several transmission clusters. The high proportion of transmission clusters observed suggests continued high-risk sexual behavior and mixing in some individuals and possibly super transmitters in this presumed low-risk cohort, but also indicates that many transmissions occur in early HIV infection. This calls for early and targeted effective prevention and treatment intervention in this population.
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
authors.forename: Anne
authors.initials: A
authors.lastname: Kapaata
authors.forename: Frederick
authors.initials: F
authors.lastname: Lyagoba
authors.forename: Deogratius
authors.initials: D
authors.lastname: Ssemwanga
authors.forename: Brian
authors.initials: B
authors.lastname: Magambo
authors.forename: Maria
authors.initials: M
authors.lastname: Nanyonjo
authors.forename: Jonathan
authors.initials: J
authors.lastname: Levin
authors.forename: Billy N
authors.initials: BN
authors.lastname: Mayanja
authors.forename: Claire
authors.initials: C
authors.lastname: Mugasa
authors.forename: Chris M
authors.initials: CM
authors.lastname: Parry
authors.forename: Pontiano
authors.initials: P
authors.lastname: Kaleebu
mesh_terms: D000328:Adult; D016000:Cluster Analysis; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000635:transmission* / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D012424:Rural Population; D017422:Sequence Analysis, DNA; D014454:Uganda / Q000453:epidemiology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D012367:RNA, Viral; D054299:env Gene Products, Human Immunodeficiency Virus; D054301:gag Gene Products, Human Immunodeficiency Virus; D054302:pol Gene Products, Human Immunodeficiency Virus