The Molecular Epidemiology and Transmission Dynamics of HIV Type 1 in a General Population Cohort in Uganda

Ssemwanga, Deogratius; Bbosa, Nicholas; Nsubuga, Rebecca N.; Ssekagiri, Alfred; Kapaata, Anne; Nannyonjo, Maria; Nassolo, Faridah; Karabarinde, Alex; Mugisha, Joseph; Seeley, Janet; Yebra, Gonzalo; Brown, Andrew; Kaleebu, Pontiano

doi:10.3390/v12111283

Cited by 4 publications

(7 citation statements)

References 68 publications

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“…Globally, it is estimated that approximately 20% of new HIV infections are due to HIV-1 circulating recombinant forms (CRFs) and unique recombinant forms (URFs), particularly in regions such as Africa, where several subtypes are known to co-circulate [2]. Previous studies investigating HIV-1 diversity in Uganda have targeted sub-genomic fragments: gag, [3] pol [4,5] and env [3]. In addition, full-length genomes in other studies were performed mainly in chronically infected individuals in rural and semi-urban areas, focusing on the southern and central regions of Uganda.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Near Full-Length Transmitted/Founder HIV-1 Subtype D and A/D Recombinant Genomes in a Heterosexual Ugandan Population (2006–2011)

Balinda

Kapaata

Xu³

et al. 2022

Viruses

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Detailed characterization of transmitted HIV-1 variants in Uganda is fundamentally important to inform vaccine design, yet studies on the transmitted full-length strains of subtype D viruses are limited. Here, we amplified single genomes and characterized viruses, some of which were previously classified as subtype D by sub-genomic pol sequencing that were transmitted in Uganda between December 2006 to June 2011. Analysis of 5′ and 3′ half genome sequences showed 73% (19/26) of infections involved single virus transmissions, whereas 27% (7/26) of infections involved multiple variant transmissions based on predictions of a model of random virus evolution. Subtype analysis of inferred transmitted/founder viruses showed a high transmission rate of inter-subtype recombinants (69%, 20/29) involving mainly A1/D, while pure subtype D variants accounted for one-third of infections (31%, 9/29). Recombination patterns included a predominance of subtype D in the gag/pol region and a highly recombinogenic envelope gene. The signal peptide-C1 region and gp41 transmembrane domain (Tat2/Rev2 flanking region) were hotspots for A1/D recombination events. Analysis of a panel of 14 transmitted/founder molecular clones showed no difference in replication capacity between subtype D viruses (n = 3) and inter-subtype mosaic recombinants (n = 11). However, individuals infected with high replication capacity viruses had a faster CD4 T cell loss. The high transmission rate of unique inter-subtype recombinants is striking and emphasizes the extraordinary challenge for vaccine design and, in particular, for the highly variable and recombinogenic envelope gene, which is targeted by rational designs aimed to elicit broadly neutralizing antibodies.

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Section: Introductionmentioning

confidence: 99%

Characterization of Near Full-Length Transmitted/Founder HIV-1 Subtype D and A/D Recombinant Genomes in a Heterosexual Ugandan Population (2006–2011)

Balinda

Kapaata

Xu³

et al. 2022

Viruses

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“…HIV-1 transmission in Uganda has been well studied, especially in rural Southwestern Uganda (which is suggested to be the geographic origin of HIV-1 sub-subtype A1 and subtype D in Uganda) [45]. To understand HIV-1 transmission dynamics in Uganda, Ssemwanga et al used 3796 HIV-1 pol sequences collected between 2003 and 2015 from Southwestern, Central, and Eastern Uganda [46]. HIV-1 subtype A infections were more common in Central Uganda, whereas subtype D infections were more common in Southwestern Uganda.…”

Section: Hiv-1 Transmission In East and Southern Africa Countriesmentioning

confidence: 99%

“…Few studies have investigated the directionality in HIV-1 transmission involving different risk groups in sSA. Recent phylogenetic analyses have shown that fishing communities do not serve as a source of HIV-1 infection to much larger populations with lower HIV-1 prevalence in Uganda [46,90,93]. In Senegal, Nascimento et al showed that 3.2% of infections in HET females were acquired from MSM, whereas 0.3% infections among MSM were acquired from HET females [94].…”

Section: Phylogenetic Analysis To Examine Sources and Direction Of Hiv-1 Transmission Between Hiv-1 Key And Vulnerable Populations And Hementioning

confidence: 99%

“…Phylogenetic studies have also revealed the role of age-disparate HET relationships in perpetuating local HIV-1 transmission in Sub-Saharan Africa [46,98,99]. In Uganda, Ssemwanga et al found that HET individuals older than 25 years were more likely to appear in phylogenetic clusters than younger individuals [48].…”

Section: Phylogenetic Analysis To Examine Sources and Direction Of Hiv-1 Transmission Between Hiv-1 Key And Vulnerable Populations And Hementioning

confidence: 99%

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The Role of Phylogenetics in Discerning HIV-1 Mixing among Vulnerable Populations and Geographic Regions in Sub-Saharan Africa: A Systematic Review

Nduva

Nazziwa

Hassan

et al. 2021

Viruses

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To reduce global HIV-1 incidence, there is a need to understand and disentangle HIV-1 transmission dynamics and to determine the geographic areas and populations that act as hubs or drivers of HIV-1 spread. In Sub-Saharan Africa (sSA), the region with the highest HIV-1 burden, information about such transmission dynamics is sparse. Phylogenetic inference is a powerful method for the study of HIV-1 transmission networks and source attribution. In this review, we assessed available phylogenetic data on mixing between HIV-1 hotspots (geographic areas and populations with high HIV-1 incidence and prevalence) and areas or populations with lower HIV-1 burden in sSA. We searched PubMed and identified and reviewed 64 studies on HIV-1 transmission dynamics within and between risk groups and geographic locations in sSA (published 1995–2021). We describe HIV-1 transmission from both a geographic and a risk group perspective in sSA. Finally, we discuss the challenges facing phylogenetic inference in mixed epidemics in sSA and offer our perspectives and potential solutions to the identified challenges.

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“…HIV sequencing is important for use in detecting drug resistant mutations, but can also provide insights about epidemic size and diversity e.g. [ 70 ] or movement between key populations by phylogenetic analysis e.g. [ 6 , 44 ].…”

Section: Introductionmentioning

confidence: 99%

A large population sample of African HIV genomes from the 1980s reveals a reduction in subtype D over time associated with propensity for CXCR4 tropism

et al. 2022

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We present 109 near full-length HIV genomes amplified from blood serum samples obtained during early 1986 from across Uganda, which to our knowledge is the earliest and largest population sample from the initial phase of the HIV epidemic in Africa. Consensus sequences were made from paired-end Illumina reads with a target-capture approach to amplify HIV material following poor success with standard approaches. In comparisons with a smaller ‘intermediate’ genome dataset from 1998 to 1999 and a ‘modern’ genome dataset from 2007 to 2016, the proportion of subtype D was significantly higher initially, dropping from 67% (73/109), to 57% (26/46) to 17% (82/465) respectively (p < 0.0001). Subtype D has previously been shown to have a faster rate of disease progression than other subtypes in East African population studies, and to have a higher propensity to use the CXCR4 co-receptor (“X4 tropism”); associated with a decrease in time to AIDS. Here we find significant differences in predicted tropism between A1 and D subtypes in all three sample periods considered, which is particularly striking the 1986 sample: 66% (53/80) of subtype D env sequences were predicted to be X4 tropic compared with none of the 24 subtype A1. We also analysed the frequency of subtype in the envelope region of inter-subtype recombinants, and found that subtype A1 is over-represented in env, suggesting recombination and selection have acted to remove subtype D env from circulation. The reduction of subtype D frequency over three decades therefore appears to be a result of selective pressure against X4 tropism and its higher virulence. Lastly, we find a subtype D specific codon deletion at position 24 of the V3 loop, which may explain the higher propensity for subtype D to utilise X4 tropism.

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The Molecular Epidemiology and Transmission Dynamics of HIV Type 1 in a General Population Cohort in Uganda

Cited by 4 publications

References 68 publications

Characterization of Near Full-Length Transmitted/Founder HIV-1 Subtype D and A/D Recombinant Genomes in a Heterosexual Ugandan Population (2006–2011)

Characterization of Near Full-Length Transmitted/Founder HIV-1 Subtype D and A/D Recombinant Genomes in a Heterosexual Ugandan Population (2006–2011)

The Role of Phylogenetics in Discerning HIV-1 Mixing among Vulnerable Populations and Geographic Regions in Sub-Saharan Africa: A Systematic Review

A large population sample of African HIV genomes from the 1980s reveals a reduction in subtype D over time associated with propensity for CXCR4 tropism

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