Differences in HIV-1 reservoir size, landscape characteristics, and decay dynamics in acute and chronic treated HIV-1 Clade C infection
Persisting HIV reservoir viruses in resting CD4 T cells and other cellular subsets are a barrier to cure efforts. Early antiretroviral therapy (ART) enables post-treatment viral control in some cases, but mechanisms remain unclear. We hypothesised that ART initiated before peak viremia impacts HIV-1...
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eLife Sciences Publications Ltd
2025-02-01
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| Online Access: | https://elifesciences.org/articles/96617 |
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| author | Kavidha Reddy Guinevere Q Lee Nicole Reddy Tatenda JB Chikowore Kathy Baisley Krista L Dong Bruce D Walker Xu G Yu Mathias Lichterfeld Thumbi Ndung'u |
| author_facet | Kavidha Reddy Guinevere Q Lee Nicole Reddy Tatenda JB Chikowore Kathy Baisley Krista L Dong Bruce D Walker Xu G Yu Mathias Lichterfeld Thumbi Ndung'u |
| author_sort | Kavidha Reddy |
| collection | DOAJ |
| description | Persisting HIV reservoir viruses in resting CD4 T cells and other cellular subsets are a barrier to cure efforts. Early antiretroviral therapy (ART) enables post-treatment viral control in some cases, but mechanisms remain unclear. We hypothesised that ART initiated before peak viremia impacts HIV-1 subtype C reservoirs. We studied 35 women at high risk of infection from Durban, South Africa, identified with hyperacute HIV by twice-weekly HIV-RNA testing. Participants included 11 starting ART at a median of 456 (297–1203) days post-onset of viremia (DPOV) and 24 at 1 (1–3) DPOV. Peripheral blood mononuclear cells (PBMCs) were used to measured total HIV-1 DNA by droplet digital PCR (ddPCR) and sequence viral reservoir genomes by full-length proviral sequencing (FLIP-seq). ART during hyperacute infection blunted peak viremia (p<0.0001), but contemporaneous total HIV-1 DNA did not differ (p=0.104). Over 1 year, a decline of total HIV-1 DNA was observed in early treated persons (p=0.0004), but not late treated. Among 697 viral genome sequences, the proviral genetic landscape differed between untreated, late treated, and early treated groups. Intact genomes after 1 year were higher in untreated (31%) versus late treated (14%) and early treated (0%). Treatment in both late and early infection caused more rapid decay of intact (13% and 51% per month) versus defective (2% and 35%) viral genomes. However, intact genomes persisted 1 year post chronic treatment but were undetectable with early ART. Early ART also reduced phylogenetic diversity of intact genomes and limited cytotoxic T lymphocyte immune escape variants in the reservoir. Overall, ART initiated in hyperacute HIV-1 subtype C infection did not impact reservoir seeding but was associated with rapid intact viral genome decay, reduced genetic complexity, and limited immune escape, which may accelerate reservoir clearance in combination with other interventional strategies. |
| format | Article |
| id | doaj-art-a90e57cffd2a440ea350d75fcc7d17fe |
| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-a90e57cffd2a440ea350d75fcc7d17fe2025-08-20T03:00:55ZengeLife Sciences Publications LtdeLife2050-084X2025-02-011310.7554/eLife.96617Differences in HIV-1 reservoir size, landscape characteristics, and decay dynamics in acute and chronic treated HIV-1 Clade C infectionKavidha Reddy0https://orcid.org/0000-0002-7024-0574Guinevere Q Lee1Nicole Reddy2Tatenda JB Chikowore3Kathy Baisley4Krista L Dong5Bruce D Walker6Xu G Yu7Mathias Lichterfeld8https://orcid.org/0000-0001-9865-8350Thumbi Ndung'u9https://orcid.org/0000-0003-2962-3992Africa Health Research Institute, Durban, South AfricaWeill Cornell Medical College, New York, United StatesAfrica Health Research Institute, Durban, South Africa; University of KwaZulu-Natal, Durban, South AfricaAfrica Health Research Institute, Durban, South Africa; University College London, London, United KingdomAfrica Health Research Institute, Durban, South Africa; London School of Hygiene and Tropical Medicine, London, United KingdomRagon Institute of MGH, MIT and Harvard, Cambridge, United States; HIV Pathogenesis Programme (HPP), The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa; Harvard Medical School, Boston, United StatesRagon Institute of MGH, MIT and Harvard, Cambridge, United States; HIV Pathogenesis Programme (HPP), The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa; Harvard Medical School, Boston, United StatesRagon Institute of MGH, MIT and Harvard, Cambridge, United States; Harvard Medical School, Boston, United StatesRagon Institute of MGH, MIT and Harvard, Cambridge, United States; Harvard Medical School, Boston, United States; Brigham and Women's Hospital, Boston, United StatesAfrica Health Research Institute, Durban, South Africa; University of KwaZulu-Natal, Durban, South Africa; University College London, London, United Kingdom; Ragon Institute of MGH, MIT and Harvard, Cambridge, United States; HIV Pathogenesis Programme (HPP), The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South AfricaPersisting HIV reservoir viruses in resting CD4 T cells and other cellular subsets are a barrier to cure efforts. Early antiretroviral therapy (ART) enables post-treatment viral control in some cases, but mechanisms remain unclear. We hypothesised that ART initiated before peak viremia impacts HIV-1 subtype C reservoirs. We studied 35 women at high risk of infection from Durban, South Africa, identified with hyperacute HIV by twice-weekly HIV-RNA testing. Participants included 11 starting ART at a median of 456 (297–1203) days post-onset of viremia (DPOV) and 24 at 1 (1–3) DPOV. Peripheral blood mononuclear cells (PBMCs) were used to measured total HIV-1 DNA by droplet digital PCR (ddPCR) and sequence viral reservoir genomes by full-length proviral sequencing (FLIP-seq). ART during hyperacute infection blunted peak viremia (p<0.0001), but contemporaneous total HIV-1 DNA did not differ (p=0.104). Over 1 year, a decline of total HIV-1 DNA was observed in early treated persons (p=0.0004), but not late treated. Among 697 viral genome sequences, the proviral genetic landscape differed between untreated, late treated, and early treated groups. Intact genomes after 1 year were higher in untreated (31%) versus late treated (14%) and early treated (0%). Treatment in both late and early infection caused more rapid decay of intact (13% and 51% per month) versus defective (2% and 35%) viral genomes. However, intact genomes persisted 1 year post chronic treatment but were undetectable with early ART. Early ART also reduced phylogenetic diversity of intact genomes and limited cytotoxic T lymphocyte immune escape variants in the reservoir. Overall, ART initiated in hyperacute HIV-1 subtype C infection did not impact reservoir seeding but was associated with rapid intact viral genome decay, reduced genetic complexity, and limited immune escape, which may accelerate reservoir clearance in combination with other interventional strategies.https://elifesciences.org/articles/96617HIV-1Clade Creservoirviral dynamics |
| spellingShingle | Kavidha Reddy Guinevere Q Lee Nicole Reddy Tatenda JB Chikowore Kathy Baisley Krista L Dong Bruce D Walker Xu G Yu Mathias Lichterfeld Thumbi Ndung'u Differences in HIV-1 reservoir size, landscape characteristics, and decay dynamics in acute and chronic treated HIV-1 Clade C infection eLife HIV-1 Clade C reservoir viral dynamics |
| title | Differences in HIV-1 reservoir size, landscape characteristics, and decay dynamics in acute and chronic treated HIV-1 Clade C infection |
| title_full | Differences in HIV-1 reservoir size, landscape characteristics, and decay dynamics in acute and chronic treated HIV-1 Clade C infection |
| title_fullStr | Differences in HIV-1 reservoir size, landscape characteristics, and decay dynamics in acute and chronic treated HIV-1 Clade C infection |
| title_full_unstemmed | Differences in HIV-1 reservoir size, landscape characteristics, and decay dynamics in acute and chronic treated HIV-1 Clade C infection |
| title_short | Differences in HIV-1 reservoir size, landscape characteristics, and decay dynamics in acute and chronic treated HIV-1 Clade C infection |
| title_sort | differences in hiv 1 reservoir size landscape characteristics and decay dynamics in acute and chronic treated hiv 1 clade c infection |
| topic | HIV-1 Clade C reservoir viral dynamics |
| url | https://elifesciences.org/articles/96617 |
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