Impact of a decade of successful antiretroviral therapy initiated at HIV-1 seroconversion on blood and rectal reservoirs
- Ghent University and Ghent University Hospital, Belgium
- Royal Free Hospital, United Kingdom
- Ghent University, Belgium
- Ghent University Hospital, Belgium
Figures
Figure 1
Patient cohorts in the cross-sectional study.
SRCV on antiretroviral therapy (ART): patient cohort with ART initiated at the time of HIV-1 seroconversion; LTNP: long-term non-progressors; Chronic ART: patients with ART initiated during the chronic phase of HIV-1 infection; Recent SRCV: recent ART-naïve seroconverters. In total, 84 patients were included in this study, 25 in SRCV on ART, 17 LTNPs, 32 Chronic ART patients, and 10 Recent SRCV. Blue arrows represent time of sampling. PHI: primary HIV-1 infection.
Figure 2
Total HIV-1 DNA (A) and integrated HIV-1 DNA (B) in four patient cohorts.
Data is shown as log10 copies/million (c/M) PBMCs and significant p-values are indicated by *. Differences between the cohorts were determined by Wilcoxon Signed Rank test.
Figure 3.
2-LTR circles (A), cell-associated HIV-1 usRNA (B) and CD4/CD8 ratio (C) in four patient cohorts.
Total HIV-1 DNA in rectal biopsies (D) in three patient cohorts (SRCV on ART, LTNP, and Chronic ART). Data is shown as log10 copies/million (c/M) PBMCs (A,B), ratio (C) or log10 c/M cells in rectal biopsies (D) and significant p-values are indicated by *. Differences between the cohorts were determined by Wilcoxon Signed Rank test.
Figure 4
Correlation of total HIV-1 DNA in rectal biopsies and blood (A).
Correlation was assessed in 46 patients in whom total HIV-1 DNA was detected both in the blood and rectal biopsies, representing patients from three cohorts: SRCV on antiretroviral therapy (ART), Chronic ART, and long-term non-progressors (LTNP). Data is shown as log10 copies/million (c/M) cells in rectal biopsies and log10 c/M peripheral blood mononuclear cells (PBMCs) in blood. Correlation of blood HIV-1 usRNA and total HIV-1 DNA (B), HIV-1 usRNA and integrated HIV-1 DNA (C), integrated HIV-1 DNA and total HIV-1 DNA (D) and CD4/CD8 ratio and integrated HIV-1 DNA (E). Data is shown as log10 c/M PBMCs in detectable patients from three cohorts: SRCV on ART, Chronic ART, and LTNP (B–E). To assess correlations between the markers, a linear regression was performed.
Tables
Table 1
Clinical and laboratory characteristics of the four patient cohorts.
| Value for cohort* | ||||
|---|---|---|---|---|
| SRCV on ART | LTNP | Chronic ART | Recent SRCV | |
| n = 25 | n = 17 | n = 32 | n = 10 | |
| Clinical characteristics | ||||
| Age (years) | 44 (34–53) | 49 (31–51) | 48 (31–53) | 39 (30–46) |
| Number of females (%) | 0 (0) | 7 (41.2) | 5 (15.6) | 1 (10) |
| Total ART duration (years) | 10.8 (4.2–11.9) | 0 | 9.8 (4.9–14.7) | 0 |
| Viremia zenith (log10HIV-1 c/ml) | 5.5 (2.4–5.9) | 2.5 (1.6–2.8) | 4.9 (1.9–5.5) | 6.2 (5.2–6.4) |
| CD4 count, nadir (cells/mm3) | 390 (107–466) | 624 (507–693) | 155 (0–266) | 440 (284–495) |
| CD4 count at sampling (cells/mm3) | 714 (476–977) | 793 (414–1010) | 624.5 (172–889) | 440 (284–604) |
| CD4/CD8 ratio | 1.10 (0.52–1.35) | 0.91 (0.36–1.47) | 0.74 (0.23–0.93) | 0.62 (0.36–0.94) |
| Virological markers | ||||
| Total HIV-1 DNA (c/106 PBMCs) | 92 (9.8–127.7) | 48 (5.4–56.5) | 137 (8.6–219.2) | 1901.3 (602.4–4786.9) |
| Integrated HIV-1 DNA (c/106 PBMCs) | 211.3 (0–589.3) | 28.2 (0–158.4) | 586.7 (131.6–918.2) | 1802.7 (367.9–5890.6) |
| HIV-1 usRNA (c/106 PBMCs) | 1.6 (0–3.7) | 0.4 (0–3.51) | 6.1 (0–10.1) | 15.5 (0.9–100.6) |
| 2-LTR circles (c/106 PBMCs) | 2.1 (0–4.3) | 0.8 (0–2.7) | 1.3 (0–2.2) | 13.3 (5.1–21.6) |
| Total HIV-1 DNA (c/106 cells) in rectal biopsies | 27.2 (22.2–61.7) | 21.3 (16.7–34.5) | 35.1 (16–77.5) | |
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*Values are reported as median (IQR); c: copies; PBMCs: peripheral blood mononuclear cells; usRNA: unspliced RNA; ART: antiretroviral therapy; SRCV on ART: early treated seroconverters; LTNP: long-term non-progressors; Chronic ART: late treated patients during chronic HIV-1 infection; Recent SRCV: acute ART-naïve seroconverters; LTR: Long terminal repeat.
Additional files
-
Supplementary file 1
Summary of primers/probe sets for PCR-based virological quantification.
- https://doi.org/10.7554/eLife.09115.008
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Impact of a decade of successful antiretroviral therapy initiated at HIV-1 seroconversion on blood and rectal reservoirs
eLife 4:e09115.
https://doi.org/10.7554/eLife.09115
