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Research Article

Early highly active antiretroviral therapy for acute HIV-1 infection preserves immune function of CD8+ and CD4+ T lymphocytes

Annette Oxenius, David A. Price, Philippa J. Easterbrook, Christopher A. O'Callaghan, Anthony D. Kelleher, Joseph A. Whelan, Glenn Sontag, Andrew K. Sewell, and Rodney E. Phillips
PNAS March 28, 2000 97 (7) 3382-3387; https://doi.org/10.1073/pnas.97.7.3382
Annette Oxenius
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David A. Price
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Philippa J. Easterbrook
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Christopher A. O'Callaghan
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Anthony D. Kelleher
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Joseph A. Whelan
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Glenn Sontag
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Andrew K. Sewell
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Rodney E. Phillips
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  1. Communicated by David Weatherall, University of Oxford, Oxford, United Kingdom (received for review November 4, 1999)

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    Figure 1

    CTL activity of SC2, SC10, and SC12 soon after infection. Chromium release assays were performed with bulk-cultured PBL of SC2 at 22 DFOSx (A), SC10 at 36 DFOSx (B), and SC12 at 30 DFOSx (C). HLA B8-expressing target cells (B-LCL) were labeled with the indicated HLA B8-binding peptides, and bulk-cultured PBL were used at an effector to target ratio of 60:1 in B, and as indicated in A and C. Spontaneous release was below 20%.

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    Figure 2

    The immune response during and after HIV infection. Thawed, uncultured PBL of SC2 (A), SC9 (B), SC19 (C), SC10 (D), SC12 (E), SC15 (F), SC11 (G), and SC18 (H) were studied. For viral load (●), data points on the baseline were below the limit of detection of the assay (<400 copies per ml). PBL were stained with tetramers specific for the HLA B8-restricted epitope FLK (□). Median values are shown and expressed as percentage of total CD8+ T cells. Initiation and duration of HAART is indicated by the black bar on top of the upper panel. IFN-γ-ELISPOT analysis is shown in the lower panels and the time of analysis is indicated by the arrows pointing to the time axis (x axis). Specific IFN-γ release indicated the number of spots induced by peptide stimulation (peptides are indicated at the x axis of the ELISPOT panels) divided by the number of spots observed without antigen stimulation. In each patient, 9–20 peptides were used to screen CD8+ T cell responses in each sample, but only those peptides that stimulated a response at some point in the study are shown. Consistently negative responses are not plotted.

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    Figure 3

    HIV-specific CD4+ T cell responsiveness. CD8-depleted PBL of SC2 (A), SC19 (B), SC10 (C), SC12 (D), SC18 (E), and SC11 (F) were stimulated with the indicated HIV-derived antigens, and specific IFN-γ secretion is shown as the number of spots induced by antigen stimulation (antigens are indicated at the x axis of the ELISPOT panels) divided by the number of spots observed without peptide stimulation. Values in parentheses indicate the months following onset of symptoms when cells were sampled and the assay performed.

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    Table 1

    Patient characterization

    Patient HLADFOSxCD4/CD8, ×106/literART
    SC21 (−)−
     A17 (+)384/2016−
     B7/822518/5994−
     Cw0701110−
     Cw0702172330/840−
     DR4/53253325/−−
     DQ7307325/663−
    382325/−−
    543475/1143−
    606449/993Z/3/I
    605401/786Z/3/I
    718588/1013Z/3/I
    760532/835PC
    1059395/860−
    1083451/1246−
    1163351/680−
    1340465/1012Z/3/E
    SC9−180 (−)−
     A1/220 (+)624/592−
     B8/13107864/792−
     Cw0175720/1056−
     Cw0701240588/569−
     DR2/11287716/913−
     DR51/52348619/716−
     DQ6/7390d/3/I
    421647/633d/3/I
    499657/570d/3/I
    560879/956d/3/I
    618701/739d/3/I
    713687/587d/3/I
    839338/463PC
    877500/529PC
    1006524/518−
    1146531/508−
    SC101 (−)−
     A1/336 (+)−
     B8/3549598/−d/3/I
     DR1/871528/592d/3/I
     DQ4/585d/3/I
    112693/751d/3/I
    153913/977d/3/I
    214603/535d/3/I
    250658/596d/3/I
    313599/509d/3/I
    376805/769d/3/I
    438600/769d/3/I
    500858/529d/3/I
    5591168/771d/3/I
    6291431/1448d/3/I
    6911321/1277d/3/I
    7531429/1166d/3/I
    7911690/1759d/3/I
    8531640/1532d/3/I
    8751971/−d/3/E
    8811223/1094d/3/E
    9591566/1386d/3/E
    1029741/734d/3/E
    10791754/1841d/3/E
    SC11−180 (−)
     A1 B824 (+)351/3042−
     Cw020132d/3/R
     DR3/1148728/1248d/3/R
     DR5271−
     DQ2/7233427/1383−
    689405/1221d/3/N
    757598/1220d/3/N
    836584/1194d/3/N
    SC12−139 (−)−
     A123 (+)−
     B8/3930589/1953−
     Cw0701353/I
     Cw070245Z/3/I
     DR2/351952/1372Z/3/I
     DR51/521101071/1283Z/3/I
     DQ2/61561176/1502Z/3/I
    2341324/1324Z/3/I
    290866/1009Z/3/I
    361928/1396d/3/I
    4871302/1261d/3/I
    5441179/1314d/3/I
    6561180/1265d/3/I
    7701526/1647d/3/I
    8152075/2752d/3/I
    832−
    8741544/3422−
    9771058/26733/I/R
    10191050/19693/I/R
    SC151 (−)227/195−
     A1/684Z/3/I
     B8/3511514/1104Z/3/I
     Bw4/625 (+)429/−Z/3/I
     Cw439477/11713/d/N
     Cw0704130697/−3/d/N
    241512/3893/d/N
    331599/4703/d/N
    SC181 (−)−
     A2/118619/631−
     B50/5812 (+)785/1170d/3/I
     Bw6/419696/721d/3/I
     Cw040189742/730−
     Cw101741009/788−
     DR3/4285643/750−
     DR52/53552853/1063−
     DQ2/8599557/1248−
    SC19−60 (−)−
     A11/2930 (+)525−
     B8/4460333/873−
     Cw0675310/868−
     Cw0701125445/1714−
     DR3/7195133/1041−
     DR52/53197232/1010d/3/S
     DQ2212335/1032d/3/S
    307298/3918d/3/S
    363534/1958d/3/S
    • All patients had a negative HIV antibody test at or before the onset of symptoms (−). First positive HIV antibody test is indicated by +. DFOSx, days following onset of symptoms; ART, antiretroviral therapy; PC, poor compliance; 3, 3TC; d, d4T; E, efavirenz; I, indinavir; N, nevirapine; R, ritonavir; S, saquinavir; Z, zidovudine. 

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    Table 2

    Peptides

    NameSequenceHLAEpitope
    GSEGSEELRSLYA1p17 71–79
    ILKILKEPVHGVA2RT 476–484
    ACQACQGVGGPGHKA11p24 349–359
    AVDAVDLSHFLKA11Nef 84–92
    QVPQVPLRPMTYKA11Nef 73–82
    FNCFNCGGEFFYA29gp120 376–384
    DCKDCKTILKALB8p24 329–337
    FLKFLKEKGGLB8Nef 92–99
    GEIGEIYKRWIIB8p24 259–267
    GGKGGKKKYKLKB8p17 24–32
    GPKGPKVKQWPLB8RT 185–183
    SQRSQRRQDILDLWIY-B13Nef 103–127
     HTQGYFPDWQNY
    RYPRYPLTFGWCYKB18Nef 134–144
    PPIPPIPVGDIYB35p24 260–268
    VPLVPLRPMTYB35Nef 74–81
    NANNANPDCKTIB51p24 325–333
    TAFTAFTIPSIB51RT 295–302
    RAIRAIEAQQHLB51gp41 557–565
    HTQHTQGYFPDWQB57Nef 116–125
    ISPISPRTLNAWB57p24 147–155
    KAFKAFSPEVIPMFB57p24 162–172
    PIVPIVLPEKDSWB57RT 410–419
    TSTTSTLQEQIGWB57p24 240–249
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Early highly active antiretroviral therapy for acute HIV-1 infection preserves immune function of CD8+ and CD4+ T lymphocytes
Annette Oxenius, David A. Price, Philippa J. Easterbrook, Christopher A. O'Callaghan, Anthony D. Kelleher, Joseph A. Whelan, Glenn Sontag, Andrew K. Sewell, Rodney E. Phillips
Proceedings of the National Academy of Sciences Mar 2000, 97 (7) 3382-3387; DOI: 10.1073/pnas.97.7.3382

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Early highly active antiretroviral therapy for acute HIV-1 infection preserves immune function of CD8+ and CD4+ T lymphocytes
Annette Oxenius, David A. Price, Philippa J. Easterbrook, Christopher A. O'Callaghan, Anthony D. Kelleher, Joseph A. Whelan, Glenn Sontag, Andrew K. Sewell, Rodney E. Phillips
Proceedings of the National Academy of Sciences Mar 2000, 97 (7) 3382-3387; DOI: 10.1073/pnas.97.7.3382
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