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. 2015 Nov 9;18(1):20497. doi: 10.7448/IAS.18.1.20497

Table 1D.

Summary of the outcome measures of efficacy assessed in therapeutic HIV vaccine clinical trials with analytical treatment interruptions: viral vectors

Vaccine Study design Primary outcome measure(s) Other relevant efficacy outcome measures Main findings References
MVA-Nef (modified vaccinia Ankara virus encoding the HIV-1 LAI Nef gene) Single-arm study

  • Safety

  • Immunogenicity

  • Time to viral rebound following ATI

  • Time to peak viremia following ATI

  • Peak viremia following ATI

  • Number of participants who resumed ART

 The vaccine was safe and immunogenic but did not prevent viral rebound during ATI. However, in the majority of participants, viral load during ATI and CD4 T cell counts were improved compared to pre-ART levels. [146]
MVA.HIVA (modified vaccinia Ankara virus encoding clade A HIV-1 Gag p24/p17 and a multi-CTL epitope) Extension of a single-arm study by Dorrell et al. [147]; in this extension study, participants were boosted then underwent an ATI

  • IL-10 production

  • Immunogenicity

  • Criteria for ART resumption (pVL and CD4 T cell count)

 Vaccination did not increase IL-10 levels. However, IL-10 levels did increase during ATI and were correlated with pVL. [148]
MVA-B (modified vaccinia Ankara virus encoding monomeric gp120 and the clade B fused Gag-Pol-Nef polyprotein)±disulfiram RCT

  • Safety and immunogenicity

  • Kinetics of viral load rebound following ATI

  • Time and criteria to resume ART

  • Cell-associated HIV-1 RNA

  • HIV-1 proviral DNA levels

 The vaccine was safe and immunogenic but did not significantly affect viral load rebound after ATI or the size of the viral reservoir, whether given alone or with disulfiram. [149]
ALVAC-HIV vCP1452 (a recombinant canarypox virus encoding HIV-1 Env, Gag and protease and part of the Nef and RT proteins) RCT

  • pVL at the end of the ATI

  • CD4 T cell count

  • Percentage of CD4 T cells

  • Kinetics of viral load rebound

  • Viral load set point following ATI

 ATI, but not vaccination, contributed to enhanced viral control. [150]
RCT

  • Immunogenicity

  • Time to resume ART (viral rebound >50 000 copies/ml following ATI)

  • CD4 T cell count

  • HIV-1 DNA in PBMCs

 Although immunogenic, the vaccine-induced immune responses were associated with reduced time to resume ART and greater viral rebound. [151]
RCT

  • Safety

  • Immunogenicity

  • Viral load set point during ATI

  • CD4 T cell count

  • Percentage of CD4 T cells

 The mean viral load set point during ATI did not differ between the two vaccine groups (second vaccine group received autologous DC loaded with ALVAC vCP1452). [152]
ALVAC vCP1452 + rgp160 Two-arm study (vaccinated participants from a previous study vs. unvaccinated participants); participants initiated ART during early HIV infection

  • Time to viral rebound after ATI

  • Initial rate of viral rebound after ATI

  • Peak viremia during ATI

  • CD4 T cell count

 ATI was followed by viral rebound in all subjects and was not affected by vaccination. [105]
ALVAC-HIV vCP1452±IL-2 RCT

  • pVL at Weeks 11 and 12 post-ATI

  • Viral load set-point during ATI

  • Peak viral load during ATI

  • CD4 T cell count

  • CD8 T cell count

  • Disease progression, opportunistic infections or acute retroviral syndrome after ATI

 Immunization with ALVAC resulted in a statistically significant reduction in viral rebound following ATI. The addition of IL-2 to ALVAC increased CD4 T cell counts but did not further reduce viral rebound. [153]
ALVAC-HIV vCP1452±Remune® RCT; participants initiated ART during acute HIV infection

  • Percentage of participants with pVL≤1000 HIV-1 RNA copies/ml at 24 weeks post-ATI

  • CD4 T cell count

  • CD8 T cell count

  • Cell-associated HIV-1 DNA and RNA

  • Viral load set point during ATI

  • Percentage of participants with pVL ≤400 HIV-1 RNA copies/ml during entire ATI period

  • Time to reach pVL > 1000 HIV-1 RNA copies/ml after ATI

 Although immunogenic, the vaccines did not induce virologic control during ATI. [106]
RCT

  • Time to viral rebound >50 HIV-1 RNA copies/ml

  • Safety

  • CD4 T cell count

  • Viral load 12 weeks after ATI

  • Viral load set point following ATI

  • Time to ART resumption

  • Time to meet criteria to resume ART

 ALVAC±Remune® was associated with an increased time to meet the predefined criteria to restart ART and tended to delay viral rebound, but did not reduce the viral set point during ATI. [120]
Viral reservoir substudy of Ref. [120]

  • Size of the viral reservoir

  • CD4 T cell count

 ALVAC±Remune® did not affect the size of the viral reservoir. [154]
ALVAC-HIV vCP1433 (a recombinant canarypox virus encoding part of HIV-1 Env, Gag, protease and multiple immunodominant Nef and Pol CTL epitopes) Single-arm study

  • Percentage of participants who remained off ART 44 weeks after the initiation of the ATI among those having at least one HIV-specific T cell response during the vaccination period

  • CD4 T cell count

  • Percentage of participants who resumed ART (pVL > 50,000 copies/ml within eight weeks of ATI or two consecutive measurements > 10,000 copies/ml any time after eight weeks of ATI)

  • CD4 and/or CD8 HIV-specific immune responses

 11% of the participants with at least one HIV-specific T cell response during vaccination remained off ART 44 weeks after the initiation of ATI. [155]
ALVAC-HIV vCP1433 + HIV Lipo6-Tfollowed by three cycles of IL-2. The Lipo-6T vaccine is a mixture of the tetanus toxoid TT-830–843 class II restricted universal CD4 T cell epitope and five HIV-1LAI peptides: Gag 17–35, Gag 235–284, Nef 66–97, Nef 116–145 and Pol 325–355. RCT

  • Percentage of participants who responded to both HIV p24 and at least one of 11 HIV peptides

  • CD4 T cell count

  • HIV-1 DNA in PBMC

  • HIV-specific CD8 T cell responses (IFN-γ production)

  • Percentage of participants experiencing virologic success following ATI

  • Viral load set point during ATI

  • Time to virologic failure

 The vaccines induced both HIV-specific CD4 and CD8 T cell responses. Vaccine-induced immune responses predicted virologic control during ATI. [109]
RCT; participants initiated ART during acute HIV infection

  • Percentage of participants with a CD4 T cell response to HIV p24 or to one HIV peptide at Week 36

  • HIV-specific CD8 T cell responses

  • Percentage of participants with virologic success at study end

  • Time without ART

  • HIV-1 DNA in PBMC

  • CD4 T cell count

 Vaccination did not induce CD4 T cell immune responses, had a transient impact on CD8 T cell IFN-γ responses and had no effect on viral rebound during ATI. [107]
rFPV vaccines (recombinant fowlpox virus that encodes HIV Gag/Pol±human IFN-γ) Extension study of an RCT by Emery et al. [156] in which participants who had initiated ART during acute HIV infection received placebo or rFPV±human IFN-γ; in this extension study, participants received a booster and then underwent ATI one week later.

  • Time-weighted mean area-under-the-curve change from baseline log pVL until ART resumption

  • Kinetics and rate of pVL rebound

  • Median time to ART resumption

 Immunization with rFPV Gag/Pol + IFN-γ, but not with rFPV Gag/Pol or placebo, was associated with a trend toward reduced plasma viral load following ATI. [108]
Replication-defective adenovirus 5 HIV-1 Gag RCT

  • Time averaged area-under-the curve analysis of pVL during ATI

  • Viral load set point after ATI

  • CD4 T cell count

 The vaccine did not significantly affect viral rebound kinetics during ATI. [157]
Follow-up study of Ref. [157]

  • pVL set point (mean of the ATI weeks 12 and 16 pVL)

  • Immunogenicity

 The majority of the initial viral suppressors had been vaccinated; this suppression was transient. [158]
Retrospective analysis of Ref. [157]

  • Cell-associated HIV-1 DNA and RNA

  • Residual viremia (SCA)

  • Immunogenicity

 Vaccination had a modest, transient impact on residual viremia. [159]