HIV Antibody Characterization as a Method to Quantify Reservoir Size During Curative Interventions

Burbelo, Peter D.; Bayat, Ahmad; Rhodes, Craig; Hoh, Rebecca; Martin, Jeffrey N.; Fromentin, Rémi; Chomont, Nicolas; Hütter, Gero; Kovacs, Joseph A.; Deeks, Steven G.

doi:10.1093/infdis/jit667

Cited by 46 publications

(62 citation statements)

References 15 publications

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“…Although routine antibody tests to confirm HIV-status cannot be recommended in this population, the strong relationship between cumulative viral load and anti-gp120 IgG levels, support a possible role for antibody quantification to assess extent of virological control or reservoir size[30]. These assays might also be used to improve clinical management since high HIV-antibody quantity or seropositivity after early-ART could be a marker of poor adherence, inappropriate dose, drug absorbance/metabolism issues, or these factors combined.…”

Section: Discussionmentioning

confidence: 99%

Reactivity of routine HIV antibody tests in children who initiated antiretroviral therapy in early infancy as part of the Children with HIV Early Antiretroviral Therapy (CHER) trial: a retrospective analysis

Payne

Mkhize

Otwombe

et al. 2015

The Lancet Infectious Diseases

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Background Early ART and virological suppression may impact on evolving antibody responses to HIV-infection. We evaluated frequency and predictors of seronegativity in infants starting early ART. Methods HIV-antibody results were compared between two of three arms of the Children with HIV Early Antiretroviral Therapy (CHER) trial: HIV-infected infants aged <12 weeks with CD4 ≥25% randomised to early-limited ART for 96 weeks (ART-96W) or deferred ART until clinical/immunological progression (ART-Def). HIV-infection was diagnosed by DNA PCR and RNA >1000 copies/ml. ART started at median age 7 and 23 weeks respectively. Antibody was measured from all available stored samples, ART-96W (n=109) and ART-Def (n=75), at trial week 84 (median age 92 (IQR 90.6–93.4) weeks) using 3 assays: 4th generation EIA HIV-antigen/antibody combination; HIV-1/2 rapid-antibody test and quantitative anti-gp120 IgG ELISA. Findings More ART-96W were seronegative than ART-Def by EIA (46% versus 11%, p<0.0001) and rapid-antibody test (53% versus 14%, p<0.0001). Anti-gp120 IgG was lower in ART-96W versus ART-Def (median 230 (133–13,129) versus 6,870 (IQR 1,706–53,645)μg/μl). Starting ART between 12-24 versus 0-12 weeks increased odds of seropositivity 13.7-fold (95%CI 3.1-60.2). All children starting ART aged >24 weeks were seropositive. Cumulative viral load to week 84 correlated with anti-gp120 IgG levels (coefficient=0.54, p<0.0001) and increased odds of seropositivity OR 1.58 (95%CI 1.1-2.3) adjusted for ART-initiation age. Interpretation Almost half children starting ART before aged 12 weeks were HIV-seronegative by at aged ∼2 years. HIV-antibody tests cannot be used to re-confirm HIV-diagnosis in children starting early-ART. Long-term consequences of seronegativity need further study. Funding Wellcome Trust, Medical Research Council, National Institutes of Health.

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Section: Discussionmentioning

confidence: 99%

Reactivity of routine HIV antibody tests in children who initiated antiretroviral therapy in early infancy as part of the Children with HIV Early Antiretroviral Therapy (CHER) trial: a retrospective analysis

Payne

Mkhize

Otwombe

et al. 2015

The Lancet Infectious Diseases

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“…The avidity and concentration of HIV antibodies appears to change with declining numbers of latently infected cells 91 and markers of T cell activation and proliferation have been shown to correlate with the number of latently infected cells in multiple studies 29 .…”

Section: Novel Biomarkers To Analyse/quantify Hiv Reservoirsmentioning

confidence: 99%

International AIDS Society global scientific strategy: towards an HIV cure 2016

Deeks¹,

Lewin²,

Ross³

et al. 2016

Nat Med

388

348

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Antiretroviral therapy is not curative. Given the challenges in providing life-long therapy to a global population of over 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy.

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“…Table 7 summarizes the prevalence and isotype/subclass distribution of antibody responses against non-Env proteins. The most frequently recognized targets are structural p17, p24 and pol -derived p31 and p66 ( table 7 ) [27,48,126,[143][144][145][146] . In fact, diagnostic tests, such as confirmatory Western blot, are based on the additional detection of p17, p24 and p31-specific IgG (e.g.…”

Section: Igg Subclass Distribution Of Env-specific Antibodies During mentioning

confidence: 99%

“…For example, it has been shown that p17, p24 and PR-specific antibodies were associated with nonprogression or a stable clinical status [45,144,145,152,160] . On the other hand, p31-specific antibodies were found to be associated with a worse prognosis, and results obtained for Tat-and Vprspecific responses were controversial ( table 7 ) [45,46,[146][147][148]155] . The use of antibody reactivity patterns as prognostic markers has not yet been established for the clinical practice.…”

Section: Igg Subclass Distribution Of Env-specific Antibodies During mentioning

confidence: 99%

HIV-Specific Antibody Responses in HIV-Infected Patients: From a Monoclonal to a Polyclonal View

Gallerano¹,

Cabauatan²,

Sibanda³

et al. 2015

Int Arch Allergy Immunol

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HIV infections represent a major global health threat, affecting more than 35 million individuals worldwide. High infection rates and problems associated with lifelong antiretroviral treatment emphasize the need for the development of prophylactic and therapeutic immune intervention strategies. It is conceivable that insights for the design of new immunogens capable of eliciting protective immune responses may come from the analysis of HIV-specific antibody responses in infected patients. Using sophisticated technologies, several monoclonal neutralizing antibodies were isolated from HIV-infected individuals. However, the majority of polyclonal antibody responses found in infected patients are nonneutralizing. Comprehensive analyses of the molecular targets of HIV-specific antibody responses identified that during natural infection antibodies are mainly misdirected towards gp120 epitopes outside of the CD4-binding site and against regions and proteins that are not exposed on the surface of the virus. We therefore argue that vaccines aiming to induce protective responses should include engineered immunogens, which are capable of focusing the immune response towards protective epitopes.

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HIV Antibody Characterization as a Method to Quantify Reservoir Size During Curative Interventions

Cited by 46 publications

References 15 publications

Reactivity of routine HIV antibody tests in children who initiated antiretroviral therapy in early infancy as part of the Children with HIV Early Antiretroviral Therapy (CHER) trial: a retrospective analysis

Reactivity of routine HIV antibody tests in children who initiated antiretroviral therapy in early infancy as part of the Children with HIV Early Antiretroviral Therapy (CHER) trial: a retrospective analysis

International AIDS Society global scientific strategy: towards an HIV cure 2016

HIV-Specific Antibody Responses in HIV-Infected Patients: From a Monoclonal to a Polyclonal View

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