The implications of viral reservoirs on the elite control of HIV-1 infection

Buckheit, Robert W.; Salgado, María; Martins, Karen O.; Blankson, Joel N.

doi:10.1007/s00018-012-1101-7

Cited by 20 publications

(7 citation statements)

References 75 publications

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“…Spontaneous control of viral replication is rare, typically occurring in fewer than 5%–10% of all persons with HIV infection [1, 5]; it is also not well understood, particularly in the African context. A better understanding of spontaneous viral control could aid in development of new HIV treatment and cure options, prevention technologies, and vaccine design [6, 7].…”

mentioning

confidence: 99%

Control of the HIV-1 Load Varies by Viral Subtype in a Large Cohort of African Adults With Incident HIV-1 Infection

Price

Rida²,

Kilembe

et al. 2019

The Journal of Infectious Diseases

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Few human immunodeficiency virus (HIV)–infected persons can maintain low viral levels without therapeutic intervention. We evaluate predictors of spontaneous control of the viral load (hereafter, “viral control”) in a prospective cohort of African adults shortly after HIV infection. Viral control was defined as ≥2 consecutively measured viral loads (VLs) of ≤10 000 copies/mL after the estimated date of infection, followed by at least 4 subsequent measurements for which the VL in at least 75% was ≤10 000 copies/mL in the absence of ART. Multivariable logistic regression characterized predictors of viral control. Of 590 eligible volunteers, 107 (18.1%) experienced viral control, of whom 25 (4.2%) maintained a VL of 51–2000 copies/mL, and 5 (0.8%) sustained a VL of ≤50 copies/mL. The median ART-free follow-up time was 3.3 years (range, 0.3–9.7 years). Factors independently associated with control were HIV-1 subtype A (reference, subtype C; adjusted odds ratio [aOR], 2.1 [95% confidence interval {CI}, 1.3–3.5]), female sex (reference, male sex; aOR, 1.8 [95% CI, 1.1–2.8]), and having HLA class I variant allele B*57 (reference, not having this allele; aOR, 1.9 [95% CI, 1.0–3.6]) in a multivariable model that also controlled for age at the time of infection and baseline CD4+ T-cell count. We observed strong associations between infecting HIV-1 subtype, HLA type, and sex on viral control in this cohort. HIV-1 subtype is important to consider when testing and designing new therapeutic and prevention technologies, including vaccines.

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confidence: 99%

Control of the HIV-1 Load Varies by Viral Subtype in a Large Cohort of African Adults With Incident HIV-1 Infection

Price

Rida²,

Kilembe

et al. 2019

The Journal of Infectious Diseases

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“…Nevertheless, a latent reservoir is established rapidly in all HIV-1-infected individuals (42). Latently infected cells can be detected in the rare individuals who spontaneously control HIV-1 infection without ART (43). Early ART restricts the size of the reservoir (22, 44) but does not block its establishment (42).…”

Section: Why Does Hiv-1 Establish Latent Infection?mentioning

confidence: 99%

The Latent Reservoir for HIV-1: How Immunologic Memory and Clonal Expansion Contribute to HIV-1 Persistence

Murray

Kwon

Farber

et al. 2016

The Journal of Immunology

126

113

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Combination antiretroviral therapy (ART) for HIV-1 infection reduces plasma virus levels to below the limit of detection of clinical assays. However, even with prolonged suppression of viral replication with ART, viremia rebounds rapidly after treatment interruption. Thus ART is not curative. The principal barrier to cure is a remarkably stable reservoir of latent HIV-1 in resting memory CD4+ T cells. Here we consider explanations for the remarkable stability of the latent reservoir. Stability does not appear to reflect replenishment from new infection events but rather normal physiologic processes that provide for immunologic memory. Of particular importance are proliferative processes that drive clonal expansion of infected cells. Recent evidence suggests that in some infected cells, proliferation is a consequence of proviral integration into host genes associated with cell growth. Efforts to cure HIV-1 infection by targeting the latent reservoir may need to consider the potential of latently infected cells to proliferate.

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“…Elite controllers (EC) who spontaneously control HIV replication without ART, preserve CD4+ T cells in the gut mucosa [41], have lower levels of immune activation and smaller HIV reservoirs [42]. Vesterbacka et al (2017) found that EC’s have a richer gut microbiota with a distinct metabolic profile that resembles that of HIV-uninfected adults, and that is vastly unique from ART-treated HIV-infected individuals (Table 1) [43**].…”

Section: Introductionmentioning

confidence: 99%