Prevalence of HIV-1 Dual Infection in Long-Term Nonprogressor–Elite Controllers

Pernas, María; Casado, Concepción; Sandonís, Virginia; Arcones, Carolina; Rodrı́guez, Carmen; Ruiz‐Mateos, Ezequiel; Arellano, Eva Ramírez de; Rallón, Norma; Val, Margarita Del; Grau, Eulàlia; López-Vazquez, Mariola; Leal, Manuel; Romero, Jorge del; Galíndez, C. López

doi:10.1097/qai.0b013e31829bdc85

Cited by 8 publications

(16 citation statements)

References 30 publications

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“…6A, right panel). This segregation supports that these were double-infected subjects, as previously reported for EC4 (19). All patients had an R5 tropism, and, in the case of TC, the tropism did not change after viral replication.…”

Section: Fig 4 Hiv-1-specific Cd8supporting

confidence: 90%

Factors Leading to the Loss of Natural Elite Control of HIV-1 Infection

Pernas

Tarancón-Díez

Rodríguez-Gallego

et al. 2018

J Virol

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100

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HIV-1 elite controllers (EC) maintain undetectable viral load (VL) in the absence of antiretroviral treatment. However, these subjects have heterogeneous clinical outcomes including a proportion loosing HIV-1 control over time. In this work we compared, in a longitudinal design, transient EC, analyzed before and after the loss of virological control, versus persistent EC. The aim was to identify factors leading to the loss of natural virological control of HIV-1-infection with a longitudinal retrospective study design. Gag-specific T-cell response was assessed by intracellular poly-cytokine production quantified by flow cytometry. Viral diversity and sequence-dating were performed in proviral DNA by PCR amplification at limiting dilution in and genes. The expression profile of 70 serum cytokines and chemokines was assessed by multiplex immunoassays. We identified transient EC as subjects with low Gag-specific T-cell polyfunctionality, high viral diversity and high proinflammatory cytokines levels before the loss of control. Gag-specific T-cell polyfunctionality was inversely associated with viral diversity in transient controllers before the loss of control (r=-0.8;=0.02). RANTES was a potential biomarker of transient control. This study identified, virological and immunological factors including inflammatory biomarkers associated with two different phenotypes within EC. These results may allow a more accurate definition of EC, which could help in a better clinical management of these individuals and in the development of future curative approaches. There is a rare group of HIV-infected patients who have the extraordinary capacity to maintain undetectable viral load levels in the absence of antiretroviral treatment, the so called HIV-1 elite controllers (EC). However, there is a proportion within these subjects that eventually loses this capability. In this work we found differences in virological and immune factors including soluble inflammatory biomarkers between subjects with persistent control of viral replication and EC that will loss the virological control. The identification of these factors could be a key point for a right medical care of those EC who are going to lose the natural control of viral replication, and for the design of future immunotherapeutic strategies using as a model the natural persistent control of HIV-infection.

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Section: Fig 4 Hiv-1-specific Cd8supporting

confidence: 90%

Factors Leading to the Loss of Natural Elite Control of HIV-1 Infection

Pernas

Tarancón-Díez

Rodríguez-Gallego

et al. 2018

J Virol

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100

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“…While subtypes B, F1 and C are common HIV-1 clades circulating in Brazil [42], subtype A1 has been only described in one case [43]. Three individuals (one EC and two VC) were dually infected with strains of the same (B) or different (B and F1) subtypes, resulting in a prevalence of dual HIV-1 infection (13%) comparable to that previously estimated in a Spanish cohort of LTNP-EC (20%) [44]. Prediction of coreceptor usage further revealed a significant frequency (30–100%) of X4-tropic clones in proviral quasispecies of two PEC and one VC.…”

Section: Discussionmentioning

confidence: 82%

Highly divergent patterns of genetic diversity and evolution in proviral quasispecies from HIV controllers

et al. 2017

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BackgroundOngoing intra-host HIV-1 evolution has been shown in individuals that naturally suppress the viremia to low levels (HIV controllers) by the analysis of the RNA in plasma compartment. Detection of evolution at the DNA proviral compartment in HIV controllers, however, has been more challenging and the precise correlation between the systemic viral suppression level and rate of reservoir’s reseeding in those individuals is not fully understood. In this sense, we examined the proviral DNA quasispecies by single genome amplification of the env gene in a cohort of 23 HIV controllers from Brazil, divided in three groups, according to the level of systemic viral suppression: (1) elite controllers with persistent undetectable viral load (PEC, n = 6); (2) elite controllers with occasional episodes of transient (51–400 copies/mL) viremia (EEC, n = 7); and (3) viremic controllers with persistent low-level (80–2000 copies/mL) viremia (VC, n = 10).ResultsThe HIV-1 diversity of the PBMC-associated proviral quasispecies in EC was significantly (P < 0.01) lower than in VC, but not significantly different between PEC and EEC groups. We detected a considerable variation in the average pairwise nucleotide distance and proportion of unique sequences in the HIV-1 proviral quasispecies of PEC and EEC. Some PEC and EEC displayed highly homogenous proviral populations with large clusters of identical sequences, while others exhibited relatively diverse proviral populations with a high proportion of unique sequences comparable to VC subjects. The long-term (10–15 years) follow-up of the HIV-1 proviral populations revealed a complete evolutionary stasis in one PEC and measurable divergence rates in one EEC [3.1 (1.2–5.6) × 10−3 substitutions/site/year and one VC [2.9 (0.7–5.1) × 10−3 substitutions/site/year].ConclusionsThere is no simple relationship between systemic viral suppression and intra-host proviral diversity or rate of reservoir’s reseeding in chronically infected HIV controllers. Our results demonstrate that very divergent patterns of intra-host viral diversity and divergence could be detected in the setting of natural suppression of HIV-1 replication and that ongoing evolution and reseeding of the PBMC proviral reservoir occurs in some elite controllers.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-017-0354-5) contains supplementary material, which is available to authorized users.

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“…In previous reports, we described several cases of DI in LTNP-EC patients [ 18 , 19 ]. In the present study, we have included two DI patients (MDM, LTNP-5) and an additional patient with similar characteristics (LTNP-15).…”

Section: Methodsmentioning

confidence: 99%

“…According to his clinical progression, this patient was also classified as LTNP-EC. Phylogenetic analysis for the detection of DI was performed as previously described [ 19 ]. Proviral DNA was obtained from 1x10 7 peripheral blood mononuclear cells (PBMC) cells by a standard phenol-extraction method.…”

Section: Methodsmentioning

confidence: 99%

HIV-1 Dual Infected LTNP-EC Patients Developed an Unexpected Antibody Cross-Neutralizing Activity

et al. 2015

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This study evaluated the neutralization breadth in dually infected (DI) HIV-1 long-term non-progressor elite controller patients (LTNP-EC) using a representative minipanel of 6 viruses from 5 different subtypes. Our results showed an improved neutralization breadth in DI LTNP-EC patients when compared with matched LTNP single-infected patients. The role of viral diversity in neutralization was estimated with the Shannon Entropy and the p-distance in viral quasispecies. We found a positive correlation between neutralization breadth and diversity within the viral quasispecies. This correlation could explain why a group of LTNP-EC patients developed a broad neutralizing response despite having undetectable levels of viremia.

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Prevalence of HIV-1 Dual Infection in Long-Term Nonprogressor–Elite Controllers

Cited by 8 publications

References 30 publications

Factors Leading to the Loss of Natural Elite Control of HIV-1 Infection

Factors Leading to the Loss of Natural Elite Control of HIV-1 Infection

Highly divergent patterns of genetic diversity and evolution in proviral quasispecies from HIV controllers

HIV-1 Dual Infected LTNP-EC Patients Developed an Unexpected Antibody Cross-Neutralizing Activity

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