Severity and Prognosis of Acute Human Immunodeficiency Virus Type 1 Illness: A Dose‐Response Relationship

Vanhems, Philippe; Lambert, Jean; Cooper, David A.; Perrin, Luc; Carr, Andrew; Hirschel, Bernard; Vizzard, Jeanette; Loés, Sabine Kinloch-de; Allard, R. W.

doi:10.1086/516289

Cited by 74 publications

(50 citation statements)

References 5 publications

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“…In contrast, these differences were not observed in chronically infected patients. Furthermore, several studies have suggested that symptomatic primary infection is associated with poorer subsequent outcomes and higher risk of disease progression (60)(61)(62). Consistent with this observation, we found that patients with an asymptomatic primary infection had significantly increased neutralization breadth that could be attributed to minor immune damage, also evidenced by higher CD4 ϩ /CD8 ϩ ratios (Fig.…”

Section: Figsupporting

confidence: 89%

Detection of Broadly Neutralizing Activity within the First Months of HIV-1 Infection

Sánchez-Merino

Fabra-García

Gonzàlez

et al. 2016

J Virol

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A fraction of HIV-1 patients are able to generate broadly neutralizing antibodies (bNAbs) after 2 to 4 years of infection. In rare occasions such antibodies are observed close to the first year of HIV-1 infection but never within the first 6 months. In this study, we analyzed the neutralization breadth of sera from 157 antiretroviral-naive individuals who were infected for less than 1 year. A range of neutralizing activities was observed with a previously described panel IMPORTANCEThere are very few individuals able to mount broadly neutralizing activity (bNA) close to the first year postinfection. It is not known how early in the infection cross-neutralizing responses can be induced. In the present study, we show that bNAbs, despite being rare, can be induced much earlier than previously thought. The identification of HIV-1-infected patients with these activities within the first months of infection and characterization of these responses will help in defining new immunogen designs and neutralization targets for vaccine-mediated induction of bNAbs. O ne of the main challenges for the development of a preventive human immunodeficiency virus type 1 (HIV-1) vaccine is the design of immunogens and immunization strategies that allow the induction of neutralizing antibody responses against multiple HIV-1 isolates. The main target of neutralizing antibodies is the trimeric envelope glycoprotein spike (Env). Unfortunately, when these recombinant proteins are used as immunogens, there is minimal induction of cross-reactive neutralizing antibody responses (1, 2). Despite these hurdles, high titers of broadly neutralizing antibodies (bNAbs) have been found in some chronically infected patients (3, 4). Data from many studies indicate that between 10 and 25% of patient sera displayed broadly neutralizing capacity against diverse HIV-1 strains (2-5), and one large study showed that 50% of sera from chronic infection can neutralize 50% of virus strains (6). Antibody responses have been studied extensively in these chronically infected patients, new bNAbs have been isolated, and the molecular determinants recognized by these antibodies have been characterized. Although these antibodies do not protect infected patients, they exert selective pressure on the virus (7-9). On the other hand, and more importantly, passive transfer of broadly neutralizing antibodies to monkeys and humanized mice effectively protects them against chimeric simianhuman immunodeficiency virus (SHIV) infection and HIV infection, respectively (10-18). Additionally, promising results have been obtained in recent years with approaches based on the production of broadly neutralizing antibodies against HIV and SHIV, or molecules resembling these antibodies, by adeno-associated vectors in animal models (19,20). In humans, passive transfer of bNAbs also has shown some efficacy in controlling viral replication in two recent studies, showing that passive transfer of mono-

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Section: Figsupporting

confidence: 89%

Detection of Broadly Neutralizing Activity within the First Months of HIV-1 Infection

Sánchez-Merino

Fabra-García

Gonzàlez

et al. 2016

J Virol

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“…HAART was initiated in nearly 60% of patients during this period, including initiation for PHIrelated severe symptoms in 20% of these patients. Previous studies on PHI have suggested that the number, duration, and/or severity of symptoms can predict faster disease progression to AIDS (23,24). Our findings are compatible with these previous studies.…”

Section: Discussionsupporting

confidence: 93%

“…In addition to these factors, events occurring during PHI could also determine the natural course of the disease. Initial studies suggested that patients with more symptoms related to primary PHI and longer duration of illness exhibit faster rates of progression to AIDS (9)(10)(11)(12)(13). Plasma viral load at a set point is also an independent predictor of disease progression (14,15).…”

Section: Introductionmentioning

confidence: 99%

Clinical Symptoms and Courses of Primary HIV-1 Infection in Recent Years in Japan

et al. 2011

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Background The natural course of HIV-1 infection includes 10 years of an asymptomatic period before the development of AIDS. However, in Japan, the disease progression process seems faster in recent years. Methods The study subjects were 108 new patients with primary HIV-1 infection during the period from 1997 through 2007. We evaluated their clinical symptoms and laboratory data, and then analyzed disease progression in 82 eligible patients. Disease progression was defined as a fall in CD4 count below 350/μL and/or initiation of antiretroviral therapy. Results Ninety percent of the patients were infected via homosexual intercourse. All patients had at least one clinical symptom (mean; 4.75±1.99) related to primary HIV-1 infection, with a mean duration of 23.2 days (±14.8) and 53.3% of them had to be hospitalized due to severe symptoms. The mean CD4 count and viral load at first visit were 390/μL (±220.1) and 4.81 log10/mL (±0.78), respectively. None developed AIDS during the study period. Estimates of risk of disease progression were 61.0% at 48 weeks and 82.2% at 144 weeks. In patients who required antiretroviral therapy, the median CD4 count was 215/μL (range, 52-858) at initiation of such therapy. Among the patients with a CD4 count of <350/μL at first visit, 53% never showed recovery of CD4 count (>350/μL) without antiretroviral therapy. Conclusion Despite possible bias in patient population, disease progression seemed faster in symptomatic Japanese patients with recently acquired primary HIV-1 infection than the previously defined natural course of the disease.

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“…vents occurring during acute human immunodeficiency virus type 1 (HIV-1) infection appear to be critical for the subsequent speed of disease progression, as indicated by the strong association between the duration and intensity of the acute infection syndrome and the time to AIDS (1)(2)(3)(4)(5). Moreover, antiretroviral treatment (ART) studies initiated during primary HIV-1 infection have shown that some rare individuals can gain spontaneous control over viral replication after treatment cessation (6), supporting the notion that changes in the earliest immunobiology may influence long-term viral control.…”

mentioning

confidence: 99%

Emergence of Individual HIV-Specific CD8 T Cell Responses during Primary HIV-1 Infection Can Determine Long-Term Disease Outcome

Streeck

Beckwith

et al. 2014

J Virol

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Events during primary HIV- 0009). While neither the breadth nor the magnitude of HIV-specific CD8 T cell responses showed an influence on the early viral set point, a broader HIV-specific CD8 T cell response targeting epitopes within HIV-1 Gag duringprimary HIV-1 infection was associated with slower disease progression. Moreover, the induction of certain HIV-specific CD8 T cell responses-but not others-significantly influenced the time to ART initiation. Individual epitope-specific CD8 T cell responses contribute significantly to HIV-1 disease control, demonstrating that the specificity of the initial HIV-specific CD8 T cell response rather than the restricting HLA class I molecule alone is a critical determinant of antiviral function. IMPORTANCEUnderstanding which factors are involved in the control of HIV-1 infection is critical for the design of therapeutic strategies for patients living with HIV/AIDS. Here, using a cohort of over 600 individuals with acute and early HIV-1 infection, we assessed in unprecedented detail the individual contribution of epitope-specific CD8 T cell responses directed against HIV-1 to control of viremia and their impact on the overall course of disease progression.

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Severity and Prognosis of Acute Human Immunodeficiency Virus Type 1 Illness: A Dose‐Response Relationship

Cited by 74 publications

References 5 publications

Detection of Broadly Neutralizing Activity within the First Months of HIV-1 Infection

Detection of Broadly Neutralizing Activity within the First Months of HIV-1 Infection

Clinical Symptoms and Courses of Primary HIV-1 Infection in Recent Years in Japan

Emergence of Individual HIV-Specific CD8 T Cell Responses during Primary HIV-1 Infection Can Determine Long-Term Disease Outcome

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