Higher Set Point Plasma Viral Load and More-Severe Acute HIV Type 1 (HIV-1) Illness Predict Mortality among High-Risk HIV-1-Infected African Women

Lavreys, Ludo; Baeten, Jared M.; Chohan, Vrasha; McClelland, R. Scott; Hassan, Wisal M.; Richardson, Barbra A.; Mandaliya, Kishorchandra; Achola, J. O. Ndinya; Overbaugh, Julie

doi:10.1086/503258

Cited by 147 publications

(124 citation statements)

References 41 publications

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“…However viral load assessed at 6 months predicted well negatively with symptoms free duration, which is in agreement with the generally accepted view that the viral set point i.e. the stable viral load attained between 6 months to 1 year, is a more reliable predictor of disease progression than initial viral load [35] [36].…”

Section: Discussionsupporting

confidence: 88%

High Incidence of Pulmonary Tuberculosis in ART Naive Remunerated Blood Donors with Human Immunodeficiency Virus Type-1 Infection: Possible Role of Iron Overload

Chattopadhya¹,

Baveja²

2018

JBM

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Iron overload is reported to be associated with immune alterations and increased susceptibility to infections. HIV infection is characterized by progressive immunodeficiency leading to invasion by opportunistic pathogens. It was of interest to find out if disease course in HIV type-1 infection could have any relation with alteration in body iron status among individuals with history of oral iron intake. A follow-up study of immunologic and virologic markers in relation to disease progression was undertaken on asymptomatic HIV-1 positive blood donors with history of oral iron intake (subgroup I) compared to those without such history (subgroup II). High serum iron was associated with elevated levels of Th 2 category of cytokines, heightened immune activation, faster decline in CD4 + T lymphocyte count and higher viral set point. Pulmonary tuberculosis (PT) was the most common AIDS related illness (ARI) (>70%) recorded among subgroup I compared to non-PT category of ARI. Median ARI free duration (months) was shorter among those who developed PT compared to those developing non-PT category of ARI i.e. 30 (95% CI as 26,32) versus 67(95% CI as 60,71) in subgroup I and 47 (95% CI as 42,49) versus 80 (95% CI as 72,87) in subgroup II (P < 0.001 for PT versus non-PT in both subgroups). Median survival duration (months) in the PT versus non-PT categories of ARI was 47 (95% CI as 42,48) versus 95 (95% CI as 90,100) in subgroup I and 71 (95% CI as 65,76) versus 107 (95% CI as 102,112) in subgroup II (P < 0.001 for PT versus non-PT in both subgroups). The present study indicates that body iron overload resulting from excess intake of iron may be associated with qualitative defects in cell mediated im-

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Section: Discussionsupporting

confidence: 88%

High Incidence of Pulmonary Tuberculosis in ART Naive Remunerated Blood Donors with Human Immunodeficiency Virus Type-1 Infection: Possible Role of Iron Overload

Chattopadhya¹,

Baveja²

2018

JBM

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“…It is also evident from this figure that QA039 had a stable and moderately high viral load, on the order of 4 to 5 log 10 copies/ml of plasma, through the almost 7 years of available follow-up. This viral load pat- tern is typical for individuals in this cohort (19,20) and suggests that hypermutation did not significantly impair HIV-1 replication in this individual.…”

Section: Resultsmentioning

confidence: 53%

“…Individuals in the present study were part of a prospective seroincident cohort of high-risk women in Mombasa, Kenya (25). Methods for determining the timing of HIV-1 infection and measuring plasma viral load by the Gen-Probe HIV-1 viral load assay and CD4 count have been described previously (19). The 28 women included in the present study had a blood sample taken within the first year of infection, were antiretroviral naive at the time of sample collection, and were not dually infected (32).…”

Section: Methodsmentioning

confidence: 99%

Analysis of the Percentage of Human Immunodeficiency Virus Type 1 Sequences That Are Hypermutated and Markers of Disease Progression in a Longitudinal Cohort, Including One Individual with a Partially Defective Vif

Piantadosi

Humes

Chohan

et al. 2009

J Virol

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Hypermutation, the introduction of excessive G-to-A substitutions by host proteins in the APOBEC family, can impair replication of the human immunodeficiency virus (HIV). Because hypermutation represents a potential antiviral strategy, it is important to determine whether greater hypermutation is associated with slower disease progression in natural infection. We examined the level of HIV-1 hypermutation among 28 antiretroviral-naive Kenyan women at two times during infection. By examining single-copy gag sequences from proviral DNA, hypermutation was detected in 16 of 28 individuals. Among individuals with any hypermutation, a median of 15% of gag sequences were hypermutated (range, 5 to 43%). However, there was no association between the level of gag hypermutation and the viral load or CD4 count. Thus, we observed no overall relationship between hypermutation and markers of disease progression among individuals with low to moderate levels of hypermutation. In addition, one individual sustained a typical viral load despite having a high level of hypermutation. This individual had 43% of gag sequences hypermutated and harbored a partially defective Vif, which was found to permit hypermutation in a peripheral blood mononuclear cell culture. Overall, our results suggest that a potential antiviral therapy based on hypermutation may need to achieve a substantially higher level of hypermutation than is naturally seen in most individuals to impair virus replication and subsequent disease progression.Interactions between the human immunodeficiency virus type 1 (HIV-1) protein Vif (for viral infectivity factor) and antiviral host factors in the APOBEC family (for apolipoprotein B mRNA editing enzyme, catalytic polypeptide) have recently attracted interest as potential targets for antiviral therapy (10,13,16,26,28,40). One of the mechanisms by which APOBEC3G, a cytidine deaminase, may impair HIV-1 replication is through the introduction of C-to-U lesions in the negative-sense DNA strand during reverse transcription (RT). This process, known as hypermutation, results in excessive G-to-A changes in the HIV-1 coding strand, leading to premature stop codons and other potentially disruptive mutations (24). APOBEC3G activity is typically counteracted by the HIV-1 protein Vif, which targets it for degradation by the proteasome (38). This prevents APOBEC from being incorporated into nascent virions and causing hypermutation. However, Vif activity in vivo is imperfect, as demonstrated by the observation of hypermutated sequences in HIV-infected individuals (9,17,18,31,42). Because hypermutation is expected to impair virus replication, recent efforts have focused on characterizing hypermutation in HIV-infected individuals and examining its relationship with disease progression.The relationship between hypermutation and markers of disease progression has been addressed in two different ways. In three studies, markers of disease progression were compared between individuals with or without hypermutation detected by population sequen...

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“…Preclinical (usually NHP) studies have established surrogate markers for vaccine efficacy. Thus far, the most relevant marker identified as a determinant of disease outcome is the reduction of plasma HIV genome RNA levels following infection (Lavreys, Baeten et al 2006). The viral set point is a consistent marker for determining disease progression; i.e.…”

Section: Evaluation Of Immunotherapies and Vaccines In Human Trialsmentioning

confidence: 99%

“…The viral set point is a consistent marker for determining disease progression; i.e. the higher the viral set point, the more likely a patient will progress to AIDS (Lavreys, Baeten et al 2006;Kelley, Barbour et al 2007) The levels of CD4+T cells in the blood of infected individuals can also act as a surrogate of disease progression (Chouquet, Autran et al 2002). However, the correlation between CD4+ T cell levels in the blood and disease progression becomes more significant closer to the onset of AIDS.…”

Section: Evaluation Of Immunotherapies and Vaccines In Human Trialsmentioning

confidence: 99%

Immunotherapies and Vaccines

Eugene¹,

Ross²

2011

HIV and AIDS - Updates on Biology, Immunology, Epidemiology and Treatment Strategies

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Higher Set Point Plasma Viral Load and More-Severe Acute HIV Type 1 (HIV-1) Illness Predict Mortality among High-Risk HIV-1-Infected African Women

Cited by 147 publications

References 41 publications

High Incidence of Pulmonary Tuberculosis in ART Naive Remunerated Blood Donors with Human Immunodeficiency Virus Type-1 Infection: Possible Role of Iron Overload

High Incidence of Pulmonary Tuberculosis in ART Naive Remunerated Blood Donors with Human Immunodeficiency Virus Type-1 Infection: Possible Role of Iron Overload

Analysis of the Percentage of Human Immunodeficiency Virus Type 1 Sequences That Are Hypermutated and Markers of Disease Progression in a Longitudinal Cohort, Including One Individual with a Partially Defective Vif

Immunotherapies and Vaccines

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