Antiretroviral Therapy for HIV-2 Infected Patients

Na, Smith; Shaw, T. R. D.; Berry, Neil; Vella, Cherelyn; Okorafor, L.; Taylor, Debra L.; Ainsworth, Jonathan; Choudhury, Aklak; Daniels, Rod S.; El-Gadi, S. M. A.; Fakoya, Ade; Moyle, Graeme; Oxford, John; Tedder, Richard S.; O’Shea, Siobhan; Ruiter, Annemiek de; Breuer, Judith

doi:10.1053/jinf.2001.0792

Cited by 41 publications

(40 citation statements)

References 22 publications

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“…In agreement with previous reports (1,19,29,40,51), we documented poor CD4 T cell recovery in ART-treated HIV-2 ϩ individuals, even in those with evidence of viral suppression. Our findings suggest that persistent hyperimmune activation may be a main determinant of this impaired immune reconstitution.…”

Section: Discussionsupporting

confidence: 93%

“…In order to further dissect the impact of cellassociated viral DNA and RNA upon HIV-2 immunopathogenesis, we assessed these parameters in patients receiving ART (Table 2). This cohort exhibited significantly lower CD4 T cell counts than untreated HIV-2 ϩ individuals did (P ϭ 0.0046), in agreement with previous reports showing a limited CD4 T cell recovery in ART-treated HIV-2 infection (1,19,29,40,51,56). Viremia levels were similar in the treated and untreated HIV-2 cohorts, due to the low-level viremia detected in some of the ART-treated HIV-2 ϩ patients ( Table 2).…”

Section: Relationship Of Plasma and Cell-associated Viral Load With Csupporting

confidence: 91%

“…Importantly, despite the lack of clinical trials of antiretroviral therapy (ART) in HIV-2 infection, the majority of reports showed poor immunological recovery in ART-treated HIV-2 ϩ patients, even in the context of suppression of viremia (1,19,29,40,51,56). A rapid emergence of drug-associated mutations in HIV-2 ϩ patients under ART has also been reported (7, 13-15, 25, 29, 41, 47, 48), suggesting that there is some ongoing viral replication.…”

mentioning

confidence: 99%

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Cell-Associated Viral Burden Provides Evidence of Ongoing Viral Replication in Aviremic HIV-2-Infected Patients

Soares¹,

Tendeiro

Foxall

et al. 2011

J Virol

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Viremia is significantly lower in HIV-2 than in HIV-1 infection, irrespective of disease stage. Nevertheless, the comparable proviral DNA burdens observed for these two infections indicate similar numbers of infected cells. Here we investigated this apparent paradox by assessing cell-associated viral replication. We found that untreated HIV-1-positive (HIV-1 ؉ ) and HIV-2 ؉ individuals, matched for CD4 T cell depletion, exhibited similar gag mRNA levels, indicating that significant viral transcription is occurring in untreated HIV-2 ؉ patients, despite the reduced viremia (undetectable to 2.6 ؋ 10 4 RNA copies/ml). However, tat mRNA transcripts were observed at significantly lower levels in HIV-2 ؉ patients, suggesting that the rate of de novo infection is decreased in these patients. Our data also reveal a direct relationship of gag and tat transcripts with CD4 and CD8 T cell activation, respectively. Antiretroviral therapy (ART)-treated HIV-2 ؉ patients showed persistent viral replication, irrespective of plasma viremia, possibly contributing to the emergence of drug resistance mutations, persistent hyperimmune activation, and poor CD4 T cell recovery that we observed with these individuals. In conclusion, we provide here evidence of significant ongoing viral replication in HIV-2 ؉ patients, further emphasizing the dichotomy between amount of plasma virus and cell-associated viral burden and stressing the need for antiretroviral trials and the definition of therapeutic guidelines for HIV-2 infection.

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Section: Discussionsupporting

confidence: 93%

Section: Relationship Of Plasma and Cell-associated Viral Load With Csupporting

confidence: 91%

mentioning

confidence: 99%

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Cell-Associated Viral Burden Provides Evidence of Ongoing Viral Replication in Aviremic HIV-2-Infected Patients

Soares¹,

Tendeiro

Foxall

et al. 2011

J Virol

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“…Approximately 38% of HIV-2 patients were also placed on a nelfinavir-containing regimen that has limited virological benefit in HIV-2 patients compared with other protease inhibitors (indinavir-ritonavir and lopinavir-ritonavir). [33][34][35] This may explain the less favourable overall outcomes seen in HIV-2 and dual infection. Initial operational obstacles linked to access issues, cost, and conservation at high temperatures were the reason for the use of nelfinavir, and most of these patients were offered a change to lopinavir-ritonavir when the thermostable formulation became available and nelfinavir was recalled by the manufacturer because of contamination.…”

Section: Discussionmentioning

confidence: 99%

Baseline characteristics, response to and outcome of antiretroviral therapy among patients with HIV-1, HIV-2 and dual infection in Burkina Faso

Harries

Zachariah

Manzi

et al. 2010

Transactions of the Royal Society of Tropical Medicine and Hygi

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“…In the French National HIV-2 Cohort (974 patients in June 2013), 61% of untreated patients had plasma viral loads below 250 copies/ml (cp/ml). Likewise, in a British study, only 8% of patients with CD4 of Ͼ500 cells/mm 3 and 62% of patients with CD4 of Ͻ300 cells/mm 3 had detectable viral loads (11), implying that 38% of patients had undetectable viral loads in an assay with a quantification limit of 100 copies/ml.…”

mentioning

confidence: 92%

New Sensitive One-Step Real-Time Duplex PCR Method for Group A and B HIV-2 RNA Load

et al. 2014

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. Analytic performances were determined in three laboratories. Clinical performances were evaluated on 100 plasma samples from HIV-2-infected patients (groups A, B, and H) by comparison with the assay currently used for the ANRS HIV-2 cohort. The specificity was 100%. Sensitivity was 50 copies/ml (cp/ml) and was optimized to 10 cp/ml. The within-run coefficients of variation in the three laboratories varied from 0.54% to 1.61% at 4 log 10 copies/ml and from 7.24% to 14.32% at 2 log 10 cp/ml. The between-run coefficients of variation varied from 2.28% to 6.43%. Of the 39 clinical samples below 2 log 10 in the current assay, the new test improved the detection or quantification of 17 samples, including eight group B samples. For quantifiable samples, similar loads were obtained with the two assays for group A samples. The median difference between the two assays for group B samples was ؉0.18 but with greater heterogeneity than for group A. The HIV-2 group H sample had similar results with the two assays. This new assay is highly sensitive and accurately quantifies the most prevalent HIV-2 groups. This test will be useful for monitoring low viral loads in HIV-2-infected patients.

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Antiretroviral Therapy for HIV-2 Infected Patients

Cited by 41 publications

References 22 publications

Cell-Associated Viral Burden Provides Evidence of Ongoing Viral Replication in Aviremic HIV-2-Infected Patients

Cell-Associated Viral Burden Provides Evidence of Ongoing Viral Replication in Aviremic HIV-2-Infected Patients

Baseline characteristics, response to and outcome of antiretroviral therapy among patients with HIV-1, HIV-2 and dual infection in Burkina Faso

New Sensitive One-Step Real-Time Duplex PCR Method for Group A and B HIV-2 RNA Load

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