Highly Active Antiretroviral Therapy and Viral Response in HIV Type 2 Infection

Mullins, Christopher; Eisen, Geoffrey; Popper, Stephen J.; Sarr, Abdoulaye; Sankalé, Jean-Louis; Berger, Judith; Wright, Sharon B.; Chang, Huilan; Coste, Gerard; Cooley, Timothy P.; Rice, Peter A.; Skolnik, Paul R.; Sullivan, Margaret M.; Kanki, Phyllis J.

doi:10.1086/421390

Cited by 36 publications

(21 citation statements)

References 32 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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“…Patient 1, whose viral load remained detectable, had stopped using this treatment due to adverse effects. Even though previous studies have reported that various HAART regimens suppress HIV-2 replication by only 0.4 to 2 log units and usually fail to achieve undetectable viral loads (1,41), viral suppression to undetectable levels was achieved for all patients taking the drugs and was maintained for as long as 3 years (range, 3 to 36 months). The reduction in the viral load was accompanied by a general increase in the percentage of CD4 cells over pretherapy levels, indicating that these patients were benefiting immunologically from this treatment.…”

Section: Discussionmentioning

confidence: 87%

Virological Response to Highly Active Antiretroviral Therapy in Patients Infected with Human Immunodeficiency Virus Type 2 (HIV-2) and in Patients Dually Infected with HIV-1 and HIV-2 in The Gambia and Emergence of Drug-Resistant Variants

et al. 2009

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Drug design, antiretroviral therapy (ART), and drug resistance studies have focused almost exclusively on human immunodeficiency virus type 1 (HIV-1), resulting in limited information for patients infected with HIV-2 and for those dually infected with HIV-1 and HIV-2. In this study, 20 patients, 12 infected with HIV-2 and 8 dually infected with HIV-1 and HIV-2, all treated with zidovudine (ZDV), lamivudine (3TC), and lopinavir-ritonavir (LPV/r), were followed up longitudinally for about 3 years. For 19/20 patients, viral loads were reduced to undetectable levels; the patient whose viral load remained detectable reported adverse effects associated with LPV/r that had caused him to stop taking all the drugs. HIV-2 strains containing mutations in both the protease and the reverse transcriptase gene that may confer drug resistance were observed in two patients with viral rebound, as early as 130 days (4.3 months) after the initiation of therapy. We conclude that the combination of ZDV, 3TC, and LPV/r is able to provide efficient and durable suppression of HIV-1 and HIV-2 for as long as 3 years in HIV-2-infected and dually infected patients. However, the emergence of HIV-1 and HIV-2 strains containing drug-resistant mutations can compromise the efficacy of this highly active ART.

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“…Highly active antiretroviral regimens (HAART) which efficiently suppress HIV-l may not be useful for HIV-2 (1), and this may adversely affect the treatment of dual infected patients (2).…”

Section: Introductionmentioning

confidence: 99%

Diagnosis of dual human immunodeficiency virus types 1 & 2 infections in a resouce-limited setting

Sagoe

Agyei²,

Lartey³

et al. 2010

E Af Med Jrnl

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Background:The presence of dual HlV-l/HIV-2 infection in Ghana and the different drug requirements for the treatment of HlV-1 and HIV-2 presents difficulties for the treatment of dual infections with both viruses. Objectives: To determine the prevalence of the dual sero-positive profile in treatment naive patients at a principal ART Clinic in Accra, Ghana and to investigate if rapid screening assays could be useful for diagnosis. Design: A cross-sectional study. Setting: A principal antiretroviral treatment centre in Accra, Ghana. Subjects: Three hundred and twenty eight antiretroviral treatment naive patients. Results: A total of 12 (3.7%) of patients seen were dual seropositive. There was a slight tendency of dual seropositive females being older than their HIV-l counterparts (p=0.088, CI=-l 0.833 to 0.753). Eight of the 12 of the dual seropositives were reactive for Genie II and were considered as possibly infected with both HIV-I and HIV-2. Seven (87.5%) of Genie II dual seropositives had strong intensities (> 1+) on both HIV-2 specific bands (sgp105 and gp36) on Innolia. CD4 counts were not significantly different in dual seropositives as compared to HIV-1 infected patients. Conclusions: Dual HIV-l/HIV-2 seropositives (and possibly infections) may be common especially in older women. The Genie II will be useful as a supplemental rapid test for rapid and accurate differentiation of HIV-l and HIV-2 antibodies at treatment centres.

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Highly Active Antiretroviral Therapy and Viral Response in HIV Type 2 Infection

Cited by 36 publications

References 32 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

Virological Response to Highly Active Antiretroviral Therapy in Patients Infected with Human Immunodeficiency Virus Type 2 (HIV-2) and in Patients Dually Infected with HIV-1 and HIV-2 in The Gambia and Emergence of Drug-Resistant Variants

Diagnosis of dual human immunodeficiency virus types 1 & 2 infections in a resouce-limited setting

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