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Evaluation of HIV-1 ambiguous nucleotide frequency during antiretroviral treatment interruption.

ABSTRACT: Nucleotide mixtures in human immunodeficiency virus type 1 (HIV-1) population sequences reflect sequence diversity. We evaluated gag and pol ambiguous nucleotide frequencies during an analytic treatment interruption (ATI) in an HIV-1 therapeutic vaccine study. The proportion of ambiguous nucleotides was significantly higher at ATI week 16 than at either the time of first detectable viremia (P < 0.001 gag and P = 0.03 reverse transcriptase) or preantiretroviral therapy (P = 0.007 gag). No significant differences were observed in the proportion of ambiguous nucleotides between those receiving vaccine and placebo. Increased HIV diversity during the ATI may represent a potentially higher barrier to success for a therapeutic as compared with a preventative vaccine targeting cell-mediated immunity.

SUBMITTER: Li JZ

PROVIDER: S-EPMC3427424 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Evaluation of HIV-1 ambiguous nucleotide frequency during antiretroviral treatment interruption.

Li Jonathan Z JZ Christensen Julie A JA Wang Hongying H Spritzler John J Kuritzkes Daniel R DR

Journal of acquired immune deficiency syndromes (1999) 20120901 1

Nucleotide mixtures in human immunodeficiency virus type 1 (HIV-1) population sequences reflect sequence diversity. We evaluated gag and pol ambiguous nucleotide frequencies during an analytic treatment interruption (ATI) in an HIV-1 therapeutic vaccine study. The proportion of ambiguous nucleotides was significantly higher at ATI week 16 than at either the time of first detectable viremia (P < 0.001 gag and P = 0.03 reverse transcriptase) or preantiretroviral therapy (P = 0.007 gag). No signifi ...[more]

PMID: 22732468

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Project description:If strategies currently in development succeed in eradicating HIV reservoirs in peripheral blood and lymphoid tissues, residual sources of virus may remain in anatomic compartments. Paired blood and semen samples were collected from 12 individuals enrolled in a randomized, double-blind, placebo-controlled therapeutic vaccine clinical trial in people with HIV (PWH) who began antiretroviral therapy (ART) during acute or early infection (ClinicalTrials registration no. NCT01859325). After the week 56 visit (postintervention), all participants interrupted ART. At the first available time points after viral rebound, we sequenced HIV-1 env (C2-V3), gag (p24), and pol (reverse transcriptase) regions amplified from cell-free HIV RNA in blood and seminal plasma using the MiSeq Illumina platform. Comprehensive sequence and phylogenetic analyses were performed to evaluate viral population structure, compartmentalization, and viral diversity in blood and seminal plasma. Compared to that in blood, HIV RNA rebound in semen occurred significantly later (median of 66 versus 42 days post-ART interruption, P < 0.01) and reached lower levels (median 164 versus 16,090 copies/ml, P < 0.01). Three of five participants with available sequencing data presented compartmentalized viral rebound between blood and semen in one HIV coding region. Despite early ART initiation, HIV RNA molecular diversity was higher in semen than in blood in all three coding regions for most participants. Higher HIV RNA molecular diversity in the genital tract (compared to that in blood plasma) and evidence of compartmentalization illustrate the distinct evolutionary dynamics between these two compartments after ART interruption. Future research should evaluate whether the genital compartment might contribute to viral rebound in some PWH interrupting ART.IMPORTANCE To cure HIV, we likely need to target the reservoirs in all anatomic compartments. Here, we used sophisticated statistical and phylogenetic methods to analyze blood and semen samples collected from 12 persons with HIV who began antiretroviral therapy (ART) during very early HIV infection and who interrupted their ART as part of a clinical trial. First, we found that HIV RNA rebound in semen occurred significantly later and reached lower levels than in blood. Second, we found that the virus in semen was genetically different in some participants compared to that in blood. Finally, we found increased HIV RNA molecular diversity in semen compared to that in blood in almost all study participants. These data suggest that the HIV RNA populations emerging from the genital compartment after ART interruption might not be the same as those emerging from blood plasma. Future research should evaluate whether the genital compartment might contribute to viral rebound in some people with HIV (PWH) interrupting ART.

Project description:IntroductionSocial disruption associated with coronavirus disease 2019 (COVID-19) threatens to impede access to regular healthcare, including for people living with HIV (PLHIV), potentially resulting in antiretroviral therapy (ART) interruption (ATI). We aimed to explore the characteristics and factors associated with ATI during the COVID-19 outbreak in China.MethodsWe conducted an online survey among PLHIV by convenience sampling through social media between 5 and 17 February 2020. Respondents were asked to report whether they were at risk of ATI (i.e. experienced ATI, risk of imminent ATI, threatened but resolved risk of ATI [obtaining ART prior to interruption]) or were not at risk of ATI associated with the COVID-19 outbreak. PLHIV were also asked to report perceived risk factors for ATI and sources of additional ART. The factors associated with the risk of ATI were assessed using logistic regression. We also evaluated the factors associated with experienced ATI.ResultsA total of 5084 PLHIV from 31 provinces, autonomous regions and municipalities in mainland China completed the survey, with valid response rate of 99.4%. The median age was 31 years (IQR 27 to 37), 96.5% of participants were men, and 71.3% were men who had sex with men. Over one-third (35.1%, 1782/5084) reported any risk of ATI during the COVID-19 outbreak, including 2.7% (135/5084) who experienced ATI, 18.0% (917/5084) at risk of imminent ATI and 14.4% (730/5084) at threatened but resolved risk. PLHIV with ATI were more likely to have previous interruptions in ART (aOR 8.3, 95% CI 5.6 to 12.3), travelled away from where they typically receive HIV care (aOR 3.0, 95% CI 2.1 to 4.5), stayed in an area that implemented citywide lockdowns or travel restrictions to control COVID-19 (aOR 2.5, 95% CI 1.4 to 4.6), and be in permanent residence in a rural area (aOR 3.7, 95% CI 2.3 to 5.8).ConclusionsA significant proportion of PLHIV in China are at risk of ATI during the COVID-19 outbreak and some have already experienced ATI. Correlates of ATI and self-reported barriers to ART suggest that social disruptions from COVID-19 have contributed to ATI. Our findings demonstrate an urgent need for policies and interventions to maintain access to HIV care during public health emergencies.

Dataset Information

Evaluation of HIV-1 ambiguous nucleotide frequency during antiretroviral treatment interruption.

Publications

Evaluation of HIV-1 ambiguous nucleotide frequency during antiretroviral treatment interruption.

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