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Clinical Outcomes Following the Use of Archived Proviral HIV-1 DNA Genotype to Guide Antiretroviral Therapy Adjustment.

ABSTRACT: Background:Evidence regarding the safety of using proviral HIV-1 DNA genotype (DNA GT) to guide antiretroviral therapy (ART) is limited. We hypothesized that HIV RNA would not increase following ART adjustment guided by DNA GT in a university HIV clinic. Methods:Data were obtained from electronic medical records of adult persons living with HIV-1 (PWH) who underwent DNA GT testing and changed ART between October 2014 and November 2017. Logistic regression was used to evaluate the effect of ART switch on HIV RNA over time. Results:Eighty-three PWH had DNA GT performed, 66 (80%) switched ART, and 59 had postswitch follow-up. Data were analyzed pre-/postswitch for these 59 PWH (median age, 54 years; 71% LWH ?10 years; 46% ?2 previous regimens; 36% recent low-level viremia; 34% unknown medication history). On DNA GT, 58% had ?1-class ART resistance, 34% ?2-class, and 10% 3-class. Median follow-up (range) was 337 (34-647) days. There was no change in probability of HIV RNA ?50 copies/mL over time (P?>?.05). At baseline, 76% had HIV RNA <50 vs 88% at last postswitch follow-up (P?=?.092). Protease inhibitor use decreased from 58% to 24% (P?

SUBMITTER: Ellis KE

PROVIDER: S-EPMC6942490 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Clinical Outcomes Following the Use of Archived Proviral HIV-1 DNA Genotype to Guide Antiretroviral Therapy Adjustment.

Ellis Kristen E KE Nawas George T GT Chan Connie C York Lawrence L Fisher Julia J Connick Elizabeth E Zangeneh Tirdad T TT

Open forum infectious diseases 20191214 1

<h4>Background</h4>Evidence regarding the safety of using proviral HIV-1 DNA genotype (DNA GT) to guide antiretroviral therapy (ART) is limited. We hypothesized that HIV RNA would not increase following ART adjustment guided by DNA GT in a university HIV clinic.<h4>Methods</h4>Data were obtained from electronic medical records of adult persons living with HIV-1 (PWH) who underwent DNA GT testing and changed ART between October 2014 and November 2017. Logistic regression was used to evaluate the ...[more]

PMID: 31915714

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Project description:BackgroundPapua Province, Indonesia is experiencing an on-going epidemic of Human Immunodeficiency Virus (HIV) infection, with an estimated 9-fold greater prevalence than the overall national rate. This study reviewed the treatment outcomes of an HIV-infected cohort on Antiretroviral Therapy (ART) and the predictors in terms of immunological recovery and virological response.MethodsART-naïve individuals in a workplace HIV program in southern Papua were retrospectively analyzed. Patients were assessed at 6, 12 and 36 months after ART initiation for treatment outcomes, and risk factors for virological suppression (viral load (VL) <1,000 copies/ml), poor immune response (CD4 <200 cells/mm3) and immunological failure (CD4 <100 cells/ mm3) after at least 6 months on ART, using a longitudinal Generalized Estimating Equations multivariate model.ResultsAssessment of 105 patients were included in the final analysis with a median age of 34 years, 88% male, median baseline CD4 236 cells/ mm3, and VL 179,000 copies/ml. There were 74, 73, and 39 patients at 6, 12, and 36 months follow-up, respectively, with 5 deaths over the entire period. For the three observation periods, 68, 80, and 75% of patents achieved virological suppression, poor immune responders decreased from 15, 16 to 10%, whilst 15, 16, 10% met the immunological failure criteria, respectively. Using multivariate analysis, the independent predictor for viral suppression at 12 and 36 months was ≥1 log decrease in VL at 6 months (OR 19.25, p<0.001). Higher baseline CD4 was significantly correlated with better immunological outcomes, and lower likelihood of experiencing immunological failure (p <0.001).ConclusionVirological response at six months after beginning ART is the strongest predictor of viral suppression at 12 and 36 months, and may help in identifying patients needing additional adherence therapy support. Higher baseline CD4 positively affects the immunological outcomes of patients. The findings indicate HIV control programs should prioritize the availability of VL testing and begin ART regardless of CD4 counts in infected patients.

Project description:The lung is an understudied site of HIV persistence. We isolated 898 subgenomic proviral sequences (nef) by single-genome approaches from blood and lung from nine individuals on long-term suppressive antiretroviral therapy (ART), and characterized genetic diversity and compartmentalization using formal tests. Consistent with clonal expansion as a driver of HIV persistence, identical sequences comprised between 8% to 86% of within-host datasets, though their location (blood vs. lung) followed no consistent pattern. The majority (77%) of participants harboured at least one sequence shared across blood and lung, supporting the migration of clonally-expanded cells between sites. The extent of blood proviral diversity on ART was also a strong indicator of diversity in lung (Spearman's ρ = 0.98, p<0.0001). For three participants, insufficient lung sequences were recovered to reliably investigate genetic compartmentalization. Of the remainder, only two participants showed statistically significant support for compartmentalization when analysis was restricted to distinct proviruses per site, and the extent of compartmentalization was modest in both cases. When all within-host sequences (including duplicates) were considered, the number of compartmentalized datasets increased to four. Thus, while a subset of individuals harbour somewhat distinctive proviral populations in blood and lung, this can simply be due to unequal distributions of clonally-expanded sequences. For two participants, on-ART proviruses were also phylogenetically analyzed in context of plasma HIV RNA populations sampled up to 18 years prior, including pre-ART and during previous treatment interruptions. In both participants, on-ART proviruses represented the most ancestral sequences sampled within-host, confirming that HIV sequences can persist in the body for decades. This analysis also revealed evidence of re-seeding of the reservoir during treatment interruptions. Results highlight the genetic complexity of proviruses persisting in lung and blood during ART, and the uniqueness of each individual's proviral composition. Personalized HIV remission and cure strategies may be needed to overcome these challenges.

Dataset Information

Clinical Outcomes Following the Use of Archived Proviral HIV-1 DNA Genotype to Guide Antiretroviral Therapy Adjustment.

Publications

Clinical Outcomes Following the Use of Archived Proviral HIV-1 DNA Genotype to Guide Antiretroviral Therapy Adjustment.

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