Dataset Information

ART in HIV-Positive Persons With Low Pretreatment Viremia: Results From the START Trial.

ABSTRACT:

Background

The benefit of immediate antiretroviral therapy (ART) at CD4 >500 cells/?L was established in the Strategic Timing of Antiretroviral Treatment (START) study. The benefits and risks of immediate ART in participants with low pretreatment viremia, including virologic suppressors, were further assessed.

Setting

Randomized prospective international study.

Methods

START participants with enrollment viremia <3000 c/mL were included. We compared clinical outcomes (grade 4 adverse events, hospitalizations, or death), plasma viremia, CD4 counts, and changes in biomarkers in immediate versus deferred ART groups.

Results

Participants (N = 1134 including 93 with viremia ?50 c/mL) had a median age of 37 years, 40% were women, and median CD4 was 713 cells/µL. Ninety-seven percent in the immediate and 29% in the deferred arm initiated ART at a median of 6 and 699 days, respectively. Clinical outcomes were experienced in 64 versus 61 patients in immediate and deferred arms (hazard ratio 1.10, 95% confidence interval: 0.77 to 1.56). The CD4 count difference was 125 cells/µL at 12 and 235 cells/µL at 36 months higher in the immediate versus deferred groups. D-dimer and VCAM levels decreased, and C-reactive protein increased, in the immediate arm at month 8. No significant changes in CD4 counts or biomarkers were observed in persons who maintained spontaneous virologic suppression.

Conclusions

START participants with low enrollment viremia experienced higher CD4 counts, greater proportion with suppressed viremia, and decreases in D-dimer levels on immediate ART despite the lack of difference in serious clinical outcomes. These data support immediate ART in people with low viremia, although equipoise remains for suppressors.

SUBMITTER: Sereti I

PROVIDER: S-EPMC6607914 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

ART in HIV-Positive Persons With Low Pretreatment Viremia: Results From the START Trial.

Sereti Irini I Gulick Roy M RM Krishnan Sonya S Migueles Stephen A SA Palfreeman Adrian A Touzeau-Römer Veronique V Belloso Waldo H WH Emery Sean S Law Matthew G MG

Journal of acquired immune deficiency syndromes (1999) 20190801 4

<h4>Background</h4>The benefit of immediate antiretroviral therapy (ART) at CD4 >500 cells/μL was established in the Strategic Timing of Antiretroviral Treatment (START) study. The benefits and risks of immediate ART in participants with low pretreatment viremia, including virologic suppressors, were further assessed.<h4>Setting</h4>Randomized prospective international study.<h4>Methods</h4>START participants with enrollment viremia <3000 c/mL were included. We compared clinical outcomes (grade ...[more]

PMID: 31241541

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Project description:OBJECTIVES:With HIV treatment prolonging survival and HIV infection now managed as a chronic illness, quality of life (QOL) is important to evaluate in persons living with HIV (PLWH). We assessed at study entry the QOL of antiretroviral-naïve PLWH with CD4 counts >?500 cells/?L in the Strategic Timing of AntiRetroviral Treatment (START) clinical trial. METHODS:QOL was assessed with: (1) a visual analogue scale (VAS) for self-assessment of overall current health; (2) the Short-Form 12-Item Version 2 Health Survey(®) (SF-12V2), for which responses are summarized into eight individual QOL domains plus component summary scores for physical health [the Physical Health Component Summary (PCS)] and mental health [the Mental Health Component Summary (MCS)]. The VAS and eight domain scores were scaled from 0 to 100. Mean QOL measures were calculated overall and by demographic, clinical and behavioural factors. RESULTS:A total of 4631 participants completed the VAS and 4119 the SF-12. The mean VAS score (with standard deviation) was 80.9?±?15.7. Mean SF-12 domain scores were lowest for vitality (66.3?±?26.4) and mental health (68.6?±?21.4), and highest for physical functioning (89.3?±?23.0) and bodily pain (88.0?±?21.4). Using multiple linear regression, PCS scores were lower (P?<?0.001) for Asians, North Americans, female participants, older participants, and those with less education, longer duration of known HIV infection, alcoholism/substance dependence and body mass index ??30?kg/m(2) . MCS scores were highest (P?<?0.001) for Africans, South Americans and older participants, and lowest for female participants, current smokers and those with alcoholism/substance dependence. CONCLUSIONS:In this primarily healthy population, QOL was mostly favourable, emphasizing that it is important that HIV treatments do not negatively impact QOL. Self-assessed physical health summary scores were higher than mental health scores. Factors such as older age and geographical region had different effects on perceived physical and mental health.

Project description:Although most HIV-infected individuals achieve undetectable viremia during antiretroviral therapy (ART), a subset have low-level viremia (LLV) of varying duration and magnitude. The impact of LLV on treatment outcomes is unclear. We investigated the association between LLV and virological failure and/or all-cause mortality among Swedish patients receiving ART.HIV-infected patients from two Swedish HIV centers were identified from the nationwide register InfCare HIV. Subjects aged ?15 years with triple agent ART were included at 12 months after treatment initiation if ?2 following viral load measurements were available. Patients with 2 consecutive HIV RNA values ?1000 copies/mL at this time point were excluded. Participants were stratified into four categories depending on viremia profiles: permanently suppressed viremia (<50 copies/mL), LLV 50-199 copies/mL, LLV 200-999 copies/mL and viremia ?1000 copies/mL. Association between all four viremia categories and all-cause death was calculated using survival analysis with viremia as a time-varying covariate, so that patients could change viremia category during follow-up. Association between the three lower categories and virological failure (?2 consecutive measurements ?1000 copies/mL) was calculated in a similar manner.LLV 50-199 copies/mL was recorded in 70/1015 patients (6.9%) and LLV 200-999 copies/mL in 89 (8.8%) during 7812 person-years of follow-up (median 6.5 years). LLV 200-999 copies/mL was associated with virological failure (adjusted hazard ratio 3.14 [95% confidence interval 1.41-7.03, p<0.01]), whereas LLV 50-199 copies/mL was not (1.01 [0.34-4.31, p = 0.99]; median follow-up 4.5 years). LLV 200-999 copies/mL had an adjusted mortality hazard ratio of 2.29 (0.98-5.32, p = 0.05) and LLV 50-199 copies/mL of 2.19 (0.90-5.37, p = 0.09).In this Swedish cohort followed during ART for a median of 4.5 years, LLV 200-999 copies/mL was independently associated with virological failure. Patients with LLV had higher rates of all-cause mortality, although not statistically significant in multivariate analysis.

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Project description:IntroductionThe MAINTAIN study is an on-going RCT comparing high-dose micronutrient and anti-oxidant supplementation versus recommended daily allowance (RDA) vitamins in slowing HIV immune deficiency progression in ART-naïve people with HIV infection.ObjectiveWe planned analysis of the first 127 participants to determine the baseline prevalence of serum micronutrient deficiencies and correlates, as well as tolerance and adherence to study interventions.MethodsParticipants receive eight capsules twice daily of 1) high-dose or 2) RDA supplements for two years and are followed-up quarterly for measures of immune deficiency progression, safety and tolerability. Regression analysis was used to identify correlates of micronutrient levels at baseline. Adherence was measured by residual pill count, self-report using the General Treatment Scale (GTS) and short-term recall HIV Adherence Treatment Scale (HATS).ResultsPrior micronutrient supplementation (within 30 days) was 27% at screening and 10% of study population, and was not correlated with baseline micronutrient levels. Low levels were frequent for carotene (24%<1 nmol/L), vitamin D (24%<40 nmol/L) and serum folate (20%<15 nmol/L). The proportion with B12 deficiency (<133 pmol/L) was 2.4%. Lower baseline levels of B12 correlated lower baseline CD4 count (r?=?0.21, p?=?0.02) with a 21 pmol/L reduction in B12 per 100 cells/µL CD4. Vitamin D levels were higher in men (p<0.001). After a median follow-up of 1.63 years, there were 19 (15%) early withdrawals from the study treatment. Mean treatment adherence using pill count was 88%. Subjective adherence by the GTS was 81% and was moderately but significantly correlated with pill count (r?=?0.29, p<0.001). Adherence based on short-term recall (HATS) was >80% in 75% of participants.ConclusionMicronutrient levels in asymptomatic HIV+ persons are in keeping with population norms, but micronutrient deficiencies are frequent. Adherence levels are high, and will permit a valid evaluation of treatment effects.Trial registrationClinicalTrials.gov NCT00798772.

Dataset Information

ART in HIV-Positive Persons With Low Pretreatment Viremia: Results From the START Trial.

Background

Setting

Methods

Results

Conclusions

Publications

ART in HIV-Positive Persons With Low Pretreatment Viremia: Results From the START Trial.

Similar Datasets

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