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Effect of age at initiation of antiretroviral therapy on treatment outcomes; A retrospective cohort study at a large HIV clinic in southwestern Uganda.

ABSTRACT: BACKGROUND:The prevalence of HIV infection among older persons is increasing yet older age at initiation of antiretroviral therapy (ART) may be associated with poorer treatment outcomes including mortality. However, majority of these studies have been done in the western world and there is limited data in resource limited settings. Our study used routinely collected health facility data to assess trends in age at initiation of ART, the effect of age at ART initiation on mortality and immunological response at a large urban hospital in south western Uganda. METHODS:We conducted a retrospective records review of patients attending the HIV clinic at Mbarara Regional Referral Hospital in western Uganda. We retrieved records for 8,533 patients who started ART between January 2006 and December 2012. Their data had been collected and stored as part of the larger International Epidemiological Database for the Evaluation of AIDS (IeDEA). Age was stratified into three categories namely; 18-34 (young adults), 35-49 (mid-age) and 50 years or older (older adults). Survival analysis procedures with Kaplan-Meier's plots were used to calculate the survival probability with mortality as the endpoint and Poisson regression analysis used to determine the adjusted relative risks (RR) of mortality. RESULTS:The proportion of young adults and patients at WHO stage I initiating ART increased steadily over the 7-year period. Older age at ART initiation (> = 50 years) was associated with a higher risk of mortality with adjusted relative risk (RR) at 1.63, (95% CI 1.26-2.11) compared to younger age. Male gender, WHO stages III and IV, lower CD4 count and lower body mass index were also all independently and significantly associated with higher risk for mortality. Older adults also had a poorer immunological response RR = 1.79 (95% CI 0.89-3.58) but was not statistically significant. CONCLUSIONS:Following ART initiation, older adults compared to the young, have a higher risk of mortality. This age group should be targeted first for 'screen and treat' approach. Optimization of ART treatment regimens for this age group is also required to reduce mortality and improve immunological response.

SUBMITTER: Ssebutinde P

PROVIDER: S-EPMC6093656 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Effect of age at initiation of antiretroviral therapy on treatment outcomes; A retrospective cohort study at a large HIV clinic in southwestern Uganda.

Ssebutinde Peter P Kyamwanga Imelda T IT Turyakira Eleanor E Asiimwe Stephen S Bajunirwe Francis F

PloS one 20180815 8

<h4>Background</h4>The prevalence of HIV infection among older persons is increasing yet older age at initiation of antiretroviral therapy (ART) may be associated with poorer treatment outcomes including mortality. However, majority of these studies have been done in the western world and there is limited data in resource limited settings. Our study used routinely collected health facility data to assess trends in age at initiation of ART, the effect of age at ART initiation on mortality and imm ...[more]

PMID: 30110364

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Project description:Abstract Background Single-nucleotide polymorphisms (SNPs) in CYP2B6 have previously been associated with a 10-fold range in trough plasma efavirenz concentrations, but associations between these SNPs and efavirenz (EFV)-mediated viral suppression and tolerability remain unclear. Methods We evaluated three SNPs in CYP2B6 (rs3745274, rs28399499, and rs4803419, Illumina OmniExpress) among HIV-infected Ugandans observed in a cohort study every 3–4 months from 2005–2015. Genotypes from these SNPs were used to group participants into previously described pharmacokinetic strata: extensive (EXT), intermediate (INT), and slow metabolizers (Figure 1). The primary outcomes were viral suppression, defined by an undetectable viral load in the first measurement a minimum of three months after ART initiation, and incident depression in the first two years, defined by a mean score >1.75 on the Hopkins Symptom Checklist. We fitted standard and generalized estimating equations (GEE) logistic regression models for viral suppression and depression, respectively. Models were adjusted for clinical and demographic covariates that reached a significance of P < 0.25 in unadjusted models. Results Among 103 participants with genotyping, there were no differences in pre-ART viral load or depression by metabolism strata (P > 0.5). Minor allele frequencies for rs3745274, rs28399499, and rs4803419 were 33%, 7%, and 4%, respectively. Approximately 79%, 78%, and 94% of participants were suppressed at their first viral load measurement in the extensive, intermediate, and slow metabolizer strata, respectively (Figure 2; P = 0.35). In adjusted models, metabolism strata were not associated with viral suppression (AORINT 0.81, 95% CI 0.26–2.56; AORSLOW 3.92, 95% CI 0.39–39.40) or with depression (AORINT 1.95, 95% CI 0.75–5.09; AORSLOW 0.72, 95% CI 0.17–3.02; Table). Conclusion We did not identify an association between efavirenz-metabolizing polymorphisms and viral suppression or depression in a cohort of HIV-infected individuals initiating ART in southwestern Uganda. Future work should reassess these relationships with larger samples and longer-term outcomes and explore additional polymorphisms that may be associated with efavirenz metabolism in this population. Disclosures P. Hunt, Merck: Consultant, Consulting fee; Gilead: Consultant, Consulting fee; Viiv: Consultant, Consulting fee

Project description:Background: The latent viral reservoir is the major obstacle to achieving HIV remission and necessitates life-long antiretroviral therapy (ART) for HIV-infected individuals. Studies in adults and children have found that initiating ART soon after infection is associated with a reduction in the size of the HIV-1 reservoir. Here we quantified cell-associated HIV-1 DNA in early-treated but currently older HIV-infected children suppressed on ART.Methods: The study participants comprised of a cohort of 146 early-treated children with HIV-1 RNA <50 copies/ml enrolled as part of a clinical trial in Johannesburg, South Africa. A stored buffy coat sample collected after a median 4.3 years on ART and where HIV-1 RNA was <50 copies/ml was tested for cell-associated HIV-1 DNA levels. An in-house, semi-nested real-time quantitative hydrolysis probe PCR assay to detect total HIV-1 subtype C proviral DNA was used. Children were followed prospectively for up to 3 years after this measurement to investigate subsequent HIV-1 RNA rebound/failure while remaining on ART. Age at ART initiation, HIV-1 RNA decline prior to HIV-1 DNA measurement and other factors were investigated.Results: A gradient between age at ART initiation and later HIV-1 DNA levels was observed. When ART was started <2 months of age, the lowest levels of cell-associated HIV-1 DNA (median 1.4 log10copies/106 cells, interquartile range [IQR] 0.95-1.55) were observed compared to ART started at 2-4 months (median 1.68, IQR 1.26-1.97) or 5-14 months of age (median1.98, IQR 1.69-2.25). A low CD4 T-cell count pre-treatment predicted higher levels of HIV-1 DNA on later testing. The probability of HIV-1 RNA rebound >50 copies/ml whilst on ART within 3 years after the DNA measurement was 2.07 (95% CI: 1.352-3.167) times greater if the HIV-1 DNA level was above the median of 55 copies/106 cells.Conclusions: Cell-associated HIV-1 DNA levels measured after more than 4 years on ART were lower the younger the age of the child when ART was initiated. This marker of the size of the viral reservoir also predicted subsequent viral rebound/treatment failure while ART was sustained. The results provide additional evidence of the benefits of prompt diagnosis and early ART initiation in newborns and infants.

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Effect of age at initiation of antiretroviral therapy on treatment outcomes; A retrospective cohort study at a large HIV clinic in southwestern Uganda.

Publications

Effect of age at initiation of antiretroviral therapy on treatment outcomes; A retrospective cohort study at a large HIV clinic in southwestern Uganda.

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