CD4+ cell count at antiretroviral therapy initiation and economic restoration in rural Uganda.
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ABSTRACT:
SUBMITTER: Venkataramani AS
PROVIDER: S-EPMC4092056 | biostudies-literature | 2014 May
REPOSITORIES: biostudies-literature
Publications
CD4+ cell count at antiretroviral therapy initiation and economic restoration in rural Uganda.
Venkataramani Atheendar S AS Thirumurthy Harsha H Haberer Jessica E JE Ii Yap Boum YB Siedner Mark J MJ Kembabazi Annet A Hunt Peter W PW Martin Jeffrey N JN Bangsberg David R DR Tsai Alexander C AC
AIDS (London, England) 20140501 8
<h4>Objective</h4>To determine whether earlier initiation of antiretroviral therapy (ART) is associated with better economic outcomes.<h4>Design</h4>Prospective cohort study of HIV-positive patients on ART in rural Uganda.<h4>Methods</h4>Patients initiating ART at a regional referral clinic in Uganda were enrolled in the Uganda AIDS Rural Treatment Outcomes study starting in 2005. Data on labor force participation and asset ownership were collected on a yearly basis, and CD4 cell counts were col ...[more]
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Project description:ObjectiveTo investigate CD4 cell count recovery following ART initiation in perinatally HIV-infected children diagnosed in later childhood.DesignObservational prospective cohort study of newly diagnosed children aged 6-15 in Harare, Zimbabwe.MethodsParticipants were enrolled into a cohort at seven primary healthcare clinics between January 2013 and January 2015. ART was initiated according to national guidelines and CD4 cell counts were performed 6-monthly over 18 months. The relationship between CD4 cell count and time on ART was investigated using regression analysis with fixed (population) and random (individual) effects, and age at ART initiation as a covariate.ResultsOf the 307 participants who initiated ART, the median age at initiation was 11.7 years (interquartile range 9.6-13.8). The addition of an individual intercept and slope as random effects significantly improved the model fit compared with a fixed effects-only model. CD4 response (using a square-root transformation) was best modelled using a two-knot linear spline, with significant effects of time on ART and age at ART initiation. Younger children had a higher CD4 cell count at ART initiation (-17.9?cells/?l per year of age), an accelerated increase during the first 3 months on ART (-38.9?cells/?l per year of age at day 84), and a sustained higher CD4 cell count.ConclusionEarlier ART initiation in older children is associated with accelerated CD4 cell count recovery and lasting immune reconstitution. Our findings support WHO guidance recommending ART initiation in all children, irrespective of disease stage and CD4 cell count.
| S-EPMC6125740 | biostudies-literature
Project description:BACKGROUND:Mitochondrial DNA (mtDNA) variation has been associated with time to progression to AIDS and adverse effects from antiretroviral therapy (ART). In this study, full mitochondrial DNA (mtDNA) sequence data from US-based adult participants in the AIDS Clinical Trials Group study 384 was used to assess associations between mtDNA variants and CD4 T-cell recovery with ART. METHODS:Full mtDNA sequence was determined using chip-based array sequencing. Sequence and CD4 cell count data was available at baseline and after ART initiation for 423 subjects with HIV RNA levels <400 copies per milliliter plasma. The primary outcome was change in CD4 count of ?100 cells per cubic millimeter from baseline. Analyses were adjusted for baseline age, CD4 cell count, HIV RNA, and naive:memory CD4 cell ratio. RESULTS:Race-stratified analysis of mtDNA variants with a minor allele frequency >1% revealed multiple mtDNA variants marginally associated (P < 0.05 before Bonferroni correction) with CD4 cell recovery. The most significant single nucleotide polymorphism associations were those tagging the African L2 haplogroup, which was associated with a decreased likelihood of ?100 cells per cubic millimeter CD4 count increase at week 48 in non-Hispanic blacks (adjusted odds ratio = 0.17; 95% confidence interval = 0.06 to 0.53; P = 0.002). CONCLUSIONS:An African mtDNA haplogroup was associated with CD4 cell recovery after ART in this clinical trial population. These initial findings warrant replication and further investigation to confirm the role of mtDNA variation in CD4 cell recovery during ART.
| S-EPMC3204178 | biostudies-literature
Project description:Pre-antiretroviral therapy (ART) inflammation and coagulation activation predict clinical outcomes in HIV-positive individuals. We assessed whether pre-ART inflammatory marker levels predicted the CD4 count response to ART.Analyses were based on data from the Strategic Management of Antiretroviral Therapy (SMART) trial, an international trial evaluating continuous vs. interrupted ART, and the Flexible Initial Retrovirus Suppressive Therapies (FIRST) trial, evaluating three first-line ART regimens with at least two drug classes. For this analysis, participants had to be ART-naïve or off ART at randomization and (re)starting ART and have C-reactive protein (CRP), interleukin-6 (IL-6) and D-dimer measured pre-ART. Using random effects linear models, we assessed the association between each of the biomarker levels, categorized as quartiles, and change in CD4 count from ART initiation to 24 months post-ART. Analyses adjusted for CD4 count at ART initiation (baseline), study arm, follow-up time and other known confounders.Overall, 1084 individuals [659 from SMART (26% ART naïve) and 425 from FIRST] met the eligibility criteria, providing 8264 CD4 count measurements. Seventy-five per cent of individuals were male with the mean age of 42 years. The median (interquartile range) baseline CD4 counts were 416 (350-530) and 100 (22-300) cells/?L in SMART and FIRST, respectively. All of the biomarkers were inversely associated with baseline CD4 count in FIRST but not in SMART. In adjusted models, there was no clear relationship between changing biomarker levels and mean change in CD4 count post-ART (P for trend: CRP, P?=?0.97; IL-6, P?=?0.25; and D-dimer, P?=?0.29).Pre-ART inflammation and coagulation activation do not predict CD4 count response to ART and appear to influence the risk of clinical outcomes through other mechanisms than blunting long-term CD4 count gain.
| S-EPMC5676307 | biostudies-literature
Project description:This study aims to characterize associations between depression symptom severity and HIV infection, both prior to and in years after ART initiation, among older adults. The Ugandan Non-Communicable Diseases & Aging Cohort Study (UGANDAC) is a study of 154 PLWH on ART and 142 community-based, HIV-negative controls. The Hopkins Checklist (HSCL), a 15-item depression scale, was used to screen for depression. We estimate differences in depressive symptoms by HIV and ART status and use multivariable log binomial regression to quantify differences in probable depression between PLWH on ART. HIV-infected and HIV-uninfected participants had a similar age (mean 52.0 vs. 51.9, p?=?0.854) and sex distribution (47.4 vs. 47.9% female, p?=?0.934). PLWH on ART had lower depression symptom severity than HIV-uninfected controls (mean score: 1.50 vs. 1.60, p?=?0.006) and a lower prevalence of probable depression (21.4 vs. 33.8%, p?=?0.017). Among 102 PLWH with pre-ART depression screening scores available, their mean depression symptom severity was similar to HIV-uninfected participants (mean 1.56 vs. 1.60, p?=?0.512). In adjusted models, PLWH on ART had a lower prevalence of probable depression than HIV-negative controls [adjusted prevalence ratio: 0.68 (95% CI 0.47-0.99)]. In an observational cohort of PLWH over 40 on long-term ART and matched, community-based HIV-uninfected controls in rural Uganda, we found a lower prevalence of self-reported depression among aging PLWH on ART.
| S-EPMC6719297 | biostudies-literature
Project description:High levels of adherence to antiretroviral therapy (ART) are necessary for achieving and maintaining optimal virological suppression, as suboptimal adherence leads to therapy failure and disease progression. It is well known that adherence to ART predicts therapy response, but it is unclear whether clinical outcomes of ART predict adherence. To examine the predictive power of current CD4+ T cell count for adherence of HIV-infected individuals to ART, we performed a cross-sectional analysis of 133 Dutch HIV patients with electronically measured adherence. In a multivariate analysis adjusting for a number of sociodemographic and clinical variables, high current CD4+ T cell count (>660 cells/mm3) was most strongly associated with lower adherence to ART (assessed as a continuous variable) during a two-month period immediately following the measurements of variables (P = 0.008). The twice-per-day (versus once-per-day) dosing regimen was also significantly associated with lower adherence (P = 0.014). In a second multivariate analysis aimed at determining the predictors of suboptimal (<100% of the doses taken) adherence, high current CD4+ T cell count was again the strongest independent predictor of suboptimal adherence to ART (P = 0.015), and the twice-per-day dosing regimen remained associated with suboptimal adherence (P = 0.025). The association between suboptimal adherence and virological suppression was significant in patients with high CD4+ T cell counts, but not in patients with low or intermediate CD4+ T cell counts (P = 0.036 and P = 0.52, respectively; P = 0.047 for comparison of the effects of adherence on virological suppression between patients with high vs. low or intermediate CD4+ T cell counts), suggesting that apart from promoting suboptimal adherence, high CD4+ T cell count also strengthens the effect of adherence on virological suppression. Therefore, sustained efforts to emphasize continued adherence are necessary, especially for patients with high CD4+ T cell counts.
| S-EPMC4607457 | biostudies-literature
Project description:BACKGROUND:HIV-infected youth in sub-Saharan Africa are less likely to initiate antiretroviral therapy (ART) than older adults. SETTING AND METHODS:Adult (?15 years) residents enumerated during a census in 32 communities in rural Kenya and Uganda named social contacts in 5 domains: health, money, emotional support, food, and free time. Named contacts were matched to other enumerated residents to build social networks among 150,395 adults; 90% were tested for HIV at baseline. Among youth (15-24 years) who were ART naive at baseline (2013-2014), we evaluated whether having ?1 network contact who was HIV infected predicted ART initiation within 3 years and modification of this association by age and strength of contact, using logistic regression with robust standard errors. RESULTS:Among 1120 HIV-infected youth who were ART naive at baseline, 805 remained alive and community residents after 3 years. Of these, 270 (33.5%) named at least one baseline HIV-infected contact; 70% (569/805) subsequently initiated ART. Youth with ?1 HIV-infected same-age baseline contact were more likely to initiate ART [adjusted odds ratio (aOR), 2.95; 95% confidence interval (CI): 1.49 to 5.86] than those with no HIV-infected contact, particularly if the contact was a strong tie (named in >1 domain; aOR, 5.33; 95% CI: 3.34 to 8.52). When nonhousehold contacts were excluded, having an HIV-infected same age contact who was a strong tie remained associated with ART initiation (aOR, 2.81; 95% CI: 1.76 to 4.49). CONCLUSIONS:Interventions that increase and strengthen existing social connections to other HIV-infected peers at the time of HIV diagnosis may increase ART initiation among HIV-infected youth.
| S-EPMC7793612 | biostudies-literature
Project description:OBJECTIVES:Understanding of progression to antiretroviral therapy (ART) eligibility and associated factors remains limited. The objectives of this analysis were to determine the time to ART eligibility and to explore factors associated with disease progression in adults with early HIV infection. METHODS:HIV-infected adults (??18 years old) with CD4 cell count >?500 cells/?l were enrolled in the study at three primary health care clinics, and a sociodemographic, behavioural and partnership-level questionnaire was administered. Participants were followed 6-monthly and ART eligibility was determined using a CD4 cell count threshold of 350 cells/?l. Kaplan?-?Meier and Cox proportional hazard regression modelling were used in the analysis. RESULTS:A total of 206 adults contributed 381 years of follow-up; 79 (38%) reached the ART eligibility threshold. Median time to ART eligibility was shorter for male patients (12.0 months) than for female patients (33.9 months). Male sex [adjusted hazard ratio (aHR) 3.13; 95% confidence interval (CI) 1.82-5.39], residing in a household with food shortage in the previous year (aHR 1.58; 95% CI 0.99-2.54), and taking nutritional supplements in the first 6 months after enrolment (aHR 2.06; 95% CI 1.11-3.83) were associated with shorter time to ART eligibility. Compared with reference CD4 cell count????559 cells/?l, higher CD4 cell count was associated with longer time to ART eligibility [aHR 0.46 (95% CI 0.25-0.83) for CD4 cell count 560-632 cells/?l; aHR 0.30 (95% CI 0.16-0.57) for CD4 cell count 633-768 cells/?l; and aHR 0.17 (95% CI 0.08-0.38) for CD4 cell count?>?768 cells/?l]. CONCLUSIONS:Over one in three adults with CD4 cell count?>?500 cells/?l became eligible for ART at a CD4 cell count threshold of 350 cells/?l over a median of 2 years. The shorter time to ART eligibility in male patients suggests a possible need for sex-specific pre-ART care and monitoring strategies.
| S-EPMC4682449 | biostudies-other
Project description:ObjectiveTo evaluate the use of routine laboratory monitoring in terms of clinical outcomes among patients receiving antiretroviral therapy (ART) in Uganda.DesignRandomised clinical trialSettingA home based ART programme in rural Uganda.ParticipantsAll participants were people with HIV who were members of the AIDS Support Organisation. Participants had CD4 cell counts <250 cells × 10(6)/L or World Health Organization stage 3 or 4 disease.InterventionsParticipants were randomised to one of three different monitoring arms: a viral load arm (clinical monitoring, quarterly CD4 counts, and viral load measurements), CD4 arm (clinical monitoring and CD4 counts), or clinical arm (clinical monitoring alone).Main outcome measuresSerious morbidity (newly diagnosed AIDS defining illness) and mortality.Results1094 participants started ART; median CD4 count at baseline was 129 cells × 10(6)/L. Median follow-up was three years. In total, 126 participants died (12%), 148 (14%) experienced new AIDS defining illnesses, and 61(6%) experienced virological failure, defined as two consecutive viral loads >500 copies/mL occurring more than three months after the start of ART. After adjustment for age, sex, baseline CD4 count, viral load, and body mass index, the rate of new AIDS defining events or death was higher in the clinical arm than the viral load arm (adjusted hazard ratio 1.83, P = 0.002) or the CD4 arm (1.49, P = 0.032). There was no significant difference between the CD4 arm and the viral load arm (1.23, P = 0.31).ConclusionIn patients receiving ART for HIV infection in Uganda, routine laboratory monitoring is associated with improved health and survival compared with clinical monitoring alone. Trial registration Clinical Trials NCT00119093.
| S-EPMC3213241 | biostudies-literature
Project description:OBJECTIVE:To explore the impact of expanded eligibility criteria for antiretroviral therapy (ART) on median CD4? cell count at ART initiation and early mortality on ART. METHODS:Analyses included all adults (?16 years) initiated on first-line ART between August 2004 and July 2012. CD4? cell count threshold 350 cells per microliter for all adults was implemented in August 2011. Early mortality was defined as any death within 91 days of ART initiation. Trends in baseline CD4? cell count and early mortality were examined by year (August to July) of ART initiation. Competing risks analysis was used to examine early mortality. RESULTS:A total of 19,080 adults (67.6% female) initiated ART. Median CD4? cell count at ART initiation was 110-120 cells per microliter over the first 6 years, increasing marginally to 145 cells per microliter in 2010-2011 and more significantly to 199 cells per microliter in 2011-2012. Overall, there were 875 deaths within 91 days of ART initiation; early mortality rate was 19.4 per 100 person-years [95% confidence interval (CI) 18.2 to 20.7]. After adjustment for sex, age, baseline CD4? cell count, and concurrent tuberculosis (TB), there was a 46% decrease in early mortality for those who initiated ART in 2011-2012 compared with the reference period 2008-2009 (subhazard ratio, 0.54; 95% CI: 0.41 to 0.71). CONCLUSIONS:Since the expansion of eligibility criteria, there is evidence of earlier access to ART and a significant reduction in early mortality rate in this primary health care programme. These findings provide strong support for national ART policies and highlight the importance of earlier ART initiation for achieving reductions in HIV-related mortality.
| S-EPMC3867341 | biostudies-literature
Project description:BackgroundEvidence favoring earlier HIV ART initiation at high CD4+ T-cell counts (CD4>350/uL) has grown, and guidelines now recommend earlier HIV treatment. However, the cost of providing ART to individuals with CD4>350 in Sub-Saharan Africa has not been well estimated. This remains a major barrier to optimal global cost projections for accelerating the scale-up of ART. Our objective was to compute costs of ART delivery to high CD4+count individuals in a typical rural Ugandan health center-based HIV clinic, and use these data to construct scenarios of efficient ART scale-up.MethodsWithin a clinical study evaluating streamlined ART delivery to 197 individuals with CD4+ cell counts >350 cells/uL (EARLI Study: NCT01479634) in Mbarara, Uganda, we performed a micro-costing analysis of administrative records, ART prices, and time-and-motion analysis of staff work patterns. We computed observed per-person-per-year (ppy) costs, and constructed models estimating costs under several increasingly efficient ART scale-up scenarios using local salaries, lowest drug prices, optimized patient loads, and inclusion of viral load (VL) testing.FindingsAmong 197 individuals enrolled in the EARLI Study, median pre-ART CD4+ cell count was 569/uL (IQR 451-716). Observed ART delivery cost was $628 ppy at steady state. Models using local salaries and only core laboratory tests estimated costs of $529/$445 ppy (+/-VL testing, respectively). Models with lower salaries, lowest ART prices, and optimized healthcare worker schedules reduced costs by $100-200 ppy. Costs in a maximally efficient scale-up model were $320/$236 ppy (+/- VL testing). This included $39 for personnel, $106 for ART, $130/$46 for laboratory tests, and $46 for administrative/other costs. A key limitation of this study is its derivation and extrapolation of costs from one large rural treatment program of high CD4+ count individuals.ConclusionsIn a Ugandan HIV clinic, ART delivery costs--including VL testing--for individuals with CD4>350 were similar to estimates from high-efficiency programs. In higher efficiency scale-up models, costs were substantially lower. These favorable costs may be achieved because high CD4+ count patients are often asymptomatic, facilitating more efficient streamlined ART delivery. Our work provides a framework for calculating costs of efficient ART scale-up models using accessible data from specific programs and regions.
| S-EPMC4669141 | biostudies-literature