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Successful antiretroviral therapy delivery and retention in care among asymptomatic individuals with high CD4+ T-cell counts above 350 cells/?l in rural Uganda.

ABSTRACT: HIV antiretroviral therapy (ART) is being rapidly scaled up in sub-Saharan Africa, including recently patients with CD4 T-cell counts above 350?cells/?l. However, concerns persist about adherence and virologic suppression among these asymptomatic, high CD4 cell count individuals.To determine the virologic efficacy and safety of ART among asymptomatic HIV-positive Ugandan adults with high CD4 cell counts above 350?cells/?l via a streamlined model of care.Prospective nonrandomized clinical study (EARLI Study: clinicaltrials.gov NCT#01479634).Prototypic rural Ugandan HIV clinic.Asymptomatic, ART-naive adults (aged >18 years, N?=?197) with CD4 at least 350?cells/?l, without pregnancy or WHO stage 3/4 illness.ART included tenofovir/emtricitabine/efavirenz, with ritonavir/lopinavir substitution for efavirenz available. Streamlined ART model included nurse-driven visits with physician back-up, basic safety laboratory monitoring with HIV viral load, clinician telephone contact, and defaulter tracking. No incentives were provided.Undetectable viral load (?400?copies/ml) at 24 and 48 weeks [intention to treat (ITT); missing?=?detectable), self-reported ART adherence, retention in care, and laboratory/clinical ART toxicities.Of the 197 patients with CD4 above 350?cells/?l, median CD4 cell count was 569?cells/?l (interquartile range 451-716). Undetectable viral load was achieved in 189 of 197 (95.9%, ITT) and 189 of 195 (96.9%, ITT) of participants at weeks 24 and 48, respectively. Self-reported adherence was 98% and 192 of 197 (97%) of the patients were retained at week 48. Laboratory adverse events and hospitalizations were rare.We demonstrate high virologic suppression, retention, and safety among asymptomatic individuals with CD4 above 350 cells/?l in a prototypic Ugandan clinic. Our results challenge current concerns that individuals with high CD4 cell count lack motivation for ART, and may not achieve sustained virologic suppression.

SUBMITTER: Jain V

PROVIDER: S-EPMC4894849 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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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.

Project description:BackgroundThe failure to increase CD4 T-cell counts in some antiretroviral therapy suppressed participants (immunodiscordance) has been related to perturbed CD4 T-cell homeostasis and impacts clinical evolution.MethodsWe evaluated different definitions of immunodiscordance based on CD4 T-cell counts (cutoff) or CD4 T-cell increases from nadir value (?CD4) using supervised random forest classification of 74 immunological and clinical variables from 196 antiretroviral therapy suppressed individuals. Unsupervised clustering was performed using relevant variables identified in the supervised approach from 191 individuals.ResultsCutoff definition of CD4 cell count 400 cells/?l performed better than any other definition in segregating immunoconcordant and immunodiscordant individuals (85% accuracy), using markers of activation, nadir and death of CD4 T cells. Unsupervised clustering of relevant variables using this definition revealed large heterogeneity between immunodiscordant individuals and segregated participants into three distinct subgroups with distinct production, programmed cell-death protein-1 (PD-1) expression, activation and death of T cells. Surprisingly, a nonnegligible number of immunodiscordant participants (22%) showed high frequency of recent thymic emigrants and low CD4 T-cell activation and death, very similar to immunoconcordant participants. Notably, human leukocyte antigen - antigen D related (HLA-DR) PD-1 and CD45RA expression in CD4 T cells allowed reproducing subgroup segregation (81.4% accuracy). Despite sharp immunological differences, similar and persistently low CD4 values were maintained in these participants over time.ConclusionA cutoff value of CD4 T-cell count 400 cells/?l classified better immunodiscordant and immunoconcordant individuals than any ?CD4 classification. Immunodiscordance may present several, even opposite, immunological patterns that are identified by a simple immunological follow-up. Subgroup classification may help clinicians to delineate diverse approaches that may be needed to boost CD4 T-cell recovery.

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Successful antiretroviral therapy delivery and retention in care among asymptomatic individuals with high CD4+ T-cell counts above 350 cells/?l in rural Uganda.

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