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Persistently Elevated C-Reactive Protein Level in the First Year of Antiretroviral Therapy, Despite Virologic Suppression, Is Associated With HIV Disease Progression in Resource-Constrained Settings.

ABSTRACT: A case-cohort analysis of human immunodeficiency virus (HIV)-infected individuals receiving antiretroviral therapy (ART) was performed within a multicountry randomized trial (PEARLS) to assess the prevalence of persistently elevated C-reactive protein (CRP) levels, based on serial measurements of CRP levels, and their association with HIV clinical failure. A persistently elevated CRP level in plasma (defined as ? 5 mg/L at both baseline and 24 weeks after ART initiation) was observed in 50 of 205 individuals (24%). A persistently elevated CRP level but not an elevated CRP level only at a single time point was independently associated with increased clinical failure, compared with a persistently low CRP level, despite achievement of virologic suppression. Serial monitoring of CRP levels could identify individuals who are at highest risk of HIV progression and may benefit from future adjunct antiinflammatory therapies.

SUBMITTER: Shivakoti R

PROVIDER: S-EPMC4779305 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Persistently Elevated C-Reactive Protein Level in the First Year of Antiretroviral Therapy, Despite Virologic Suppression, Is Associated With HIV Disease Progression in Resource-Constrained Settings.

Shivakoti Rupak R Yang Wei-Teng WT Berendes Sima S Mwelase Noluthando N Kanyama Cecilia C Pillay Sandy S Samaneka Wadzanai W Santos Breno B Poongulali Selvamuthu S Tripathy Srikanth S Riviere Cynthia C Lama Javier R JR Cardoso Sandra W SW Sugandhavesa Patcharaphan P Balagopal Ashwin A Gupte Nikhil N Semba Richard D RD Campbell Thomas B TB Bollinger Robert C RC Gupta Amita A

The Journal of infectious diseases 20151129 7

A case-cohort analysis of human immunodeficiency virus (HIV)-infected individuals receiving antiretroviral therapy (ART) was performed within a multicountry randomized trial (PEARLS) to assess the prevalence of persistently elevated C-reactive protein (CRP) levels, based on serial measurements of CRP levels, and their association with HIV clinical failure. A persistently elevated CRP level in plasma (defined as ≥ 5 mg/L at both baseline and 24 weeks after ART initiation) was observed in 50 of 20 ...[more]

PMID: 26621909

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Project description:ObjectiveNumber of People Living with Human Immune-deficiency Virus in Ghana is over 300,000 and unmet need for antiretroviral therapy is approximately 60%. This study sought to determine the quality of antiretroviral therapy services in selected ART sites in Ghana using the input-process-outcome approach.MethodsThis is a descriptive cross-sectional case study that employed modified normative evaluation to assess quality of antiretroviral therapy services in the Oti and Volta regions of Ghana among People Living with HIV (n = 384) and healthcare providers (n = 16). The study was conducted from 11 March to 9 May 2019.ResultsResources for managing HIV clients were largely available with the exception of viral load machines, reagents for CD4 counts, and antifungals such as Fluconazole and Cotrimoxazole. Patients enrolled on antiretroviral therapy within 2 weeks was 71% and clients retained in care within 2 weeks of enrolment was 90%. Approximately 26% of enrolled clients recorded viral load suppression; 33% of People Living with HIV who were not insured with the National Health Insurance Scheme paid for some antiretrovirals and cotrimoxazole. Adherence to ART and Cotrimoxazole were 95% and 88%, respectively, using pill count on their last three visits. Time spent with clinical team was among the worst rated (mean = 2.98, standard deviation = 0.54) quality indicators by patients contrary to interpersonal relationship with health provider which was among the best rated (mean = 3.25, standard deviation = 0.41) indicators.ConclusionObserved quality care gaps could potentially reverse gains made in HIV prevention and control in Ghana if not addressed timely; an important value addition of this study is the novel application of input-process-outcome approach in the context of antiretroviral therapy services in Ghana. There is also the need for policy dialogue on inclusion of medications for prophylaxis in antiretroviral therapy on the National Health Insurance Scheme to promote adherence and retention.

Project description:ObjectiveTo evaluate associations between hair antiretroviral hair concentrations as an objective, cumulative adherence metric, with self-reported adherence and virologic outcomes.DesignAnalysis of cohort A of the ACTG-A5288 study. These patients in resource-limited settings were failing second-line protease inhibitor-based antiretroviral therapy (ART) but were susceptible to at least one nucleoside reverse transcriptase inhibitor (NRTI) and their protease inhibitor, and continued taking their protease inhibitor-based regimen.MethodsAntiretroviral hair concentrations in participants taking two NRTIs with boosted atazanavir (n = 69) or lopinavir (n = 112) were analyzed at weeks 12, 24, 36 and 48 using liquid-chromatography--tandem-mass-spectrometry assays. Participants' self-reported percentage of doses taken in the previous month; virologic failure was confirmed HIV-1 RNA at least 1000 copies/ml at week 24 or 48.ResultsFrom 181 participants with hair samples (61% women, median age: 39 years; CD4+ cell count: 167 cells/μl; HIV-1 RNA: 18 648 copies/ml), 91 (50%) experienced virologic failure at either visit. At 24 weeks, median hair concentrations were 2.95 [interquartile range (IQR) 0.49-4.60] ng/mg for atazanavir, 2.64 (IQR 0.73--7.16) for lopinavir, and 0.44 (IQR 0.11--0.76) for ritonavir. Plasma HIV-1 RNA demonstrated inverse correlations with hair levels (rs -0.46 to -0.74) at weeks 24 and 48. Weaker associations were seen with self-reported adherence (rs -0.03 to -0.24). Decreasing hair concentrations were significantly associated with virologic failure, the hazard ratio (95% CI) for ATV, LPV, and RTV were 0.69 (0.56-0.86), 0.77 (0.68-0.87), and 0.12 (0.06-0.27), respectively.ConclusionProtease inhibitor hair concentrations showed stronger associations with subsequent virologic outcomes than self-reported adherence in this cohort. Hair adherence measures could identify individuals at risk of second-line treatment failure in need of interventions.

Project description:The World Health Organization (WHO) guidelines on antiretroviral therapy (ART) define treatment failure as 2 consecutive viral loads (VLs) ≥1000 copies/mL. There is, however, little evidence supporting 1000 copies as an optimal threshold to define treatment failure. Objective of this study was to assess the correlation of the WHO definition with the presence of drug-resistance mutations in patients who present with 2 consecutive unsuppressed VL in a resource-limited setting.In 10 nurse-led clinics in rural Lesotho children and adults on first-line ART for ≥6 months received a first routine VL. Those with plasma VL ≥80 copies/mL were enrolled in a prospective study, receiving enhanced adherence counseling (EAC) and a follow-up VL after 3 months. After a second unsuppressed VL genotypic resistance testing was performed. Viruses with major mutations against ≥2 drugs of the current regimen were classified as "resistant".A total of 1563 adults and 191 children received a first routine VL. Of the 138 adults and 53 children with unsuppressed VL (≥80 copies/mL), 165 (116 adults; 49 children) had a follow-up VL after EAC; 108 (74 adults; 34 children) remained unsuppressed and resistance testing was successful. Ninety of them fulfilled the WHO definition of treatment failure (both VL ≥1000 copies/mL); for another 18 both VL were unsuppressed but with <1000 copies/mL. The positive predictive value (PPV) for the WHO failure definition was 81.1% (73/90) for the presence of resistant virus. Among the 18 with VL levels between 80 and 1000 copies/mL, thereby classified as "non-failures", 17 (94.4%) harbored resistant viruses. Lowering the VL threshold from 1000 copies/mL to 80 copies/mL at both determinations had no negative influence on the PPV (83.3%; 90/108).The current WHO-definition misclassifies patients who harbor resistant virus at VL below 1000 c/mL as "nonfailing." Lowering the threshold to VL ≥80 copies/mL identifies a significantly higher number of patients with treatment-resistant virus and should be considered.

Project description:IntroductionACTG A5288 was a strategy trial conducted in diverse populations from multiple continents of people living with HIV (PLWH) failing second-line protease inhibitor (PI)-based antiretroviral therapy (ART) from 10 low- and middle-income countries (LMICs). Participants resistant to lopinavir (LPV) and/or multiple nucleotide reverse transcriptase inhibitors started on third-line regimens that included raltegravir (RAL), darunavir/ritonavir (DRV/r) and/or etravirine (ETR) according to their resistance profiles. At 48 weeks, 87% of these participants achieved HIV-1 RNA ≤200 copies/ml. We report here long-term outcomes over 144 weeks.MethodsStudy participants were enrolled from 2013 to 2015, prior to the availability of dolutegravir in LMICs. "Extended Follow-up" of the study started after the last participant enrolled had reached 48 weeks and included participants still on antiretroviral (ARV) regimens containing RAL, DRV/r and/or ETR at that time. RAL, DRV/r and ETR were provided for an additional 96 weeks (giving total follow-up of ≥144 weeks), with HIV-1 RNA measured at 48 and 96 weeks and CD4 count at 96 weeks after entry into Extended Follow-up. Proportion of participants with HIV-1 RNA ≤200 copies/ml was estimated every 24 weeks, using imputation if necessary to handle the different measurement schedule in Extended Follow-up; mean CD4 count changes were estimated using loess regression.Results and discussionOf 257 participants (38% females), at study entry, median CD4 count was 179 cells/mm3 , and HIV-1 RNA was 4.6 log10 copies/ml. Median follow-up was 168 weeks (IQR: 156-204); 15 (6%) participants were lost to follow-up and 9 (4%) died. 27/246 (11%), 26/246 (11%) and 13/92 (14%) of participants who started RAL, DRV/r and ETR, respectively, discontinued these drugs; only three due to adverse events. 87%, 86%, 83% and 80% of the participants had HIV-1 RNA ≤200 copies/ml at weeks 48, 96, 144 and 168 (95% CI at week 168: 74-85%), respectively. Mean increase from study entry in CD4 count at week 168 was 265 cells/mm3 (95% CI 247-283).ConclusionsThird-line regimens comprising of RAL, DRV/r and/or ETR were very well tolerated and had high rates of durable virologic suppression among PLWH in LMICs who were failing on second-line PI-based ART prior to the availability of dolutegravir.

Project description:BackgroundThe results of international clinical trials that are assessing when to initiate antiretroviral therapy (ART) will not be available for several years.ObjectiveTo inform HIV treatment decisions about the optimal CD4 threshold at which to initiate ART in South Africa while awaiting the results of these trials.DesignCost-effectiveness analysis by using a computer simulation model of HIV disease.Data sourcesPublished data from randomized trials and observational cohorts in South Africa.Target populationHIV-infected patients in South Africa.Time horizon5-year and lifetime.PerspectiveModified societal.InterventionNo treatment, ART initiated at a CD4 count less than 0.250 x 10(9) cells/L, and ART initiated at a CD4 count less than 0.350 x 10(9) cells/L.Outcome measuresMorbidity, mortality, life expectancy, medical costs, and cost-effectiveness.Results of base-case analysisIf 10% to 100% of HIV-infected patients are identified and linked to care, a CD4 count threshold for ART initiation of 0.350 x 10(9) cells/L would reduce severe opportunistic diseases by 22,000 to 221,000 and deaths by 25,000 to 253,000 during the next 5 years compared with ART initiation at 0.250 x 10(9) cells/L; cost increases would range from $142 million (10%) to $1.4 billion (100%). Either ART initiation strategy would increase long-term survival by at least 7.9 years, with a mean per-person life expectancy of 3.8 years with no ART and 12.5 years with an initiation threshold of 0.350 x 10(9) cells/L. Compared with an initiation threshold of 0.250 x 10(9) cells/L, a threshold of 0.350 x 10(9) cells/L has an incremental cost-effectiveness ratio of $1200 per year of life saved.Results of sensitivity analysisInitiating ART at a CD4 count less than 0.350 x 10(9) cells/L would remain cost-effective over the next 5 years even if the probability that the trial would demonstrate the superiority of earlier therapy is as low as 17%.LimitationThis model does not consider the possible benefits of initiating ART at a CD4 count greater than 0.350 x 10(9) cells/L or of reduced HIV transmission.ConclusionEarlier initiation of ART in South Africa will probably reduce morbidity and mortality, improve long-term survival, and be cost-effective. While awaiting trial results, treatment guidelines should be liberalized to allow initiation at CD4 counts less than 0.350 x 10(9) cells/L, earlier than is currently recommended.Primary funding sourceNational Institute of Allergy and Infectious Diseases and the Doris Duke Charitable Foundation.

Dataset Information

Persistently Elevated C-Reactive Protein Level in the First Year of Antiretroviral Therapy, Despite Virologic Suppression, Is Associated With HIV Disease Progression in Resource-Constrained Settings.

Publications

Persistently Elevated C-Reactive Protein Level in the First Year of Antiretroviral Therapy, Despite Virologic Suppression, Is Associated With HIV Disease Progression in Resource-Constrained Settings.

Similar Datasets

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