Failure of immunologic criteria to appropriately identify antiretroviral treatment failure in Uganda

Reynolds, Steven J.; Nakigozi, Gertrude; Newell, Kevin; Ndyanabo, Anthony; Galiwongo, Ronald; Boaz, Iga; Quinn, Thomas C.; Gray, Ron; Wawer, Maria J.; Serwadda, David

doi:10.1097/qad.0b013e3283262a78

Cited by 164 publications

(135 citation statements)

References 6 publications

(6 reference statements)

Supporting

Mentioning

120

Contrasting

Order By: Relevance

“…As a result, the World Health Organization (WHO) has advocated using clinical criteria and CD4 cell counts to identify individuals failing ART regimens. However, immunological (decline in CD4 cell count) and clinical criteria for failure are very poor predictors of virological failure [4][5][6], and their use results in regimen changes for patients who are not failing, or, at the other extreme, accumulated resistance mutations at the time of switch. WHO recommends viral load testing when available and has identified a target virological suppression rate of 70% for patients on ART for a year in resource-limited settings [7].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of treatment outcomes for patients on first‐line regimens in US President's Emergency Plan for AIDS Relief (PEPFAR) clinics in Uganda: predictors of virological and immunological response from RV288 analyses

et al. 2014

View full text Add to dashboard Cite

ObjectivesViral load (VL) monitoring is recommended, but seldom performed, in resource-constrained countries. RV288 is a US President's Emergency Plan for AIDS Relief (PEPFAR) basic programme evaluation to determine the proportion of patients on treatment who are virologically suppressed and to identify predictors of virological suppression and recovery of CD4 cell count. Analyses from Uganda are presented here. MethodsIn this cross-sectional, observational study, patients on first-line antiretroviral therapy (ART) (efavirenz or nevirapine + zidovudine/lamivudine) from Kayunga District Hospital and Kagulamira Health Center were randomly selected for a study visit that included determination of viral load (HIV-1 RNA), CD4 cell count and clinical chemistry tests. Subjects were recruited by time on treatment: 6-12, 13-24 or > 24 months. Logistic regression modelling identified predictors of virological suppression. Linear regression modelling identified predictors of CD4 cell count recovery on ART. ResultsWe found that 85.2% of 325 subjects were virologically suppressed (viral load < 47 HIV-1 RNA copies/ml). There was no difference in the proportion of virologically suppressed subjects by time on treatment, yet CD4 counts were higher in each successive stratum. Women had higher median CD4 counts than men overall (406 vs. 294 cells/μL, respectively; P < 0.0001) and in each time-on-treatment stratum. In a multivariate logistic regression model, predictors of virological suppression included efavirenz use [odds ratio (OR) 0.47; 95% confidence interval (CI) 0.22-1.02; P = 0.057], lower cost of clinic visits (OR 0.815; 95% CI 0.66-1.00; P = 0.05), improvement in CD4 percentage (OR 1.06; 95% CI 1.014-1.107; P = 0.009), and care at Kayunga vs. Kangulamira (OR 0.47; 95% CI 0.23-0.92; P = 0.035). In a multivariate linear regression model of covariates associated with CD4 count recovery, time on highly active antiretroviral therapy (ART) (P < 0.0001), patient satisfaction with care (P = 0.038), improvements in total lymphocyte count (P < 0.0001) and haemoglobin concentration (P = 0.05) were positively associated, whereas age at start of ART (P = 0.0045) was negatively associated with this outcome. ConclusionsHigh virological suppression rates are achievable on first-line ART in Uganda. The odds of virological suppression were positively associated with efavirenz use and improvements in CD4 cell percentage and total lymphocyte count and negatively associated with the cost of travel to The US President's Emergency Plan for AIDS Relief (PEPFAR), launched in 2002, has played a major role in the rapid scale-up of and expanded access to ART in resourcelimited countries, particularly in sub-Saharan Africa. In the opening session of the 20th Conference on Retroviruses and Opportunistic Infections (CROI 2013), Dr Thomas Frieden, Director of the Centers for Disease Control and Prevention (CDC), articulated the goals of interventions in the global HIV epidemic, stating, 'the proportion of patients with viral suppression should be the p...

show abstract

Section: Introductionmentioning

confidence: 99%

Evaluation of treatment outcomes for patients on first‐line regimens in US President's Emergency Plan for AIDS Relief (PEPFAR) clinics in Uganda: predictors of virological and immunological response from RV288 analyses

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Neither clinical findings nor CD4 cell counts are adequate predictors of viral suppression, and in fact management by CD4 cell counts alone can lead to unnecessary treatment changes (1). VL testing is the only reliable marker for the early detection of the failure of antiretroviral therapy (17,20).…”

mentioning

confidence: 99%

Comparative Evaluation of the ExaVir Load Version 3 Reverse Transcriptase Assay for Measurement of Human Immunodeficiency Virus Type 1 Plasma Load

Labbett¹,

Garcı́a-Dı́az²,

Fox³

et al. 2009

J Clin Microbiol

View full text Add to dashboard Cite

In resource-limited settings, the virological monitoring of antiretroviral therapy is limited by high cost and the lack of infrastructure. The Cavidi ExaVir Load assay employs a simple and inexpensive enzyme-linked immunosorbent assay format to measure human immunodeficiency virus (HIV) reverse transcriptase activity, which correlates with plasma RNA load. The version 3 assay has been described as having improved precision and sensitivity. There are limited data on its performance relative to those of current real-time assays

show abstract

“…Viral load monitoring is more reliable than CD4 monitoring as an early way to detect HIV drug resistance in these patients. 10 Given that this patient population suffers concurrently from two deadly diseases and generally experiences poor treatment outcomes, 11 routine virologic monitoring for DR-TB patients with HIV coinfection should be considered, even in the context of limited resources. We recommend that all DR-TB/HIV coinfected patients receive viral load testing at the start of DR-TB treatment and every 6 months while on DR-TB treatment.…”

Section: Discussionmentioning

confidence: 99%

Drug-Resistant Tuberculosis Treatment Complicated by Antiretroviral Resistance in HIV Coinfected Patients: A Report of Six Cases in Lesotho

Satti

McLaughlin²,

Seung³

2013

The American Society of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

Abstract. Treating drug-resistant tuberculosis (DR-TB) is particularly challenging in high human immunodeficiency virus (HIV) prevalence settings. Neither antiretroviral resistance testing nor viral load monitoring is widely available in sub-Saharan Africa, and antiretroviral resistance can complicate the clinical management for DR-TB/HIV coinfected patients. We describe six cases of antiretroviral resistance in DR-TB patients with HIV coinfection in Lesotho. Two patients died before or immediately after antiretroviral resistance was detected by genotyping; the remaining four patients were switched to effective antiretroviral therapy (ART) regimens. Favorable DR-TB treatment outcomes in coinfected patients require successful management of their HIV infection, including treatment with an effective ART regimen. Coinfected patients undergoing DR-TB treatment may require closer monitoring of their response to ART, including routine viral load testing, to ensure that they receive an effective ART regimen concurrent with DR-TB treatment.

show abstract

Failure of immunologic criteria to appropriately identify antiretroviral treatment failure in Uganda

Cited by 164 publications

References 6 publications

Evaluation of treatment outcomes for patients on first‐line regimens in US President's Emergency Plan for AIDS Relief (PEPFAR) clinics in Uganda: predictors of virological and immunological response from RV288 analyses

Evaluation of treatment outcomes for patients on first‐line regimens in US President's Emergency Plan for AIDS Relief (PEPFAR) clinics in Uganda: predictors of virological and immunological response from RV288 analyses

Comparative Evaluation of the ExaVir Load Version 3 Reverse Transcriptase Assay for Measurement of Human Immunodeficiency Virus Type 1 Plasma Load

Drug-Resistant Tuberculosis Treatment Complicated by Antiretroviral Resistance in HIV Coinfected Patients: A Report of Six Cases in Lesotho

Contact Info

Product

Resources

About