Unnecessary Antiretroviral Treatment Switches and Accumulation of HIV Resistance Mutations; Two Arguments for Viral Load Monitoring in Africa

Sigaloff, Kim C.E.; Hamers, Raph L; Wallis, Carole L.; Kityo, Cissy; Siwale, Margaret; Ive, Prudence; Botes, Mariëtte E.; Mandaliya, Kishor; Wellington, Maureen; Osibogun, Akin; Stevens, Wendy; Vugt, Michèle van; Wit, Tobias F. Rinke de

doi:10.1097/qai.0b013e318227fc34

Cited by 169 publications

(141 citation statements)

References 33 publications

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“…Even with good clinical practice in Uganda, where intensive adherence counseling is the first course of action when therapy failure is suspected, our results suggest the more than half of the possible switches to a second-line regimen would have been unnecessary. A similar finding has also recently been reported from a study of ART treatment-switching practices in six African countries (39). The greatly increased cost of second-line ART that includes a boosted PI suggests that routine VL testing could save costs by avoiding unnecessary treatment switches.…”

Section: Discussionsupporting

confidence: 65%

Field Study of Dried Blood Spot Specimens for HIV-1 Drug Resistance Genotyping

Parry

Parkin

Diallo³

et al. 2014

J Clin Microbiol

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h Dried blood spots (DBS) are an alternative specimen type for HIV drug resistance genotyping in resource-limited settings. Data relating to the impact of DBS storage and shipment conditions on genotyping efficiency under field conditions are limited. We compared the genotyping efficiencies and resistance profiles of DBS stored and shipped at different temperatures to those of plasma specimens collected in parallel from patients receiving antiretroviral therapy in Uganda. Plasma and four DBS cards from anti-coagulated venous blood and a fifth card from finger-prick blood were prepared from 103 HIV patients with a median viral load (VL) of 57,062 copies/ml (range, 1,081 to 2,964,191). DBS were stored at ambient temperature for 2 or 4 weeks or frozen at ؊80°C and shipped from Uganda to the United States at ambient temperature or frozen on dry ice for genotyping using a broadly sensitive in-house method. Plasma (97.1%) and DBS (98.1%) stored and shipped frozen had similar genotyping efficiencies. DBS stored frozen (97.1%) or at ambient temperature for 2 weeks (93.2%) and shipped at ambient temperature also had similar genotyping efficiencies. Genotyping efficiency was reduced for DBS stored at ambient temperature for 4 weeks (89.3%, P ‫؍‬ 0.03) or prepared from finger-prick blood and stored at ambient temperature for 2 weeks (77.7%, P < 0.001) compared to DBS prepared from venous blood and handled similarly. Resistance profiles were similar between plasma and DBS specimens. This report delineates the optimal DBS collection, storage, and shipping conditions and opens a new avenue for cost-saving ambient-temperature DBS specimen shipments for HIV drug resistance (HIVDR) surveillances in resource-limited settings.

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Section: Discussionsupporting

confidence: 65%

Field Study of Dried Blood Spot Specimens for HIV-1 Drug Resistance Genotyping

Parry

Parkin

Diallo³

et al. 2014

J Clin Microbiol

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“…In settings with limited settings to routine viral load monitoring, WHO recommends targeted viral load strategy to confirm treatment failure diagnosed based on clinical and immunological criteria. Despite the fact that targeted viral load strategy may delay switching to second line and thereby increase the risk of disease progression, it helps to avoid unnecessary switching to second line that could have happened when clinical and immunological criteria were used alone [15].…”

Section: Discussionmentioning

confidence: 99%

Accuracy of WHO immunological criteria in identifying virological failure among HIV-infected adults on First line antiretroviral therapy in Mwanza, North-western Tanzania

et al. 2017

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Background: Optimal HIV treatment monitoring remains a big challenge in resource limited settings. Guidelines recommend the use of clinical and immunological criteria in resource limited settings due to unavailability of viral load monitoring; however their utility is questionable. This study aimed at assessing the accuracy of immunological criteria in detecting treatment failure among HIV infected Tanzanian adults receiving first line ART. Methods:A clinic based cross sectional study was conducted between February and July 2011 at Bugando Medical centre (BMC) HIV care and treatment clinic (CTC) involving HIV infected patients aged 18 years and above, receiving first line ART; followed up for at least 1 year. Viral load was tested for every enrolled patient. Standard WHO criteria were used to define immunological failure. Virological failure was defined as one viral load measurement of >5000 copies/ml and was used as a gold standard. A 2 × 2 table was used to assess the accuracy of immunological criteria in detecting treatment failure. Results:A total of 274 HIV-infected adults were enrolled into the study. Out of these, 65.7% were females, the median age was 39 years , the median BMI 21.9 kg/m 2 . Out of the 274 study participants 156 (56.9%) had immunological failure. Only 60 of the study participants (21.9%) had viral load >5000. Only 42 patients (70%) were found to have both immunological failure and virological failure. The sensitivity of immunological criteria in detecting treatment failure was 70%, specificity 46.7%, positive predictive and negative predictive values of 26.9 and 84.7% respectively. Conclusion: WHO immunological criteria have low sensitivity and positive predictive value for detecting treatment failure. Relying on CD4 counts for treatment monitoring would therefore lead to misclassifications of treatment failure that could result into unnecessary or delayed switch to second line ART. Access to viral load monitoring is important to avoid these misclassifications.

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“…However, reduced susceptibility to these first-line drugs and the consequent switching to second-line drugs would at least partly undo early ART successes and result in higher expenditures and increasing numbers of patients on failing regimens with no options for effective second-line or salvage therapies (4,5).…”

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confidence: 99%

Development and Evaluation of an Affordable Real-Time Qualitative Assay for Determining HIV-1 Virological Failure in Plasma and Dried Blood Spots

et al. 2013

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h Virological failure (VF) has been identified as the earliest, most predictive determinant of HIV-1 antiretroviral treatment (ART) failure. Due to the high cost and complexity of virological monitoring, VF assays are rarely performed in resource-limited settings (RLS). Rather, ART failure is determined by clinical monitoring and to a large extent immunological monitoring. This paper describes the development and evaluation of a low-cost, dried blood spot (DBS)-compatible qualitative assay to determine VF, in accordance with current WHO guideline recommendations for therapy switching in RLS. The assay described here is an internally controlled qualitative real-time PCR targeting the conserved long terminal repeat domain of HIV-1. This assay was applied to HIV-1 subtypes A to H and further evaluated on HIV-1 clinical plasma samples from South Africa (n ‫؍‬ 191) and Tanzania (n ‫؍‬ 42). Field evaluation was performed in Uganda using local clinical plasma samples (n ‫؍‬ 176). Furthermore, assay performance was evaluated for DBS. This assay is able to identify VF for all major HIV-1 group M subtypes with equal specificity and has a lower detection limit of 1.00E؉03 copies/ml for plasma samples and 5.00E؉03 copies/ml for DBS. Comparative testing yielded accurate VF determination for therapy switching in 89% to 96% of samples compared to gold standards. The assay is robust and flexible, allowing for "open platform" applications and producing results comparable to those of commercial assays. Assay design enables application in laboratories that can accommodate real-time PCR equipment, allowing decentralization of testing to some extent. Compatibility with DBS extends access of sampling and thus access to this test to remote settings.

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Unnecessary Antiretroviral Treatment Switches and Accumulation of HIV Resistance Mutations; Two Arguments for Viral Load Monitoring in Africa

Cited by 169 publications

References 33 publications

Field Study of Dried Blood Spot Specimens for HIV-1 Drug Resistance Genotyping

Field Study of Dried Blood Spot Specimens for HIV-1 Drug Resistance Genotyping

Accuracy of WHO immunological criteria in identifying virological failure among HIV-infected adults on First line antiretroviral therapy in Mwanza, North-western Tanzania

Development and Evaluation of an Affordable Real-Time Qualitative Assay for Determining HIV-1 Virological Failure in Plasma and Dried Blood Spots

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