Human Immunodeficiency Virus-1 Drug Resistance Patterns Among Adult Patients Failing Second-Line Protease Inhibitor-Containing Regimens in Namibia, 2010–2015

Sawadogo, Souleymane; Shiningavamwe, Andreas; Roscoe, Clay; Baughman, Andrew L.; Negussie, Taffa; Mutandi, Gram; Yang, Chunfu; Hamunime, Ndapewa; Agolory, Simon

doi:10.1093/ofid/ofy014

Cited by 5 publications

(4 citation statements)

References 8 publications

(7 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, as the access to ART continues to expand rapidly worldwide, often without adequate virological monitoring of patients on ART, emergence and transmission of HIV drug resistance (HIVDR) is a valid concern [ 2 ]. Studies in resource-limited settings have suggested that transmitted HIVDR in recently HIV-infected populations or pre-treatment HIVDR (PDR) in ART eligible patients is rising in countries where access to ART has been expanded [ 3 – 11 ], while acquired HIVDR (ADR) in patients on ART has been detected in majority of the patients failing ART [ 4 , 9 , 12 – 16 ].…”

Section: Introductionmentioning

confidence: 99%

Utilization of dried blood spot specimens can expedite nationwide surveillance of HIV drug resistance in resource-limited settings

et al. 2018

Self Cite

View full text Add to dashboard Cite

IntroductionSurveillance of HIV drug resistance (HIVDR) is crucial to ensuring the continued success of antiretroviral therapy (ART) programs. With the concern of reduced genotyping sensitivity of HIV on dried blood spots (DBS), DBS for HIVDR surveillance have been limited to ART-naïve populations. To investigate if DBS under certain conditions may also be a feasible sample type for HIVDR testing in ART patients, we piloted nationwide surveys for HIVDR among ART patients using DBS in two African countries with rapid scale-up of ART.MethodsEDTA-venous blood was collected to prepare DBS from adult and pediatric ART patients receiving treatment during the previous 12–36 months. DBS were stored at ambient temperature for two weeks and then at -80°C until shipment at ambient temperature to the WHO-designated Specialized HIVDR Laboratory at CDC in Atlanta. Viral load (VL) was determined using NucliSENS EasyQ® HIV-1 v2.0 kits; HIVDR genotyping was performed using the ATCC HIV-1 Drug Resistance Genotyping kits.ResultsDBS were collected from 1,368 and 1,202 ART patients; 244 and 255 these specimens had VL ≥1,000 copies/mL in Kenya and Tanzania, respectively. The overall genotyping rate of those DBS with VL ≥1,000 copies/mL was 93.0% (95% CI: 89.1%-95.6%) in Kenya and 91.8% (87.7%-94.6%) in Tanzania. The turnaround times for the HIVDR surveys from the time of collecting DBS to completing laboratory testing were 6.5 months and 9.3 months for the Kenya and Tanzania surveys, respectively.ConclusionsThe study demonstrates a favorable outcome of using DBS for nationwide surveillance of HIVDR in ART patients. Our results confirm that DBS collected and stored at ambient temperature for two weeks, and shipped with routine courier services are a reliable sample type for large-scale surveillance of acquired HIVDR.

show abstract

Section: Introductionmentioning

confidence: 99%

Utilization of dried blood spot specimens can expedite nationwide surveillance of HIV drug resistance in resource-limited settings

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…In a systematic review of second-line ART failure in sub-Saharan Africa [ 10 ], the second-line failure rate among 18,550 people was 15 per 100 person years. In reports from clinical centers where HIV-1 genotyping had been performed in these patients, wildtype genotypes were observed in 12–58% of tested individuals [ 11 – 14 ]. Consistent with this, in genotyping at screening for the A5288 study of people from multiple LMICs failing second-line ART and hence being considered for possible third-line ART, approximately half (278, 51%) of 545 participants had no resistance to the PI they were taking and had no or minimal resistance to NRTIs and so continued their PI-based regimen.…”

Section: Discussionmentioning

confidence: 99%

Predictors of virologic outcome among people living with HIV who continue a protease inhibitor-based antiretroviral regimen following virologic failure with no or limited resistance

et al. 2023

View full text Add to dashboard Cite

Background Treatment management after repeated failure of antiretroviral therapy (ART) is difficult due to resistance and adherence challenges. For people who have failed non-nucleoside reverse transcriptase inhibitor-(NNRTI-) and protease inhibitor-(PI-) based regimens with no or limited resistance, remaining on PI-based ART is an option. Using data from an ART strategy trial (A5288) in low/middle-income countries which included this option, we explored whether predictors can be identified distinguishing those who experienced further virologic failure from those who achieved and maintained virologic suppression. Methods A5288 enrolled people with confirmed HIV-1 RNA ≥ 1000 copies/mL after ≥ 24 weeks of PI-based ART and prior failure on NNRTI-based ART. This analysis focused on the 278 participants with no resistance to the PI being taken and no or limited nucleoside reverse transcriptase inhibitor (NRTI) resistance, who continued their PI with flexibility to change NRTIs. Proportional hazards models were used to evaluate predictors of virologic failure during follow-up (VF: confirmed HIV-1 RNA ≥ 1000 copies/mL at ≥ 24 weeks of follow-up). Results 56% of participants were female. At study entry, median age was 40 years, time on ART 7.8 years, CD4 count 169 cells/mm3, HIV-1 RNA 20,444 copies/mL; and 37% had NRTI resistance. The estimated proportion experiencing VF increased from 39% at week 24 to 60% at week 96. In multivariable analysis, significant predictors at study entry of VF were higher HIV-1 RNA (adjusted hazard ratio: 2.20 for ≥ 10,000 versus < 10,000 copies/mL), lower age (1.96 for < 30 versus ≥ 30 years), NRTI resistance (1.74 for present versus absent), lower CD4 count (1.73 for < 200 versus ≥ 200 cells/mm3), and shorter ART duration (1.62 for < 10 versus ≥ 10 years). There was a strong trend in proportion with VF at week 96 with the number of these five risk factors that a participant had, varying from 8% for zero, to 31%, 40%, 73%, and 100% for one, two, three, and four/five. Only 13% of participants developed new NRTI or PI resistance mutations. Conclusion A simple count of five predictors might have value for identifying risk of continued VF. Novel antiretroviral and adherence support interventions are needed to improve virologic outcomes for higher risk individuals.

show abstract

“…The prevalence estimates of overall, drug class and drug-specific resistance observed in this study are broadly comparable to those observed in other countries [ 15 – 17 ] and in a recent retrospective non-representative convenience sample of 366 HIVDR genotypes obtained by Namibia's ART program during the period 2010 to 2015. [ 18 ]…”

Section: Discussionmentioning

confidence: 99%

High levels of HIV drug resistance among adults failing second-line antiretroviral therapy in Namibia

et al. 2020

Self Cite

View full text Add to dashboard Cite

To support optimal third-line antiretroviral therapy (ART) selection in Namibia, we investigated the prevalence of HIV drug resistance (HIVDR) at time of failure of second-line ART. A cross-sectional study was conducted between August 2016 and February 2017. HIV-infected people ≥15 years of age with confirmed virological failure while receiving ritonavir-boosted protease inhibitor (PI/r)-based second-line ART were identified at 15 high-volume ART clinics representing over >70% of the total population receiving second-line ART. HIVDR genotyping of dried blood spots obtained from these individuals was performed using standard population sequencing methods. The Stanford HIVDR algorithm was used to identify sequences with predicted resistance; genotypic susceptibility scores for potential third-line regimens were calculated. Two hundred thirty-eight individuals were enrolled; 57.6% were female. The median age and duration on PI/r-based ART at time of enrolment were 37 years and 3.46 years, respectively. 97.5% received lopinavir/ritonavir-based regimens. The prevalence of nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), and PI/r resistance was 50.6%, 63.1%, and 13.1%, respectively. No significant association was observed between HIVDR prevalence and age or sex. This study demonstrates high levels of NRTI and NNRTI resistance and moderate levels of PI resistance in people receiving PI/r-based second-line ART in Namibia. Findings underscore the need for objective and inexpensive measures of adherence to identify those in need of intensive adherence counselling, routine viral load monitoring to promptly detect virological failure, and HIVDR genotyping to optimize selection of third-line drugs in Namibia.

show abstract

Human Immunodeficiency Virus-1 Drug Resistance Patterns Among Adult Patients Failing Second-Line Protease Inhibitor-Containing Regimens in Namibia, 2010–2015

Cited by 5 publications

References 8 publications

Utilization of dried blood spot specimens can expedite nationwide surveillance of HIV drug resistance in resource-limited settings

Utilization of dried blood spot specimens can expedite nationwide surveillance of HIV drug resistance in resource-limited settings

Predictors of virologic outcome among people living with HIV who continue a protease inhibitor-based antiretroviral regimen following virologic failure with no or limited resistance

High levels of HIV drug resistance among adults failing second-line antiretroviral therapy in Namibia

Contact Info

Product

Resources

About