Increased Mortality With Delayed and Missed Switch to Second-Line Antiretroviral Therapy in South Africa

Bell-Gorrod, Helen; Court, Richard; Schomaker, Michael; Maartens, Gary; Murphy, Richard A.

doi:10.1097/qai.0000000000002313

Cited by 19 publications

(29 citation statements)

References 22 publications

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“…In short, routine VL monitoring reduces mortality when used together with adherence support [ 48 ] and a timely switch to effective treatment [ 49 , 50 ], but ensuring coverage of VL and second-line ART for those with a diagnosis of virological failure remains a huge challenge. When coverage is low, the overall benefit from VL scale-up might be lower than anticipated.…”

Section: Discussionmentioning

confidence: 99%

Predictors of virological failure among people living with HIV receiving first line antiretroviral treatment in Myanmar: retrospective cohort analysis

Mesic

Spina

Mar³

et al. 2021

AIDS Res Ther

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Background Progress toward the global target for 95% virological suppression among those on antiretroviral treatment (ART) is still suboptimal. We describe the viral load (VL) cascade, the incidence of virological failure and associated risk factors among people living with HIV receiving first-line ART in an HIV cohort in Myanmar treated by the Médecins Sans Frontières in collaboration with the Ministry of Health and Sports Myanmar. Methods We conducted a retrospective cohort study, including adult patients with at least one HIV viral load test result and having received of at least 6 months’ standard first-line ART. The incidence rate of virological failure (HIV viral load ≥ 1000 copies/mL) was calculated. Multivariable Cox’s regression was performed to identify risk factors for virological failure. Results We included 25,260 patients with a median age of 33.1 years (interquartile range, IQR 28.0–39.1) and a median observation time of 5.4 years (IQR 3.7–7.9). Virological failure was documented in 3,579 (14.2%) participants, resulting in an overall incidence rate for failure of 2.5 per 100 person-years of follow-up. Among those who had a follow-up viral load result, 1,258 (57.1%) had confirmed virological failure, of which 836 (66.5%) were switched to second-line treatment. An increased hazard for failure was associated with age ≤ 19 years (adjusted hazard ratio, aHR 1.51; 95% confidence intervals, CI 1.20–1.89; p < 0.001), baseline tuberculosis (aHR 1.39; 95% CI 1.14–1.49; p < 0.001), a history of low-level viremia (aHR 1.60; 95% CI 1.42–1.81; p < 0.001), or a history of loss-to-follow-up (aHR 1.24; 95% CI 1.41–1.52; p = 0.041) and being on the same regimen (aHR 1.37; 95% CI 1.07–1.76; p < 0.001). Cumulative appointment delay was not significantly associated with failure after controlling for covariates. Conclusions VL monitoring is an important tool to improve programme outcomes, however limited coverage of VL testing and acting on test results hampers its full potential. In our cohort children and adolescents, PLHIV with history of loss-to-follow-up or those with low-viremia are at the highest risk of virological failure and might require more frequent virological monitoring than is currently recommended.

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Section: Discussionmentioning

confidence: 99%

Predictors of virological failure among people living with HIV receiving first line antiretroviral treatment in Myanmar: retrospective cohort analysis

Mesic

Spina

Mar³

et al. 2021

AIDS Res Ther

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“…Our study observed a mortality rate of 3.9/100PYS for those who did not have a treatment modification, and 3.0/100PYS for those who did without ART interruption. Delayed switch from first-line to second-line ART has been shown to be associated with increased mortality in resource-limited settings [26,27]. This study observed no differences in survival outcomes after second-line ART failure, however, the benefits of treatment modification were seen with greater CD4 increase in those who had their treatment modified without interruption, while those who had treatment interruption were less likely to achieve undetectable VL compared with those who remained on the same failing second-line regimen.…”

Section: Discussionmentioning

confidence: 99%

Treatment Modification after Second-Line Failure among People Living with HIV in Asia-Pacific

et al. 2019

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Background: The World Health Organization recommends continuation with the failing second-line regimen if third-line option is not available. We investigated treatment outcomes among people living with HIV in Asia who continued with failing second-line regimens compared with those who had treatment modifications after failure. Methods: Treatment modification was defined as a change of two antiretrovirals, a drug class change or treatment interruption (TI), all for >14 days. We assessed factors associated with CD4 changes and undetectable viral load (UVL <1,000 copies/ml) at 1 year after second-line failure using linear and logistic regression, respectively. Survival time was analysed using competing risk regression. Results: Of the 328 patients who failed second-line ART in our cohorts, 208 (63%) had a subsequent treatment modification. Compared with those who continued the failing regimen, the average CD4 cell increase was higher in patients who had a modification without TI (difference =77.5, 95% CI 35.3, 119.7) while no difference was observed among those with TI (difference =-5.3, 95% CI -67.3, 56.8). Compared with those who continued the failing regimen, the odds of achieving UVL was lower in patients with TI (OR=0.18, 95% CI 0.06, 0.60) and similar among those who had a modification without TI (OR=1.97, 95% CI 0.95, 4.10), with proportions of UVL 60%, 22% and 75%, respectively. Survival time was not affected by treatment modifications. Conclusions: CD4 cell improvements were observed in those who had treatment modification without TI compared with those on the failing regimen. When no other options are available, maintaining the same failing ART combination provided better VL control than interrupting treatment.

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“…Third, among people with confirmed viral failure, a systematic review, 26 and more recent individual studies, 4 27-29 have found that only 30%-60% are switched to second-line ART. Even among patients who are switched, this can take a further 3-12 months, [27][28][29] with delays of even a few months being associated with increased risk of opportunistic infections and mortality, particularly among people with low CD4 counts. 1 4 27-29 Taken together, these data highlight the need for interventions to reduce delays and improve the management of viraemia.…”

Section: Problems With Management Of Viraemiamentioning

confidence: 99%

Protocol for a randomised feasibility study of Point-Of-care HIV viral load testing to Enhance Re-suppression in South Africa: the POwER study

et al. 2021

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IntroductionAccess to HIV viral load testing remains difficult for many people on antiretroviral therapy (ART) in low-income and middle-income countries. Weak laboratory and clinic systems often delay the detection and management of viraemia, which can lead to morbidity, drug resistance and HIV transmission. Point-of-care testing could overcome these challenges. We aim to assess whether it is feasible to conduct a randomised trial of point-of-care viral load testing to manage viraemia.Methods and analysisWe will conduct an open-label, single-site, individually randomised, feasibility study of Point-Of-care HIV viral load testing to Enhance Re-suppression, in Durban, South Africa. We will enrol approximately 100 people living with HIV who are aged ≥18 years, receiving first-line ART but with recent viraemia ≥1000 copies/mL, and randomise them 1:1 to receive point-of-care viral load or standard laboratory viral load monitoring, after 12 weeks. All participants will continue to receive care from public sector healthcare workers following South African HIV management guidelines. Participants with persistent viraemia ≥1000 copies/mL will be considered for switching to second-line ART. We will compare the proportion in each study arm who achieve the primary outcome of viral suppression <50 copies/mL at 24 weeks after enrolment. Additional outcomes include proportions retained in the study, proportions with HIV drug resistance, time to viral load results and time to switching to second-line ART. We will assess implementation of point-of-care viral load testing using process evaluation data, and through interviews and focus groups with healthcare workers.Ethics and disseminationUniversity of Oxford Tropical Research Ethics Committee and the Biomedical Research Ethics Committee of the University of KwaZulu-Natal have approved the study. We will present results to stakeholders, and through conferences and open-access, peer-reviewed journals.Trial registration numberPACTR202001785886049.

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Increased Mortality With Delayed and Missed Switch to Second-Line Antiretroviral Therapy in South Africa

Cited by 19 publications

References 22 publications

Predictors of virological failure among people living with HIV receiving first line antiretroviral treatment in Myanmar: retrospective cohort analysis

Predictors of virological failure among people living with HIV receiving first line antiretroviral treatment in Myanmar: retrospective cohort analysis

Treatment Modification after Second-Line Failure among People Living with HIV in Asia-Pacific

Protocol for a randomised feasibility study of Point-Of-care HIV viral load testing to Enhance Re-suppression in South Africa: the POwER study

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