Marginal Structural Models to Assess Delays in Second-Line HIV Treatment Initiation in South Africa

Rohr, Julia; Ive, Prudence; Horsburgh, C. Robert; Berhanu, Rebecca; Shearer, Kate; Maskew, Mhairi; Long, Lawrence; Sanne, Ian; Bassett, Jean; Ebrahim, Osman; Fox, Matthew P.

doi:10.1371/journal.pone.0161469

Cited by 34 publications

(42 citation statements)

References 42 publications

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“…Previous reports from sub-Saharan African settings have consistently shown low and delayed switching from first-to second-line ART (even when VL-monitoring is present), which have been linked to poorer treatment outcomes, increased mortality and the risk of the development and transmission of resistance [8,32,[60][61][62][63]. In our sites, 80% of first-line treatment failures were switched to second-line, an encouraging figure that is higher than in similar programmes (43%, Swaziland; 33%, Mozambique [50,64] three-test failure algorithm or the non-capture of VL-tests in the electronic database.…”

Section: Discussionmentioning

confidence: 99%

Point‐of‐care viral load monitoring: outcomes from a decentralized HIV programme in Malawi

Nicholas¹,

Poulet²,

Wolters³

et al. 2019

J Intern AIDS Soc

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Introduction Routinely monitoring the HIV viral load ( VL ) of people living with HIV ( PLHIV ) on anti‐retroviral therapy ( ART ) facilitates intensive adherence counselling and faster ART regimen switch when treatment failure is indicated. Yet standard VL ‐testing in centralized laboratories can be time‐intensive and logistically difficult in low‐resource settings. This paper evaluates the outcomes of the first four years of routine VL ‐monitoring using Point‐of‐Care technology, implemented by Médecins Sans Frontières ( MSF ) in rural clinics in Malawi. Methods We conducted a retrospective cohort analysis of patients eligible for routine VL ‐ testing between 2013 and 2017 in four decentralized ART ‐clinics and the district hospital in Chiradzulu, Malawi. We assessed VL ‐testing coverage and the treatment failure cascade (from suspected failure (first VL >1000 copies/ mL ) to VL suppression post regimen switch). We used descriptive statistics and multivariate logistic regression to assess factors associated with suspected failure. Results and Discussion Among 21,400 eligible patients, VL ‐testing coverage was 85% and VL suppression was found in 89% of those tested. In the decentralized clinics, 88% of test results were reviewed on the same day as blood collection, whereas in the district hospital the median turnaround‐time for results was 85 days. Among first‐line ART patients with suspected failure (N = 1544), 30% suppressed ( VL <1000 copies/ mL ), 35% were treatment failures (confirmed by subsequent VL ‐testing) and 35% had incomplete VL follow‐up. Among treatment failures, 80% (N = 540) were switched to a second‐line regimen, with a higher switching rate in the decentralized clinics than in the district hospital (86% vs. 67%, p < 0.01) and a shorter median time‐to‐switch (6.8 months vs. 9.7 months, p < 0.01). Similarly, the post‐switch VL ‐testing rate was markedly higher in the decentralized clinics (61% vs. 26%, p < 0.01). Overall, 79% of patients with a post‐switch VL ‐test were suppressed. Conclusions Viral load testing at the point‐of‐care in Chiradzulu, Malawi achieved high coverage and good drug regimen switch rates among those identified as treatment failures. In...

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Section: Discussionmentioning

confidence: 99%

Point‐of‐care viral load monitoring: outcomes from a decentralized HIV programme in Malawi

Nicholas¹,

Poulet²,

Wolters³

et al. 2019

J Intern AIDS Soc

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“…In agreement with our study, Johnston and colleagues had previously shown for a large multicentre cohort in Johannesburg a high reluctance among healthcare providers to switch patients to second-line ART - even after confirmed treatment failure [ 11 ]. Rohr and colleagues reported from a large cohort of nine clinics in South Africa that only about half of the patients failing first-line therapy were switched to second line within 12 months after the diagnosis of treatment failure [ 26 ]. These South African studies were conducted in large, well-established HIV care centres.…”

Section: Discussionmentioning

confidence: 99%

“…These figures are in line with earlier reports from South Africa [ 12 , 27 ]. In the cohort study of Rohr et al, after switch to second line, 14% experienced confirmed virologic failure on second line, 42% remained in care with regular VL monitoring, 12% remained in care but had missed VL monitoring visits, 30% stopped attending the clinic and 2% died [ 26 ]. In a randomized controlled trial conducted in three West African countries, 65% achieved viral suppression (<50 copies/mL) after switch to second line [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

When patients fail UNAIDS’ last 90 ‐ the “failure cascade” beyond 90‐90‐90 in rural Lesotho, Southern Africa: a prospective cohort study

Labhardt¹,

Ringera²,

Lejone³

et al. 2017

Journal of the International AIDS Society

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Introduction: HIV-infected individuals on first-line antiretroviral therapy (ART) in resource-limited settings who do not achieve the last “90” (viral suppression) enter a complex care cascade: enhanced adherence counselling (EAC), repetition of viral load (VL) and switch to second-line ART aiming to achieve resuppression. This study describes the “failure cascade” in patients in Lesotho.Methods: Patients aged ≥16 years on first-line ART at 10 facilities in rural Lesotho received a first-time VL in June 2014. Those with VL ≥80 copies/mL were included in a cohort. The care cascade was assessed at four points: attendance of EAC, result of follow-up VL after EAC, switch to second-line in case of sustained unsuppressed VL and outcome 18 months after the initial unsuppressed VL. Multivariate logistic regression was used to assess predictors of being retained in care with viral resuppression at follow-up.Results: Out of 1563 patients who underwent first-time VL, 138 (8.8%) had unsuppressed VL in June 2014. Out of these, 124 (90%) attended EAC and 116 (84%) had follow-up VL (4 died, 2 transferred out, 11 lost, 5 switched to second-line before follow-up VL). Among the 116 with follow-up VL, 36 (31%) achieved resuppression. Out of the 80 with sustained unsuppressed VL, 58 were switched to second-line, the remaining continued first line. At 18 months’ follow-up in December 2015, out of the initially 138 with unsuppressed VL, 56 (41%) were in care and virally suppressed, 37 (27%) were in care with unsuppressed VL and the remaining 45 (33%) were lost, dead, transferred to another clinic or without documented VL. Achieving viral resuppression after EAC (adjusted odds ratio (aOR): 5.02; 95% confidence interval: 1.14–22.09; p = 0.033) and being switched to second-line in case of sustained viremia after EAC (aOR: 7.17; 1.90–27.04; p = 0.004) were associated with being retained in care and virally suppressed at 18 months of follow-up. Age, gender, education, time on ART and level of VL were not associated.Conclusions: In this study in rural Lesotho, outcomes along the “failure cascade” were poor. To improve outcomes in this vulnerable patient group who fails the last “90”, programmes need to focus on timely EAC and switch to second line for cases with continuous viremia despite EAC.

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“…However, on the ground, switch delays in South Africa are nearly twice that—a median of 3.4 months—with 37% of patients with first-line ART failure in South Africa failing to switch. 4 …”

Section: The Causes and Costs Of Late Or Missed Second-line Switchmentioning

confidence: 99%

Second-Line Antiretroviral Therapy in Sub-Saharan Africa: It Is Time to Mind the Gaps

Murphy

Court

Maartens

et al. 2017

AIDS Research and Human Retroviruses

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The delay between first-line antiretroviral therapy (ART) failure and initiation of second-line ART in resource-limited settings can be prolonged. Increasing evidence links delayed antiretroviral switch with increased risk for opportunistic infection (OI) and death, particularly in patients with advanced HIV at the time of first-line failure. As access to viral load (VL) monitoring widens beyond a few countries, mechanisms are needed to optimize the use of routine virologic monitoring and assure that first-line regimen failure results in prompt second-line switch. For patients with advanced HIV or OI at the time of first-line failure, a targeted fast track to second-line ART should be considered, involving a switch to second-line ART during a single visit. To derive the maximum benefit from both the current expansion of VL monitoring and the falling costs of second-line ART, clinics and healthcare workers should be given the tools and training to detect and switch patients with regimen failure before HIV disease progression.

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Marginal Structural Models to Assess Delays in Second-Line HIV Treatment Initiation in South Africa

Cited by 34 publications

References 42 publications

Point‐of‐care viral load monitoring: outcomes from a decentralized HIV programme in Malawi

Point‐of‐care viral load monitoring: outcomes from a decentralized HIV programme in Malawi

When patients fail UNAIDS’ last 90 ‐ the “failure cascade” beyond 90‐90‐90 in rural Lesotho, Southern Africa: a prospective cohort study

Second-Line Antiretroviral Therapy in Sub-Saharan Africa: It Is Time to Mind the Gaps

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