Virological suppression and clinical management in response to viremia in South African HIV treatment program: A multicenter cohort study

Hermans, Lucas E; Carmona, Sergio; Nijhuis, Monique; Tempelman, Hugo; Richman, Douglas D.; Moorhouse, Michelle; Grobbee, Diederick E.; Venter, François; Wensing, Annemarie M. J.

doi:10.1371/journal.pmed.1003037

Cited by 42 publications

(46 citation statements)

References 44 publications

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“…In keeping with the available literature [18,20,22,23,24,25], we capture in our model that very high levels (76%, refer to Table 1) of people with a single viral load value more than 1000 copies/ml have drug resistance to EFV and thus likely do require a change in regimen; underlining the limited scope for second-line preservation among failing patients.…”

Section: Discussionmentioning

confidence: 98%

“…In terms of achieving sufficient adherence, while there is evidence to support counselling for adherence at the time of ART initiation [67], by the time a person previously suppressed on ART presents with a high viral load it is much less certain whether the intervention will be useful and whether any resuppression achieved will be durable [25,68]. For individuals who admit to having poor adherence it may still be reasonable to provide the opportunity to resuppress their viral load on first-line ART.…”

Section: Discussionmentioning

confidence: 99%

“…Resuppression after a single viral load more than 1000 copies/ml has been reported to occur in 20–50% of individuals, but with suppression being particularly unlikely if drug resistance is present [20,21]. For those that do resuppress virus, the duration of resuppression is often limited, particularly if preceded by months of high-level viraemia, as is commonly the case [18,22,23,24,25]. Finally, although the CD4 + cell count at ART initiation has slowly increased in African contexts, patients who fail first-line ART continue to have advanced immunodeficiency at failure making rapid viral resuppression urgent [26].…”

Section: Introductionmentioning

confidence: 99%

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Simplifying switch to second-line antiretroviral therapy in sub Saharan Africa

Shroufi

Cutsem

Cambiano³

et al. 2019

Aids

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Background: Many individuals failing first-line antiretroviral therapy (ART) in sub-Saharan Africa never initiate second-line ART or do so after significant delay. For people on ART with a viral load more than 1000 copies/ml, the WHO recommends a second viral load measurement 3 months after the first viral load and enhanced adherence support. Switch to a second-line regimen is contingent upon a persistently elevated viral load more than 1000 copies/ml. Delayed second-line switch places patients at increased risk for opportunistic infections and mortality. Methods: To assess the potential benefits of a simplified second-line ART switch strategy, we use an individual-based model of HIV transmission, progression and the effect of ART which incorporates consideration of adherence and drug resistance, to compare predicted outcomes of two policies, defining first-line regimen failure for patients on efavirenz-based ART as either two consecutive viral load values more than 1000 copies/ml, with the second after an enhanced adherence intervention (implemented as per current WHO guidelines) or a single viral load value more than 1000 copies/ml. We simulated a range of setting-scenarios reflecting the breadth of the sub-Saharan African HIV epidemic, taking into account potential delays in defining failure and switch to second-line ART. Findings: The use of a single viral load more than 1000 copies/ml to define ART failure would lead to a higher proportion of persons with nonnucleoside reverse-transcriptase inhibitor resistance switched to second-line ART [65 vs. 48%; difference 17% (90% range 14–20%)], resulting in a median 18% reduction in the rate of AIDS-related death over setting scenarios (90% range 6–30%; from a median of 3.1 to 2.5 per 100 person-years) over 3 years. The simplified strategy also is predicted to reduce the rate of AIDS conditions by a median of 31% (90% range 8–49%) among people on first-line ART with a viral load more than 1000 copies/ml in the past 6 months. For a country of 10 million adults (and a median of 880 000 people with HIV), we estimate that this approach would lead to a median of 1322 (90% range 67–3513) AIDS deaths averted per year over 3 years. For South Africa this would represent around 10 215 deaths averted annually. Interpretation: As a step towards reducing unnecessary mortality associated with delayed second-line ART switch, defining failure of first-line efavirenz-based regimens as a single viral load more than 1000 copies/ml should be considered.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Simplifying switch to second-line antiretroviral therapy in sub Saharan Africa

Shroufi

Cutsem

Cambiano³

et al. 2019

Aids

View full text Add to dashboard Cite

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“…This may pose an additional burden to already overstretched clinic staff, laboratories, national HIV programs, and budgets. Already using a threshold of 1,000 copies/mL, many national programs struggle to provide timely adherence support, follow-up VL, and switch to second-line ART regimens [ 36 , 37 ]. Conversely, with the large-scale introduction of dolutegravir-containing first-line ART regimens in sub-Saharan Africa, overall higher suppression rates can be expected, counterbalancing the additional burden imposed if the threshold is lowered.…”

Section: Discussionmentioning

confidence: 99%

Switch to second-line versus continued first-line antiretroviral therapy for patients with low-level HIV-1 viremia: An open-label randomized controlled trial in Lesotho

Amstutz

Nsakala²,

Vanobberghen

et al. 2020

PLoS Med

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Background Current World Health Organization (WHO) antiretroviral therapy (ART) guidelines define virologic failure as two consecutive viral load (VL) measurements ≥1,000 copies/mL, triggering empiric switch to next-line ART. This trial assessed if patients with sustained low-level HIV-1 viremia on first-line ART benefit from a switch to second-line treatment. Methods and findings This multicenter, parallel-group, open-label, superiority, randomized controlled trial enrolled patients on first-line ART containing non-nucleoside reverse transcriptase inhibitors (NNRTI) with two consecutive VLs ≥100 copies/mL, with the second VL between 100–999 copies/mL, from eight clinics in Lesotho. Consenting participants were randomly assigned (1:1), stratified by facility, demographic group, and baseline VL, to either switch to second-line ART (switch group) or continued first-line ART (control group; WHO guidelines). The primary endpoint was viral suppression (<50 copies/mL) at 36 weeks. Analyses were by intention to treat, using logistic regression models, adjusted for demographic group and baseline VL. Between August 1, 2017, and August 7, 2019, 137 individuals were screened, of whom 80 were eligible and randomly assigned to switch ( n = 40) or control group ( n = 40). The majority of participants were female (54 [68%]) with a median age of 42 y (interquartile range [IQR] 35–51), taking tenofovir disoproxil fumarate/lamivudine/efavirenz (49 [61%]) and on ART for a median of 5.9 y (IQR 3.3–8.6). At 36 weeks, 22/40 (55%) participants in the switch versus 10/40 (25%) in the control group achieved viral suppression (adjusted difference 29%, 95% CI 8%–50%, p = 0.009). The switch group had significantly higher probability of viral suppression across different VL thresholds (<20, <100, <200, <400, and <600 copies/mL) but not for <1,000 copies/mL. Thirty-four (85%) participants in switch group and 21 (53%) in control group experienced at least one adverse event (AE) ( p = 0.002). No hospitalization or death or other serious adverse events were observed. Study limitations include a follow-up period too short to observe differences in clinical outcomes, missing values in CD4 cell counts due to national stockout of reagents during the study, and limited generalizability of findings to other than NNRTI-based first-line ART regimens. Conclusions In this study, switching to second-line ART among patients with sustained low-level HIV-1 viremia resulted in a higher proportion of participants with viral suppression. These results endorse lowering the threshold for virologic failure in future WHO guidelines. Trial registration The trial is registered at ClinicalTrials.gov, NCT03088241 .

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“… 7 Switch to second line therapy among patients with viral failure when adherence interventions are unsuccessful is also important for preventing morbidity and mortality, although delays in appropriate switch are common. 8 – 10 Better DSD interventions are needed for viremic patients to most appropriately target services to improve population-level VS. Integrated DSD models are also needed that reduce common barriers to care for all patients and provide tailored services to viremic and virally suppressed patients alike.…”

Section: Introductionmentioning

confidence: 99%