Risk of Virological Failure and Drug Resistance During First and Second-Line Antiretroviral Therapy in a 10-Year Cohort in Senegal

Beaudrap, Pierre De; Thiam, Moussa; Diouf, A.; Touré-Kâne, Coumba; Ngom-Gueye, Ndeye Fatou; Vidal, Nicole; Mboup, Souleymane; Ndoye, Ibrahim; Sow, Papa Salif; Delaporte, Eric

doi:10.1097/qai.0b013e31827a2a7a

Cited by 40 publications

(34 citation statements)

References 30 publications

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“…The prevalences of unsuppressed viral load and antiretroviral drug resistance were comparable between women and men, in accordance with some studies [22, 23] including 1 in Yaoundé [10]. By contrast, men were more vulnerable to virologic failure than women in other studies [18, 24–26].…”

Section: Discussionsupporting

confidence: 88%

Virologic Failure and Human Immunodeficiency Virus Drug Resistance in Rural Cameroon With Regard to the UNAIDS 90-90-90 Treatment Targets

Boullé

Guichet

Kouanfack

et al. 2016

Open Forum Infectious Diseases

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Background.In rural Africa, data on virologic effectiveness of antiretroviral treatment (ART) are not sufficient to assess the gap with the UNAIDS 90-90-90 treatment targets. We investigated the prevalences of unsuppressed viral load and antiretroviral drug resistance and the profile of genotypic resistance mutations among patients routinely treated in rural Cameroon.Methods.A cross-sectional study was performed in 2013–2014 among patients ≥15 years and on first-line ART for ≥6 months in a district hospital. Patients were offered free access to human immunodeficiency virus viral load testing. Genotypic drug resistance testing was done when the viral load was >1000 copies/mL. Multivariate logistic regression models were used to assess the relationship of unsuppressed viral load or antiretroviral drug resistance with sociodemographic and medical characteristics.Results.Of 407 patients (women 74.9%, median age 41.8 years, median time on ART 29.2 months), 96 (23.6%; 95% confidence interval [CI], 19.5–28.0) had unsuppressed viral load and 74 (18.2%; 95% CI, 14.6–22.3) had antiretroviral drug resistance. The prevalences of unsuppressed viral load and resistance increased with time on ART, from 12.0% and 8.0% in the 6- to 12-month group to 31.3% and 27.1% in the >72-month group, respectively. All 74 patients with antiretroviral drug resistance were resistant to nonnucleoside reverse-transcriptase inhibitors, and 57 of them were also resistant to nucleoside reverse-transcriptase inhibitors.Conclusions.Our estimations were among the highest observed in the west and central African region. The proportion of patients with virologic failure should be divided at least by 2 to reach the UNAIDS 90-90-90 treatment targets.

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Section: Discussionsupporting

confidence: 88%

Virologic Failure and Human Immunodeficiency Virus Drug Resistance in Rural Cameroon With Regard to the UNAIDS 90-90-90 Treatment Targets

Boullé

Guichet

Kouanfack

et al. 2016

Open Forum Infectious Diseases

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“…An analysis of 10 treatment programmes in Africa and South America found an immunological failure rate of 3.3 per 100 person-years [18], which was lower than in our study (20.3 per 100 person-years). Studies of ART failure in the neighbouring countries of Senegal and Gambia focused primarily on virological failure [19–21]. The value of VL testing as a more sensitive and early indicator of treatment failure is increasingly recognized, and it is the gold standard for monitoring the response to ART [2,22,23].…”

Section: Discussionmentioning

confidence: 99%

Lack of awareness of treatment failure among HIV‐1‐infected patients in Guinea‐Bissau – a retrospective cohort study

Jespersen

Hønge

Medina

et al. 2015

Journal of the International AIDS Society

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IntroductionWith more people receiving antiretroviral treatment (ART), the need to detect treatment failure and switch to second-line ART has also increased. We assessed CD4 cell counts (as a marker of treatment failure), determined the rate of switching to second-line treatment and evaluated mortality related to treatment failure among HIV-infected patients in Guinea-Bissau.MethodsIn this retrospective cohort study, adult patients infected with HIV-1 receiving ≥6 months of ART at an HIV clinic in Bissau were included from June 2005 to July 2014 and followed until January 2015. Treatment failure was defined as 1) a fall in CD4 count to baseline (or below) or 2) CD4 levels persistently below 100 cells/µL after ≥6 months of ART. Cox hazard models, with time since six months of ART as the time-varying coefficient, were used to estimate the hazard ratio for death and loss to follow-up.ResultsWe assessed 1,591 HIV-1-infected patients for immunological treatment failure. Treatment failure could not be determined in 594 patients (37.3%) because of missing CD4 cell counts. Among the remaining 997 patients, 393 (39.4%) experienced failure. Only 39 patients (9.9%) with failure were switched from first- to second-line ART. The overall switching rate was 3.1 per 100 person-years. Mortality rate was higher in patients with than without treatment failure, with adjusted hazard rate ratios (HRRs) 10.0 (95% CI: 0.9–107.8), 7.6 (95% CI: 1.6–35.5) and 3.1 (95% CI: 1.5–6.3) in the first, second and following years, respectively. During the first year of follow-up, patients experiencing treatment failure had a higher risk of being lost to follow-up than patients not experiencing treatment failure (adjusted HRR 4.4; 95% CI: 1.7–11.8).ConclusionsWe found a high rate of treatment failure, an alarmingly high number of patients for whom treatment failure could not be assessed, and a low rate of switching to a second-line therapy. These factors could lead to an increased risk of resistance development and excess mortality.

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“…6 A delayed regimen switch or continuing the same regimen with no virologic efficacy in patients with virologic failure leads to accrued resistance. 7–10 This in turn leads to increased mortality in HIV-infected patients and to the spread of resistant viruses in the population. 11 There is an urgent need to evaluate the effectiveness and cost-effectiveness of different treatment strategies after ART failure in settings with no resistance tests, in order to help countries appropriately utilize 2 nd - and 3 rd -line regimens.…”

Section: Introductionmentioning

confidence: 99%

Clinical Impact and Cost-Effectiveness of Making Third-Line Antiretroviral Therapy Available in Sub-Saharan Africa

Ouattara

Ross

Yazdanpanah

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Objective In sub-Saharan Africa, HIV-infected adults who fail 2nd-line antiretroviral therapy (ART) often do not have access to 3rd-line ART. We examined the clinical impact and cost-effectiveness of making 3rd-line ART available in Côte d’Ivoire. Methods We used a simulation model to compare four strategies following 2nd-line ART failure: continue 2nd-line ART [C-ART2]; continue 2nd-line ART with an adherence reinforcement intervention [AR-ART2]; immediate switch to 3rd-line ART [IS-ART3]; and continue 2nd-line ART with adherence reinforcement, switching patients with persistent failure to 3rd-line ART [AR-ART3]. Third-line ART consisted of a boosted-darunavir plus raltegravir-based regimen. Primary outcomes were 10-year survival and lifetime incremental cost effectiveness ratios (ICERs), in $/year of life saved (YLS). ICERs below $3,585 (3 times the country per capita GDP) were considered cost-effective. Results Ten-year survival was 6.0% with C-ART2, 17.0% with AR-ART2, 35.4% with IS-ART3, and 37.2% with AR-ART3. AR-ART2 was cost-effective ($1,100/YLS). AR-ART3 had an ICER of $3,600/YLS and became cost-effective if the cost of 3rd-line ART decreased by <1%. IS-ART3 was less effective and more costly than AR-ART3. Results were robust to wide variations in the efficacy of 3rd-line ART and of the adherence reinforcement, as well as in the cost 2nd-line ART. Conclusion Access to 3rd-line ART combined with an intense adherence reinforcement phase, used as a tool to distinguish between patients who can still benefit from their current 2nd-line regimen and those who truly need 3rd-line ART would provide substantial survival benefits. With minor decreases in drug costs, this strategy would be cost-effective.

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Risk of Virological Failure and Drug Resistance During First and Second-Line Antiretroviral Therapy in a 10-Year Cohort in Senegal

Abstract: In this cohort, virological outcomes for first-line treatments were good compared with those from high-resource settings. However, the rate of virological failure for second-line treatment was high, probably because of accumulation of resistances.

Cited by 40 publications

References 30 publications

Virologic Failure and Human Immunodeficiency Virus Drug Resistance in Rural Cameroon With Regard to the UNAIDS 90-90-90 Treatment Targets

Virologic Failure and Human Immunodeficiency Virus Drug Resistance in Rural Cameroon With Regard to the UNAIDS 90-90-90 Treatment Targets

Lack of awareness of treatment failure among HIV‐1‐infected patients in Guinea‐Bissau – a retrospective cohort study

Clinical Impact and Cost-Effectiveness of Making Third-Line Antiretroviral Therapy Available in Sub-Saharan Africa

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