Virological outcomes of second-line protease inhibitor-based treatment for human immunodeficiency virus type 1 in a high-prevalence rural South African setting: a competing-risks prospective cohort analysis

Collier, Dami, Iwuji, Collins, Derache, Anne, De Oliveira, Tulio, Okesola, Nonhlanhla, Calmy, Alexandra, Dabis, Francois, Pillay, Deenan and Gupta, Ravindra K (2017) Virological outcomes of second-line protease inhibitor-based treatment for human immunodeficiency virus type 1 in a high-prevalence rural South African setting: a competing-risks prospective cohort analysis. Clinical Infectious Diseases, 64 (8). pp. 1006-1016. ISSN 1058-4838

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Abstract

Background. Second-line antiretroviral therapy (ART) based on ritonavir-boosted protease inhibitors (bPIs) represents the only available option after first-line failure for the majority of individuals living with human immunodeficiency virus (HIV) worldwide. Maximizing their effectiveness is imperative.

Methods. This cohort study was nested within the French National Agency for AIDS and Viral Hepatitis Research (ANRS) 12249 Treatment as Prevention (TasP) cluster-randomized trial in rural KwaZulu-Natal, South Africa. We prospectively investigated risk factors for virological failure (VF) of bPI-based ART in the combined study arms. VF was defined by a plasma viral load >1000 copies/mL ≥6 months after initiating bPI-based ART. Cumulative incidence of VF was estimated and competing risk regression was used to derive the subdistribution hazard ratio (SHR) of the associations between VF and patient clinical and demographic factors, taking into account death and loss to follow-up.

Results. One hundred one participants contributed 178.7 person-years of follow-up. Sixty-five percent were female; the median age was 37.4 years. Second-line ART regimens were based on ritonavir-boosted lopinavir, combined with zidovudine or tenofovir plus lamivudine or emtricitabine. The incidence of VF on second-line ART was 12.9 per 100 person-years (n = 23), and prevalence of VF at censoring was 17.8%. Thirteen of these 23 (56.5%) virologic failures resuppressed after a median of 8.0 months (interquartile range, 2.8-16.8 months) in this setting where viral load monitoring was available. Tuberculosis treatment was associated with VF (SHR, 11.50 [95% confidence interval, 3.92-33.74]; P < .001).

Conclusions. Second-line VF was frequent in this setting. Resuppression occurred in more than half of failures, highlighting the value of viral load monitoring of second-line ART. Tuberculosis was associated with VF; therefore, novel approaches to optimize the effectiveness of PI-based ART in high-tuberculosis-burden settings are needed.

Item Type: Article
Keywords: HIV, antiretroviral therapy, protease inhibitor, second line, virological failure, Adolescent, Adult, Aged, Aged, 80 and over, Anti-HIV Agents, Female, Genotype, HIV Infections, HIV Protease Inhibitors, HIV-1, Humans, Male, Middle Aged, Prevalence, Prospective Studies, Rural Population, South Africa, Treatment Outcome, Tuberculosis, Viral Load, Young Adult
Schools and Departments: Brighton and Sussex Medical School > Global Health and Infection
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 15 May 2020 10:53
Last Modified: 15 May 2020 11:00
URI: http://sro.sussex.ac.uk/id/eprint/91269

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