HIV virologic failure and its predictors among HIV-infected adults on antiretroviral therapy in the African Cohort Study

INTRODUCTION The 2016 WHO consolidated guidelines on the use of antiretroviral drugs defines HIV virologic failure for low and middle income countries (LMIC) as plasma HIV-RNA ≥ 1000 copies/mL. We evaluated virologic failure and predictors in four African countries. MATERIALS AND METHODS We included HIV-infected participants on a WHO recommended antiretroviral therapy (ART) regimen and enrolled in the African Cohort Study between January 2013 and October 2017. Studied outcomes were virologic failure (plasma HIV-RNA ≥ 1000 copies/mL at the most recent visit), viraemia (plasma HIV-RNA ≥ 50 copies/mL at the most recent visit); and persistent viraemia (plasma HIV-RNA ≥ 50 copies/mL at two consecutive visits). Generalized linear models were used to estimate relative risks with their 95% confidence intervals. RESULTS 2054 participants were included in this analysis. Viraemia, persistent viraemia and virologic failure were observed in 396 (19.3%), 160 (7.8%) and 184 (9%) participants respectively. Of the participants with persistent viraemia, only 57.5% (92/160) had confirmed virologic failure. In the multivariate analysis, attending clinical care site other than the Uganda sitebeing on 2nd line ART (aRR 1.8, 95% CI 1·28-2·66); other ART combinations not first line and not second line (aRR 3.8, 95% CI 1.18-11.9), a history of fever in the past week (aRR 3.7, 95% CI 1.69-8.05), low CD4 count (aRR 6.9, 95% CI 4.7-10.2) and missing any day of ART (aRR 1·8, 95% CI 1·27-2.57) increased the risk of virologic failure. Being on 2nd line therapy, the site where one receives care and CD4 count < 500 predicted viraemia, persistent viraemia and virologic failure. CONCLUSION In conclusion, these findings demonstrate that HIV-infected patients established on ART for more than six months in the African setting frequently experienced viraemia while continuing to be on ART. The findings also show that being on second line, low CD4 count, missing any day of ART and history of fever in the past week remain important predictors of virologic failure that should trigger intensified adherence counselling especially in the absence of reliable or readily available viral load monitoring. Finally, clinical care sites are different calling for further analyses to elucidate on the unique features of these sites.

[1]  M. Robb,et al.  Noninfectious Comorbidity in the African Cohort Study (AFRICOS). , 2018, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[2]  J. Bartlett,et al.  Predictors of non-adherence to antiretroviral therapy among HIV infected patients in northern Tanzania , 2017, PloS one.

[3]  S. Billong,et al.  Immuno-virological response and associated factors amongst HIV-1 vertically infected adolescents in Yaoundé-Cameroon , 2017, PloS one.

[4]  T. Klimkait,et al.  When patients fail UNAIDS’ last 90 - the “failure cascade” beyond 90-90-90 in rural Lesotho, Southern Africa: a prospective cohort study , 2017, Journal of the International AIDS Society.

[5]  A. Szymczak,et al.  Meeting the WHO 90% target: antiretroviral treatment efficacy in Poland is associated with baseline clinical patient characteristics , 2017, Journal of the International AIDS Society.

[6]  M. Gisslén,et al.  Virological failure and all-cause mortality in HIV-positive adults with low-level viremia during antiretroviral treatment , 2017, PloS one.

[7]  C. Leen,et al.  Durability of viral suppression with first-line antiretroviral therapy in patients with HIV in the UK: an observational cohort study , 2017, The lancet. HIV.

[8]  R. Wanyenze,et al.  Factors Associated with Virological Non-suppression among HIV-Positive Patients on Antiretroviral Therapy in Uganda, August 2014–July 2015 , 2017, BMC Infectious Diseases.

[9]  A. Wensing,et al.  Factors associated with time to achieve an undetectable HIV RNA viral load after start of antiretroviral treatment in HIV-1-infected pregnant women , 2017, Journal of virus eradication.

[10]  T. Quinn,et al.  Low Rates of Transmitted Drug Resistance Among Newly Identified HIV-1 Seroconverters in Rural Rakai, Uganda. , 2016, AIDS research and human retroviruses.

[11]  A. Sönnerborg,et al.  Sweden, the first country to achieve the Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) 90‐90‐90 continuum of HIV care targets , 2016, HIV medicine.

[12]  P. Harrigan,et al.  Predictors of viral suppression and rebound among HIV-positive men who have sex with men in a large multi-site Canadian cohort , 2016, BMC Infectious Diseases.

[13]  Jennifer F Hoy,et al.  Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society-USA Panel. , 2016, JAMA.

[14]  N. Fullman,et al.  Evaluating facility‐based antiretroviral therapy programme effectiveness: a pilot study comparing viral load suppression and retention rates , 2016, Tropical medicine & international health : TM & IH.

[15]  J. Baeten,et al.  Younger Age Predicts Failure to Achieve Viral Suppression and Virologic Rebound Among HIV-1-Infected Persons in Serodiscordant Partnerships. , 2016, AIDS research and human retroviruses.

[16]  Jessica G. Young,et al.  Comparative effectiveness of immediate antiretroviral therapy versus CD4-based initiation in HIV-positive individuals in high-income countries: observational cohort study. , 2015, The lancet. HIV.

[17]  A. Crampin,et al.  A comparative analysis of national HIV policies in six African countries with generalized epidemics , 2015, Bulletin of the World Health Organization.

[18]  J. Skarbinski,et al.  Human immunodeficiency virus transmission at each step of the care continuum in the United States. , 2015, JAMA internal medicine.

[19]  R. Kosgei,et al.  Factors Associated with Virological Failure and Suppression after Enhanced Adherence Counselling, in Children, Adolescents and Adults on Antiretroviral Therapy for HIV in Swaziland , 2015, PloS one.

[20]  S. Strasser,et al.  90-90-90 – Charting a steady course to end the paediatric HIV epidemic , 2015, Journal of the International AIDS Society.

[21]  H. Kibuuka,et al.  Evaluation of treatment outcomes for patients on first‐line regimens in US President's Emergency Plan for AIDS Relief (PEPFAR) clinics in Uganda: predictors of virological and immunological response from RV288 analyses , 2015, HIV medicine.

[22]  Yusnarida Eka Nizmi,et al.  PERAN UNAIDS (THE JOINT UNITED NATIONS PROGRAMME ON HIV/AIDS) DALAM PENANGANAN HIV/AIDS DI ZIMBABWE , 2015 .

[23]  H. Xing,et al.  HIV virological failure and drug resistance among injecting drug users receiving first-line ART in China , 2014, BMJ Open.

[24]  J. Bartlett,et al.  Association of First-Line and Second-Line Antiretroviral Therapy Adherence , 2014, Open forum infectious diseases.

[25]  E. Poveda,et al.  High prevalence of subtype F in newly diagnosed HIV-1 persons in northwest Spain and evidence for impaired treatment response , 2014, AIDS.

[26]  Sarah Fidler,et al.  Adherence to antiretroviral therapy in adolescents living with HIV: systematic review and meta-analysis , 2014, AIDS.

[27]  M. Peeters,et al.  Extraordinary heterogeneity of virological outcomes in patients receiving highly antiretroviral therapy and monitored with the World Health Organization public health approach in sub-saharan Africa and southeast Asia. , 2014, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[28]  D. Zannou,et al.  Predictive Factors of Plasma HIV Suppression during Pregnancy: A Prospective Cohort Study in Benin , 2013, PloS one.

[29]  A. Hatzakis,et al.  Effect of HIV type 1 subtype on virological and immunological response to combination antiretroviral therapy: evidence for a more rapid viral suppression for subtype A than subtype B-infected Greek individuals. , 2013, AIDS research and human retroviruses.

[30]  M. Arnedo,et al.  Monitoring HIV Viral Load in Resource Limited Settings: Still a Matter of Debate? , 2012, PloS one.

[31]  D. Pillay,et al.  Global trends in antiretroviral resistance in treatment-naive individuals with HIV after rollout of antiretroviral treatment in resource-limited settings: a global collaborative study and meta-regression analysis , 2012, The Lancet.

[32]  K. White,et al.  Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3, non-inferiority trial , 2012, The Lancet.

[33]  T. F. Rinke de Wit,et al.  Patterns of HIV-1 drug resistance after first-line antiretroviral therapy (ART) failure in 6 sub-Saharan African countries: implications for second-line ART strategies. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[34]  A. Abimiku,et al.  Update on HIV-1 diversity in Africa: a decade in review. , 2012, AIDS reviews.

[35]  C. Sabin,et al.  British HIV Association guidelines for the routine investigation and monitoring of adult HIV‐1‐infected individuals 2011 , 2012, HIV medicine.

[36]  L. Held,et al.  Improved virological outcome in White patients infected with HIV-1 non-B subtypes compared to subtype B. , 2011, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[37]  O. Kirk,et al.  Factors associated with HIV-1 virological failure in an outpatient clinic for HIV-infected people in Haiphong, Vietnam , 2011, International journal of STD & AIDS.

[38]  A. Wensing,et al.  Virological follow-up of adult patients in antiretroviral treatment programmes in sub-Saharan Africa: a systematic review. , 2010, The Lancet. Infectious diseases.

[39]  Hannah Green,et al.  Effect of HIV-1 subtype on virologic and immunologic response to starting highly active antiretroviral therapy. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[40]  M. Cortina-Borja,et al.  Time to undetectable viral load after highly active antiretroviral therapy initiation among HIV-infected pregnant women. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[41]  D. Pillay,et al.  Impact of human immunodeficiency virus type 1 subtypes on virologic response and emergence of drug resistance among children in the Paediatric European Network for Treatment of AIDS (PENTA) 5 trial. , 2002, The Journal of infectious diseases.

[42]  C. Sabin,et al.  Reasons for modification and discontinuation of antiretrovirals: results from a single treatment centre , 2001, AIDS.

[43]  M. Moroni,et al.  Insights into the reasons for discontinuation of the first highly active antiretroviral therapy (HAART) regimen in a cohort of antiretroviral naïve patients , 2000, AIDS.