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

Date Published: February 5, 2019

Publisher: Public Library of Science

Author(s): Francis Kiweewa, Allahna Esber, Ezra Musingye, Domonique Reed, Trevor A. Crowell, Fatim Cham, Michael Semwogerere, Rosemary Namagembe, Alice Nambuya, Cate Kafeero, Allan Tindikahwa, Leigh Anne Eller, Monica Millard, Huub C. Gelderblom, Babajide Keshinro, Yakubu Adamu, Jonah Maswai, John Owuoth, Valentine Chepkorir Sing’oei, Lucas Maganga, Emmanuel Bahemana, Samoel Khamadi, Merlin L. Robb, Julie A. Ake, Christina S. Polyak, Hannah Kibuuka, Luis Menéndez-Arias.

http://doi.org/10.1371/journal.pone.0211344

Abstract

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.

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.

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. 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.

Partial Text

The goal of antiretroviral therapy (ART) for HIV infection is to achieve and maintain virologic suppression, thereby preventing disease progression and transmission. In 2014, the Joint United Nations Programme on HIV/AIDS (UNAIDS) set the 90-90-90 global targets for elimination of HIV, whereby the third 90 represents a target to achieve viral suppression in at least 90% of patients initiating ART by 2020 [1], Abrams and Strasser [2]. The 2016 WHO consolidated antiretroviral guidelines define virologic suppression for a public health approach as HIV RNA < 1000 copies/mL [3]. By the end of 2016, at least 19 million people living with HIV globally had initiated ART [4]. Of these, 72% were living in sub-Saharan Africa [5]. The public health impact of this achievement will depend on the extent to which those initiating ART are able to achieve and maintain virologic suppression [6]. Between January 2013 and October 2017, 2678 HIV-infected participants enrolled in AFRICOS. Of these, 2577 (96·2%) had viral load data for the most recent visit. After excluding 523 participants on ART for less than six months, 2054 HIV-infected participants were included in the final analysis (Fig 2). Our study evaluated the prevalence of virologic failure and factors associated with virologic failure in a large African HIV cohort receiving ART based on the WHO’s public health approach. Our findings showed that viraemia at the most recent visit occurred commonly, while persistent viraemia and virologic failure occurred less frequently. In conclusion, this multi-center analysis demonstrates 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. We have shown that clinical care sites home to AFRICOS are different and that further analyses will be required to elucidate on the unique features of these sites. We have also demonstrated that low BMI, low CD4 count, and history of fever in the past week remain important predictors of virologic failure that should be used as a marker for intensified adherence counselling especially in the absence of reliable or readily available viral load monitoring. Finally, younger age and single marital status are associated with virologic failure, which has implications for programmatic treatment monitoring practices.   Source: http://doi.org/10.1371/journal.pone.0211344

 

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