Patterns of adherence to antiretroviral therapy and HIV drug resistance over time in the Stratall ANRS 12110/ESTHER trial in Cameroon

Abstract

ObjectivesThe emergence of HIV drug resistance is a crucial issue in Africa, where second-line antiretroviral therapy (ART) is limited, expensive and complex. We assessed the association between adherence patterns and resistance emergence over time, using an adherence measure that distinguishes low adherence from treatment interruptions, in rural Cameroon. MethodsWe performed a cohort study among patients receiving nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART in nine district hospitals, using data from the Stratall trial (2006−2010). Genotypic mutations associated with antiretroviral drug resistance were assessed when 6-monthly HIV viral loads were > 5000 HIV-1 RNA copies/mL. ART adherence data were collected using face-to-face questionnaires. Combined indicators of early (1−3 months) and late (6 months to t − 1; t is the time point when the resistance had been detected) adherence were constructed. Multivariate logistic regression and Cox models were used to assess the association between adherence patterns and early (at 6 months) and late (after 6 months) resistance emergence, respectively. ResultsAmong 456 participants (71% women; median age 37 years), 45 developed HIV drug resistance (18 early and 27 late). Early low adherence (< 80%) and treatment interruptions (> 2 days) were associated with early resistance [adjusted odds ratio (95% confidence interval) 8.51 (1.30-55.61) and 5.25 (1.45-18.95), respectively]. Early treatment interruptions were also associated with late resistance [adjusted hazard ratio (95% confidence interval) 3.72 (1.27-10.92)]. ConclusionsThe emergence of HIV drug resistance on first-line NNRTI-based regimens was associated with different patterns of adherence over time. Ensuring optimal early adherence through specific interventions, adequate management of drug stocks, and viral load monitoring is a clinical and public health priority in Africa. IntroductionIn resource-limited countries, the most frequently prescribed first-line antiretroviral regimens for HIV-infected patients include two nucleoside reverse transcriptase inhibitors (NRTIs) and one nonnucleoside reverse transcriptase inhibitor (NNRTI) [1]. Lamivudine (an NTRI), nevirapine and efavirenz (both NNRTIs) are most commonly used because of their effectiveness and their availability as components of generic, low-cost, easy-to-use, fixed-dose combinations [2][3][4][5][6][7][8][9][10][11][12]. However, the drawback of these drugs is a low genetic barrier to resistance [13]. Consequently, patients who take them are more likely to develop HIV drug resistance, which in turn limits the efficacy of antiretroviral therapy (ART).In sub-Saharan Africa, the emergence of HIV drug resistance is a serious issue, for both the health system and for the individual. Resistance emergence during first-line therapy increases the risk of HIV-related morbidity and mortality, and of HIV transmission (including transmission of drug-resistant viruses) [14]. Moreover, second-line treatment options are limited and involve considerabl...

Adverse Drug Reactions and Clinical Outcomes in Patients Initiated on Antiretroviral Therapy: A Prospective Cohort Study From Ethiopia

“…The findings of this study regarding patient groups at risk of ADRs are especially important in that they suggest a number of practical interventions that could be readily implemented in clinical practice to minimise patients' risk of developing ADRs. This would represent a significant advance in HIV/AIDS management in Ethiopia as our study demonstrated that severe ADRs were associated with not only self-reported non-adherence with therapy (the importance of optimal adherence to ART in BMI body mass index, ADR adverse drug reaction, OR odds ratio, CI confidence interval optimising patient outcomes is well-recognised [22,23]) but also a poorer patient outcome in terms of gain in BMI.…”

“…Patients who experienced severe ADRs were non-adherent, as reported in other studies [25,39], and experienced a lower increase in BMI. Early non-adherence to first-line regimens is associated with emergence of early and late regimen failure [22,40] and increasing treatment costs [41]. To our knowledge, no previous studies have reported that severe ADRs were associated with a decreased gain in BMI.…”

Cost Effectiveness of Potential ART Adherence Monitoring Interventions in Sub-Saharan Africa

“…Average adherence in each 3 month period for an individual is determined from the underlying tendency to adhere (which is a lifelong value for the individual, unless changed as a result of an adherence intervention) with within-person period-to-period variability (Fig 1) [6, 15–24]. Each patient thus has a certain higher or lower tendency to adhere but their actual adherence varies over time, both at random and according to the presence of symptoms (with drug toxicity or presence of WHO stage 4 disease leading to a decrease in adherence) and age (tendency for increasing adherence with age).…”

Factors Associated with Non-Adherence to Antiretroviral Therapy among Adults living with HIV/AIDS in Arsi Zone, Oromia

“…Antiretroviral therapy has improved the health of many human immunodeficiency virus (HIV) positive individuals who otherwise would have died. Treatment efficacy relies, however, on sustained adherence, which constitutes a serious challenge to those receiving antiretroviral therapy [3]. The regimens are often complicated and can include varying dosing schedules, dietary restrictions, and adverse effects [4].Consistently high levels of adherence are necessary for reliable viral suppression [5] and prevention of resistance [6], disease progression, and death [7].…”