Determinants of Antiretroviral Treatment Success and Adherence in People With Human Immunodeficiency Virus Treated for Tuberculosis

Abstract

Introduction In people living with HIV (PWH) with advanced disease, rates of virologic success may be lower than expected. The Reflate TB2 trial did not show non-inferiority of raltegravir versus efavirenz in PWH with tuberculosis. We aimed to identify factors associated with virologic success and higher adherence in the trial. Methods In this analysis, we included participants enrolled in the Reflate TB 2 trial with adherence data available. The primary outcome was virologic success (HIV-1 RNA < 50 copies/mL) at week 48 and the secondary outcome was adherence as assessed by the pill count adherence ratio. We used logistic regression to study determinants of virologic success and optimal adherence in 2 separate analyses. Results 444 participants were included in the present analysis. Over the 48-week follow-up period, 290/444 (65%) participants had a pill count adherence ratio ≥95%. At week 48, 288/444 (65%) participants were in virologic success. In the multivariate analysis, female sex (aOR 1·77 (95%CI 1·16 - 2·72), p = 0·0084), lower baseline HIV-1 RNA levels (<100,000, aOR 2·29 (95%CI 1·33 - 3·96), p = 0·0087) and pill count adherence ratio ≥95% (aOR 2·38 (95%CI 1·56 - 3·62), p < 0·0001), were independently associated with virologic success. Antiretroviral pill burden was the only factor associated with pill count adherence ratio ≥95% (OR 0·81 (95% CI 0·71-0·92), p = 0·0018). Conclusions In PWH with tuberculosis receiving raltegravir or efavirenz-based regimens, female sex, optimal adherence and baseline HIV-1 RNA <100,000 copies/mL were associated with virologic success and the number of antiretroviral tablets taken daily was a strong predictor of adherence.

Successful Multidrug-Resistant Tuberculosis Treatment Without HIV Viral Suppression: A Missed Opportunity

“…Others have recently linked twice-daily dosing of ART to lower adherence and reduced viral suppression rates during treatment for drug-sensitive TB. 9,10 This could be a mechanism underlying the association seen in this sample; however, we are unable to confirm this with the data at hand. For those not switching ART regimens while taking bedaquiline, the reasons underpinning the association are also unclear.…”

“…In people with drug-sensitive TB and HIV, increased pill burden with twice-daily dosing of ART was significantly associated with poorer ART adherence and lack of HIV viral suppression at 48 weeks after treatment initiation. 9,10 The type of MDR-TB regimen used may also affect HIV outcomes. Older MDR-TB regimens that included injectable medications had significant adverse effects such as hearing loss and required painful daily injections during the intensive phase of treatment, yet they rarely required adjusting ART regimens.…”

Incidence and Predictors of Tuberculosis-associated IRIS in People With HIV Treated for Tuberculosis: Findings From Reflate TB2 Randomized Trial

“…We conducted a secondary analysis of the ANRS 12 300 Reflate TB 2 trial. The design and study results have been reported previously [ 16 , 17 ]. Between September 2015 and January 2018, ART-naïve adults with HIV-1 (age ≥18 years) with TB who had initiated TB treatment within the prior 8 weeks were randomized (1:1) to start ART with either raltegravir 400 mg twice daily or efavirenz 600 mg once daily, both in association with tenofovir disoproxil fumarate and lamivudine.…”