Antiretroviral treatment interruption and resumption within 16 weeks among HIV-positive adults in Jinan, China: a retrospective cohort study

Abstract

Background: Treatment interruption has been found to increase the risk of opportunistic infections and death among HIV-positive adults, posing a challenge to fully realizing antiretroviral therapy (ART). However, it has been observed that short-term interruption (<16 weeks) was not associated with significant increases in adverse clinical events. There remains a dearth of evidence concerning the interruption and resumption of ART after short-term discontinuation in China.

Methods: HIV-positive adults who initiated ART in Jinan between 2004 and 2020 were included in this study. We defined ART interruption as more than 30 consecutive days off ART and used Cox regression to identify predictors of interruption. ART resumption was defined as a return to ART care within 16 weeks following discontinuation, and logistic regression was used to identify barriers.

Results: A total of 2,506 participants were eligible. Most of them were male [2,382 (95%)] and homosexual [2,109 (84%)], with a median age of 31 (IQR: 26-40) years old. Of all participants, 312 (12.5%) experienced a treatment interruption, and the incidence rate of interruption was 3.2 (95% CI: 2.8-3.6) per 100 person-years. A higher risk of discontinuation was observed among unemployed individuals [adjusted hazard ratio (aHR): 1.45, 95% CI: 1.14-1.85], with a lower education level (aHR: 1.39, 95% CI: 1.06-1.82), those with delayed ART initiation (aHR: 1.43, 95% CI: 1.10-1.85), receiving Alafenamide Fumarate Tablets at ART initiation (aHR: 5.19, 95% CI: 3.29-8.21). About half of the interrupters resumed ART within 16 weeks, and participants who delayed ART initiation, missed the last CD4 test before the interruption and received the "LPV/r+NRTIs" regimen before the interruption were more likely to discontinue treatment for the long term.

Conclusion: Antiretroviral treatment interruption remains relatively prevalent among HIV-positive adults in Jinan, China, and assessing socioeconomic status at treatment initiation will help address this issue. While almost half of the interrupters returned to care within 16 weeks, further focused measures are necessary to reduce long-term interruptions and maximize the resumption of care as soon as possible to avoid adverse clinical events.

Keywords: HIV; antiretroviral therapy; resumption; retention; treatment interruption.

Figure 1

Forest plot of univariate and multivariable Cox regression of the first treatment interruption among HIV-infected adults. HR, hazard ratio; aHR, adjusted hazard ratio; CI, confidence interval; ART, antiretroviral therapy; TDF, tenofovir; AZT, zidovudine; NRTIs, nucleoside reverse transcriptase inhibitors; NNRTIs, non-nucleoside reverse transcriptase inhibitors; E/C/F/TAF, Elvitegravir/cobicistat/Emtricitabine/Tenofovir alafenamide fumarate. Multivariable analysis: factors with P-values ≤ 0.05 in univariate analysis were included in multivariable Cox regression analysis, including gender, age group, marriage status, education level, employment, transmission route, WHO stage, treatment facility, time from HIV diagnosis to ART initiation and drug regimen at baseline.

Figure 2

Cumulative probability of treatment interruption stratified by risk factors: (A) education level, (B) employment, (C) time between HIV diagnosis and ART initiation, and (D) baseline ART regimen. ART, antiretroviral therapy; AZT, zidovudine; TDF, tenofovir; NRTIs, nucleoside reverse transcriptase inhibitors; NNRTIs, non-nucleoside reverse transcriptase inhibitors; E/C/F/TAF, Elvitegravir/cobicistat/Emtricitabine/Tenofovir alafenamide fumarate. Log-rank tests were used to measure the statistical difference.

Figure 3

Kaplan-Meier curve for the probability of remaining discontinued within 48 weeks since the date of first treatment interruption. The solid line is the Kaplan-Meier estimated overall curve, shaded area is the 95% confidence band.

Figure 4

Forest plot of univariate and multivariable logistic regression of ART resumption after short-term interruption. OR, odds ratio; aOR, adjusted odds ratio; CI, confidence interval; ART, antiretroviral therapy; TDF, tenofovir; AZT, zidovudine; NRTIs, nucleoside reverse transcriptase inhibitors; NNRTIs, non-nucleoside reverse transcriptase inhibitors; LVP/r, lopinavir/ritonavir. Multivariable analysis: factors with P-values ≤ 0.05 in univariate analysis were included in multivariable logistic regression analysis, including time from HIV diagnosis to ART initiation, last CD4 count before interruption, last ART regimen before interruption and year of interruption.