Incident tuberculosis as a risk factor for viral non-suppression 48 weeks among patients switched to dolutegravir based therapy with recycled nucleoside reverse transcriptase inhibitors in Lusaka, Zambia

BACKGROUND: Dolutegravir (DTG) based therapy has been hailed as the missing key to quickly curb the HIV epidemic in resource-limited settings. Inadequate viral load testing had slowed the rate at which individuals currently on nucleoside reverse transcriptase inhibitors (NRTI)-based regimens could be transitioned to DTG based therapy. However, as evidence emerges on the utility of recycled NRTIs, it remains to be known which factors could contribute to viral non suppression on Dolutegravir based therapy.
METHODS: We conducted a retrospective sub-analysis for individuals enrolled in the VISEND study at the University Teaching Hospital in Lusaka, Zambia; with a baseline viral load >1000 copies/ml at the time of the switch and analysed virological outcomes at 48weeks post transition. Data on patient demographics, duration of previous antiretroviral therapy, and occurrence of opportunistic infections. Descriptive statistics were computed using STATA version 13. Viral suppression rates, Incidence rate ratios, and Multivariate logistic regressions for common factors associated with treatment failure were computed
RESULTS: 786 records were screened, with 675 individuals with baseline viral load >1000copies/ml whilst on Tenofovir + Lamivudine + Efavirenz (TLE) meeting eligibility. 375 individuals were transitioned to Tenofovir Disoproxil Fumarate + Lamivudine + Dolutegravir (TLD) or Tenofovir Alafenamide +Emtricitabine + Dolutegravir (TafED) and 300 were to Zidovudine + Lamivudine + boosted Lopinavir or Atazanavir (AZT/3TC/LPV-r or ATV-r). Viral suppression rate was 87.9% on PI-based therapy versus 94.7% on TLD/TafED at 48 weeks (p-value = 0.002). There was a three-fold higher chance of virological failure with a TB event during the 48 weeks (p = 0.022) but no significant difference in TB outcomes between the groups nor any other significant factors associated with virological non suppression.

Variable	Crude OR [95% CI]	Adjusted OR [95% CI]	P value
Male Gender	2.14 (1.3 -3.69)	1.95 (1.08 -3.53)	0.027
Extremes of age ('¤20 or'¥60)	1.71 (0.87 -3.38)	1.55 (0.77 ' 3.10)	0.215
TB Event	3.19 (1.13- 8.93)	3.46 (1.19 -10.01)	0.022
Baseline BMI	0.94 (0.88 -1.01)	0.98 (0.91-1.04)	0.533
Missed visit(s)	0.95 (0.44 -2.07)	0.98 (0.44 -2.16)	0.914

CONCLUSIONS: The results of this study emphasise the need for thorough screening for TB for patients being transitioned to DTG based therapy with recycled NRTI backbone and the need for prospective follow-up studies to establish utility of newer molecules such as Tenofovir Alafenamide/Emtricitabine/Dolutegravir with antituberculous therapy.