Does TB influence viral suppression in HIV patients on DTG-based therapy?
16 Aug 2022
bởiAudrey Abella
Incident tuberculosis (TB) appears to be a risk factor for virologic non-suppression (ie, viral load of >1,000 copies/mL) in HIV patients who have transitioned to dolutegravir (DTG)-based therapy with recycled NRTIs*, according to a retrospective subanalysis of the VISEND study.
“It is so important to look for the occurrence of TB in patients on DTG-based therapy, especially when transitioning them to second-line therapy with recycled NRTIs,” said presenting author Dr Nyuma Mbewe from the University Teaching Hospital, Lusaka, Zambia, at AIDS 2022. “Because if not, this is a possibility for emergent DTG resistance and … [TB IRIS**] whilst they do have TB.”
“Whilst there have been some studies … that did not show any TB-associated IRIS, we felt that the situation would be different in our patient population, especially as Zambia is one of the top 30 countries in the world with TB and HIV co-infections,” she continued.
The 144-week open-label, noninferiority VISEND study comprised 1,201 treatment-experienced people living with HIV who were initially on TDF***/lamivudine/efavirenz. Arm A participants (viral load <1,000 copies/mL) were switched to either TDF/lamivudine/DTG (TLD; n=209) or TAF***/emtricitabine/DTG (TAFED; n=209). Those in arm B (viral load ≥1,000 copies/mL) were switched to DTG- (n=208 [TLD] and 211 [TAFED]) or PI#-based therapy (n=167 [AZT/3TC/LPV-r##] and 197 [AZT/3TC/ATV-r##]). [AIDS 2022, abstract OALBB0105]
The current analysis included those in arm B. Most participants were between 20 and 60 years (94 percent), female (62 percent), and had a baseline CD4 count >200 cells/mm3 (82 percent).
Overall, there were 35 incident TB cases by week 48, 32 of which occurring in arm B (n=14 [DTG] and 18 [PI]). More than 50 percent of the cases were diagnosed within 50 days. All TB patients completed TB treatment within 48 weeks.
In terms of viral non-suppression at week 48, the rate was lower with DTG- vs PI-based therapy (6 percent vs 13 percent).
When evaluating the presence of incident TB among non-suppressed patients, five were reported – three of which coming from the DTG arm (including one case of extrapulmonary TB [TB meningitis]). This implies that more non-suppressed patients on DTG-based therapy had incident TB, noted Mbewe. “There was a higher chance of virologic failure with a TB event during the 48 weeks … [N]ot having TB was associated with being [virologically] suppressed at the end of the study period.”
Other factors significantly associated with viral non-suppression among those on DTG-based therapy were age 20–59 years (adjusted odds ratio [adjOR], 3.44; p=0.021) and CD4 counts (adjORs, 8.32; p=0.012 [50–200 cells/mm3] and 18.43; p=0.001 [>200 cells/mm3]).
Three of the four reported deaths at week 48 were attributed to TB.
The study is the largest cohort of patients on DTG with recycled NRTIs and adds to the growing evidence reflecting the use of DTG-based therapy with recycled NRTIs in resource-constrained settings. However, Mbewe noted that they were unable to properly characterize IRIS, as the CD4 counts were only evaluated at baseline, 6 months, and 48 weeks. “Additionally, we were not able to measure drug levels to be assured of adherence, [and] not all TB was microbiologically confirmed.”
“[Nonetheless, our findings] emphasize the need for thorough screening for TB for patients being transitioned to DTG-based therapy with recycled NRTI backbone,” said Mbewe.