Dolutegravir/Lamivudine as a First-Line Regimen in a Test-and-Treat Setting for Newly Diagnosed People Living With HIV

Charlotte-Paige Rolle; Mezgebe Berhe; Tulika Singh; Roberto Ortiz; Anson Wurapa; Moti Ramgopal; Peter A. Leone; Jessica E. Matthews; Marybeth Dalessandro; Mark R. Underwood; Konstantinos Angelis; Brian R. Wynne; Deanna Merrill; Christopher Nguyen; Jean van Wyk; Andrew R. Zolopa

Disclosures

AIDS. 2021;35(12):1957-1965. 

In This Article

Results

Study Participants

Of 133 participants screened, 131 were enrolled and included in the ITT-E and safety populations. Demographics and baseline characteristics are shown in Table 1. Fifty-five (42%) participants had a current psychiatric disorder and 11 (8%) reported previous psychiatric disorders. Fifteen (11%) participants discontinued study by Week 24: seven were lost to follow-up, five withdrew consent, and three discontinued based on physician decision (two had false-positive HIV tests at diagnosis, one missed several scheduled appointments). Through Week 24, eight (6%) participants switched from DTG/3TC but remained on study, five for baseline HBV co-infection, one for baseline M184V, and two for other reasons (adverse event of rash and participant decision). Two participants with baseline HBV co-infection did not modify their ART regimen, as their repeat HBV DNA tests came back unquantifiable, and investigators felt there was no evidence of active HBV replication. One additional participant switched from DTG/3TC after the Week 24 HIV-1 RNA assessment because of incident pregnancy.

Efficacy

At Week 24, 102 of 131 [78% (95% CI, 70–85%)] participants achieved HIV-1 RNA less than 50 copies/ml (ITT-E missing = failure analysis; Table 2); this includes five participants who had the initial DTG/3TC regimen modified before Week 24. Of the remaining 29 participants, nine (7%) had HIV-1 RNA at least 50 copies/ml at Week 24, 15 (11%) discontinued from study, and five (4%) missed the HIV-1 RNA assessment while on study (three due to the COVID-19 pandemic). Among participants with available HIV-1 RNA data under any ART at Week 24 (n = 111), 102 (92%) had HIV-1 RNA less than 50 copies/ml, and 109 (98%) had HIV-1 RNA less than 200 copies/ml (observed analysis; Table 2). Ninety-seven of 131 [74% (95% CI, 66–81%)] participants achieved HIV-1 RNA less than 50 copies/ml and were still on DTG/3TC at Week 24 (FDA Snapshot analysis; Table 2). Two participants met confirmed virologic failure criteria (virologic rebound) at Week 24, with both remaining on DTG/3TC at the discretion of the investigator until results of subsequent HIV-1 resistance testing became available. No treatment-emergent HIV resistance-associated mutations were detected. Of the nine evaluable participants with HIV-1 RNA at least 50 copies/ml at Week 24, all had baseline HIV-1 RNA more than 100 000 copies/ml (four of whom had baseline HIV-1 RNA > 500 000 copies/ml). Seven of these nine participants had HIV-1 RNA less than 200 copies/ml in the Week 24 window, and the other two had HIV-1 RNA 302 and 247 copies/ml at Week 24; these two participants met confirmed virologic failure criteria, and their baseline viral loads were 13 987 640 and 159 214 copies/ml, respectively. All nine participants had a decline at least 2.8 log10 copies/ml from baseline HIV-1 RNA values (see Supplemental Digital Content 2, http://links.lww.com/QAD/C190, table showing viral load during study for participants with HIV-1 RNA ≥ 50 copies/ml at Week 24).

Of the eight participants who switched from DTG/3TC before Week 24, five achieved HIV-1 RNA less than 50 copies/ml; the other three did not have available Week 24 data (Table 3). At Week 24, six of the seven participants with baseline HBV co-infection achieved HIV-1 RNA less than 50 copies/ml, two on DTG/3TC (who had no active HBV replication) and four on modified ART; the other participant was on study but missing data in the Week 24 window (a late Week 24 visit showed HIV-1 RNA less than 50 copies/ml in this participant). No treatment-emergent HBV resistance-associated mutations were detected through Week 24. The participant with baseline M184V mutation achieved HIV-1 RNA less than 50 copies/ml by Week 8, then switched to another regimen (DTG/rilpivirine FDC) and withdrew consent at Week 12 because of relocation.

Median time to suppression was 35 days (95% CI, 30–55). At Week 24, median change from baseline in CD4+ cell count and CD4+/CD8+ cell count ratio under DTG/3TC treatment was 170 cells/μl [interquartile range (IQR), 90–255] and 0.26 (IQR, 0.12–0.42), respectively.According to the ITT-E missing = failure analysis, the proportion of participants achieving HIV-1 RNA less than 50 copies/ml was consistent across baseline demographic subgroups including current sex [female, 9/11 (82%); male, 93/120 (78%)], age [<50 years, 86/111 (77%); ≥50 years, 16/20 (80%)], and race [white, 52/65 (80%); non-white, 50/66 (76%)]. Among participants with baseline HIV-1 RNA at least 1000 000 and those with CD4+ cell count less than 200 cells/μl, 8/10 (80%) and 25/37 (68%) achieved HIV-1 RNA less than 50 copies/ml at Week 24, respectively. Of the 12 participants with CD4+ cell count less than 200 cells/μl who did not reach HIV-1 RNA less than 50 copies/ml at Week 24, seven remained on study with HIV-1 RNA at least 50 copies/ml at Week 24 and five discontinued (three lost to follow-up, one physician decision, one participant decision). Among the 19 participants with baseline HIV-1 RNA at least 500 000 copies/ml, 13 (68%) were suppressed to less than 50 copies/ml at Week 24, four remain on study with HIV-1 RNA at least 50 copies/ml at Week 24 (three achieved HIV-1 RNA < 200 copies/ml), and two discontinued.

Among nine participants with available viral load assessment at Week 24 under any ART regimen and baseline HIV-1 RNA at least 1000 000 copies/ml, eight (89%) achieved HIV-1 RNA less than 50 copies/ml (observed analysis; Figure 1).

Figure 1.

Proportion of participants with plasma HIV-1 RNA less than 50 copies/ml at Week 24 among participants with available HIV-1 RNA assessment by baseline (a) HIV-1 RNAa and (b) CD4+ cell count (observed analysis). aOne (<1%) participant had missing plasma HIV-1 RNA results at baseline.

Safety

Eighty-five (65%) participants experienced an adverse event on DTG/3TC through Week 24 (Table 4). The most commonly reported adverse events (occurring in >5% of participants) were headache, diarrhea, and fatigue. Nine (7%) participants experienced a drug-related adverse event; all drug-related adverse events were grade 1 except for grade 2 headache and pruritis, which occurred in one participant, and grade 2 increased weight in another. Only one adverse event led to discontinuation of DTG/3TC, a grade 1 rash that resolved after discontinuing study treatment. SAEs occurred in two (2%) participants under DTG/3TC treatment: cellulitis (n = 1) and streptococcal bacteremia (n = 1); none were fatal. Psychiatric disorders were reported in 19 (15%) participants under DTG/3TC treatment; the most common were anxiety (n = 6, 5%), insomnia (n = 6, 5%), and depression (n = 5, 4%). Thirteen of these 19 participants had current or prior psychiatric conditions at baseline. All psychiatric adverse events were grade 1 or 2.

At baseline, median (IQR) weight was 74.2 kg (66.0–86.7). At Week 24, median (IQR) weight under treatment with DTG/3TC was 78.8 kg (68.7–90.1) for a median (IQR) percentage increase in body weight from baseline of 5.2% (1.4–8.4%). Few grade 3 or 4 chemistry toxicities occurred under DTG/3TC treatment: decreased creatinine clearance using the Chronic Kidney Disease Epidemiology Collaboration equation (n = 7, 5%), increased creatinine (n = 2, 2%), increased aspartate aminotransferase (n = 1, <1%), increased bilirubin (n = 1, <1%), and increased glucose (n = 1, <1%).

Symptom bother score

At baseline, median (IQR) symptom bother score was 8 (3–21). At Week 24, median (IQR) decrease from baseline in symptom bother score under DTG/3TC treatment using LOCF data was 3 (10–0).

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