Effectiveness and Safety of Dolutegravir Two-Drug Regimens in Virologically Suppressed People Living With HIV

A Systematic Literature Review and Meta-Analysis of Real-World Evidence

Y S Punekar; D Parks; M Joshi; S Kaur; L Evitt; V Chounta; M Radford; D Jha; S Ferrante; S Sharma; J Van Wyk; A de Ruiter

Disclosures

HIV Medicine. 2021;22(6):423-433. 

In This Article

Results

Studies Included

In total, the systematic literature review identified 394 studies from 530 publications that investigated DTG in PLHIV (Figure 1). Of these, a total of 118 studies assessed DTG as a dual therapy (with 3TC or RPV) and reported data for effectiveness and/or discontinuations. Of the 118 studies, 82 studies were excluded as they included treatments other than DTG + 3TC and DTG + RPV, reported data at time points other than 48 or 96 weeks, or investigated treatment-naïve patients. Only two studies were identified investigating dual therapy in treatment-naïve patients; therefore, this analysis focused on treatment-experienced patients. Of the 36 studies in treatment-experienced suppressed patients, only seven studies reported effectiveness and/or discontinuation data for DTG + 3TC and 11 studies for DTG + RPV in cohorts believed to be unique and distinct from each other. Outcomes of interest (meta-analysis inputs) for studies providing W48 data are presented in Table 1 and those for studies providing W96 data are presented in Table S3. Results from a quality evaluation using the Downs and Black assessment tool can be found in Table S4.

Figure 1.

PRISMA flow chart showing studies published from 2013 to 2019 investigating the use of dolutegravir (DTG) + lamivudine (3TC) and DTG + rilpivirine (RPV) in people living with HIV-1 (PLHIV). *One study evaluated both DTG + 3TC and DTG + RPV. ART, antiretroviral therapy; SGA, subgroup available; SLR, systematic literature review.

Dual Therapy With DTG + 3TC

Study and patient characteristics for the selected six studies with 48-week data are presented in Table 1. Males comprised 68.4–77.4% of the PLHIV. The mean age of PLHIV ranged from 48.5 to 59 years and all PLHIV were treatment-experienced suppressed. Most PLHIV switched from triple therapy.[33–35] Some populations also had PLHIV with resistance mutations including the M184I/V mutation for 3TC resistance.[33–36] PLHIV in Reynes et al.[36] were considered heavily pre-treated, whereas Hidalgo-Tenorio et al.[35] and Gagliardini et al.[37] included a population with no history of VF.

Outcomes. Five publications reported VF and VS data at W48; three publications reported data that enabled the calculation of VSS at W48 (Table 1). Overall, the meta-analysis showed that treatment of virologically suppressed patients with DTG + 3TC resulted in VF in 1.0% (95% CI: 0.3–2.0) of patients at W48 (Figure 2a), with similar results reported at W96 (1.0%; 95% CI: 0.2–2.2; Figure S1a). The VSS value was 85.0% (95% CI: 82.3–87.5) and 87.9% (95% CI: 76.6–96.0) at W48 (Figure 2b) and W96 (Figure S1b), respectively. The VSOT was 98.8% (95% CI: 97.7–99.7) at W48 (Figure 2c), and 98.4% (95% CI: 96.4–99.7) at W96 (Figure S1c). Heterogeneity between studies was assessed and found to be not significant enough to affect the analysis. Funnel plot analyses indicated that no publication bias was present in VF, VSOT and VSS data (P = 0.340, 0.228 and 0.706, respectively,) at WK48. Three publications reported data for discontinuations at WK48. Overall, the meta-analysis showed that treatment with DTG + 3TC in virologically suppressed PLHIV led to discontinuations in 13.6% (95% CI: 11.1–16.2) of patients at W48 (Figure 2d). The proportion of discontinuations at W96 was 11.6% (95% CI: 4.50; 21.1); Figure S1d). At W48, heterogeneity was 0% and funnel plot analyses indicated no publication bias (P = 0.877).

Figure 2.

Summary of week 48 meta-analysis data for dolutegravir (DTG) + lamivudine (3TC) treatment in people living with HIV-1 (PLHIV): (a) viral failure (VF); (b) viral suppression using snapshot algorithm (VSS); (c) viral suppression on treatment (VSOT); and (d) discontinuations. CI, confidence interval; Wt, weight.

Dual Therapy With DTG + RPV

Study and patient characteristics for the selected 10 studies included in the W48 analyses are presented in Table 1. In general, males accounted for 50–96% of the participants. The mean age of participants ranged from 49 to 57 years and all PLHIV were treatment-experienced and suppressed on current therapy. Some of the studies reported patient populations that could be considered heavily pre-treated (Diaz et al.[38] median 4.3 ARTs; Casado et al.: mean 6.1 prior regimens; and Revuelta-Hererro et al.: median 5 prior regimens (median 4 prior ARTs). In Diaz et al.,[38] patients had a long history of ART (median 19.4 years). Some studies reported populations that contained patients with known resistance mutations.[34,38–41]

Outcomes. Of DTG + RPV studies, eight publications reported VF and VSS data, and nine publications reported VSOT at W48 (Table 1). Overall, the meta-analysis showed that treatment with DTG + RPV in virologically suppressed PLHIV resulted in VF in 0.6% (95% CI: 0.0–1.6) of patients at W48 (Figure 3a), with similar results reported at W96 (1.4%; 95% CI: 0.4–2.7%; Figure S2a). The VSS values were 92.4% (95% CI: 85.0–97.7) and 92.8% (95% CI: 90.1–95.1) at weeks 48 (Figure 3b) and 96 (Figure S2b), respectively. The VSOT values were 98.5% (95% CI: 97.6–99.2) at W48 (Figure 3c) and 97.3% (95% CI: 94.7–99.1) at W96 (Figure S2c). At W48, heterogeneity values for VF, VSS and VSOT were 0%, 86.6%, and 0%, respectively, at W48. Funnel plot analyses indicated that no publication bias was present in VF, VSOT and VSS data (P = 0.591, 0.214, and 0.190, respectively), at W48. Eight publications reported data for discontinuations at W48. Overall, the meta-analysis showed that treatment with DTG + RPV in virologically suppressed PLHIV led to discontinuations in 7.2% (95% CI: 2.1–14.4) of PLHIV at W48 (Figure 3d). Slightly lower results were reported at W96 (5.7%; 95% CI: 3.7–8.2; Figure S2d). Heterogeneity was 86.5% and funnel plot analyses indicated no publication bias (P = 0.265).

Figure 3.

Summary of week 48 meta-analysis data for dolutegravir (DTG) + rilpivirine (RPV) treatment in people living with HIV-1 (PLHIV): (a) viral failure (VF); (b) viral suppression using snapshot algorithm (VSS); (c) viral suppression on treatment (VSOT); and (d) discontinuations. CI, confidence interval; Wt, weight.

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