Weight and BMI Changes Following Initiation of Emtricitabine/Tenofovir Alafenamide Co-Formulated with Darunavir or Co-Administered with Dolutegravir in Overweight or Obese, ART-Naïve People Living with HIV-1

Figures & data

Table 1 Baseline Demographics and Clinical Characteristics

	Weighted Population^a
	DRV/c/FTC/TAF Cohort	DTG + FTC/TAF Cohort	Standardized Difference^b
	N= 76	N= 88
Demographic characteristics
Age at the index date (years), mean ± SD [median]	51.2 ± 11.7 [55.0]	51.5 ± 12.6 [54.0]	2.8%
Female sex at birth, n (%)	23 (30.7)	28 (31.4)	1.6%
Race, n (%)
Black	27 (35.6)	28 (31.4)	8.8%
White	26 (33.8)	36 (41.5)	16.1%
Other/Unknown	23 (30.7)	24 (27.0)	8.0%
Unknown	15 (19.0)	20 (22.9)	9.4%
Hispanic	6 (8.1)	3 (3.3)	20.7%
Other	3 (3.5)	1 (0.9)	18.2%
US geographic region, n (%)
South	54 (71.1)	56 (63.9)	15.4%
West	11 (14.6)	15 (17.6)	8.3%
Midwest	6 (7.7)	5 (5.3)	9.7%
Northeast	5 (6.7)	12 (13.2)	22.0%
Insurance plan type, n (%)
Insurance plan information available (in claims)	72 (94.7)	87 (98.7)	22.7%
Commercial	55 (71.4)	60 (68.3)	6.8%
Medicaid	9 (12.2)	12 (13.3)	3.2%
Medicare	8 (11.1)	12 (13.5)	7.4%
Other/Unknown	0 (0.0)	3 (3.6)	27.4%
Year of the index date, n (%)
2018–2019	46 (60.4)	56 (63.3)	6.0%
2020–2021	30 (39.6)	32 (36.7)	6.0%
Clinical characteristics
Quan-CCI (excluding HIV-1 symptoms), mean ± SD [median]	0.3 ± 0.6 [0.0]	0.3 ± 0.7 [0.0]	3.8%
Other physical comorbidities, n (%)
Hypertension	13 (16.5)	13 (14.3)	6.0%
Dyslipidemia/hyperlipidemia	11 (14.1)	7 (7.8)	20.5%
Obesity	6 (8.0)	6 (6.9)	4.0%
Type II diabetes mellitus	4 (4.9)	6 (6.7)	7.9%
Prediabetes	2 (3.0)	3 (3.7)	3.9%
BMI (kg/m^2), mean ± SD [median]	33.2 ± 6.5 [31.9]	32.7 ± 6.0 [31.2]	6.8%
Weight (kg), mean ± SD [median]	99.4 ± 20.6 [98.4]	98.0 ± 18.7 [94.4]	6.9%
Antihypertensives, n (%)	17 (22.3)	18 (20.1)	5.3%
Medications associated with weight gain,^c n (%)	12 (16.2)	17 (19.7)	9.1%
Medications associated with weight loss,^d n (%)	6 (7.8)	7 (8.0)	0.5%

Notes: ^aOf note, the number of PLWH reported in this weighted population represents the sum of weights for the corresponding PLWH, rounded to the nearest integer. The proportions displayed were calculated prior to the rounding and may be slightly different than if they were calculated based on rounded numbers. ^bFor continuous variables, the standardized difference is calculated by dividing the absolute difference in means of the DRV/c/FTC/TAF cohort and the DTG + FTC/TAF cohort by the pooled standard deviation of both groups. The pooled standard deviation is the square root of the average of the squared standard deviations. For categorical variables with two levels, the standardized difference is calculated using the following equation where P is the respective proportion of participants in each group: (P_{DTG + FTC/TAF}-P_{DRV/c/FTC/TAF})/√([p1+ p2]/2), where p1=P_{DTG + FTC/TAF}(1-P_{DTG + FTC/TAF}) and p2=P_{DRV/c/FTC/TAF}(1-P_{DRV/c/FTC/TAF}). ^cMedications associated with weight gain included anticonvulsants (divalproex, pregabalin, perampanel), antidepressants (escitalopram, citalopram, tricyclic antidepressants, mirtazapine, paroxetine, monoamine oxidase inhibitors), antidiabetic medications (insulins, sulfonylureas, thiazolidinediones, meglitinides), antipsychotics (quetiapine, olanzapine, risperidone, clozapine, thioridazine), corticosteroids, antihistamines (cyproheptadine), beta blockers, alpha blockers, hormonal therapy, and appetite stimulants. ^dMedications associated with weight loss included anticonvulsants (topiramate, lamotrigine, zonisamide, felbamate, stiripentol), antidepressants (bupropion, venlafaxine, desvenlafaxine), antidiabetic medications (sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 agonists, pramlintide), antipsychotics (ziprasidone), growth hormone releasing hormone (tesamorelin, ipamorelin, sermorelin), ADHD medications, appetite suppressants, and anti-obesity medications.

Abbreviations: BMI, body mass index; CCI, Charlson comorbidity index; c, cobicistat; DRV, darunavir; DTG, dolutegravir; FTC, emtricitabine; PLWH, people living with HIV-1; SD, standard deviation; TAF, tenofovir alafenamide; US, United States.

Figure 1 Identification of the study population.

Abbreviations: ART, antiretroviral therapy; BMI, body mass index; c, cobicistat; CKD, chronic kidney disease; DRV, darunavir; DTG, dolutegravir; ESRD, end-stage renal disease; FTC, emtricitabine; PLWH, people living with HIV-1; TAF, tenofovir alafenamide.

Figure 2 Continued.

Figure 2 Kaplan Meier curves of time to weight/BMI increase above threshold. (a) Time to weight increase ≥5%. (b) Time to weight increase ≥10%. (c) Time to BMI increase ≥5%. (d) Time to BMI increase ≥10%.

Notes: (a) Of note, the number of PLWH reported in this weighted population represents the sum of weights for the corresponding PLWH, rounded to the nearest integer. The proportions displayed were calculated prior to the rounding and may be slightly different than if they were calculated based on rounded numbers. (b) Refers to the population at risk of having the event at that point in time (ie, PLWH who have not had the event and have not been lost to follow-up).

Abbreviations: BMI, body mass index; c, cobicistat; CI, confidence interval; DRV, darunavir; DTG, dolutegravir; FTC, emtricitabine; IQR, interquartile range; NR, not reached; PLWH, people living with HIV-1; TAF, tenofovir alafenamide.

Figure 3 Comparison of time to weight or BMI increase outcome.

Notes: *Significant at the 5% level. (a) Of note, the number of PLWH reported in this weighted population represents the sum of weights for the corresponding PLWH, rounded to the nearest integer. The proportions displayed were calculated prior to the rounding and may be slightly different than if they were calculated based on rounded numbers. (b) A hazard ratio >1 indicates that the DTG + FTC/TAF cohort had a higher risk of a weight or BMI increase than the DRV/c/FTC/TAF cohort. (c) Non-parametric 95% bootstrap CIs and p-values were obtained from 500 bootstrap resamples. At each bootstrap resample, the inverse probability of treatment weights were re-estimated. (d) Data not available, given that the Cox proportional hazard models for these outcomes did not converge.

Abbreviations: BMI, body mass index; c, cobicistat; CI, confidence interval; DRV, darunavir; DTG, dolutegravir; FTC, emtricitabine; HR, hazard ratio; PLWH, people living with HIV-1; TAF, tenofovir alafenamide.

Table 2 Baseline BMI Category and Proportion of PLWH with BMI Category Shifts^a During Follow-Up

Baseline BMI Category	DRV/c/FTC/TAF Cohort (N=76)^b
	Follow-Up BMI Category^c
	BMI <25 kg/m^2	BMI 25–29 kg/m^2	BMI 30–34 kg/m^2	BMI 35–39 kg/m^2	BMI ≥40 kg/m^2	Total
	n (%)	n (%)	n (%)	n (%)	n (%)	n
BMI 25–29 kg/m^2 (overweight)	1 (2.7)	23 (69.0)	10 (28.3)			34
BMI 30–34 kg/m^2 (class 1 obesity)		2 (16.3)	13 (83.7)			15
BMI 35–39 kg/m^2 (class 2 obesity)			2 (20.2)	9 (71.8)	1 (8.0)	12
BMI ≥40 kg/m^2 (class 3 obesity)				4 (26.4)	11 (73.6)	15
Baseline BMI Category	DTG + FTC/TAF Cohort (N=88)^b
	Follow-Up BMI Category^c
	BMI <25 kg/m^2	BMI 25–29 kg/m^2	BMI 30–34 kg/m^2	BMI 35–39 kg/m^2	BMI ≥40 kg/m^2	Total
	n (%)	n (%)	n (%)	n (%)	n (%)	n
BMI 25–29 kg/m^2 (overweight)	3 (8.4)	24 (70.8)	7 (20.8)			34
BMI 30–34 kg/m^2 (class 1 obesity)		6 (19.3)	17 (59.5)	4 (15.7)	2 (5.5)	29
BMI 35–39 kg/m^2 (class 2 obesity)		1 (9.2)	2 (15.9)	9 (61.5)	2 (13.4)	14
BMI ≥40 kg/m^2 (class 3 obesity)				1 (10.1)	10 (89.9)	11

Notes: ^aBlue shading indicates patients who had a decrease between the baseline and latest follow-up BMI category. Green shading indicates patients who had no change between the baseline and latest follow-up BMI category. Yellow shading indicates patients who had an increase between the baseline and latest follow-up BMI category. Dark grey shading indicates that no patients were observed experiencing these increases between the baseline and latest follow-up BMI category. ^bOf note, the number of PLWH reported in this weighted population represents the sum of weights for the corresponding PLWH, rounded to the nearest integer. The proportions displayed were calculated prior to the rounding and may be slightly different than if they were calculated based on rounded numbers. ^cEvaluated based on the on-treatment measurement furthest from the index date.

Abbreviations: BMI, body mass index; c, cobicistat; DRV, darunavir; DTG, dolutegravir; FTC, emtricitabine; PLWH, people living with HIV-1; TAF, tenofovir alafenamide.