Short Communication: No Significant Changes in Weight and Body Fat Mass in Suppressed HIV-Infected Patients Switched to Dual Combination Lamivudine Plus Dolutegravir or Raltegravir

Abstract

Weight gain associated with integrase inhibitor-based treatment has become a critical issue in the clinical management of HIV infection. We analyzed changes in weight and body fat mass in 54 virologically suppressed patients who switched to lamivudine plus raltegravir or dolutegravir. Overall, after 12 months we reported a not significant increase in weight (median, +1.74 kg; p = .223) and total fat mass (median, +1.13 kg; p = .188), and these changes were comparable between groups. The median change in lumbar spine bone mineral density (BMD) [interquartile range (IQR)] was +0.02 g/cm² (−0.02, +0.05; p = .786), and the median change in femur neck BMD (IQR) was +0.04 g/cm² (−0.03, +0.06; p = .598), and changes were comparable between groups. In conclusion, the switch to dolutegravir/lamivudine or raltegravir/lamivudine dual therapy in virologically suppressed patients did not produce significant increases in weight and body fat mass after a 12-month follow-up, in association with not significant changes in BMD.

The beginning of combination antiretroviral therapy (cART), including one integrase strand transfer inhibitor (INSTI), has been associated with excess weight gain, and this adverse effect has become a troubling issue among Clinicians because of its possible cardiometabolic consequences.

Several cohort studies have reported a significant weight increase in treatment-naive HIV-infected patients starting an INSTI-based cART, but clinical data about weight change in virologically suppressed patients switching to an INSTI-based regimen are conflicting.¹ Some clinical studies have described a significant increase in body weight in suppressed subjects who switched to an INSTI-based combination, particularly in women, blacks, and older patients.^2,3 However, other authors did not find a clear evidence of an overall increase in rate of weight gain following a switch to INSTI-based regimens.⁴ In a recent retrospective study, a significantly greater weight increase was observed in 37 virologically suppressed patients switched to dolutegravir/rilpivirine dual regimen compared to 17 subjects switched to darunavir/lamivudine dual combination, but fat mass increase was similar in both groups.⁵

We performed an observational retrospective analysis to evaluate changes in weight and body fat mass in HIV-1-infected patients switched to a dual antiretroviral regimen constituted by lamivudine (300 mg once daily) plus raltegravir (400 mg twice or 1200 mg once daily) (RAL group) or lamivudine (300 mg once daily) plus dolutegravir (50 mg once daily) (DTG group) in our Clinic of Infectious Diseases. We enrolled only patients with HIV RNA <20 copies/mL for at least 12 months before the switch and with a 12-month follow-up after the switch. Current work is a substudy of a larger observational study, which is under consideration for publication and which evaluated efficacy and safety of these dual maintenance regimens.

Enrolled subjects underwent a whole-body dual-energy X-ray absorptiometry (DEXA) through a Hologic instrument (QDR 4500A, Hologic Inc., Bedford, MA) performed by the same operator at the switch (+3 months) and after 12 months (+3 months). The DEXA criteria for osteopenia and osteoporosis diagnosis were a T-score between −1 and −2.5 and less than −2.5 at the femoral neck, respectively.⁶

Demographic, clinical, and laboratory data were recorded at the switch of therapy and after 12 months, including body weight and body mass index (BMI). All patients provided written informed consent to data collection.

Overall, 54 patients were enrolled in the study: 25 in RAL group and 29 in DTG group. Median age [interquartile range (IQR)] was 47.9 years (41.4, 55.8), 39 patients (72%) were males, median current CD4+ lymphocyte count (IQR) was 613 cells/mm³ (498, 809), median duration (IQR) of current antiretroviral treatment was 46.3 months (34.2, 58.2), and median duration (IQR) of plasma HIV RNA <50 copies/mL with current antiretroviral regimen was 42.9 months (30.5, 55.2). At baseline median weight (IQR) was 72.9 kg (62.1, 84.2), median BMI (IQR) was 24.6 kg/m² (23.7, 25.8), and seven patients (13%) had BMI >25 kg/m². A previous diagnosis of type 2 diabetes mellitus was present in a significant percentage of patients (15%), which was comparable in both groups. Eight patients (15%) had a previous AIDS-defining condition, and 5 (9%) were coinfected with hepatitis C virus (HCV). Osteopenia was present in 20 patients (37%) and osteoporosis in 6 (11%). Current cART preceding the switch included tenofovir disoproxil fumarate in 10 cases in RAL group (40%) and in 12 cases in DTG group (41%; p = −344), while it included one boosted protease inhibitor in five patients in RAL group (20%) and in seven patients in DTG group (24%; p = .166). The reasons for switch to dual therapy were request of simplification in 18 cases (33%), gastrointestinal symptoms in 15 (28%), dyslipidemia in 13 (24%), renal toxicity in 12 (22%), and reduced bone mineral density (BMD) in 10 (19%).

Baseline characteristics of study patients are summarized in Table 1, and all variables were comparable between groups.

Table 1.

Baseline Characteristics of the 54 Patients Enrolled in the Study

	Total	3TC + RAL	3TC + DTG	p
No. of patients	54	25	29
Males, n (%)	39 (72)	19 (76)	20 (69)	.122
White subjects, n (%)	47 (87)	22 (88)	25 (86)	.378
Age (years), median (IQR)	47.9 (41.4–55.8)	47.2 (40.1–53.3)	49.1 (42.8–56.5)	.166
HIV transmission risk category, n (%)
IDU	8 (15)	3 (12)	5 (17)	.512
MSM	31 (57)	15 (60)	16 (55)	.271
Heterosexual	15 (28)	7 (28)	8 (28)	.299
CD4+ cell count nadir (cells/mm³), median (IQR)	176 (92–256)	184 (102–279)	167 (83–244)	.109
Current CD4+ lymphocyte count (cells/mm³), median (IQR)	613 (498–809)	625 (483–817)	577 (431–776)	.218
Duration of HIV infection (years), median (IQR)	8.9 (5.5–11.7)	8.2 (5.1–10.8)	9.4 (5.9–12.3)	.538
Previous AIDS diagnosis, n (%)	8 (15)	3 (12)	5 (17)	.714
Duration of current ARV therapy (months), median (IQR)	46.3 (34.2–58.2)	49.1 (36.2–60.3)	44.6 (31.4–55.2)	.371
Cumulative exposure to ARV therapy (years), median (IQR)	8.4 (5.2–11.1)	7.9 (4.8–10.5)	8.7 (5.6–11.8)	.556
Duration of plasma HIV RNA <50 copies/mL with current ARV therapy (months), median (IQR)	42.9 (30.5–55.2)	45.4 (33.4–57.2)	41.2 (27.6–51.5)	.491
Patients with hypertension, n (%)	14 (26)	6 (24)	8 (28)	.317
Patients with diabetes mellitus, n (%)	8 (15)	3 (12)	5 (17)	.598
Patients with chronic hepatitis C, n (%)	5 (9)	2 (8)	3 (10)	.728
Weight (kg), median (IQR)	72.9 (62.1–84.2)	72.5 (61.3–82.4)	74.4 (62.6–85.1)	.201
BMI (kg/m²), median (IQR)	24.6 (23.7–25.8)	24.2 (23.6–25.5)	24.8 (23.9–26.1)	.881
Patients with BMI >25 kg/m², n (%)	7 (13)	3 (12)	4 (14)	.556
Total fat mass (kg), median (IQR)	18.8 (15.5–29.2)	18.7 (15.2–28.3)	19.1 (15.8–29.4)	.624
Total lean mass (kg), median (IQR)	53.9 (43.2–65.1)	53.2 (44.2–64.3)	55.2 (44.9–66.1)	.417
Lumbar spine BMD (g/cm²), median (IQR)	0.91 (0.76–1.07)	0.89 (0.74–1.03)	0.93 (0.78–1.09)	.254
Femur neck BMD (g/cm²), median (IQR)	0.78 (0.68–0.87)	0.75 (0.66–0.84)	0.81 (0.69–0.88)	.392
Patients with osteopenia, n (%)	20 (37)	9 (36)	11 (38)	.719
Patients with osteoporosis, n (%)	6 (11)	2 (8)	4 (14)	.807

3TC, lamivudine; ARV, antiretroviral; BMD, bone mineral density; BMI, body mass index; DTG, dolutegravir; IDU, injection drug users; IQR, interquartile range; MSM, men who have sex with men; RAL, raltegravir.

After 12 months we reported an increase in weight, BMI, total fat mass, and body fat percentage in both groups, but all changes were statistically not significant. In detail, the median increase in weight (IQR) was +1.74 kg (+0.96, +2.51; p = .223) in all patients, +1.58 kg (+0.73, +2.18; p = .418) in RAL group, and +2.09 kg (+1.28, +2.95; p = .184) in DTG group. The median increase in BMI (IQR) was +0.68 kg/m² (+0.44, +0.83; p = .571) in all patients, +0.62 kg/m² (+0.39, +0.74; p = .718) in RAL group, and +0.75 kg/m² (+0.49, +0.88; p = .626) in DTG group. The number of patients with BMI >25 kg/m² was unchanged (seven subjects, 13%). The median increase in body fat mass (IQR) was +1.13 kg (+0.94, +1.26; p = .188) in all patients, +0.92 kg (+0.71, +1.24; p = .591) in RAL group, and +1.24 kg (+1.02, +1.43; p = .817) in DTG group. The median increase in body fat percentage (IQR) was +5.7% (+3.8, +7.6; p = .379) in all patients, +5.1% (+3.2, +7.4; p = .729) in RAL group, and +6.3% (+3.9, +8.1; p = .448) in DTG group.

With regard to changes in bone density, we observed an increase in both groups, although all changes were statistically not significant. The median increase in lumbar spine BMD (IQR) was +0.02 g/cm² (−0.02, +0.05; p = .786) in all patients, +0.02 g/cm² (−0.03, +0.04; p = .816) in RAL group, and +0.03 g/cm² (−0.01, +0.06; p = .905) in DTG group. The median increase in femur neck BMD (IQR) was +0.04 g/cm² (−0.03, +0.06; p = .598) in all patients, +0.03 g/cm² (−0.05, +0.07; p = .923) in RAL group, and +0.04 g/cm² (−0.04, +0.07; p = .672) in DTG group. The numbers of patients with osteopenia and osteoporosis did not change during the follow-up.

Overall, there were only two cases of virological failure during the 12-month follow-up (one case in each group), and genotypic analysis at the time of virological failure demonstrated no resistance mutations in both cases. The median increase in the CD4+ T lymphocyte count (IQR) was +44 cells/mm³ (−12, +109; p = .677) and comparable between groups. During the 12-month follow-up a slight increase in total cholesterol levels and a slight decrease in triglyceride levels were observed in both groups, but the median changes in serum lipid concentration were statistically not significant. The median change in total cholesterol concentration (IQR) was +11 mg/dL (−14, +38; p = .801), and the median change in triglyceride concentration (IQR) was −28 mg/dL (−59, +5; p = .067).

Efficacy and safety of dolutegravir/lamivudine dual combination as maintenance regimen in suppressed patients have been demonstrated in several observational and randomized studies.^7,8 However, data about change in body weight and fat mass in patients switching to this dual combination are lacking. In a recent retrospective study, a not significant increase in body fat mass and body fat percentage was reported after 12 months in 23 HIV-infected persons switched to lamivudine plus dolutegravir, and changes were comparable to those observed in 16 controls switched to lamivudine plus boosted atazanavir. Moreover, authors reported also after 12 months a significant improvement both in spine and femur BMD in the lamivudine/dolutegravir group.⁹

Clinical data about the raltegravir/lamivudine dual combination as maintenance regimen are very limited. In two small observational studies, switching to raltegravir plus lamivudine in patients with viral suppression maintained virological efficacy and was well tolerated, but no data about change in weight and fat mass were collected.^10,11

In our study, the switch to dolutegravir/lamivudine or raltegravir/lamivudine did not produce significant increases in weight and body fat mass after a 12-month follow-up, and reported changes were comparable between groups. Obviously our study has evident limitations, including mostly the retrospective design and the small sample size. Moreover, given the study population, the results of present work may not be generalized to all ethnic groups. Nevertheless, our study supports further the good tolerability of maintenance regimens constituted by lamivudine plus dolutegravir or raltegravir.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This study was supported by internal funding.

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