Weight Change When Initiating,Switching to,and Discontinuing Integrase Strand Transfer Inhibitors in People Living with HIV

Abstract

Further investigations into the relationship between integrase strand transfer inhibitors (INSTIs) and weight gain are required, especially whether ceasing INSTI results in weight loss. We evaluated weight changes associated with different antiretroviral (ARV) regimens. A retrospective longitudinal cohort study was conducted using data extracted from the electronic clinical database at the Melbourne Sexual Health Centre, Australia, from 2011 to 2021. The association between weight change per time unit and ARV use in people living with HIV (PLWH) and the factors associated with weight changes when using INSTIs were estimated using a generalized estimated equation model. We included 1540 PLWH contributing 7476 consultations and 4548 person-years of data. ARV-naive PLWH initiating INSTIs gained an average of 2.55 kg/year (95% confidence interval 0.56 to 4.54; p = 0.012), while those using protease inhibitors and non-nucleoside reverse transcriptase inhibitors had no significant weight change. When switching off INSTIs, there was no significant weight change (p = 0.055). These weight changes were adjusted for age, gender, time on ARVs, and/or use of tenofovir alafenamide (TAF). Weight gain was the main reason PLWH ceased INSTIs. In addition, risk factors for weight gain in INSTI users were age younger than 60 years, male gender, and concomitant use of TAF. Weight gain was found among PLWH using INSTIs. After INSTI discontinuation, PLWH's weight stopped rising, but no weight loss was observed. Careful weight measurement after initiating INSTIs and early initiation of strategies to avoid weight gain will be important to prevent permanent weight gain and the associated morbidity.

Introduction

There were about 1.5 million new human immunodeficiency virus (HIV) infections globally and ∼38 million people living with HIV (PLWH) in 2020.¹ Since there is no effective cure for HIV, consistently taking antiretrovirals (ARVs) is critical to prevent onward transmission and reduce the morbidity and mortality rate in PLWH.²

Integrase strand transfer inhibitors (INSTIs) are the most effective and well-tolerated ARVs² and are recommended as first-line therapy for HIV worldwide.^2
–4 However, there have been mixed reports of INSTIs associated with weight gain since 2017,^5

–9 with the mechanism of weight gain from INSTIs remaining unclear.^10

–13 Two studies reported significant weight gain in PLWH using INSTIs compared with those using protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs),^5,8 but others reported no significant differences in weight gain between PLWH using INSTIs and PIs.^6,7,9,14 Heterogeneity of weight gain has also been reported between different INSTIs. Bictegravir (BIC) and dolutegravir (DTG) were associated with a greater weight gain than other INSTIs after 2 years of follow-up,^5,6 but one study from Italy found no significant difference between different INSTIs when measuring weight changes at 12 months.⁹

In addition, the concomitant use of INSTIs with tenofovir alafenamide (TAF) or abacavir may synergistically increase patients' weight more than using each of them independently.^5,15 Weight gain was observed in both ARV-naive and ARV-experienced PLWH when initiating INSTIs.^5,15,16 This finding reduced the possibility that weight gain from INSTI was only a return-to-health effect.^7,15,17 Previously reported risk factors for weight gain with INSTI use included people of Black or Hispanic ethnicity, women, lower CD4 count, higher HIV viral load, younger age, deferred ARV, and a higher baseline body mass index (BMI).^5,15,18 One issue of great concern is that unwanted weight gain may cause patients to stop their INSTIs. There was a report of patients discontinuing their DTG-based regimen because of weight gain of 4–12 kg,¹⁹ suggesting that patients are making a trade-off between excessive weight gain from using INSTIs despite the proven advantages of INSTIs.

Therefore, further investigation into the relationship between weight gain and INSTIs is crucial to prevent additional burdens (i.e., weight-related morbidity and mortality rate) to the health care system.²⁰ In addition, whether the discontinuation of INSTIs will reverse patients' weight gain to pre-INSTI weight or not is unclear. This study aimed to evaluate weight changes among PLWH on different ARVs with a focus on initiating INSTIs, switching ARVs to INSTIs, and discontinuing INSTIs.

Methods

Study setting

A retrospective cohort study was conducted to investigate weight change and its association with the type of ARV used among PLWH attending the Melbourne Sexual Health Center (MSHC) in Melbourne, Australia, from January 2011 to February 2021. MSHC is the largest HIV service in Victoria, with more than 1600 PLWH visiting the center annually. It is estimated that about 7800 PLWH in Victoria in 2021,^21,22 and around 33% of those were registered as clients at MSHC.²³

Data extraction

We extracted data from the electronic medical database at MSHC. The following data were extracted: age, gender, weight, height, BMI, consultation date, ARV used, CD4 nadir, HIV viral load, concurrent medications, smoking status, medical history, date of HIV diagnosis, and systolic and diastolic blood pressure. Most data were regularly measured and recorded by the health provider (i.e., physician, nurse or pharmacist) at the MSHC every 6–12 months. However, during the COVID-19 pandemic (from 2020 onward), weights were recorded by clinicians in the center or self-reported by patients through telehealth consultation.²⁴ The height and patient characteristic data (e.g., smoking status) were selected from the latest patient record. BMI was calculated using the weight and height data available on the database. Baseline weight was obtained closest to the ARV initiation or switching date, within 6 months before and 1 month after.

Records were excluded if there was no weight measurement, no baseline weight captured, no ARV used, or duplicated data. Outliers were defined as records with mismatched data between consultation and nursing notes and were excluded from our analyses.

Study participants

We included all PLWH who were at least 18 years old, attended MSHC, used ARVs, and had available weight records between January 2011 and February 2021. Only those with a baseline weight measurement when commencing or switching ARVs were included in the analyses. Overweight patients were defined as those with a BMI of more than 25 kg/m². A consent waiver was obtained for this study since we used data obtained from routine clinical practice.

Statistical analysis

A generalized estimated equation (GEE) was used to analyze the association between weight change per time unit and ARV use in all analyses (i.e., weight change per year, weight change when switching to or off INSTIs, and risk factors of weight gain when using INSTIs). Multiple weight records for each individual were clustered in the analysis. The exchangeable correlation structure was used in all analyses; the independent correlation structure was used only when the analysis could not be achieved. The reasons for INSTI discontinuation were described using descriptive statistics.

We presented the weight change per year with their respective 95% confidence intervals (95% CIs) and p value. A significant weight change after starting or switching an ARV was defined as having a p value <0.05. The mean weight changes were also compared between ARVs, and if its 95% CI of the weight changes between ARVs overlaps, it indicated no significant difference in weight change between ARVs. We calculated the person-years from the number of PLWH included in the analyses and the time each person living with HIV used each ARV. We adjusted weight change using age, gender, time on each ARV, and the concomitant use of TAF (where relevant) as potential confounders.

Descriptive statistics were used to summarize the sociodemographic characteristics, reporting the number and percentage for categorical variables and reporting a mean (±standard deviation) for continuous variables. The overall age and weight were calculated based on when they changed and commenced each ARV class. All analyses were performed using Stata BE 17.0 (StataCorp LP, College Station, TX).

This study was approved by the Alfred Hospital Research and Ethics Committee in Victoria, Australia (665/20).

Results

Demographic characteristics of patients starting different ARVs

We extracted 22,707 consultations from 2647 PLWH visiting the center from January 2011 to February 2021. Of these, 1107 PLWH (15,231 consultations) were excluded due to no weight record, duplicated records, no ARV used, or no baseline weight recorded. There were 1540 PLWH whose data were included, contributing 7476 consultations and 4548 person-years of data. All PLWH had a baseline weight recorded when starting an ARV, and at least one weight change was captured. The number of PLWH with a baseline weight at the commencement or switching ARVs included in the analyses was 1292 for INSTIs, 147 for PIs, and 369 for NNRTIs.

Overall, there was no significant difference in baseline weight, BMI, and proportion of current smokers between groups. Overall, the mean weight was 75.85 kg, and the mean BMI was 25.79 kg/m². The overall mean age was 40.16 years (±12.21), and 89.61% were males. However, the mean age, proportion of each gender, CD4 nadir, and the proportion of ARV-naive PLWH were different between groups (Table 1).

Table 1.

Baseline Demographic Characteristics of Individuals Using Different Antiretrovirals (N = 1540)

	INSTI (N = 1292)	PI (N = 147)	NNRTI (N = 369)	p
Mean age (years)	34.45 (±12.23)	38.94 (±10.69)	36.72 (±12.87)	<0.001^*
Gender
Male	1169 (90.48%)	125 (85.03%)	303 (82.11%)	<0.001^*
Female	112 (8.67%)	20 (13.61%)	66 (17.89%)
Others	11 (0.85%)	2 (1.36%)	0 (0.00%)
Mean weight (kg)	76.36 (±15.61)	77.03 (±17.31)	74.63 (±16.91)	0.09
Mean BMI (kg/m²)	24.35 (±4.23)	26.69 (±5.54)	25.26 (±5.43)	0.38
Mean CD4 nadir (cells/μL)	317.29 (±209.961)	283.77 (±207.96)	304.89 (±145.37)	<0.001^*
Current smoker	123 (9.52%)	14 (9.52%)	37 (10.03%)	0.58
ARV-naive	405 (31.35%)	30 (20.41%)	121 (32.79%)	<0.001^*

Continuous variables were reported as mean (±standard deviation). Categorical variables were reported as the number of PLWH (%). Patients can be included in more than one group as each patient could use more than one type of ARV.

p < 0.05.

ARVs, antiretrovirals; BMI, body mass index; INSTIs, integrase strand transfer inhibitors; NNRTIs, non-nucleoside reverse transcriptase inhibitors; PIs, protease inhibitors; PLWH, people living with HIV.

Weight change per year when starting ARVs in ARV-naive patients

There was a significant weight gain in 199 ARV-naive PLWH when starting INSTIs, but not PIs or NNRTIs. ARV-naive PLWH using INSTIs gained an average of 2.55 kg/year (95% CI: 0.56 to 4.54; p = 0.012), while those using PIs and NNRTIs had no significant weight change, at −4.12 kg/year (95% CI: −21.56 to 13.33; p = 0.644) and 0.65 kg/year (95% CI: −1.74 to 3.05; p = 0.592), respectively. Regarding different INSTI types, ARV-naive PLWH initiating BIC and DTG gained weight significantly; 5.97 kg/year (95% CI: 3.54 to 8.40; p < 0.001) for those on BIC, and 4.30 kg/year (95% CI: 3.62 to 4.97; p < 0.001) for those on DTG. In contrast, elvitegravir (EVG) or raltegravir (RAL) was not associated with significant weight change, with p = 0.249 and p = 0.543, respectively (Table 2).

Table 2.

Weight Change per Year When Starting Antiretrovirals in Antiretroviral-Naive Patients

		Unadjusted			Adjusted
	N/Obs	Weight change (kg/year)	95% CI	p	Weight change (kg/year)	95% CI	p
INSTIs	199/312	2.57	0.68 to 4.47	0.008^*	2.55	0.56 to 4.54	0.012^*
DTG	91/136	4.42	3.95 to 4.89	<0.001^*	4.30	3.62 to 4.97	<0.001^*
EVG	36/61	−3.28	−9.82 to 3.27	0.327	−4.24	−11.45 to 2.97	0.249
BIC	68/103	5.78	3.35 to 8.22	<0.001^*	5.97	3.54 to 8.40	<0.001^*
RAL	9/13	5.20	−11.62 to 22.02	0.545	2.78	−13.53 to 19.10	0.738
PIs	17/24	−3.39	−20.66 to 14.07	0.146	−4.12	−21.56 to 13.33	0.644
NNRTIs	61/96	0.88	−1.51 to 3.28	0.469	0.65	−1.74 to 3.05	0.592

Weight change is represented as kilogram change per year. Weight changes, 95% CI, and p values were determined from the generalized estimated equation models with the Gaussian family. Age, gender, time on each ARV, and use of TAF were adjusted.

p < 0.05.

ARV, antiretroviral; BIC, bictegravir; CI, confidence interval; DTG, dolutegravir; EVG, elvitegravir; INSTIs, integrase strand transfer inhibitors; N, number of participants; NNRTIs, non-nucleoside reverse transcriptase inhibitors; Obs, number of observations or consultations; PIs, protease inhibitors; RAL, raltegravir; TAF, tenofovir alafenamide.

Weight change per year when switching to or discontinuing INSTI

Annual weight changes among 289 PLWH when switching to (N = 236) or discontinuing (N = 53) INSTIs were assessed. In this analysis, there were 450 person-years of data for the switch from non-INSTIs to INSTIs and 46 person-years of data for the switch from INSTIs to non-INSTIs. PLWH switching from non-INSTI to all INSTI agents gained weight significantly, except for PLWH switching to BIC (Tables 3 and 4).

Table 3.

Unadjusted Weight Change per Year When Switching to or Discontinuing Integrase Strand Transfer Inhibitors

	Switch from non-INSTIs to INSTIs				Switch from INSTIs to non-INSTIs
	N/Obs	Weight change (kg/year)	95% CI	p	N/Obs	Weight change (kg/year)	95% CI	p
INSTIs	236/656	0.71	0.49 to 0.93	<0.001^*	53/144	0.54	−0.11 to 1.19	0.106
DTG	92/266	0.80	0.50 to 1.10	<0.001^*	31/95	0.49	−1.39 to 2.36	0.612
BIC	47/102	0.76	−0.87 to 2.39	0.360	5/7	3.81	−2.52 to 10.15	0.238
EVG	78/231	0.67	0.18 to 1.17	0.008^*	10/22	2.06	−0.50 to 4.61	0.115
RAL	14/37	0.62	−0.02 to 1.27	0.059	14/37	0.80	−0.66 to 2.26	0.284

Data are represented as kilogram weight change per year. Weight changes, 95% CI, and p values were determined from the generalized estimated equation models with the Gaussian family.

p < 0.05

BIC, bictegravir; CI, confidence intervals; DTG, dolutegravir; EVG, elvitegravir; INSTIs, integrase strand transfer inhibitors; N, number of participants; Obs, number of observations or consultations; RAL, raltegravir.

Table 4.

Adjusted Weight Change When Switching to or Discontinuing Integrase Strand Transfer Inhibitors

	Switch from non-INSTIs to INSTIs				Switch from INSTIs to non-INSTIs
	N/Obs	Weight change (kg/year)	95% CI	p	N/Obs	Weight change (kg/year)	95% CI	p
INSTIs	236/656	0.71	0.48 to 0.93	<0.001^*	53/144	0.82	−0.02 to 1.65	0.055
DTG	92/266	0.65	0.31 to 0.99	<0.001^*	31/95	1.04	−0.19 to 2.25	0.097
BIC	47/102	1.20	−0.40 to 2.79	0.142	5/7	0.47	−4.87 to 5.82	0.861
EVG	78/231	0.54	0.02 to 1.07	0.041^*	10/22	1.59	−0.85 to 4.02	0.201
RAL	14/37	1.09	0.29 to 1.89	0.008^*	7/23	1.30	0.16 to 2.43	0.025^*

Data are represented as kilogram weight change per year. Weight changes, 95% CI, and p values were determined from the generalized estimated equation models with the Gaussian family. Age, gender, time on ARV, and concomitant use of TAF were adjusted in the adjusted analysis.

p < 0.05.

ARV, antiretroviral; BIC, bictegravir; CI, confidence interval; DTG, dolutegravir; EVG, elvitegravir; INSTIs, integrase strand transfer inhibitors; N, number of participants; Obs, number of observations or consultations; RAL, raltegravir; TAF, tenofovir alafenamide.

Regarding INSTI discontinuation, PLWH switching from INSTIs to non-INSTIs, regardless of INSTI types, had no significant weight change at 0.82 kg/year (95% CI: −0.02 to 1.65; p = 0.055). Only PLWH on RAL continued to gain weight after discontinuing the drug, at 1.30 kg/year (95% CI: 0.16 to 2.43; p = 0.025) (Table 3). However, there was no significant weight change for PLWH switching off INSTIs in the unadjusted weight change result. The two main reasons for ceasing INSTIs were weight gain (35.8%) and precautions/contraindications/drug interactions (32.1%).

Risk factors for weight gain associated with INSTI use

We found that PLWH using INSTIs who were 60 years or younger gained significant weight at 0.71 kg/year (95% CI: 0.59 to 0.84; p < 0.001), while PLWH using INSTIs older than 60 years gained weight at 0.11 kg/year (95% CI: −0.21 to 0.43; p = 0.497). In addition, a significant weight gain was found in males (n = 1169) at 0.61 kg/year (95% CI: 0.50 to 0.73; p < 0.001), while there was no significant weight gain in females (n = 112) at 0.46 kg/year (95% CI: −0.12 to 1.05; p = 0.123). In addition, concomitant use of INSTIs and TAF caused significant weight gain at 0.71 kg/year (95% CI: 0.52 to 0.91; p < 0.001) (Table 5).

Table 5.

Risk Factors of Weight Gain When Using Integrase Strand Transfer Inhibitors

Risk factors	Weight change (kg/year)	95% CI	p
Age (years)
≤60	0.71	0.59 to 0.84	<0.001^*
>60	0.11	−0.21 to 0.43	0.497
Gender
Male	0.61	0.50 to 0.73	<0.001^*
Female	0.46	−0.12 to 1.05	0.123
Others^a	0.01	−1.77 to 1.79	0.994
Concomitant ARVs
TAF	0.71	0.52 to 0.91	<0.001^*

Data are represented as kilogram weight change per year. Weight changes, 95% CI, and p values were determined from the generalized estimated equation models with the Gaussian family.

Transgender or unknown.

p < 0.05.

ARVs, antiretrovirals; CI, confidence interval; TAF, tenofovir alafenamide.

Discussion

Our study found that ARV-naive PLWH gained weight while using INSTIs, but there was no significant weight loss when INSTIs were discontinued. Our study provides the first observational study describing weight changes after INSTI discontinuation from a real-world cohort.²⁵ This adds to the growing literature to help inform clinical decision-making about weight management from INSTIs, where no current consensus in recommendations exists. Specifically, our study results highlight the importance of preventing weight gain with initiating INSTI treatment, given that no weight loss was found on cessation.

PLWH using INSTIs appeared to gain weight, whereas PLWH using PIs or NNRTIs did not gain weight in our study. In 2017–2021, several studies reported that PLWH using INSTIs gained more weight than PLWH using PIs.^5,8,9,15 Meanwhile, the result of three cohort studies by Bourgi et al.,⁶ Martinez-Sanz et al.,⁷ and Ruderman et al.²⁶ found that INSTI and PI appeared to have similar effects on PLWH's weight. The different results could potentially arise from the different ARVs in each analysis. For instance, Ruderman et al.²⁶ only included darunavir in the PI class, whereas our study included all PIs used at MSHC, such as darunavir and atazanavir. Despite the inconsistent data comparing the effects of PIs and INSTIs on weight, INSTIs seem likely to be associated with significant weight gain in PLWH.

Further, some heterogeneity of weight change between different INSTIs was observed in previous studies.^5,6,8,27 In the studies comparing weight change between PLWH using DTG, EVG, and RAL, DTG was found to cause the most weight gain.^6,8 However, there was some inconsistency when comparing BIC and DTG regarding which drug caused more weight gain.^5,27 Meanwhile, EVG and RAL have been observed to cause the least weight gain in all studies.^5,6,8 Our study found weight gain associated with BIC and DTG, but not EVG and RAL. In addition, our results cannot be used to estimate the effect of weight gain in the long term. A study of the effect of switching from a PI or efavirenz to INSTIs showed that weight gain from INSTIs might favor patients' lipid profiles.²⁸ A long-term study on the effect of weight gain from INSTIs on the metabolic profile is required.

Unfortunately, the weight gain from INSTIs was the main reason PLWH stopped using INSTIs at our center. We also found that the extra weight appeared to be irreversible, although, among those who ceased INSTI, we saw no further significant weight gain in either the unadjusted or adjusted analysis. A previous case report demonstrated that 2 years after switching from EVG to efavirenz, there was a decline in PLWH's weight to the pre-INSTI level.²⁹ Our study found that PLWH switching off INSTIs did not lose weight regardless of the type of INSTI. After adjusting for age, gender, time on ARV, and TAF use, PLWH who switched off RAL kept gaining weight after the discontinuation. However, the findings relating to individual INSTI should be interpreted cautiously, given our small sample size of PLWH using INSTIs [e.g., RAL (n = 7)].

In addition, a cohort exploring reasons for selecting ARVs in PLWH in Europe showed that 33% of clinicians selected INSTIs as a first-line regimen, while 31% of the clinicians hesitated to choose INSTIs due to their comorbidities.³⁰ A discrete choice experiment survey in Australia also showed that 16% of the PLWH in the survey were concerned about weight gain as a side effect of INSTIs more than other side effects (e.g., risk of heart attack or kidney problems).³¹ Our study is the first to provide substantial data on changes in weight after ceasing INSTI use. Our study, together with previous studies,^30,31 may inform clinical decision-making regarding INSTI use.

In the previous studies, risk factors for weight gain observed when using INSTIs were Black or Hispanic race, women, lower CD4 count, higher HIV RNA viral load, younger age, deferred ARV, and higher baseline BMI.^5,15,18 In our study, the risk factors were the concomitant use of INSTIs with TAF, age younger than 60 years, and male sex. However, we could not draw conclusions on the effect of INSTIs on women's weight because most participants in our study were men, reflecting the Australian HIV epidemic. Further studies from other settings are required to confirm our findings. Regarding CD4 nadir, although Sax et al.⁵ reported a negative correlation between CD4 level and weight in PLWH using INSTIs, the correlation between CD4 nadir and weight changes when using different ARVs was not statistically significant in our study.

Also, since not all patients in our study had height records, we could not calculate BMI changes, which could be another aspect to improve in future studies. One issue complicating the analysis of weight gain over time in any group is the background weight gain in a similar group of people without HIV. As far as we are aware, such data are not available, although, for Australians, the average weight gain is about 0.34 kg/year from repeated cross-sectional samples between 1999 and 2012.³² Further, the yearly increases appear to be slowing in some groups and are less in men than women. Our results should be assessed with these national trends in mind.

Some authors have hypothesized that weight gain in PLWH is due to the return to health effect.²⁵ Yet, there is an inconsistency with this argument because Kerchberger et al.¹⁵ found that INSTI users gained more weight than other ARV classes regardless of viral load and CD4 cell count. However, their study only included women, and so, the results may not be generalizable to men. Our study provided more data for male PLWH. We analyzed weight change when switching to INSTIs, and found that patients gained significant amounts of weight even when switching from another ARV to an INSTI. These results support the argument that weight gain from INSTIs was not from only the return-to-health effect. Nevertheless, the evidence suggests that INSTIs are associated with weight gain in both treatment-naive patients and patients who switched to INSTIs.

The strengths of this study are that the data come from a real-world cohort with a large sample size, over an extended follow-up, and data recorded mainly by clinicians and not self-reported. Since clinical trial inclusion and exclusion criteria are stringent, their results may not represent all PLWH. Our study, in contrast, represents a more realistic weight change in PLWH in the real world. Unlike previous studies, which had less than a thousand participants,^{9,16,33
–35} our sample size is large (1540 patients with 7476 recorded weights) because we audited the electronic health records from the largest HIV center in Australia over 10 years. Likewise, all those with outlier weight measurements were manually excluded to increase the accuracy of the results. Most importantly, we are the first to measure the effect of INSTI discontinuation on weight change, which can guide clinicians in managing weight gain from INSTIs in PLWH. One of the approaches could be discontinuing INSTIs and switching from TAF to tenofovir disoproxil fumarate (TDF), as TDF was found to prevent weight gain.³⁶ This suggestion requires further investigation since TAF is perceived to be safer than TDF in the long term.³⁷ Further studies are required to measure weight change when switching from TAF to TDF.

There were several limitations to our study. First, we did not measure all the potential confounding factors, such as diet or activity levels that may have differed systematically between PLWH in different groups. Second, we only had sufficient data for half of the PLWH managed at the center; therefore, selection bias may be associated with those with and without data that could have influenced our results. Specifically, our estimates may be exaggerated if weights were preferentially recorded in those who gained weight. Also, some weight measurements were self-reports during COVID-19. Thus, weights may be inconsistently measured on different scales.

Third, our results may not be generalizable to females or thinner individuals given that the majority of PLWH in our study were male and the average BMI of included participants was about 26 (i.e., overweight), which itself can be a risk for weight gain.³⁸ We adjusted our findings with available covariates to mitigate some of these limitations. Lastly, some analyses (e.g., switching off RAL) could not be achieved since the sample was too small to obtain a robust result, and in others, with only moderate numbers, the level of precision was less.

To conclude, INSTI use in PLWH was associated with weight gain, while in general, use of the other ARVs was not associated with significant weight gain. We also noted that when INSTI was ceased and replaced with another ARV, the weight gain ceased but did not reverse to pre-INSTI weight. Also, weight gain from INSTI use should be monitored closely, as PLWH stopped using INSTIs due to weight gain. The risk factors for weight gain when using INSTIs were younger age, male, and concomitant use of TAF.

Footnotes

Acknowledgments

We are grateful to all clients at the MSHC included in this study; and to the staff at the MSHC for their work and support in the implementation of the study.

Authors' Contributions

J.J.O. conceptualized the study. W.T., J.J.O., and E.P.F.C. analyzed the data with inputs from C.K.F., J.H., and all the authors reviewed. J.J.O. and E.P.F.C. supervised the statistical analysis. J.J.O. and W.T. contributed to data mining. W.T. wrote the first draft of the article and generated the tables. W.T., J.J.O., C.K.F., and E.P.F.C. contributed to the writing. All authors revised and approved the final article.

Author Disclosure Statement

J.H.'s institution received reimbursement for her time on Advisory Boards for Gilead Sciences and ViiV Healthcare. The other authors report no potential conflicts of interest.

Funding Information

J.J.O. and E.P.F.C. are supported by a National Health and Medical Research Council (NHMRC) Emerging Leadership Investigator Grant (GNT1193955 and GNT1172873, respectively). C.K.F. is supported by an Australian NHMRC Leadership Investigator Grant (GNT1172900).

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Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Available from: www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf [Last accessed: March 30, 2021].

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