Maternal anthropometry, body composition and fat distribution by HIV status and antiretroviral therapy class in South African women

Abstract

Background.

Pregnancy affects adiposity, which may be influenced by HIV infection or antiretroviral therapy (ART). The objective of this study was to examine adiposity measures in the perinatal period, by HIV status and ART class.

Methods.

214 women (113 women with HIV [WWH], 71 initiated ART post-conception) enrolled between 24–28 weeks gestation and followed until 6–12 months postpartum, were assessed for longitudinal weight and cross-sectional postpartum anthropometry. A subset of 65 (52 WWH, 42 initiated ART post-conception) had cross-sectional adiposity (body composition and fat distribution) measured at 6–12 months postpartum using dual-energy X-ray absorption (DXA) scan. Multivariable linear and modified Poisson regression, adjusted for maternal age, pre-pregnancy body mass index, socio-economic status and postpartum months, examined associations of HIV status and post-conception ART (dolutegravir-based [DTG] vs efavirenz-based [EFV]) with anthropometry and adiposity outcomes.

Results.

At enrolment, the median age was 30 years (IQR, 26–34) and 82% were multiparous. Between pre-pregnancy and postpartum, women gained an average of 2.33 kg (0.90 kg WWH), 30% lost weight (35% WWH) and 48% gained weight (38% WWH). WWH gained weight slower during pregnancy (0.27 vs 0.38 kg/week, p=0.03) and were less likely to gain weight postpartum (RR=0.72 95% CI 0.55, 0.93; p=0.01) compared to women without HIV. Postpartum, mean BMI was 32 kg/m² (SD=7.33) and 58% (53% WWH) of women had obesity. HIV was not associated with cross-sectional measures of postpartum anthropometry and adiposity. Among WWH, compared to EFV-based ART, DTG-based ART was not associated with weight gain during pregnancy or anthropometry and adiposity postpartum.

Conclusion.

Despite high rates of postpartum weight gain and obesity, no significant differences were observed in anthropometry and adiposity measures by HIV status and post-conception ART. Nonetheless, these findings underscore the need for interventions to support healthy weight gain in pregnancy and postpartum weight loss to minimise pregnancy-associated obesity.

INTRODUCTION

Obesity in the perinatal period is an important driver of pregnancy complications and long-term adverse maternal metabolic health (1, 2). It has been reported that over one-third of women with HIV (WWH) experience higher gestational weight gain (GWG) than recommended by the Institute of Medicine (IOM) (3, 4) and retain and/or gain weight postpartum (5, 6). A meta-analysis of 21 countries in Sub-Saharan Africa (SSA) suggested that excessive GWG could exacerbate the high burden of non-communicable diseases (NCDs), including higher type 2 diabetes (T2D) risk among WWH (7). In addition, excessive GWG has long-term deleterious consequences for offspring. Specifically, a longitudinal study of school-aged children found that excessive GWG was associated with childhood obesity among 7–11 year old children (8). WWH may, in particular, be more susceptible to weight gain related to the use of dolutegravir-(DTG)-based antiretroviral therapy (ART) (9, 10), which is first line HIV treatment in SSA, including in pregnancy. Notably, randomized controlled trials in SSA countries, including Botswana, South Africa and Uganda found greater weight gain during the postpartum period in women who initiated DTG-based ART in pregnancy compared to those who initiated efavirenz (EFV)-based ART (11, 12). However, there is limited data on trajectories of weight change from pregnancy to postpartum among WWH overall, and those initiating DTG-based ART in pregnancy.

Although weight and body mass index (BMI) are widely used measures due to their ease of measurement, direct measures of body composition and fat distribution have been shown to be better predictors of future health outcomes (13, 14). For example, in a longitudinal study among SSA women, the accumulation of central body fat, particularly visceral adipose tissue (VAT) predicted the development of T2D 13 years before its onset (15). Another meta-analysis reported that higher visceral fat mass was associated with a 4-fold risk of T2D among women while fat-free mass reduced the risk (16). Historically, older nucleoside reverse transcriptase inhibitors (NRTIs) ART such as thymidine analogues and protease inhibitors (PI) have been associated with abdominal fat redistribution linked to metabolic dysregulation and long-term risk of metabolic disorders (17). Although alterations in body composition have been minimised with non-NRTI ART, the risk of metabolic disorders might persist due to DTG-related weight gain (18). However, there is a lack of data describing the body fat depot that is most affected by DTG-based ART initiation in pregnancy. To address this evidence gap, we followed WWH (initiating DTG- or EFV-based ART) and without HIV attending an antenatal care clinic in Cape Town from 24–28 weeks gestation age (GA) to 6–12 months postpartum. The objective of this study was to examine trajectories of weight change, anthropometry and body fat distribution in the perinatal period, comparing these by HIV status and post-conception ART class.

Methods

Study design and population

A total of pregnant WWH (n=200) and without HIV (n=200) (≥18 years of age) were recruited between November 2019 and June 2022 and enrolled into a prospective cohort study called the CArdioMetabolic complications in Pregnancy (CAMP) study (19, 20). Briefly, participants completed three study visits, enrolment at 24–28 weeks gestation (baseline), and follow-up at 33–38 weeks gestation and 6 months postpartum. Women receiving treatment for diabetes or hypertension were excluded from the study. The recruitment coincided with the transition from EFV-based ART to DTG-based ART in South African antenatal care clinics, which took place from 2019. As a result, WWH in CAMP were either using pre- or post-conception EFV-based (tenofovir 300 mg + [emtricitabine 200 mg or lamivudine 300 mg] + efavirenz 600 mg) or DTG-based (tenofovir 300 mg + [emtricitabine 200 mg or lamivudine 300 mg] + dolutegravir 50mg) ART provided as a fixed-dose combination pill taken once daily. The CAMP study took place at the Gugulethu primary healthcare facility in Cape Town. Gugulethu is a township situated 18 km south-east of Cape Town in the Western Cape Province, South Africa.

Two study populations were included. Firstly, of the 400 participants, we included 214 women who were followed longitudinally and attended their postpartum visit between 6–12 months, and we compared anthropometry measures between WWH (on pre- and post-conception ART) and those without HIV (Figure 1). Secondly, of the 214, we included a subset of 65 women who had cross-sectional DXA scan measures between 6–12 months, and we compared WWH (on pre- and post-conception ART) and those without HIV. For both study populations, the ART comparison was restricted to women who initiated ART post-conception and we compared post-conception DTG- vs EFV-based ART. The study protocols were reviewed and approved by the Faculty of Health Sciences Human Research Ethics Committee of the University of Cape Town. All women provided written informed consent prior to study participation.

Figure 1.

Participant enrolment and retention flowchart showing the selection of participants included in the different analysis conducted. GA - gestional age, ART - antiretroviral therapy, EFV - efavirenz, DTG - dolutegravir, PI - protease inhibitor, DXA - dual-energy X-ray absorptiometry.

Measures

Exposure and outcome assessments

The main exposures included HIV status and post-conception ART class (EFV- vs DTG-based). Both HIV status and ART regimen (including the timing of initiation) were collected through self-report and confirmed using medical records.

Longitudinal weight trajectory outcomes

Longitudinal weight outcomes included the rate of weight gain or loss (measured as average gain or loss in kilograms per week) and total weight change (kgs) between pre-pregnancy and postpartum. Total weight change was calculated as postpartum weight minus pre-pregnancy weight and categorised as lost weight (< 2 kg), stayed same (+/− 2 kg) and gained weight (> 2kg) (5). Weight was self-reported pre-pregnancy and measured by study staff at 24–28 weeks gestation, 33–38 weeks gestation and 6–12 months postpartum. Although some authors have criticized self-reported pre-pregnancy weights, (21); others have shown that self-reported vs measured pre-pregnancy weights are similar (22). Weight (kg) measurements were conducted with the participants wearing light clothing and no shoes, using a calibrated scale (Charder, Taichung City, Taiwan) accurate to within 0.2 kg.

Postpartum anthropometry outcomes

Postpartum anthropometry outcomes were weight, body mass index (BMI), waist and hip circumferences, waist-hip ratio and visceral adiposity index. BMI was calculated as weight divided by squared height, categorised as underweight (<18.5), normal (18.5–24.9), overweight (25.0–29.9) and obese (≥30.0) in kg/m². Waist (at the umbilicus) and hip (at the largest protrusion of the buttocks) circumferences were measured using a metal anthropometric tape measure (Seca, Birmingham, United Kingdom). Visceral adiposity index (VAI), a marker of adipose tissue dysfunction (23), was calculated as waist circumference (cm)/(36.58+[BMI*1.89]) * (triglycerides [mmol/L]/0.81) *(1.52/high-density lipoprotein [mmol/L]) (23). Triglycerides and high-density lipoprotein used in this formula were measured in serum samples collected after a 10–12 hour fast; testing was performed in real time by the ISO 15189-accredited South African National Health Laboratory Services using an enzymatic colorimetric test (Roche cobasTM 6000 analyser, Roche Diagnostics, Basel, Switzerland).

Postpartum body composition and fat distribution outcomes

Whole body DXA scan (Hologic Discovery-W [S/N 71201], Bedford, MA, USA, software version 12.7.3.7), operated by a trained study radiographer, was used to measure total body composition and regional distribution of fat (kg) and fat-free mass (kg) (24) in a sub-set of women postpartum. In-vivo precision was previously determined in our laboratory for fat-free soft tissue mass (FFSTM) (0.7%) and fat mass (FM) (1.67%) by measuring 30 individuals twice on the same day with repositioning (25). Total body composition included subtotal (minus head) fat mass (FM), FFSTM and total body FM presented relative to total body mass and reported as a percentage (%BF). Regional fat distribution included trunk, arm, leg, android, and gynoid FM (expressed in kg). In addition, VAT and subcutaneous adipose tissue (SAT) were estimated using DXA software algorithms developed for South African women (26).

Covariates

Maternal socio-demographic and clinical data were collected via trained interviewer-administered questionnaires at baseline, in the participants home language. Socio-economic status (SES) was a composite score based on level of education, employment status, type of housing, and presence of a toilet, running water, electricity, fridge, telephone, and television in the house (27); which were categorised into tertiles corresponding to lower, middle and higher SES group. Alcohol use was measured using a 3-item Alcohol Use Disorders Identification Test-Consumption (AUDIT-C; range 0–12). An AUDIT-C score ≥3 indicates hazardous drinking in the previous 12 months for women (28). Perceived household food insecurity was assessed using a measure adapted from the Household Food Insecurity Access Scale and was categorized as ‘yes’ and ‘no’ (29). Gestational age at enrolment was primarily determined by an ultrasound (89%) operated by an experienced research sonographer, the remaining 11% were assessed by either symphysis fundal height measurement or last menstrual period. Self-reported pre-pregnancy weight was used to calculate pre-pregnancy BMI. Postpartum months period (months) since delivery was calculated as the date of postpartum visit attendance minus delivery date which was confirmed from obstetric records.

Statistical Analysis

The analysis was divided into three parts, i) longitudinal weight trajectory analysis which included all participants with valid weight measurements at enrolment (24–28 weeks gestation), 33–38 weeks gestation and 6–12 months postpartum (n=214), ii) cross-sectional postpartum anthropometry analysis which included all participants with complete data on anthropometry at 6–12 months postpartum (n=214), and iii) cross-sectional postpartum body composition and fat distribution analysis which included all participants with complete data for DXA scans at 6–12 months postpartum (n=65). In all three analyses, we compared measures of anthropometry, body composition and body fat distribution by HIV status and post-conception ART regimen (EFV- vs DTG-based). Post-conception ART group included women that were ART naïve and those that were re-initiating ART. Because there were so few women on DTG prior to conception (N=9), no pre-conception ART initiator analysis was conducted. Linear regression models were fit to estimate the associations between HIV status, post-conception ART and continuous anthropometry measures; and modified Poisson regression was used for categorical total weight change and BMI category. Similarly in a subset, linear regression models were used to examine the associations between HIV status, ART and continuous body composition and fat distribution measures. Models for both HIV status and ART were adjusted for maternal age, pre-pregnancy BMI, SES and postpartum months since delivery. All data were analysed using STATA version 15.0 (Stata Corporation, College Station, TX, USA) and R Studio (R Foundation, Vienna, Austria).

RESULTS

Participant characteristics

A total of 214 women (113 WWH) were assessed for longitudinal weight trajectories and cross-sectional postpartum anthropometry, and 65 (52 WWH) for cross-sectional postpartum body composition and fat distribution. Overall, at enrolment, the median age was 30 years (IQR, 26–34), gestational age was 25 weeks (IQR, 24–27) and 82% of women were multiparous (Table 1). The median pre-pregnancy BMI was 31 kg/m² (IQR, 26–36), with 26% (n=55) living with overweight and 56% (n=120) living with obesity. Of the 120 women with obesity, 61 (51%) did not have HIV and 59 (49%) were WWH. WWH were more likely to be older (32 vs 28 years, p<0.01) and multiparous (89 vs 73%, p<0.01), and were less likely to have higher SES (32 vs 53%, p<0.01) compared to those without HIV. Among WWH, 63% (n=71) initiated ART post-conception (DTG 75% [n=53]; EFV 25% [n=18]). Median postpartum months since delivery was 8.1 months (IQR, 6.6–10.1); WWH attended the postpartum visit earlier than women without HIV (7.6 vs 9.4 months, p=0.02). Women assessed in this sub-study (n=214) had similar demographic characteristics as the overall CAMP cohort (n=400) (Supplemental Table 1).

Table 1.

Pregnancy (baseline) characteristics, overall and stratified by maternal HIV status

		HIV status
	Total N = 214	Without HIV N = 101	With HIV N = 113
Demographics
Age (years) *
Median (IQR)	30 (26–34)	28 (23–31)	32 (28–35)
Gestational age (weeks)
Median (IQR)	25 (24–27)	25 (24–27)	26 (24–27)
Pre-pregnancy BMI (kg/m2)
Underweight (<18.5)	0 (0)	0 (0)	0 (0)
Normal (18.5–24.9)	39 (18)	19 (19)	20 (18)
Overweight (25–29.9)	55 (26)	21 (21)	34 (30)
Obese (≥30)	120 (56)	61 (60)	59 (52)
Median (IQR)	31 (26–36)	32 (28–37)	30 (26–35)
Parity*
Primiparous	39 (18)	27 (27)	12 (11)
Multiparous	175 (82)	74 (73)	101 (89)
Median (IQR)	3 (2–3)	2 (1–3)	3 (2–4)
Socio-economic status*
Lower	69 (32)	25 (25)	44 (39)
Middle	55 (26)	22 (22)	33 (29)
Higher	90 (42)	54 (53)	36 (32)
Perceived food insecurity
No	168 (78)	80 (79)	88 (78)
Yes	46 (22)	21 (21)	25 (22)
Hazardous alcohol use
No	196 (92)	93 (92)	103 (91)
Yes	18 (8)	8 (8)	10 (9)
HIV characteristics for women on post-conception ART
	WWH on post-conception ART (n= 71)	Post-conception ART
		EFV-based (n= 18)	DTG-based (n= 53)
ART duration (days)*
Median (IQR)	1.20 (0.63–2.00)	2.58 (1.33–3.73)	0.97 (0.47–1.87)
CD4 count (cells/μL)
≤350	20 (28)	6 (33)	14 (26)
351–500	14 (20)	4 (22)	10 (19)
>500	17 (24)	7 (39)	10 (19)
Median (IQR)	422 (275–578)	481 (293–579)	403 (260–574)

^*p<0.05. Missing data: pre-pregnancy BMI n=1, CD4 count n=20. For maternal HIV characteristics, n=1 on Protease Inhibitor-based ART. BMI - body mass index, WWH - women with HIV, ART - antiretroviral therapy, EFV - efavirenz, DTG - dolutegravir

Longitudinal weight trajectory analysis

At pre-pregnancy, WWH had slightly lower weight (WWH 78 kg vs without HIV 82 kg, p=0.12) and gained weight more slowly throughout pregnancy (between pre-pregnancy and 24–28 weeks GA [0.16 kg/week WWH vs 0.23 kg/week without HIV, p<0.01]; between 24–28 weeks GA and 33–28 weeks GA [0.27 kg/week WWH vs 0.38 kg/week without HIV, p=0.03]) compared to women without HIV (Figure 2A). However, the rate of weight loss between 33–38 weeks GA and 6–12 months postpartum did not differ by HIV status (−0.13 kg/week WWH vs −0.13 kg/week without HIV, p=0.87). Among WWH, no differences were observed in the rate of weight gain in pregnancy, or the rate of postpartum weight loss between those that initiated EFV- and DTG-based ART (Figure 2B).

Figure 2.

Rate of weight gain/loss between consecutive visits from pre-pregnancy to postpartum period by HIV status (A) and post-conception ART (B), the p-values indicate group differences in weekly rate of weight gain/loss between visits. Categorised postpartum total weight change (postpartum weight minus pre-pregnancy weight) by HIV status (C) and post-conception ART (D) is also shown, categories were lost weight (less than 2 kg), stayed same (+/− 2 kg) and gained weight (more than 2kg). Risk Ratios (RR) from modified Poisson regression in panels C and D are show associations for HIV status with the risk of (i) losing weight vs staying the same and (ii) gaining weight vs staying the same and for associations of post-conception DTG-based ART (vs. EFV-based ART) on the same weight gain/loss outcomes. Models in panels C and D were adjusted for maternal age, pre-pregnancy BMI, SES and postpartum months since delivery. Abbrev: ART - antiretroviral therapy, EFV - efavirenz, DTG - dolutegravir, GA - gestational age.

Between pre-pregnancy and postpartum, overall mean total weight change was 2.33 kg (SD=8.45); and 65 (30%) lost weight, 46 (22%) stayed the same and 103 (48%) gained weight. A higher proportion of WWH lost weight (35% WWH vs 26% without HIV) or stayed the same (27% WWH vs 15% without HIV), and a lower proportion gained weight (38% WWH vs 59% without HIV) postpartum compared to women without HIV; p<0.01 (Figure 2C). In models adjusted for age, pre-pregnancy BMI, SES and postpartum months since delivery, WWH were less likely to gain weight postpartum (RR=0.72 95% CI 0.55, 0.93; p=0.01) compared to women without HIV. In models adjusted for the same covariates, among WWH, there was no evidence that DTG-initiation in pregnancy was associated with higher postpartum weight gain (RR=1.72 95% CI 0.73, 4.02) compared to those that initiated EFV-based ART (Figure 2D). Similarly, there were no apparent differences in trajectories of absolute weight over time (Supplemental Figure 1A–B) and total weight change distribution (Supplemental Figure 1C–D) by HIV status and ART regimen.

Cross-sectional postpartum anthropometry analysis

Overall, mean BMI at 6–12 months postpartum was 32 kg/m² (SD=7.33): 2 (1%) underweight, 39 (18%) normal, 49 (23%) with overweight and 124 (58%) with obesity. Obese BMI was prevalent among WWH, as well as those without HIV (53% WWH vs 63% without HIV, p=0.50) (Table 2). Using unadjusted regression models, WWH had lower anthropometry measures, but all differences were attenuated after adjusting for confounders. In models adjusted for the same covariates, among WWH, although there were modest increases in hip circumference (mean difference=1.95 95% CI −3.16, 7.05) and overweight (RR=1.60 95% CI 0.74, 3.46) among women that initiated DTG-based ART compared to EFV-based ART, there was no evidence of significant differences in all postpartum anthropometry measures by ART regimen.

Table 2.

Differences in postpartum anthropometry by HIV and post-conception ART regimen

	HIV status				Post-conception ART regimen
	Without HIV N = 101 Mean (± SD)	With HIV N = 113 Mean (± SD)	‘With HIV’ Unadjusted mean difference (95% CI)	‘With HIV’ Adjusted mean difference (95% CI)*	EFV-based N=18 Mean (± SD)	DTG-based N=53 Mean (± SD)	‘DTG-based ART’ Unadjusted mean difference (95% CI)*	‘DTG-based ART’ Adjusted mean difference (95% CI)*
Weight (kg)	86.3 (19.9)	79.1 (19.8)	−7.14 (−12.49, −1.78)	−1.66 (−5.14, 1.82)	76.0 (17.6)	80.1 (21.0)	4.09 (−6.89, 15.07)	1.30 (−5.61, 8.20)
BMI (kg/m2)	33.7 (7.4)	31.0 (7.0)	−2.73 (−4.68, −0.79)	−0.66 (−1.65, 0.33)	29.7 (6.5)	31.0 (7.1)	1.35 (−2.44, 5.15)	0.20 (−1.53, 1.93)
Waist circumference (cm)	103.5 (16.3)	97.5 (13.6)	−5.93 (−9.96, −1.90)	−2.23 (−5.26, 0.81)	94.7 (13.1)	97.2 (13.6)	2.48 (−4.84, 9.79)	1.01 (−4.24, 6.25)
Hip circumference (cm)	117.4 (14.5)	112.1 (13.8)	−5.30 (−9.11, −1.49)	−2.41 (−5.35, 0.52)	109.3 (15.5)	113.2 (12.9)	3.92 (−3.46, 11.29)	1.95 (−3.16, 7.05)
Waist-hip ratio	0.88 (0.09)	0.87 (0.07)	−0.01 (−0.03, 0.01)	−0.05 (−0.03, 0.02)	0.87 (0.06)	0.86 (0.07)	−0.01 (−0.05, 0.03)	−0.01 (−0.05, 0.03)
Visceral adiposity index	1.4 (0.8)	1.3 (0.8)	−0.01 (−0.23, 0.20)	0.03 (−0.21, 0.27)	1.29 (0.61)	1.32 (0.89)	0.03 (−0.42, 0.48)	0.01 (−0.47, 0.46)
	N (%)		Risk ratio (95% CI)	Risk ratio (95% CI)	N (%)		Risk ratio (95% CI)	Risk ratio (95% CI)
BMI (kg/m2)
Underweight (<18.5)	1 (1)	1 (1)	0.52 (0.03, 7.94)	1.02 (0.89, 1.16)	1 (5)	0 (0)	Not estimable	Not estimable
Normal (18.5–24.9)	13 (13)	26 (23)	1.00 (ref)	1.00 (ref)	4 (22)	13 (25)	1.00 (ref)	1.00 (ref)
Overweight (25–29.9)	23 (23)	26 (23)	0.78 (0.54, 1.13)	0.90 (0.63, 1.28)	3 (17)	13 (25)	1.17 (0.45, 3.03)	1.60 (0.74, 3.46)
Obese (≥30)	64 (63)	60 (53)	0.84 (0.71, 1.00)	0.96 (0.82, 1.14)	10 (56)	27 (51)	0.05 (0.63, 1.41)	0.80 (0.60, 1.07)

^*Adjusted for age, pre-pregnancy BMI, socio-economic status and postpartum time since delivery; reference – women without HIV for HIV models and EFV-based ART for post-conception ART models. ART – antiretroviral therapy, EFV – efavirenz, DTG – dolutegravir, BMI – body mass index. Bold indicate p-value<0.05

Cross-sectional postpartum DXA-derived body composition and body fat distribution

WWH had lower body composition and fat distribution compared to those without HIV (Table 3). However, after adjusting for age, pre-pregnancy BMI, SES and postpartum months since delivery, these differences were no longer significant. Among WHIV, initiation of DTG-based ART compared to EFV-based ART in pregnancy did not affect postpartum body composition and fat distribution.

Table 3.

Differences in postpartum fat distribution by HIV and post-conception ART regimen

	HIV status				Post-conception ART regimen
	Without HIV N = 13 Mean (± SD)	With HIV N = 52 Mean (± SD)	‘With HIV’ Unadjusted mean difference (95% CI)	‘With HIV’ Adjusted mean difference (95% CI)*	EFV-based N=13 Mean (± SD)	DTG-based N=29 Mean (± SD)	‘DTG-based ART’ Unadjusted mean difference (95% CI)*	‘DTG-based ART’ Adjusted mean difference (95% CI)*
Fat mass (kg)	45.9 (14.6)	34.2 (13.3)	−11.73 (−20.15, −3.31)	−6.24 (−14.32, 1.85)	30.8 (11.4)	35.7 (14.5)	4.89 (−4.30, 14.08)	−2.28 (−10.49, 5.93)
Fat-free mass (kg)	45.6 (6.5)	39.8 (6.9)	−5.84 (−10.09, −1.59)	−4.12 (−8.49, 0.25)	36.5 (5.01)	41.2 (7.5)	4.71 (0.09, 9.32)	−0.44 (−4.67, 3.79)
Body fat (%)	49.1 (5.9)	45.3 (6.4)	−3.80 (−7.69, 0.95)	−0.43 (−3.59, 4.45)	44.4 (7.6)	45.8 (6.3)	1.35 (−3.18, 5.89)	0.59 (−3.42, 4.61)
Trunk FM (kg)	21.3 (7.6)	15.6 (6.6)	−5.71 (−9.91, −1.51)	−2.88 (−6.76, 0.99)	14.0 (5.7)	16.1 (7.3)	2.05 (−2.56, 6.66)	−1.79 (−5.52, 1.94)
Arm FM (kg)	5.7 (2.6)	4.3 (2.3)	−1.45 (−2.90, −0.01)	−0.02 (−1.84, 1.89)	3.5 (1.4)	4.5 (2.1)	0.99 (−0.28, 2.27)	0.33 (−1.15, 1.82)
Leg FM (kg)	17.9 (6.1)	13.9 (5.1)	−3.96 (−7.27, −0.65)	−1.82 (−4.86, 1.22)	13.3 (4.8)	14.9 (5.4)	2.62 (−0.91, 6.16)	0.20 (−2.78, 3.19)
Android FM (kg)	3.7 (1.5)	2.7 (1.3)	−1.02 (−1.85, −0.19)	−0.36 (−1.09, 0.36)	2.3 (1.1)	2.8 (1.4)	0.51 (−0.38, 1.40)	−0.17 (−0.88, 0.55)
Gynoid FM (kg)	7.9 (2.4)	6.2 (2.2)	−1.70 (−3.10, −0.30)	−0.59 (−1.93, 0.75)	5.6 (2.2)	6.5 (2.3)	0.87 (−0.68, 2.43)	−0.14 (−1.46, 1.17)
Visceral adipose tissue (VAT, cm2)	166.7 (64.7)	117.4 (54.0)	−49.22 (−84.05, −14.38)	−19.38 (−47.03, 8.27)	99.6 (48.7)	121.8 (54.9)	22.27 (−13.58, 58.13)	−1.19 (−27.93, 25.55)
Subcutaneous adipose tissue (SAT, cm2)	551.9 (168.4)	442.2 (158.3)	−109.67 (−208.97, −10.37)	−19.12 (−114.29, 76.01)	411.0 (157.3)	456.8 (168.3)	45.85 (−65.50, 157.20)	−21.92 (−119.24, 75.41)
VAT-SAT ratio	0.29 (0.07)	0.26 (0.06)	−0.04 (−0.07, 0.01)	−0.01 (−0.06, 0.03)	0.23 (0.05)	0.26 (0.07)	0.03 (−0.01, 0.07)	0.02 (−0.02, 0.06)

^*Adjusted for age, pre-pregnancy BMI, socio-economic status and postpartum time since delivery; reference – women without HIV for HIV models and EFV-based ART for post-conception ART models. ART - antiretroviral therapy, EFV - efavirenz, DTG - dolutegravir, FFSTM – fat free soft tissue mass, FM - fat mass

DISCUSSION

In this cohort of women from a peri-urban setting in South Africa followed from pre-pregnancy to 6–12 months postpartum, we investigated longitudinal weight trajectories, and cross-sectional postpartum anthropometry, body composition and fat distribution by HIV status and post-conception ART class. HIV infection was associated with slower weight gain in pregnancy and reduced risk of postpartum weight gain. However, there were no significant differences by HIV status and post-conception ART class for the other anthropometry and DXA-derived adiposity measures. Despite this, over one-third of both WWH and without HIV gained weight postpartum, and over half had obese BMI postpartum.

Although weight gain in pregnancy is needed for optimal development of the foetus, gaining too much or too little can adversely affect both maternal and child health outcomes (2, 30). WWH were lighter at antenatal care entry and they proceeded to gain weight more slowly in pregnancy, and were less likely to gain weight postpartum, compared to women without HIV. In addition, at the postpartum period, WWH had lower values of other anthropometry and body composition or fat distribution measures, compared to women without HIV. However, all differences were attenuated after accounting for potential confounders including age, pre-pregnancy BMI, SES and postpartum months since delivery. These results indicate that HIV-related differences in these characteristics drive the differences in anthropometry and body composition or body fat distribution but not the HIV infection itself. On the other hand, it’s worth noting that WWH were compared to women without HIV that have considerably elevated measures of adiposity. Therefore, these findings of lower weight gain among WWH should not be equated to a higher risk of undernutrition, as it was the case in the pre-lifelong ART era (31).

Among WWH, several studies have reported increased weight and adiposity associated with DTG-based ART initiation (9, 10, 32, 33). However, the risk of metabolic disease depends on the body site or body fat depot in which the body fat is deposited. To our knowledge, there is no data on post-conception DTG-based ART and body composition or body fat distribution assessed using a gold standard technique, such as DXA, in SSA postpartum women. Although we observed slightly higher weight gain between pre-pregnancy and postpartum, as well as modest increases in overweight and hip circumference postpartum in DTG- vs EFV-based ART initiators, there was no evidence of significant differences. These findings differ from randomised controlled studies conducted in South Africa, Uganda and Botswana which found significantly higher weight gain among postpartum WWH that initiated DTG-based ART in pregnancy compared to other ART classes (11, 12). In our study we also found that initiation of DTG-based ART in pregnancy was not associated with postpartum trunk, visceral or android FM which are body fat depots linked to metabolic disease risk. This is in contrast to findings of greater increases in trunk FM in non-pregnant women on DTG-based ART followed to 144 weeks in the ADVANCE South African trial (18). A shorter follow-up time in our study might explain these discrepancies, highlighting a need for more studies in pregnant and postpartum women with longer follow-up periods.

For both WWH and without HIV, a notably high proportion entered pregnancy with obesity and gained weight and/or developed obesity postpartum. These rates are higher than those obtained in a study that was conducted in this setting 4 years ago (5), suggesting that postpartum obesity might be going up among WWH and without HIV in this population. For women residing in resource-limited settings, contributors to obesity are myriad, in part, involving the consumption of high-energy dense foods due to their affordability, sedentary lifestyle, as well as pregnancy weight gain and related postpartum weight retention/gain (4, 5, 34), in addition to the potential effect of ART regimen for WWH (3). Considering the greater baseline risk of metabolic co-morbidities such as T2D and cardiovascular diseases among WWH (35), high levels of postpartum weight gain and obesity, as observed among those without HIV, are likely to increase the burden of these metabolic complications over time. Regardless of HIV or ART effects, escalating levels of obesity among women of reproductive age in low-middle income countries is a public health concern that urgently needs attention.

Our study is not without limitations. Firstly, we note that there was a variation in the timing of the postpartum visit attendance which may have led to increased variability in anthropometry and adiposity measures assessed. However, to account for this we restricted the analysis to 6–12 months postpartum, and included time since delivery (in months) in the regression models. Secondly, by restricting to women with a visit between 6–12 months postpartum (mostly due to COVID-19-related restrictions), we may have induced selection bias. However, the sample included in this analysis had similar demographic characteristics as the full cohort, suggesting that possible selection bias is unlikely to meaningfully change our results. In addition, we had a small sample size for post-conception DTG-based vs EFV-based ART comparisons which may have limited the detection of significant differences and may help to account for differences with some previous studies suggesting higher postpartum weight gain for women on DTG (11, 12). Strengths of this study include that it is among the first to explore the effect of DTG-based ART on robust measures of body composition and body fat distribution among SSA followed across the peripartum period; thereby contributing to addressing evidence gap in this topic in high HIV-burdened settings.

Conclusions

In South African women assessed from pre-pregnancy to postpartum period, we observed no significant differences in anthropometry, body composition and fat distribution measures, including weight and body fat change by HIV status and post-conception ART class. Our findings, particularly those using objective measures of body composition and fat distribution, are in a relatively small cohort. Larger cohort studies are needed to confirm the impact of DTG-based ART on maternal body composition and fat distribution using robust measures such as DXA, particularly in low-middle income settings where the majority of WWH reside. Despite this, over one-third of WWH and without HIV gained weight relative to prior to pregnancy and half had obese BMI by 6–12 months postpartum. These findings underscore the need for interventions to support healthy weight gain in pregnancy and postpartum weight loss to minimise pregnancy-associated obesity which has potential to affect long-term maternal and child metabolic health.

Supplementary Material

Supplemental Figure 1. Maternal weight trajectory from pre-pregnancy to postpartum period by HIV status (A) and post-conception ART-regimen (B), the p-values indicate group differences in mean absolute weight at each visit. Distribution of postpartum total weight change (postpartum weight minus pre-pregnancy weight) by HIV status (C) and post-conception ART-regimen (D) is also shown. Abbrev: ART - antiretroviral therapy, EFV - efavirenz, DTG - dolutegravir.