Prevalence of obesity, hypertension and diabetes among people living with HIV in South Africa: a systematic review and meta-analysis.

BACKGROUND: HIV has become a manageable chronic condition due to the success and scale-up of antiretroviral therapy (ART). Globally, South Africa has the highest number of people living with HIV (PLHIV) and research evidence indicates that countries with the highest burden of PLHIV have a substantial burden of obesity, hypertension (HPT) and type 2 diabetes (T2D). We sought to summarize the burden of these three common NCDs among PLHIV in South Africa. METHODS: In this systematic review, multiple databases were searched for articles reporting on the prevalence of obesity, HPT, and T2D among PLHIV in South Africa published since journal inception until March 2022. A meta-analysis was conducted using random-effects models to obtain pooled prevalence estimates of the three NCDs. Heterogeneity was assessed using X2 test on Cochran's Q statistic. RESULTS: We included 32 studies, with 19, 22 and 18 studies reporting the prevalence of obesity, HPT, and T2D among PLHIV, respectively. The overall prevalence of obesity, HPT, and T2D was 23.2% [95% CI 17.6; 29.9], 25.5% [95% CI 15.6; 38.7], and 6.1% [95% CI 3.8; 9.7] respectively. The prevalence of obesity was significantly higher among women (P = 0.034) compared to men, however the prevalence of HPT and T2D did not differ by sex. The prevalence of each of the three NCDs did not differ significantly between rural, urban, and peri-urban areas. The prevalence of obesity and T2D was higher in studies conducted between 2013 and 2022 compared to studies conducted between 2000 and 2012, while the prevalence of HPT was higher between 2000 and 2012 compared to between 2013 and 2022. CONCLUSIONS: These findings suggest that South Africa is experiencing a syndemic of NCDs among people PLHIV highlighting the need to increase cost-effective interventions and management strategies that involve integrated HIV and NCD care in the South African setting.

Maternal weight trajectories and associations with infant growth in South African women.

BACKGROUND: Despite the close relationship between pre-pregnancy body mass index (BMI), gestational weight gain (GWG) and postpartum weight (PPW), these factors are often studied separately. There are no data characterising longitudinal weight trajectories among pregnant and postpartum women in urban African populations. We examined maternal weight trajectories from pregnancy through to 12 months postpartum, factors associated with higher weight trajectory class membership and associations of weight trajectories with infant growth at 12 months. METHODS: Data from 989 women were examined for weight trajectories from first antenatal care visit in pregnancy to 12 months postpartum using latent-class growth models. Baseline factors associated with class membership were assessed using multinomial logistic regression. Of the enrolled women, 613 of their infants were assessed for growth at 12 months. Anthropometry measurements for mothers and infants were conducted by a trained study nurse. Associations between maternal weight trajectory class and infant weight-for-age (WAZ), length-for-age (LAZ), weight-for-length (WLZ) at 12 months of age were analysed using linear regression. RESULTS: Four distinct classes of maternal weight trajectories were identified. The classes included consistent low (29%), consistent medium (37%), medium-high (24%) and consistent high (10%) trajectories. Similar to trends observed with medium-high trajectory, baseline factors positively associated with consistent high class membership included age (OR 1.05, 95% CI 1.01-1.09), pre-pregnancy BMI (OR 2.24, 95% CI 1.97-2.56), stage 1 hypertension (OR 3.28, 95% CI 1.68-6.41), haemoglobin levels (OR 1.39, 95% CI 1.11-1.74) and parity (OR 1.39, 95% CI 1.15-1.67); living with HIV (OR 0.47, 95% CI 0.30-0.74) was inversely associated. In adjusted analyses, compared to consistent medium weight trajectory, consistent low weight trajectory (mean difference -0.41, 95% CI -0.71;-0.12) was associated with decreased, and consistent high weight trajectory (mean difference 1.21, 95% CI 0.59-1.83) with increased infant WAZ at 12 months of age. CONCLUSION: Identification of unique longitudinal weight trajectory groupings might inform comprehensive efforts targeted at improving healthy maternal weight and infant outcomes.

Pregnancy outcomes in women living with HIV and HIV-negative women in South Africa: Cohort analysis based on bias-corrected gestational age.

BACKGROUND: Antiretroviral therapy (ART) use during pregnancy may be associated with adverse outcomes, but findings have been inconsistent, at least in part due to unreliably estimated gestational age. OBJECTIVE: To quantify the association between HIV status, ART initiation timing and adverse birth outcomes, with reliably assessed gestational age at booking, in a public sector primary care facility in Cape Town, South Africa. METHODS: Pregnant women, HIV-negative or living with HIV (WLHIV), were enrolled at first antenatal care visit and followed through delivery. Ultrasound-assessed gestational age was deemed the gold standard. Based on quantitative bias analysis for outcome misclassification, gestational age by non-ultrasound assessment was corrected using multiple overimputation, which deals with missing data and measurement error simultaneously. Using bias-corrected gestational age, birth outcomes were compared between WLHIV and HIV-negative women, and among WLHIV who initiated ART before versus during pregnancy, further divided into trimesters. RESULTS: Of 3952 women enrolled, 37% were WLHIV (mostly using tenofovir + emtricitabine + efavirenz). Last menstrual period (LMP)-based gestational age was identified to be biased, and LMP measures were thus corrected using multiple overimputation. Comparing WLHIV and HIV-negative women, adjusted risk ratio (aRR) of overall pregnancy loss was 1.26 (95% confidence interval [CI] 0.98, 1.61); aRR of preterm delivery was 1.02 (95% CI 0.88, 1.20); aRR of small for gestational age infants was 1.43 (95% CI 1.14, 1.80). Among WLHIV, outcomes were similar by ART initiation timing. CONCLUSIONS: In this routine care cohort, risk of SGA, and possibly of pregnancy loss, was increased in WLHIV compared with HIV-negative women, with no evidence of increased risk of preterm delivery. Further research is needed to improve mechanistic understanding of the contribution of ART to adverse birth outcomes to optimize treatment for pregnant WLHIV and ensure optimal maternal and infant outcomes.

Relationship between pre-pregnancy maternal body mass index and infant weight trajectories in HIV-exposed and HIV-unexposed infants.

BACKGROUND: Maternal HIV and antiretroviral therapy (ART) exposure in utero may influence infant weight, but the contribution of maternal y body mass index (BMI) to early life overweight and obesity is not clear. OBJECTIVE: To estimate associations between maternal BMI at entry to antenatal care (ANC) and infant weight through approximately 1 year of age and to evaluate whether associations were modified by maternal HIV status, maternal HIV and viral load, breastfeeding intensity through 6 months or timing of entry into ANC. METHODS: We followed HIV-uninfected and -infected pregnant women initiating efavirenz-based ART from first antenatal visit through 12 months postpartum. Infant weight was assessed via World Health Organization BMI and weight-for-length z-scores (WLZ) at 6 weeks, 3, 6, 9 and 12 months. We used multivariable linear mixed-effects models to estimate associations between maternal BMI and infant z-scores over time. RESULTS: In 861 HIV-uninfected infants (454 HIV-exposed; 407 HIV-unexposed), nearly 20% of infants were overweight or obese by 12 months of age, regardless of HIV exposure status. In multivariable analyses, increasing maternal BMI category was positively associated with higher infant BMIZ and WLZ scores between 6 weeks and 12 months of age and did not differ by HIV exposure status. However, HIV-exposed infants had slightly lower BMIZ and WLZ trajectories through 12 months of age, compared with HIV-unexposed infants across all maternal BMI categories. Differences in BMIZ and WLZ scores by HIV exposure were not explained by timing of entry into ANC or maternal viral load pre-ART initiation, but z-scores were slightly higher for HIV-exposed infants who were predominantly or exclusively versus partially breastfed. CONCLUSIONS: These findings suggest maternal BMI influences early infant weight gain, regardless of infant HIV exposure status. Intervention to reduce maternal BMI may help to address growing concerns about obesity among HIV-uninfected children.

Determining antenatal medicine exposures in South African women: a comparison of three methods of ascertainment.

BACKGROUND: In the absence of clinical trials, data on the safety of medicine exposures in pregnancy are dependent on observational studies conducted after the agent has been licensed for use. This requires an accurate history of antenatal medicine use to determine potential risks. Medication use is commonly determined by self-report, clinician records, and electronic pharmacy data; different data sources may be more informative for different types of medication and resources may differ by setting. We compared three methods to determine antenatal medicine use (self-report, clinician records and electronic pharmacy dispensing records [EDR]) in women attending antenatal care at a primary care facility in Cape Town, South Africa in a setting with high HIV prevalence. METHODS: Structured, interview-administered questionnaires recorded self-reported medicine use. Data were collected from clinician records and EDR on the same participants. We determined agreement between these data sources using Cohen's kappa and, lacking a gold standard, used Latent Class Analysis to estimate sensitivity, specificity and positive predictive value (PPV) for each data source. RESULTS: Between 55% and 89% of 967 women had any medicine use documented depending on the data source (median number of medicines/participant = 5 [IQR 3-6]). Agreement between the datasets was poor regardless of class except for antiretroviral therapy (ART; kappa 0.6-0.71). Overall, agreement was better between the EDR and self-report than with either dataset and the clinician records. Sensitivity and PPV were higher for self-report and the EDR and were similar for the two. Self-report was the best source for over-the-counter, traditional and complementary medicines; clinician records for vaccines and supplements; and EDR for chronic medicines. CONCLUSIONS: Medicine use in pregnancy was common and no single data source included all the medicines used. ART was the most consistently reported across all three datasets but otherwise agreement between them was poor and dependent on class. Using a single data collection method will under-estimate medicine use in pregnancy and the choice of data source should be guided by the class of the agents being investigated.

Growth patterns of infants with in- utero HIV and ARV exposure in Cape Town, South Africa and Lusaka, Zambia.

BACKGROUND: Infants born HIV-exposed yet remain uninfected (HEU) are at increased risk of poorer growth and health compared to infants born HIV-unexposed (HU). Whether maternal antiretroviral treatment (ART) in pregnancy ameliorates this risk of poorer growth is not well understood. Furthermore, whether risks are similar across high burden HIV settings has not been extensively explored. METHODS: We harmonized data from two prospective observational studies conducted in Cape Town, South Africa, and Lusaka, Zambia, to compare weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length (WLZ) Z-scores between infants who were HEU and HU, converting infant anthropometric measures using World Health Organisation Growth Standards adjusted for age and sex. Linear mixed effects models were fit to identify risk factors for differences in anthropometrics at 6-10 weeks and 6 months by infant HIV exposures status and by timing of exposure to maternal ART, either from conception or later in gestation. RESULTS: Overall 773 mother-infant pairs were included across two countries: women living with HIV (WLHIV), 51% (n = 395) with 65% on ART at conception and 35% initiating treatment in pregnancy. In linear mixed effects models, WAZ and WLZ at 6-10 weeks were lower among infants who were HEU vs HU [ß = - 0.29 (95% CI: - 0.46, - 0.12) and [ß = - 0.42 (95% CI: - 0.68, - 0.16)] respectively after adjusting for maternal characteristics and infant feeding with a random intercept for country. At 6 months, LAZ was lower [ß = - 0.28 CI: - 0.50, - 0.06)] among infants who were HEU, adjusting for the same variables, with no differences in WAZ and WLZ. Within cohort evaluations identified different results with higher LAZ among infants who were HEU from Zambia at 6-10 weeks, [ß = + 0.34 CI: + 0.01, + 0.68)] and lower LAZ among infants who were HEU from South Africa [ß = - 0.30 CI: - 0.59, - 0.01)] at 6 months, without other anthropometric differences at either site. CONCLUSION: Infant growth trajectories differed by country, highlighting the importance of studying contextual influences on outcomes of infants who were HEU.

Low Immune Activation in Early Pregnancy Is Associated With Preterm But Not Small-for-gestational-age Delivery in Women Infected With Human Immunodeficiency Virus Initiating Antiretroviral Therapy in Pregnancy: A Prematurity Immunology in HIV-infected Mothers and their Infants Study (PIMS) Case-control Study in Cape Town, South Africa.

BACKGROUND: Mechanisms underlying an association between human immunodeficiency virus (HIV) or antiretroviral therapy (ART) during pregnancy with risk of preterm delivery (PTD) and small-for-gestational-age (SGA) remain unclear. We explored the association between cellular immune activation and PTD or SGA in women with HIV initiating ART during or before pregnancy. METHODS: Women with HIV enrolled at median 15 weeks' gestation, were analyzed for immune markers, and matched on ART initiation timing (15 women initiated pre- and 15 during pregnancy). There were 30 PTD (delivery <37 weeks), 30 SGA (weight for age ≤10th percentile) cases, and 30 controls (term, weight for gestational age >25th percentile) as outcomes. Lymphocytes, monocytes, and dendritic cell populations and their activation status or functionality were enumerated by flow cytometry. RESULTS: PTD cases initiating ART in pregnancy showed decreased CD8+ T cell, monocyte, and dendritic cell activation; increased classical (CD14+CD16-) and intermediate (CD14+CD16+) monocyte frequencies; and decreased inflammatory monocytes (CD14dimCD16+) compared with SGA cases and term controls (all P < .05). Allowing for baseline viral load, the immune markers remained significantly associated with PTD but only in women initiating ART in pregnancy. Lower monocyte activation was predictive of PTD. TLR ligand-induced interferon-α and macrophage inflammatory protein-1ß levels in monocytes were significantly lower in PTD women initiating ART in pregnancy. CONCLUSION: Low immune activation, skewing toward anti-inflammatory monocytes, and lower monocyte cytokine production in response to TLR ligand stimulation were associated with PTD but not SGA among women initiating ART in, but not before, pregnancy, suggesting immune anergy to microbial stimulation as a possible underlying mechanism for PTD in women initiating ART in pregnancy.

Lower birth weight-for-age and length-for-age z-scores in infants with in-utero HIV and ART exposure: a prospective study in Cape Town, South Africa.

BACKGROUND: Successful scale-up of antiretroviral therapy (ART) during pregnancy has minimized infant HIV acquisition, and over 1 million infants are born HIV-exposed but uninfected (HEU), with an increasing proportion also exposed in utero to maternal ART. While benefits of ART in pregnancy outweigh risks, some studies have reported associations between in utero ART exposure and impaired fetal growth, highlighting the need to identify the safest ART regimens for use in pregnancy. METHODS: We compared birth anthropometrics of infants who were HEU with those HIV-unexposed (HU) in Cape Town, South Africa. Pregnant women had gestational age assessed by ultrasound at enrolment. Women living with HIV were on ART (predominately tenofovir-emtricitabine-efavirenz) either prior to conception or initiated during pregnancy. Birth weights and lengths were converted to weight-for-age (WAZ) and length-for-age (LAZ) z-scores using Intergrowth-21st software. Linear regression was used to compare mean z-scores adjusting for maternal and pregnancy characteristics. RESULTS: Among 888 infants, 49% (n = 431) were HEU and 51% (n = 457) HU. Of 431 HEU infants, 62% (n = 268) were exposed to HIV and antiretrovirals (ARVs) from conception and 38% (n = 163) were exposed to ARVs during gestation but after conception (median fetal ARV exposure of 21 weeks [IQR; 17-26]). In univariable analysis, infants who were HEU had lower mean WAZ compared with HU [ß = - 0.15 (95% Confidence Interval (CI): - 0.28, - 0.020)]. After adjustment for maternal age, gravidity, alcohol use, marital and employment status the effect remained [adjusted ß - 0.14 (95%CI: - 0.28, - 0.01]. Similar differences were noted for mean LAZ in univariable [ß - 0.20 (95%CI: - 0.42, - 0.01] but not multivariable analyses [adjusted ß - 0.18 (95%CI: - 0.41, + 0.04] after adjusting for the same variables. Mean WAZ and LAZ did not vary by in utero ARV exposure duration among infants who were HEU. CONCLUSION: In a cohort with high prevalence of ART exposure in pregnancy, infants who were HEU had lower birth WAZ compared with those HU. Studies designed to identify the mechanisms and clinical significance of these disparities, and to establish the safest ART for use in pregnancy are urgently needed.

Association between food intake and obesity in pregnant women living with and without HIV in Cape Town, South Africa: a prospective cohort study.

BACKGROUND: Although global nutrition/dietary transition resulting from industrialisation and urbanisation has been identified as a major contributor to widespread trends of obesity, there is limited data in pregnant women, including those living with HIV in South Africa. We examined food-based dietary intake in pregnant women with and without HIV at first antenatal care (ANC) visit, and associations with maternal overweight/obesity and gestational weight gain (GWG). METHODS: In an urban South African community, consecutive women living with (n = 479) and without (n = 510) HIV were enrolled and prospectively followed to delivery. Interviewer-administered non-quantitative food frequency questionnaire was used to assess dietary intake (starch, protein, dairy, fruits, vegetables, legumes, oils/fats) at enrolment. Associations with maternal body mass index (BMI) and GWG were examined using logistic regression models. RESULTS: Among women (median age 29 years, IQR 25-34), the prevalence of obesity (BMI ≥ 30 kg/m2) at first ANC was 43% and that of excessive GWG (per IOM guidelines) was 37% overall; HIV prevalence was 48%. In women without HIV, consumption of potato (any preparation) (aOR 1.98, 95% CI 1.02-3.84) and pumpkin/butternut (aOR 2.13, 95% CI 1.29-3.49) for 1-3 days a week increased the odds of overweight/obesity compared to not consuming any; milk in tea/coffee (aOR 6.04, 95% CI 1.37-26.50) increased the odds of excessive GWG. Consumption of eggs (any) (aOR 0.52, 95% CI 0.32-0.86) for 1-3 days a week reduced the odds of overweight/obesity while peanut and nuts consumption for 4-7 days a week reduced the odds (aOR 0.34, 95% CI 0.14-0.80) of excessive GWG. In women with HIV, consumption of milk/yoghurt/maas to drink/on cereals (aOR 0.35, 95% CI 0.18-0.68), tomato (raw/cooked) (aOR 0.50, 95% CI 0.30-0.84), green beans (aOR 0.41, 95% CI 0.20-0.86), mixed vegetables (aOR 0.49, 95% CI 0.29-0.84) and legumes e.g. baked beans, lentils (aOR 0.50, 95% CI 0.28-0.86) for 4-7 days a week reduced the odds of overweight/obesity; tomato (raw/cooked) (aOR 0.48, 95% CI 0.24-0.96) and mixed vegetables (aOR 0.38, 95% CI 0.18-0.78) also reduced the odds of excessive GWG. CONCLUSIONS: Diet modification may promote healthy weight in pregnant women living with and without HIV.

Elevated body mass index during pregnancy and gestational weight gain in HIV-infected and HIV-uninfected women in Cape Town, South Africa: association with adverse birth outcomes.

OBJECTIVES: To examine the association between maternal body mass index (BMI) and gestational weight gain (GWG) and adverse birth outcomes in HIV-infected and HIV-uninfected women. METHODS: In an urban South African community, 2921 consecutive HIV-infected and HIV-uninfected pregnant women attending primary healthcare services were assessed at their first antenatal visit. A subset of HIV-infected women enrolled in a longitudinal study was assessed three times during pregnancy. All women had birth outcome data from medical records and study questionnaires. In analyses, the associations between BMI, GWG, maternal factors and adverse birth outcomes were assessed with logistic regression models. RESULTS: The estimated pre-pregnancy BMI median was 29 kg/m2 (IQR, 24-34) overall, 29 kg/m2 (IQR, 24-34) for HIV-uninfected and 28 kg/m2 (IQR, 24-34) for HIV-infected women; HIV prevalence was 38%. In adjusted models, increased BMI in the overall cohort was positively associated with age, haemoglobin and parity at first antenatal visit. Maternal obesity was associated with increased likelihood of having high birthweight (aOR 2.54, 95% CI 1.39-4.66) and large size for gestational age (aOR 1.66, 95% CI 1.20-2.31) infants. In the subset cohort, GWG was associated with increased likelihood of spontaneous preterm delivery (aOR 4.35, 95% CI 1.55-12.21) and high birthweight (aOR 3.00, 95% CI 1.22-7.34) infants. CONCLUSION: Obesity during pregnancy is prevalent in this setting and appears associated with increased risk of adverse birth outcomes in both HIV-infected and HIV-uninfected women. Weight management interventions targeting women of child-bearing age are needed to promote healthy pregnancies and reduce adverse birth outcomes.

OBJECTIFS: Examiner l'association entre l'indice de masse corporelle maternelle (IMC) et le gain de poids gestationnel (GPG) et les résultats de naissance défavorables chez les femmes infectées et non infectées par le VIH. MÉTHODES: Dans une communauté urbaine sud-africaine, 2921 femmes enceintes consécutives infectées et non infectées par le VIH visitant les services de soins de santé primaires ont été évaluées lors de leur première visite prénatale. Un sous-ensemble de femmes infectées par le VIH inscrites à une étude longitudinale a été évalué trois fois pendant la grossesse. Toutes les femmes avaient des données sur les résultats à la naissance provenant des dossiers médicaux et des questionnaires d'étude. Dans les analyses, les associations entre l'IMC, le GPG, les facteurs maternels et les résultats de naissance défavorables ont été évalués en utilisant des modèles de régression logistique. RÉSULTATS: L'IMC médian estimé avant la grossesse était globalement de 29 kg/m2 (IQR, 24-34) pour les femmes non infectées par le VIH et 28 kg/m2 (IQR, 24 -34) pour celles infectées par le VIH; La prévalence du VIH était de 38%. Dans les modèles ajustés, l'augmentation de l'IMC dans la cohorte globale était positivement associée à l'âge, à l'hémoglobine et à la parité lors de la première visite prénatale. L'obésité maternelle a été associée à une augmentation de la probabilité d'avoir un nourrisson avec un poids élevé à la naissance (ORa 2,54, IC95%: 1,39-4,66) et une grande taille pour l'âge gestationnel (ORa 1,66, IC95%: 1,20-2,31). Dans la cohorte du sous-ensemble, le GPG était associé à une probabilité accrue d'accouchement prématuré spontané (aOR 4,35, IC95%: 1,55-12,21) et à des nourrissons avec un poids de naissance élevé (aOR 3,00, IC95%: 1,22-7,34). CONCLUSION: L'obésité pendant la grossesse est répandue dans ce contexte et semble associée à un risque accru d'accouchements défavorables chez les femmes infectées et non infectées par le VIH. Des interventions de prise en charge du poids ciblant les femmes en âge de procréer sont nécessaires pour promouvoir des grossesses saines et réduire les issues de naissance défavorables.

Does HIV infection modify the relationship between pre-pregnancy body mass index and adverse birth outcomes?

BACKGROUND: South Africa faces dual epidemics of HIV and obesity; however, little research has explored whether HIV status influences associations between pre-pregnancy body mass index (BMI) and adverse birth outcomes. OBJECTIVES: To examine associations between pre-pregnancy body mass index (BMI) and adverse birth outcomes, and if they differ by HIV status. METHODS: We followed HIV-uninfected and -infected pregnant women initiating antiretroviral therapy (ART) from first antenatal visit through delivery. HIV-infected women initiated ART (tenofovir-emtricitabine/lamivudine-efavirenz) in pregnancy. Estimated pre-pregnancy BMI (kg/m2 ) was categorised as underweight (<18.5), normal (18.5-24.9), overweight (25.0-29.9), and obese (≥30.0). We used modified Poisson regression to estimate risk ratios (RR) for associations between pre-pregnancy BMI and adverse birth outcomes and explored modification by HIV status. RESULTS: Among 1116 women (53% HIV-infected), 44% of HIV-uninfected women and 36% of HIV-infected women were classified as obese; 4% of women were underweight. Overall, 12% of infants were delivered preterm (<37 weeks), 10% small for gestational age (SGA, <10th percentile), and 9% large for gestational age (LGA, >90th percentile). Compared to HIV-uninfected women, HIV-infected women on ART had less LGA (5% vs 13%) but more SGA (12% vs 8%), and a similar proportion of preterm (13% vs 11%) infants. Pre-pregnancy BMI was not associated with preterm birth. Among HIV-uninfected women, obesity modestly increased the risk of LGA (RR 1.34, 95% confidence interval [CI] 0.82, 2.19), and underweight modestly elevated the risk of SGA (RR 1.66, 95% CI 0.79, 3.46). These associations were attenuated among HIV-infected women (RR 1.07, 95% CI 0.44, 2.64 for LGA, and RR 1.34, 95% CI 0.49, 3.64 for SGA). CONCLUSIONS: In this urban African setting of high HIV prevalence, pre-pregnancy obesity was common and did not vary by HIV status. In HIV-uninfected women, obesity increased the risk of LGA and being underweight the risk of SGA, compared with among HIV-uninfected women.

Blood pressure trajectories during pregnancy and associations with adverse birth outcomes among HIV-infected and HIV-uninfected women in South Africa: a group-based trajectory modelling approach.

BACKGROUND: High blood pressure (BP) late in pregnancy is associated with preterm delivery (PTD); BP has also been associated with HIV and antiretroviral therapy (ART), but whether the relationship between BP assessed longitudinally over pregnancy and PTD and low birthweight (LBW) is modified by HIV/ART is unclear. We hypothesise the presence of distinctive BP trajectories and their association with adverse birth outcomes may be mediated by HIV/ART status. METHODS: We recruited pregnant women at a large primary care facility in Cape Town. BP was measured throughout pregnancy using automated monitors. Group-based trajectory modelling in women with ≥3 BP measurements identified distinct joint systolic and diastolic BP trajectory groups. Multinomial regression assessed BP trajectory group associations with HIV/ART status, and Poisson regression with robust error variance was used to assess risk of PTD and LBW. RESULTS: Of the 1583 women in this analysis, 37% were HIV-infected. Seven joint trajectory group combinations were identified, which were categorised as normal (50%), low normal (25%), high normal (20%), and abnormal (5%). A higher proportion of women in the low normal group were HIV-infected than HIV-uninfected (28% vs. 23%), however differences were not statistically significant (RR 1.27, 95% CI 0.98-1.63, reference category: normal). In multivariable analyses, low normal trajectory (aRR0.59, 0.41-0.85) was associated with decreased risk of PTD, while high normal (aRR1.48, 1.12-1.95) and abnormal trajectories (aRR3.18, 2.32-4.37) were associated with increased risk of PTD, and abnormal with increased risk of LBW (RR2.81, 1.90-4.15). CONCLUSIONS: While HIV/ART did not appear to mediate the BP trajectories and adverse birth outcomes association, they did provide more detailed insights into the relationship between BP, PTD and LBW for HIV-infected and uninfected women.

Measurement of ß-oxidation capacity of biological samples by respirometry: a review of principles and substrates.

Oxidation of fatty acids is a major source of energy in the heart, liver, and skeletal muscle. It can be measured accurately using respirometry in isolated mitochondria, intact cells, and permeabilized cells or tissues. This technique directly measures the rate of oxygen consumption or flux at various respiratory states when appropriate substrates, uncouplers, and inhibitors are used. Acylcarnitines such as palmitoylcarnitine or octanoylcarnitine are the commonly used substrates. The ß-oxidation pathway is prone to feedforward inhibition resulting from accumulation of short-chain acyl-CoA and depletion of CoA, but inclusion of malate or carnitine prevents accumulation of these intermediaries and CoA depletion.

Cardiometabolic Health in Pregnancy and Postpartum: Findings From a Prospective Cohort Study in South Africa.

Background: The cardiometabolic impact of HIV infection and treatment with antiretroviral therapy (ART) in pregnancy and the postpartum period remains unclear. Methods: We enrolled pregnant persons with (PHIV) and without HIV in Cape Town, South Africa, who were ≥18 years old at 24-28 weeks' gestation and followed them up to 32 months postpartum. We estimated associations between HIV status and cardiometabolic risk including body mass index (BMI), obesity (BMI ≥30 kg/m2), blood pressure (BP; elevated systolic BP ≥130 and/or diastolic ≥85 mmHg), lipid levels, and metabolic syndrome according to the Joint Interim Statement criteria using multivariable log binomial or linear regression models. Subgroup analyses compared PHIV on efavirenz (EFV)- vs dolutegravir (DTG)-based ART. Results: Among 400 participants (n = 200 without HIV, n = 200 PHIV), 52% had prepregnancy obesity and 9% had elevated BP. Postpartum, 57% were classified with obesity, 31% had elevated BP, and 29% had metabolic syndrome. In multivariable analyses, HIV was associated with a lower BMI prepregnancy but not postpartum; however, mean indices were in the obese range regardless of HIV status. Neither BMI nor obesity prepregnancy or postpartum differed by ART regimen. Among PHIV, participants on DTG had higher levels of elevated BP in pregnancy and postpartum, compared with PHIV on EFV. Conclusions: We observed high levels of obesity, elevated BP, and metabolic syndrome in the perinatal period but few differences by HIV status. Participants on DTG may be more likely to have elevated BP in pregnancy and postpartum. Monitoring of cardiometabolic health for pregnant persons on DTG is warranted.

Measurement of body composition in postpartum South African women living with and without HIV infection.

Background: While several methodologies are available to measure adiposity, few have been validated in sub-Saharan African (SSA) and none in postpartum African women living with HIV (WLHIV). We compared bioelectrical impendence analysis (BIA) and air displacement plethysmography (ADP) against dual x-ray absorptiometry (DXA) in South African women and examined differences by HIV and body mass index (BMI) status. Methods: Lin's concordance correlation coefficient (CCC) test was used to examine fat mass (FM), fat free mass (FFM), and total body fat percent (%BF) difference between BIA vs. DXA, and ADP vs. DXA in women living with HIV (n = 57) and without HIV (n = 25). The Bland Altman test was used to assess mean differences and the direction of bias. Results: The median age was 31 years (IQR, 26-35) and months postpartum were 11 (IQR, 7-16), 44% of the women had obesity. Lin's CCC for BIA and ADP vs. DXA were both 0.80 for %BF and 0.97 for FM, and 0.86 and 0.80 for FFM, respectively. Mean differences (DXA-BIA and ADP estimates) were 0.22 ± 4.54% (p = 0.54) and 3.35 ± 3.27% (p < 0.01) for %BF, -0.82 ± 3.56 kg (p = 0.06) and 1.43 ± 2.68 kg (p = 0.01) for FM, -1.38 ± 3.61 kg (p = 0.01) and - 3.34 ± 2.37 kg (p < 0.01) for FFM, respectively. BIA overestimated %BF in WLHIV and underestimated it in women with obesity. Conclusion: Body composition measurements using BIA and ADP correlated well with DXA, thereby providing alternative, safe tools for measuring postpartum FM and FFM in SSA women, including WLHIV.

Inflammatory markers in pregnancy are associated with postpartum weight in South African women living with HIV on antiretroviral therapy.

BACKGROUND: Postpartum weight (PPW) contributes to long-term obesity, a growing concern in persons with HIV (PWH). We investigated whether inflammatory markers in pregnancy may be involved in postpartum (PP) obesity in PWH. SETTING: A total of 57 pregnant PWH enrolled at ≤14 weeks gestation (T1) in Gugulethu antenatal care clinic in Cape Town and followed through 48 weeks PP were included. METHODS: Plasma soluble (s) CD14, sCD163, leptin, tumour necrosis factor receptor 1 (TNFR-1), resistin, adiponectin, and interleukin-6 (IL-6) were assayed in duplicate using the Luminex platform. We considered each inflammatory marker at T1 (n=57) and T3 (29-36 weeks gestation, n=31) as a separate exposure of interest. Linear mixed effects models were fit to examine whether each exposure was associated with average PPW and PPW trajectories; linear regression was used for associations with PPW change between T1 and 48 weeks. RESULTS: Median age was 32 years (IQR, 29-35), 98% were multigravida, and 49% had a BMI≥30 kg/m2. Higher T1 sCD14 levels were associated with higher average weight through 48 weeks PP (ß = 0.002, p=0.04), and T3 sCD14 with higher PPW gain (ß = 0.007, p=0.04). Leptin (ß = 0.414, p<0.01), TNFR-1 (ß = 11.048, p<0.01) and resistin (ß = 0.714, p=0.01) at T3 were associated with higher average PPW, and IL-6 (ß = 2.266, p=0.02) with PPW gain. CONCLUSION: These findings suggest that low-grade inflammation in pregnancy may play a role in postpartum obesity, pointing to potential mechanisms with implications for long-term cardiometabolic health in PWH.

An observational cohort study to investigate the impact of dolutegravir in pregnancy and its obesogenic effects on the metabolic health of women living with HIV and their children: Study protocol.

INTRODUCTION: Dolutegravir (DTG)-based antiretroviral therapy is the World Health Organization's preferred first-line regimen for all persons with HIV, including pregnant women. While DTG has been implicated as an obesogen associated with greater weight gain compared to other antiretrovirals, there is a paucity of data in pregnant women and their children. The Obesogenic oRigins of maternal and Child metabolic health Involving Dolutegravir (ORCHID) study is investigating associations between DTG, weight gain, and metabolic outcomes in the context of HIV. MATERIALS & METHODS: ORCHID is a prospective observational study taking place in Cape Town, South Africa (NCT04991402). A total of 1920 pregnant women with and without HIV infection are being followed from ≤18 weeks gestational age to 24 months postpartum with their children. Participants attend eleven study visits: 3 antenatal, delivery, and 7 postnatal visits. Several embedded sub-studies address specific scientific aims. Primary outcome measurements in mothers include anthropometry, blood pressure, body composition, dysglycemia, insulin resistance (IR), and dyslipidemia. Other maternal measures include demographics, resting energy expenditure, viral load, physical activity, dietary intake, hepatic steatosis, and repository specimens. Sub-study measurements include markers of adipose inflammation, gut integrity, and satiety/hunger, subcutaneous adipose tissue morphology and mitochondrial function, and metabolomics. Primary outcome measurements in children include anthropometry, adipose tissue mass, dysglycemia, IR, and dyslipidemia. Other variables include fetal growth, birth outcomes, medical/breastfeeding history, caloric intake, neurodevelopment, and repository specimens. Sub-study measurements include metabolites/lipid subspecies in umbilical cord blood, as well as breast milk composition and DTG exposure. DISCUSSION: ORCHID will play a pivotal role in defining obesogenic mechanisms and clinical consequences of DTG use in pregnancy in women with HIV and their children. It will provide insights into metabolic disease risk reduction in the context of HIV/DTG, identify intervention targets, and inform public health approaches to diminish chronic metabolic co-morbidities for women and children.

Gestational weight gain and adverse birth outcomes in South African women with HIV on antiretroviral therapy and without HIV: a prospective cohort study.

INTRODUCTION: Outside of pregnancy, evidence shows that persons with HIV initiating or switching to dolutegravir (DTG)-based antiretroviral therapy (ART) experience greater weight gain compared to those on other ART classes. However, there are few data on the impact of DTG-based ART on gestational weight gain (GWG) in sub-Saharan Africa where HIV is most common. According to the National Academy of Medicine (NAM), GWG below and above NAM guidelines is associated with adverse birth outcomes. Therefore, the objective of this study was to describe GWG by HIV status and ART regimen, and examine the associations with adverse birth outcomes. METHODS: We enrolled pregnant women with HIV (WHIV) and without HIV (≥18 years) in a peri-urban primary healthcare facility in Cape Town, South Africa between 2019 and 2022. GWG was study-measured at 24-28 (baseline) and 33-38 weeks gestation and converted to GWG rate (kg/week) in accordance with NAM guidelines. GWG z-scores were generated using the INTEGROWTH-21 and US standards to account for differing lengths of gestation. Birth outcome data were obtained from medical records. Associations of GWG z-score with adverse birth outcomes were assessed using multivariable linear or log-binomial regression. RESULTS: Among 292 participants (48% WHIV), median age was 29 years (IQR, 25-33), median pre-pregnancy body mass index (BMI) was 31 kg/m2 (IQR, 26-36) and 20% were primiparous at baseline. The median weekly rate of GWG was 0.30 kg/week (IQR, 0.12-0.50), 35% had GWG below NAM standards (59% WHIV) and 48% had GWG above NAM standards (36% WHIV). WHIV gained weight more slowly (0.25 vs. 0.37 kg/week, p<0.01) than women without HIV. Weekly rate of GWG did not differ by ART regimen (DTG-based ART 0.25 vs. efavirenz-based ART 0.27 kg/week, p = 0.80). In multivariable analyses, GWG z-score was positively associated with continuous birth weight (mean difference = 68.53 95% CI 8.96, 128.10) and categorical high birth weight of >4000 g (RR = 2.18 95% CI 1.18, 4.01). CONCLUSIONS: Despite slower GWG among WHIV, nearly half of all women gained weight faster than recommended by the NAM. GWG was positively associated with infant birth weight. Interventions to support healthy GWG in sub-Saharan Africa are urgently needed.

Associations of HIV and antiretroviral therapy with gestational diabetes in South Africa.

OBJECTIVE: To estimate associations of HIV status and antiretroviral (ART) regimen with gestational diabetes (GDM) and postpartum glucose metabolism. DESIGN: Prospective cohort study. METHODS: We enrolled pregnant persons with HIV (PWH) and without HIV in Cape Town, South Africa who were at least 18 years of age at 24-28 weeks' gestation and followed up to 26 months postpartum. Participants were tested for GDM in pregnancy and for diabetes postpartum using a 75 g 2 h oral glucose tolerance test (OGTT) and diagnosed via WHO criteria. We estimated associations of HIV status and ART regime [efavirenz (EFV) versus dolutegravir (DTG)] with GDM and postpartum impaired glucose metabolism using multivariable log binomial or linear regression models. RESULTS: Among 397 participants [median age 30 (interquartile range (IQR) 25-34; n  = 198 without HIV, n  = 199 PWH], the prevalence of GDM was 6% (9 PWH versus 3% without HIV). In multivariable analyses, PWH were at higher risk of GDM [risk ratio (RR) 3.9, 95% confidence interval (CI) 1.4-10.7] after adjustment for prepregnancy BMI and other confounders. GDM risk did not differ by ART regimen (unadjusted prevalence 8.1% DTG versus 5.6% EFV, adjusted RR 1.1, 95% CI 0.2-6.6). Few participants had diabetes, impaired glucose tolerance (IGT), or impaired fasting glucose postpartum ( n  = 13, 6%) with no differences by HIV or ART status. CONCLUSION: In a setting of universal GDM testing, PWH had an increased risk of impaired glucose metabolism during pregnancy but not postpartum. Among PWH, GDM risk was similar regardless of EFV or DTG use. Given concerns about DTG and weight gain, diabetes risk should continue to be monitored.

The effects of Syzygium aromaticum-derived oleanolic acid on kidney function of male Sprague-Dawley rats and on kidney and liver cell lines.

Studies indicate that Syzygium spp-derived oleanolic acid (OA) enhances renal function of streptozotocin (STZ)-induced diabetic rats as evidenced by its reversal of the previously reported inability of the kidney to excrete Na(+) in these animals. We postulated that OA influences Na(+) excretion in the proximal tubule, the site where two-thirds of filtered NaCl is reabsorbed through a process mediated by transport proteins. Therefore, the study investigated the effects of OA on proximal tubular Na(+) handling in male Sprague-Dawley rats using renal lithium clearance (C(Li)). Renal C(Li) has been used widely in animal and clinical studies to assess proximal tubular function. Sub-chronic doses of OA were administered to rats twice every third day for 5 weeks. Rats treated with deionized water served as control animals. Cytotoxicity of OA on kidney and liver cell lines was assessed by the MTT and comet assays. OA increased Na(+) excretion of conscious male Sprague-Dawley rats from week 3 to week 5. By the end of the 5-week experimental period, OA treatment significantly reduced (p < 0.05) plasma creatinine concentration of STZ-induced diabetic rats with a concomitant elevation in glomerular filtration rate (GFR). Acute OA infusion was also associated with increases in fractional excretion of sodium (FE(Na)) and lithium (FE(Li)) in anesthetized rats in the absence of significant changes in GFR. The MTT assay studies demonstrated that OA increased the metabolic activity of kidney and liver cell lines. Taken together with previous observations, this study implicates the proximal tubule in OA-evoked increases in urinary Na(+) output.