Gestational diabetes in women living with HIV in Botswana: lower rates with dolutegravir‐ than with efavirenz‐based antiretroviral therapy

Mmasa, Keolebogile N; Powis, Kathleen M.; Sun, Shan; Makhema, Joseph; Mmalane, Mompati; Kgole, Samuel; Masasa, Gosego; Moyo, Sikhulile; Gerschenson, Mariana; Mohammed, Terence; Legbedze, Justine; Abrams, Elaine J.; Kurland, Irwin J.; Geffner, Mitchell E.; Jao, Jennifer

doi:10.1111/hiv.13120

Cited by 11 publications

(9 citation statements)

References 27 publications

(39 reference statements)

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“…[33] However, another study found a protective effect of DTG against gestational diabetes. [34] We did not find an association between INSTI exposure and any other adverse maternal and/or pregnancy outcomes, including gestational diabetes, SGA, spontaneous abortion, stillbirth, or preterm birth. Other studies have identified an association between INSTI exposure during pregnancy and preterm birth.…”

Section: (Which Was Not Certified By Peer Review)contrasting

confidence: 64%

Congenital Malformations and Preeclampsia Associated with Integrase Inhibitor Use in Pregnancy

Smith

Fought

Sung

et al. 2022

Preprint

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Background: Antiretroviral therapy (ART) decreases perinatal HIV transmission, but concerns exist regarding maternal and infant safety. We compared the incidence of congenital malformations and other adverse outcomes in pregnancies exposed to integrase inhibitor (INSTI) versus non-INSTI ART. Setting: Single-site review of all pregnancies among women living with HIV between 2008 and 2018. Methods: We used binomial family generalized estimating equations to model the relationship of congenital anomalies and pregnancy outcomes with exposure to INSTI or dolutegravir (DTG) versus non-INSTI ART. Results: Among 257 pregnancies, 77 women received ≥1 INSTI (54 DTG, 14 elvitegravir, 15 raltegravir), 167 received non-INSTI, and 3 had missing data. Forty-nine congenital anomalies were identified among 36 infants. Infants with first-trimester DTG or any first-trimester INSTI exposure had higher odds of congenital anomalies than infants with first-trimester non-INSTI exposure (OR=2.55; 95%CI=1.07-6.10; OR=2.61; 95%CI=1.15-5.94, respectively). Infants with INSTI exposure after the second trimester had no increased odds of anomalies. Women with INSTI exposure had higher odds of preeclampsia (OR=4.73; 95%CI=1.70-13.19). Among women who received INSTI, grade ≥3 laboratory abnormalities were noted in 2.6% while receiving the INSTI and 3.9% while not receiving the INSTI, versus 16.2% in women who received non-INSTI. There was no association between INSTI exposure and other pregnancy outcomes. Conclusion: First-trimester INSTI exposure may be associated with increased rates of congenital anomalies. Use of INSTI during pregnancy was also associated with preeclampsia in our cohort. These findings underscore the need for continued monitoring of the safety of INSTI in pregnancy.

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Section: (Which Was Not Certified By Peer Review)contrasting

confidence: 64%

Congenital Malformations and Preeclampsia Associated with Integrase Inhibitor Use in Pregnancy

Smith

Fought

Sung

et al. 2022

Preprint

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“…The higher prevalence of GDM in pregnant women living with HIV, however, has not been reported in studies from the United States and Botswana, where GDM prevalence was similar in women living with and without HIV. 16,17 Women in those studies had similar CD4 counts and antiretroviral therapy coverage as our cohort, but were mainly on protease or integrase inhibitor-based regimens. They also had higher BMIs and age than women in our cohort.…”

Section: Discussionmentioning

confidence: 79%

The Association of Gestational Diabetes with HIV Infection and Tuberculosis in Indian Women

Chebrolu

Alexander

Bhosale

et al. 2022

The American Journal of Tropical Medicine and Hygiene

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Infection of HIV is associated with an increased diabetes risk, which also increases tuberculosis risk. It is unknown if similar associations exist with gestational diabetes (GDM). We screened pregnant women living with and without HIV for GDM using oral glucose tolerance testing. In a subgroup of women with latent tuberculosis (positive interferon-gamma [IFN-γ] release assay), we used supernatants from tuberculosis antigen tubes to compare cytokine levels from women with and without GDM, matched by age and HIV status. Of 234 women, 21 (9%) had GDM, 13.9% living with HIV, and 6.5% without HIV (P = 0.06). Compared with women without GDM, women with GDM had lower median IFN-γ (19.1 versus 141.9 pg/mL, P = 0.03) and interleukin-2 (18.7 versus 249 pg/mL, P < 0.01). Our study suggests that HIV infection is associated with an increased risk of GDM, which is associated with decreased Mycobacterium tuberculosis immune responses. Gestational diabetes screening should be prioritized in tuberculosis-endemic countries, especially in women living with HIV.

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“…Women ≥35 years were most likely to develop GD in our population, which could be a proxy for age‐related weight gain [ 57 ]. A recent study in Botswana reported similar findings with GD risk increasing linearly with each year of age (aOR: 1.10, 1.04–1.17) [ 42 ]. Maternal age is also related to gravidity, which was accounted for in the modelling strategy; however, evidence from the general population indicates that the incidence of GD is three‐ to six‐fold higher among women over 40 years of age [ 58 ], and a significant proportion of women who develop GD in their first pregnancy are at greater risk of developing GD in subsequent pregnancies [ 59 , 60 ].…”

Section: Discussionmentioning

confidence: 58%

“…A comparative analysis of randomized clinical trials has shown that weight gain is greater in more recent trials with the use of newer ART regimens [ 44 ], which is consistent with post‐marketing observational studies of integrase inhibitors [ 45 ]. Preliminary studies of WLWH on integrase inhibitors during pregnancy show no cause for concern regarding gestational weight gain [ 42 , 46 ]; however, a risk prediction model based on data from South Africa suggests that treatment emergent obesity with dolutegravir‐based regimens (with tenofovir alafenamide or disoproxil and emtricitabine) for obese women (BMI ≥30 kg/m 2 ) versus those with normal BMI could increase the risk of GD four‐fold (RR: 4.31, 95% CI: 3.18–5.85) [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

“…While the use of population‐level surveillance data on pregnant WLWH was a study strength, it was also a source of limitations as several important variables were not collected. This includes BMI, a GD risk factor in the general population [ 73 , 74 ] and among WLWH [ 42 ] that could not be accounted for in our analyses. Approximately 41% of WLWH in the UK are overweight [ 75 ], with an increasing trend in general obesity reported nationally [ 29 ], highlighting complex interactions with GD that could not be elucidated in our study.…”

Section: Discussionmentioning

confidence: 99%

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Gestational diabetes in women living with HIV in the UK and Ireland: insights from population‐based surveillance data

et al. 2023

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Introduction The prevalence of gestational diabetes (GD) is increasing globally. While universal risk factors for GD are reasonably well understood, questions remain regarding risks for women living with HIV (WLWH). We aimed to describe GD prevalence, evaluate associated maternal risk factors and assess specific birth outcomes in WLWH in the UK and Ireland. Methods We analysed all pregnancies (≥24 weeks’ gestation) in women diagnosed with HIV before delivery, reported to the UK‐based Integrated Screening Outcomes Surveillance Service between 2010 and 2020. Every report of GD was considered as a case. A multivariable logistic regression model, adjusted for women with more than one pregnancy fitted with generalized estimating equations (GEE) assessed the effect of independent risk factors. Results There were 10,553 pregnancies in 7916 women, of which 460 (4.72%) pregnancies had reported GD. Overall, the median maternal age was 33 years (Q1:29–Q3:37), and 73% of pregnancies were in Black African women. WLWH with GD (WLWH‐GD) were older (61% vs. 41% aged ≥35 years, p < 0.001) and more likely to be on treatment at conception (74% vs. 64%, p < 0.001) than women without GD. WLWH‐GD were more likely to have a stillbirth (odds ratio [OR]: 5.38, 95% CI: 2.14–13.5), preterm delivery (OR: 2.54, 95% CI: 1.95–3.32) and fetal macrosomia (OR: 1.14, 95% CI: 1.04–1.24). Independent risk factors for GD included estimated year of delivery (GEE‐adjusted odds ratio [GEE‐aOR]: 1.14, 95% CI: 1.10–1.18), advanced maternal age (≥35 years) (GEE‐aOR: 2.87, 95% CI: 1.54–5.34), Asian (GEE‐aOR: 2.63, 95% CI: 1.40–4.63) and Black African (GEE‐aOR: 1.55, 95% CI: 1.13–2.12) ethnicity. Timing and type of antiretroviral therapy showed no evidence of a relationship with GD in multivariable analyses; however, women with a CD4 count ≤350 cells/μl were 27% less likely to have GD than women with CD4 counts >350 cells/μl (GEE‐aOR: 0.73, 95% CI: 0.50–0.96). Conclusions GD prevalence increased over time among WLWH but was not significantly different from the general population. Maternal age, ethnicity and CD4 count were risk factors based on available data. Stillbirth and preterm delivery were more common in WLWH‐GD than other WLWH over the study period. Further studies are required to build upon these results.

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Gestational diabetes in women living with HIV in Botswana: lower rates with dolutegravir‐ than with efavirenz‐based antiretroviral therapy

Cited by 11 publications

References 27 publications

Congenital Malformations and Preeclampsia Associated with Integrase Inhibitor Use in Pregnancy

Congenital Malformations and Preeclampsia Associated with Integrase Inhibitor Use in Pregnancy

The Association of Gestational Diabetes with HIV Infection and Tuberculosis in Indian Women

Gestational diabetes in women living with HIV in the UK and Ireland: insights from population‐based surveillance data

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