Intramuscular depot medroxyprogesterone acetate accentuates bone loss associated with tenofovir disoproxil fumarate-containing antiretroviral therapy initiation in young women living with HIV (the BONE: CARE study): a prospective cohort study in Uganda

Matovu, Flavia; Kiwanuka, Noah; Scholes, Delia; Musoke, Philippa; Fowler, Mary Glenn; Beksinska, Mags; Pettifor, John Μ.; Brown, Todd T.; Kiweewa, Flavia Matovu; Nakabiito, Clemensia; Nawagi, Faith; Kamira, Betty; Isingel, Esther; Bule, Stephen; Kukundakwe, Violet; Kateregga, Andrew; Musisi, Mary; Namayanja, Paula Mubiru; Mirembe, Dorothy; Mbabali, Mary Speciosa; Mulebeke, Sarah; Nabisere, Joselyne; Nakakande, Joyce; Matovu, Nicholas; Nakaye, Dorah; Wynne, Joshua; Mulumba, Faith; Mukasa, Restituta; Ssewanyana, Masitula; Nabunya, Hadijah Kalule; Biira, Florence Asiimwe; Kyomukama, Erinah; Nampiira, Suzan; Zalwago, Aisha; Namuganga, Margaret l; Mwebaza, Deborah; Namuli, Prossy Ethel; Tulina, Caroline; Kikonyogo, Florence Sempa; Nabatanzi, Regina Bukenya; Muwawu, Rosemary; Musisi, Jane Nsubuga; Saava, Margaret Nakato; Najjemba, Mary Mukasa Kagwa; Kaahwa, Winfred; Mukalazi, Rose Namwanje; Takhuli, Miriam Magomu; Sawsan, Osman; Mugenyi, M; Mugagga, Mary Agnes; Sserugo, Francis; Namuddu, Agnes; Kemigisha, Doreen; Nakyeyune, Justine; Nassozi, Caroline Kawuma; Asello, Juliet; Nakawungu, Zaam Zinda; Kaboggoza, Olivia Higiro; Ssebabi, Sarah Babirye; Birungi, Bertha; Ssentogo, Ruth Lutabi; Mubiru, Michael; Nansamba, Winnie; Kalungi, Stella Nalusiba; Bukenya, Luke Erismus; Asiimwe, Prossy; Bazira, James Amos; Katongole, Sulaiman; Twinomujuni, Wenceslaus; Nakacwa, Susan; Baddokwaya, Joanita Nankya; Elwana, Alice Margaret; Nanyonjo, Juliet; Adikini, Susan; Nalwoga, Justine; Rwanzogyera, Godfrey; Okello, Fabian; Kiiza, Daniel Kabenge; Mayanja, Emmanuel; Katongole, Francis; Kiwewa, Max; Onen, Francis; Mutebo, Joseph; Mukasa, Dick; Tamale, Joshua; Kibirige, Ismael; Nabwana, Martin

doi:10.1016/s2214-109x(22)00080-8

Cited by 8 publications

(6 citation statements)

References 25 publications

(38 reference statements)

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“…A 2022 randomized controlled trial conducted in Uganda and including 265 women living with HIV raised concerns of accelerated bone loss with concurrent use of intramuscular DMPA and TDF. 49 Although both intramuscular DMPA and TDF have been shown to be independently associated with decreased bone density, this was the first prospective study to demonstrate their combined deleterious effect, which is almost a 2-fold decrease in bone mineral density loss as opposed to women on either DMPA or TDF. This trend was observed at different CD4 cell counts and unlikely to be related to uncontrolled HIV infection.…”

Section: Etonogestrel/levonorgestrel Implantsmentioning

confidence: 82%

“…However, adverse effects unrelated to contraceptive or HIV treatment may be of concern with tenofovir disoproxil fumarate (TDF), a commonly used nucleoside reverse transcriptase inhibitor (NRTI) and first‐line medication. A 2022 randomized controlled trial conducted in Uganda and including 265 women living with HIV raised concerns of accelerated bone loss with concurrent use of intramuscular DMPA and TDF 49 . Although both intramuscular DMPA and TDF have been shown to be independently associated with decreased bone density, this was the first prospective study to demonstrate their combined deleterious effect, which is almost a 2‐fold decrease in bone mineral density loss as opposed to women on either DMPA or TDF.…”

Section: Contraceptive Options For People Living With Hivmentioning

confidence: 96%

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Contraception and Abortion Care for People Living With HIV: A Clinical Guide for Reproductive Health Practitioners

Yang,

Allen,

Cambou

et al. 2023

J Midwife Womens Health

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People capable of pregnancy are disproportionately affected by HIV. Family planning needs and services are often unmet in this population, and clinical care guidelines regarding contraceptive options and abortion care are not well elucidated. Individuals living with HIV often face unique barriers in accessing contraception and abortion services due to internalized stigma, medically complex care (eg, drug–drug interactions, adverse effects of antiretroviral therapy), and distrust of health care providers. There is also a lack of clarity among reproductive health, primary, and infectious disease care providers on best‐practice contraceptive counseling and contraceptive care for individuals living with HIV, given limited opportunities to enhance expertise in reproductive infectious disease. In this review, we summarize existing and updated evidence and clinical considerations regarding contraceptive counseling and abortion care in this population.

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Section: Etonogestrel/levonorgestrel Implantsmentioning

confidence: 82%

Section: Contraceptive Options For People Living With Hivmentioning

confidence: 96%

Contraception and Abortion Care for People Living With HIV: A Clinical Guide for Reproductive Health Practitioners

Yang,

Allen,

Cambou

et al. 2023

J Midwife Womens Health

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“…The BONE: CARE study in young Ugandan women with HIV initiating TDF-containing ART, found those using DMPA experienced accentuated bone loss. Women taking both TDF-ART and DMPA, had twice the loss of bone compared with women taking TDF-ART without DMPA, or women not on ART using DMPA [5 ▪▪ ]. There is clearly a need for more bone friendly ART and acceptable bone-sparing contraceptives for these women.…”

Section: Bone Health In Women With Hivmentioning

confidence: 99%

Gender and sex considerations in HIV and bone health

Tang

Alexander

Hoy

2023

Current Opinion in HIV and AIDS

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Purpose of reviewPeople with HIV (PWHIV) are at increased risk for osteoporosis and fractures, because of the effects of HIV and inflammation and antiretroviral therapy (ART) initiation as well as traditional risk factors. This review from recent literature focuses on sex differences in rates of bone disease, risk of fractures, and effects of ART. Recent findingsWomen with HIV in resource-constrained settings experience bone loss because of the additive effect of initiating TDF-containing ART during pregnancy, lactation, and menopause. Children and adolescents experience lower bone accrual during the pubertal growth years. There has been less focus on bone health in recent trials of ART containing tenofovir alafenamide and/or integrase inhibitors. Very few clinical trials or studies compare sex-specific changes in inflammation, immune activation, response to ART and bone turnover or change in BMD resulting in significant knowledge gaps. SummaryMore data is needed to determine changes in prevalence of osteopenia, osteoporosis, and fractures in the era of immediate initiation of ART at high CD4 cell counts and the use of more bone-friendly ART. The longterm effects of ART and low bone mass on fractures in the ageing population of PWHIV is yet to be realized. Keywordsantiretroviral therapy, bone mineral density, fracture, gender, HIV BONE HEALTH IN CHILDREN AND ADOLESCENTS WITH HIVOver 90% of children with perinatally acquired HIV live in resource-limited settings, and will experience the highest lifetime exposure to HIV and ART. Peak bone mass accrual occurs around puberty, and lower peak bone mass is a major determinant of subsequent osteoporosis and fractures in adults. ART initiated during growth and reproductive years is therefore a risk factor for osteoporosis. ART containing TDF and/or ritonavir-boosted protease inhibitors has the greatest negative impact on bone accrual in children and adolescents compared with

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“…Tenofovir disoproxil fumarate (TDF) and intramuscular depot medroxyprogesterone acetate (DMPA-IM) are independently associated with bone loss 1 2. This cohort study conducted in Uganda in 2016–2017 assessed the combined effects of DMPA-IM and TDF initiation on bone mineral density (BMD) in women aged 18–35 3. Participants (n=521) were classified based on HIV status, TDF use and DMPA-IM use.…”

Section: Bone Loss In Young Women Living With Hiv Receiving Intramusc...mentioning

confidence: 99%

Research news in clinical context

Tan¹,

Daskalopoulou

Thomson-Glover

2022

Sex Transm Infect

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Intramuscular depot medroxyprogesterone acetate accentuates bone loss associated with tenofovir disoproxil fumarate-containing antiretroviral therapy initiation in young women living with HIV (the BONE: CARE study): a prospective cohort study in Uganda

Cited by 8 publications

References 25 publications

Contraception and Abortion Care for People Living With HIV: A Clinical Guide for Reproductive Health Practitioners

Contraception and Abortion Care for People Living With HIV: A Clinical Guide for Reproductive Health Practitioners

Gender and sex considerations in HIV and bone health

Research news in clinical context

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