TY - JOUR
T1 - 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)
T2 - a prospective cohort study in Uganda
AU - BONE: CARE Study Team
AU - Kiweewa Matovu, Flavia
AU - Kiwanuka, Noah
AU - Nabwana, Martin
AU - Scholes, Delia
AU - Musoke, Philippa
AU - Glenn Fowler, Mary
AU - Beksinska, Mags E.
AU - Pettifor, John M.
AU - Brown, Todd T.
AU - Kiweewa, Flavia Matovu
AU - Nakabiito, Clemensia
AU - Nawagi, Faith
AU - Kamira, Betty
AU - Isingel, Esther
AU - Bule, Stephen
AU - Kukundakwe, Violet
AU - Kateregga, Andrew
AU - Musisi, Mary (Maria)
AU - Namayanja, Paula Mubiru
AU - Mirembe, Dorothy
AU - Mbabali, Mary Speciosa
AU - Mulebeke, Sarah
AU - Nabisere, Joselyne
AU - Nakakande, Joyce
AU - Matovu, Nicholas
AU - Nakaye, Dorah
AU - Wynne, Joshua
AU - Mulumba, Faith
AU - Mukasa, Restituta
AU - Ssewanyana, Masitula
AU - Nabunya, Hadijah Kalule
AU - Biira, Florence Asiimwe
AU - Kyomukama, Erinah
AU - Nampiira, Suzan
AU - Zalwago, Aisha
AU - Namuganga, Margaret l.
AU - Mwebaza, Deborah
AU - Namuli, Prossy Ethel
AU - Tulina, Caroline
AU - Kikonyogo, Florence Sempa
AU - Nabatanzi, Regina Bukenya
AU - Muwawu, Rosemary
AU - Musisi, Jane Nsubuga
AU - Saava, Margaret Nakato
AU - Najjemba, Mary Mukasa Kagwa
AU - Kaahwa, Winfred
AU - Mukalazi, Rose Namwanje
AU - Takhuli, Miriam Magomu
AU - Sawsan, Osman
AU - Mugenyi, Margaret
N1 - Funding Information:
The BONE: CARE Study is supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) under award number R01AI118332. TTB is supported in part by K24 AI120834 (NIAID). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was presented in part at the AIDS 2020 Virtual 23rd International AIDS Conference, July 6–10, 2020, as an oral presentation (abstract OAB0105). We thank the study participants, NIAID (the funder), Melanie Bacon (NIAID and NIH Program Officer), the Consortium for Advanced Research and Training in Africa for offering PhD training support for FKM, the Makerere University School of Public Health, Makerere University–Johns Hopkins University Research Collaboration. Monica L Nolan, Faith Nawagi, Deo Wabwire, Betty Kamira, Esther Isingel, and the rest of the BONE: CARE Study staff who implemented the study, as well as the following recruitment sites: the Makerere University Joint AIDS Programme, the AIDS Support Organization, Reach out Mbuya, the China–Uganda Friendship Hospital–Naguru, the Kiruddu National Referral Hospital, and Kampala Capital City Authority clinics (Kiswa, Kisenyi, Kawaala, Kitebi, Komamboga, and Kisugu Health Centres).
Funding Information:
The BONE: CARE Study is supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) under award number R01AI118332. TTB is supported in part by K24 AI120834 (NIAID). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was presented in part at the AIDS 2020 Virtual 23rd International AIDS Conference, July 6–10, 2020, as an oral presentation (abstract OAB0105). We thank the study participants, NIAID (the funder), Melanie Bacon (NIAID and NIH Program Officer), the Consortium for Advanced Research and Training in Africa for offering PhD training support for FKM, the Makerere University School of Public Health, Makerere University–Johns Hopkins University Research Collaboration., Monica L Nolan, Faith Nawagi, Deo Wabwire, Betty Kamira, Esther Isingel, and the rest of the BONE: CARE Study staff who implemented the study, as well as the following recruitment sites: the Makerere University Joint AIDS Programme, the AIDS Support Organization, Reach out Mbuya, the China–Uganda Friendship Hospital–Naguru, the Kiruddu National Referral Hospital, and Kampala Capital City Authority clinics (Kiswa, Kisenyi, Kawaala, Kitebi, Komamboga, and Kisugu Health Centres).
Publisher Copyright:
© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license
PY - 2022/5
Y1 - 2022/5
N2 - Background: Tenofovir disoproxil fumarate (TDF) and intramuscular depot medroxyprogesterone acetate (DMPA-IM) are independently associated with reduced bone mineral density (BMD). We aimed to assess the combined effects of DMPA-IM use and TDF initiation on BMD in young adult women living with HIV over two years, compared with age-matched people without HIV. Methods: Th BONE: CARE study was a prospective cohort study that recruited women aged 18–35 years from 11 HIV care and general health facilities in Kampala, Uganda. The participants were classified into four groups on the basis of their combination of HIV status, TDF use, and DMPA-IM use, as follows: women living with HIV initiating TDF-containing antiretroviral therapy (ART) with DMPA-IM (HIV positive, DMPA positive, and TDF positive); women living with HIV using DMPA-IM but not eligible for ART as per local guidelines at the time of enrolment into the study (HIV positive, DMPA positive, and TDF negative); women living with HIV initiating TDF-containing ART without DMPA-IM (HIV positive, DMPA negative, and TDF positive); and controls without HIV using non-hormonal contraceptives (HIV negative, DMPA negative, and TDF negative). BMD of the lumbar spine, total hip, and femoral neck were measured using semiannual dual-energy x-ray absorptiometry at enrolment and at intervals every 6 months thereafter. We assessed percentage change in mean BMD. Findings: Between March 30, 2016, and Oct 19, 2017, we enrolled 265 women living with HIV initiating ART (159 DMPA-IM users and 106 non-hormonal contraceptive users), 187 women living with HIV using DMPA-IM but not ART, and 69 controls without HIV. Mean age was 26·1 years (SD 4·2). BMD declined significantly from baseline in women living with HIV on TDF with versus without DMPA-IM at the lumbar spine (–3·406% [95% CI –3·969 to –2·844] vs –1·111% [–1·929 to –0·293]; p<0·0001), total hip (–3·856% [–4·449 to –3·264] vs –1·714% [–2·479 to –0·949]; p=0·0002), and femoral neck (–4·422% [–5·078 to –3·766] vs –1·999% [–3·022 to –0·976]; p=0·0002), increased in controls at the lumbar spine (1·5% change), and remained unchanged at total hip and femoral neck (–0·1% change). Concurrent use of TDF and DMPA-IM resulted in significantly greater BMD decline (p<0·0001) than TDF alone (lumbar spine –2·677% [95% CI –3·743 to –1·611]; p<0·0001; total hip –2·518% [–3·575 to –1·461]; p<0·0001; and femoral neck –2·907 [–4·132 to –1·683]; p<0·0001) or than controls (lumbar spine –4·970% [–6·391 to –3·549]; p<0·0001; total hip –4·151% [–5·579 to –2·724]; p<0.0001; and femoral neck –4·773% [–6·424 to –3·122]; p<0·0001) Interpretation: Concomitant DMPA-IM use resulted in a doubling of BMD loss in women living with HIV initiating TDF-containing ART. Identification of safer contraceptive and bone-sparing ART options should be prioritised for optimal care of women living with HIV. Funding: National Institute of Allergy and Infectious Diseases of the US National Institutes of Health.
AB - Background: Tenofovir disoproxil fumarate (TDF) and intramuscular depot medroxyprogesterone acetate (DMPA-IM) are independently associated with reduced bone mineral density (BMD). We aimed to assess the combined effects of DMPA-IM use and TDF initiation on BMD in young adult women living with HIV over two years, compared with age-matched people without HIV. Methods: Th BONE: CARE study was a prospective cohort study that recruited women aged 18–35 years from 11 HIV care and general health facilities in Kampala, Uganda. The participants were classified into four groups on the basis of their combination of HIV status, TDF use, and DMPA-IM use, as follows: women living with HIV initiating TDF-containing antiretroviral therapy (ART) with DMPA-IM (HIV positive, DMPA positive, and TDF positive); women living with HIV using DMPA-IM but not eligible for ART as per local guidelines at the time of enrolment into the study (HIV positive, DMPA positive, and TDF negative); women living with HIV initiating TDF-containing ART without DMPA-IM (HIV positive, DMPA negative, and TDF positive); and controls without HIV using non-hormonal contraceptives (HIV negative, DMPA negative, and TDF negative). BMD of the lumbar spine, total hip, and femoral neck were measured using semiannual dual-energy x-ray absorptiometry at enrolment and at intervals every 6 months thereafter. We assessed percentage change in mean BMD. Findings: Between March 30, 2016, and Oct 19, 2017, we enrolled 265 women living with HIV initiating ART (159 DMPA-IM users and 106 non-hormonal contraceptive users), 187 women living with HIV using DMPA-IM but not ART, and 69 controls without HIV. Mean age was 26·1 years (SD 4·2). BMD declined significantly from baseline in women living with HIV on TDF with versus without DMPA-IM at the lumbar spine (–3·406% [95% CI –3·969 to –2·844] vs –1·111% [–1·929 to –0·293]; p<0·0001), total hip (–3·856% [–4·449 to –3·264] vs –1·714% [–2·479 to –0·949]; p=0·0002), and femoral neck (–4·422% [–5·078 to –3·766] vs –1·999% [–3·022 to –0·976]; p=0·0002), increased in controls at the lumbar spine (1·5% change), and remained unchanged at total hip and femoral neck (–0·1% change). Concurrent use of TDF and DMPA-IM resulted in significantly greater BMD decline (p<0·0001) than TDF alone (lumbar spine –2·677% [95% CI –3·743 to –1·611]; p<0·0001; total hip –2·518% [–3·575 to –1·461]; p<0·0001; and femoral neck –2·907 [–4·132 to –1·683]; p<0·0001) or than controls (lumbar spine –4·970% [–6·391 to –3·549]; p<0·0001; total hip –4·151% [–5·579 to –2·724]; p<0.0001; and femoral neck –4·773% [–6·424 to –3·122]; p<0·0001) Interpretation: Concomitant DMPA-IM use resulted in a doubling of BMD loss in women living with HIV initiating TDF-containing ART. Identification of safer contraceptive and bone-sparing ART options should be prioritised for optimal care of women living with HIV. Funding: National Institute of Allergy and Infectious Diseases of the US National Institutes of Health.
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U2 - 10.1016/S2214-109X(22)00080-8
DO - 10.1016/S2214-109X(22)00080-8
M3 - Article
C2 - 35427526
AN - SCOPUS:85128148459
SN - 2214-109X
VL - 10
SP - e694-e704
JO - The Lancet Global Health
JF - The Lancet Global Health
IS - 5
ER -