Abstract
Introduction and Objective
In May 2018, the World Health Organization and other regulatory authorities released a safety alert for dolutegravir related to a risk of neural tube defects among women exposed to dolutegravir at the time of conception. Models of how drug safety information can be shared effectively in the shortest time are necessary to prevent interruptions of public health programs. We sought to describe an implementation process to inform and support women already on dolutegravir-based regimens at the time of conception to make informed choices following the safety alert of a potential teratogenicity risk. We describe the choices made by women, as well as determine the factors associated with women’s choices to switch off dolutegravir.
Methods
A clinic response plan was developed in the first week following the alert and clinic staff were trained on safety guidance. All women aged < 55 years taking dolutegravir were identified from the clinic database and contacted by phone for earlier appointments. Non-menopausal and non-surgically sterilized women were referred for urine pregnancy testing and evaluation of pregnancy intentions in the following 12 months and effective family planning was offered. We describe the coverage of women who received the communication as well as the fidelity to the outlined plan from 21 May to 12 September, 2018. We used modified a Poisson regression analysis to determine factors associated with switching off dolutegravir.
Results
Of all active patients in the clinic, 9% (690/7963) were identified as female aged < 55 years taking dolutegravir. Ninety-five percent (656/690) were reviewed by September 2018 and informed of the safety alert, implying a high level of uptake. Fidelity to standard operating procedures was also high at 72%. Twenty-two percent (146/656) of patients were menopausal or surgically sterilized. Five hundred and ten women were of reproductive potential with a median age (interquartile range) of 37 years (30–42 years). Five percent (23/510) were human chorionic gonadotrophin positive and all initial ultrasound reports revealed no deformities. Twenty-one percent (108/510) had intentions to conceive and opted to stop taking dolutegravir with 90% (97/108) switching to efavirenz. Seventy-nine percent (402/510) opted to remain taking dolutegravir. However, only 40% (160/402) chose effective contraceptive methods and 60% (242/402) opted for condoms only/no contraceptive method.
Conclusions
A rapid well-coordinated response ensured prompt communication of the dolutegravir safety warning. The process developed by the clinic can act as a model for response during drug safety alerts. Women made informed decisions with most opting to remain taking dolutegravir; however, effective contraception uptake was low.
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Acknowledgements
We acknowledge the clinic staff who contributed to the effective roll out of this project including Farida Mayanja, Geraldine Kisa, Elizabeth Tindyebwa, Joseph Mawejje, Swalha Namanda, Eriphase Mugabi, and Leah Mbabazi. We also acknowledge the patients we provided care for at the Infectious Diseases Institute.
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There was no funding obtained for this study.
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Mohammed Lamorde reports grants and non-financial support from ViiV, grants and personal fees from Mylan, and grants from Janssen Pharmaceuticals, outside the submitted work. Eva Agnes Odongpiny Laker, Arnold Arinaitwe, Noela Owarwo, Annet Onzia, Benson Nasasira, Abdullah Wailagala, Ivan Kalule, Godwin Anguzu, Agnes Kiragga, Kay Seden, Isaac Lwanga, Barbara Castelnuovo, and Rachel Musomba have no conflicts of interest that are directly relevant to the content of this article.
Ethics Approval
Analysis and publication of data obtained from the Infectious Diseases Institute Adult Clinic are approved and annually renewed by the School of Medicine Research and Ethics Committee, Makerere University Medical School (reference no. 2009-120) and the Uganda National Council for Science and Technology. All information is analyzed after removing unique personal identifiers.
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Patients provided written or oral consent to participate in the study.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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EL had final responsibility for the decision to publish. AA, NO, OA, NB, WA, AG, KS, RM, AG, IL, RM, BC, and ML all contributed to the design, data analysis, and interpretation of results. AG and AK were responsible for data extraction from the clinic database. EL, AA, NO, OA, NB, WA, KS, RM, AG, IL, RM, BC, and ML contributed to the drafting of the manuscript, reviewed the paper for substantial intellectual content, and approved the final manuscript.
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Laker, E.A.O., Arinaitwe, A., Owarwo, N. et al. The Potential Teratogenicity Alert for Women Conceiving on Dolutegravir-Based Regimens: An Assessment of Risk Communication by an Urban HIV Clinic in Uganda and Choices made by Women. Drug Saf 43, 1133–1140 (2020). https://doi.org/10.1007/s40264-020-00974-9
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DOI: https://doi.org/10.1007/s40264-020-00974-9