HIV-infected adolescents on anti-retroviral therapy: a retrospective descriptive cohort study of breast abnormalities documented during routine care

Transcription

1 HIV-infected adolescents on anti-retroviral therapy: a retrospective descriptive cohort study of breast abnormalities documented during routine care Presented by: Dr Jackie Dunlop Jackie Dunlop, Cynthia Firnhaber, Wiedaad Slemming, Kathryn Schnippel, Caroline Makura, Sarah Rayne, Leon Levin

2 Introduction Gynaecomastia related to ART in adult males is well documented Few studies have described this phenomenon in adolescents In a UK study, 3% (56/1873) of a paediatric and adolescent HIV clinic cohort developed gynaecomastia/breast hypertrophy In South Africa, one case of a prepubescent girl who developed EFV-related gynaecomastia was documented Kenny J et al, PediatrInfect Dis J, 2016 van RamshorstMS et al, BMC Pediatr, 2013

3 Hypothesis: Are particular antiretrovirals related to the development of breast conditions in adolescents with HIV? DzwonekA et al, PediatrInfect Dis J. 2006

4 Methods Retrospective review of routinely collected medical records Study population included: Patients aged Currently receiving antiretroviral therapy Presented at clinics from 1 January to 31 December Sites: Alexandra Clinic, Right to Care Paediatric Clinic and Witkoppen Health and Welfare Clinic Reviewed records for mention of breast and then described information

5 Normal breast development (N=594) 1% Sex differences Abnormal breast events (N=37) 0% 47% p value = % 52% 66% Male Female Not recorded

6 Age p value < for UK cohort * minimum and maximum age unavailable Kenny J et al, Pediatr Infect Dis J, 2016

7 Breast abnormalities identified No description Breast lump 1 1 Normal breast development (594) Gynaecomastia/ Lipomastia 3 Abnormal breast (37) Lipomastia Gynaecomastia 4 12 All included patients Breast buds Enlargement abnormal breast events

8 ART exposure Abnormal breast (n=37) EFV exposure Count (%) 37 (100%) Accumulative time on EFV based median (IQR) 5.5yrs ( ) regimen D4T exposure Count (%) 22 (59.5%) Accumulative time on D4T based median (IQR) 4.9yrs ( ) regimen

9 Interventions D4T to ABC 3 ATV/r EFV to ATZ/r 2 No intervention (20) Drug substitution (19) EFV to LPV/r EFV to NVP 2 9 ABC-3TC-EFV to Lamivudine Mono Monotherapy EFV to NVP, D4T-DDI to ABC-3TC 1 1 Lifestyle interventions (1) Tamoxifen (1) EFV to LPV/r and D4T to TDF 1

10 Comparison with other gynaecomastia studies IRIS HYPOTHESIS: Gynaecomastia is caused by an IRIS phenomenon Median exposure time to EFV before breast abnormalities=5.5y IRIS is an unlikely aetiology in this cohort Hypogonadism HYPOTHESIS: Gynaecomastia caused by HIV-related hypogonadism One patient who developed breast abnormalities was receiving hormone injections Not well explored in this cohort Lipodystrophy HYPOTHESIS: Breast abnormalities are part of fat accumulation Sonography can distinguish fatty/glandular predominance 46% (19/41) of breast abnormalities experienced in patients with comorbid lipodystrophy QaziNA et al, AIDS, 2002 Biglia A et al, ClinInfect Dis RossouwT et al, South AfrJ HIV Med. 2013

11 Comparison with other gynaecomastia studies Pubertal gynaecomastia HYPOTHESIS: Gynaecomastia is caused by normal pubertal hormonal changes 4-69% of adolescent males report an increase in breast size Peak age between 13 and 14 years old Breast abnormalities were reported later in this cohort (15.5yrs) Oestrogen receptor activation by EFV HYPOTHESIS: EFV use causes breast abnormalities Current use of EFV was associated with the onset of breast abnormalities (p<0.0005) All patients had received EFV as part of their current or a previous regimen Substitution of EFV led to resolution of the condition in 3/17 cases No other intervention led to resolution LemaineV et al, SeminPlastSurg,2013 MerciéP et al, AIDS,2001 van RamshorstMS et al, BMC Pediatr, 2013

12 Study limitations No control group Reliance on clinician reporting of breast abnormalities during routine consultation Substantial interaction between clinicians at all three sites may have led to similar management of abnormal breast conditions

13 Conclusions 6% of patients aged years on ART had experienced breast abnormalities Strong significance associated with breast abnormalities in adolescents on ART: EFV use Older age Only 51% received an intervention with a drug substitution being the most common Phenomenon likely ARV-related (EFV), interacting with pubertal hormonal changes

14 Acknowledgements: Right to Care Research Team: Prof Cindy Firnhaber, Kathryn Schnippel, Caroline Makura Yvonne Masumbuka and Jabu Mabuyakhulu Helen Joseph Breast Clinic Drs Sarah Rayne and Dr Carol Benn Alexandra Clinic: Dr Sharon Patz and Sr Thembi Mazibuko Right to Care Paediatric Clinic Dr Leon Levin, Mamosa Kekana Witkoppen Health and Welfare Centre Dr Jean Bassett Dr Holly France and Dr Sanlie Untiedt

15 References 1. BigliaA, Blanco JL, Martı E, et al. Gynecomastia among HIV-Infected Patients Is Associated with Hypogonadism : A Case-Control Study. Clin Infect Dis. 2004;39(November 15): DzwonekA, ClapsonM, WitheyS, Bates A, NovelliV. Severe gynaecomastia in an African boy with perinatallyacquired human immunodeficiency virus infection receiving highly active antiretroviral therapy. PediatrInfect Dis J. 2006;25(2): doi: /01.inf b2. 3. Kenny J, DoerholtK, Gibb DM, Judd A. Who Gets Severe Gynecomastia Among HIV-Infected Children In The UK And Ireland? Pediatr Infect Dis J. 2016;November 2:1-11. doi: /inf Lemaine V, Cayci C, Simmons PS, Petty P. Gynecomastia in Adolescent Males. Semin Plast Surg. 2013;1(212): Mercié P, Viallard J-F, Thiébaut R, et al. Efavirenz-associated breast hypertrophy in HIV-infected patients. AIDS. 2001;15(1): doi: /jop QaziNA, MorleseJF, King DM, Ahmad RS, GazzardBG, Nelson MR. Gynaecomastia without lipodystrophy in HIV-1-seropositive patients on efavirenz: an alternative hypothesis. AIDS. 2002;16(3): doi: / Rossouw T, Botes M, Conradie F. Overview of HIV-related lipodystrophy. South Afr J HIV Med. 2013;14(1). 2006;25(2): doi: /01.inf b2. 8. van RamshorstMS, Kekana M, Struthers HE, McIntyre J a, Peters RPH. Efavirenz-induced gynecomastia in a prepubertal girl with human immunodeficiency virus infection: a case report. BMC Pediatr. 2013;13(1):120. doi: /