Letters to the Editor
13.
14.
15.
16.
17.
GeSida Study 8114. J Int AIDS Soc. 2014;17 (4 suppl 3):19795. Gantner P, Reinhart S, Partisani M, et al. Switching to emtricitabine, tenofovir and rilpivirine as single tablet regimen in virologically suppressed HIV-1-infected patients: a cohort study. HIV Med. 2014;16(2):132–136. Gazaignes S, Resche-Rigon M, Yang C, et al. Efficacy and safety of rilpivirine-based regimens in treatment-experienced HIV-1 infected patients: a prospective cohort study. J Int AIDS Soc. 2014;17(4 suppl 3): 19796. Wu PY, Cheng CY, Luo YZ, et al. Safety of rilpivirine plus nucleoside reversetranscriptase inhibitors in HIV-infected Taiwanese with a higher prevalence of hepatitis virus infection. J Int AIDS Soc. 2014;17(4 suppl 3):19580. Sax PE, DeJesus E, Mills A, et al; GS-US236-0102 Study Team. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks. Lancet. 2012;379: 2439–2448. Greig SL, Deeks ED. Abacavir/dolutegravir/ lamivudine single-tablet regimen: a review of its use in HIV-1 infection. Drugs. 2015;75(5): 503–514.
Premenstrual Disorders Among Perinatally HIV-Infected Adolescents To the Editors:
INTRODUCTION With antiretroviral therapy (ART), many children born with HIV survive and grow into adolescence. In some countries, over 30% of HIVpositive perinatally infected children are now above the age of 121,2 and about half of them are females.1 Girls with severe HIV disease can experience delayed onset of puberty.3,4 With earlier treatment, maturation timing seems to be normalized.4 Comparably, ART Supported by TREAT Asia/amfAR, The Foundation for AIDS Research, through a grant from ViiV Healthcare. The authors have no conflicts of interest to disclose. The views expressed are those of the authors and should not be construed to represent the positions of the US Army or the Department of Defense.
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use and higher CD4 counts have been linked to lower rates of persistent menstrual problems in behaviorally HIV-infected women.5 However, the presence of a regular menstrual cycle has been related to premenstrual syndrome (PMS) in women in the general population, with onset in the adolescent years.6 PMS is a group of physical, emotional, and behavioral symptoms in the luteal phase of the menstrual cycle, which interferes with the daily functioning of women.7 Premenstrual dysphoric disorder (PMDD), the most severe form of PMS, is included in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).6,8,9 Here, we report the prevalence of PMS and PMDD in a cohort of perinatally HIV-infected Thai adolescents compared with that of healthy controls. In addition, we evaluated factors associated with the prevalence of PMS in HIV-positive adolescents. To the best of our knowledge, this is the first report on PMS prevalence in perinatally HIVinfected adolescents.
METHODS We conducted a cross-sectional assessment of PMS in perinatally HIVinfected adolescents in 5 sites throughout Thailand: The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok; Faculty of Medicine, Khon Kaen; Phra Chomklao Hospital, Phetchaburi; Phrapokklao Hospital, Chanthaburi; and Chiangrai Prachanukroh Hospital, Chiangrai. To participate in the assessment, HIV-positive adolescents had to be between 12 and 24 years, perinatally infected, self-aware of HIV status, postmenarche, and not pregnant; all participants in the HIV-positive group were sexually active. Healthy controls, with no history of HIV infection, were enrolled from first-year university students in Bangkok. All participants (and their caregivers if younger than 18 years) gave consent. The study was approved by the Institutional Review Board of the Faculty of Medicine, Chulalongkorn University, Bangkok, and by the respective institutional review boards at each site. For evaluation of PMS/PMDD, with the permission of the university, we used a premenstrual symptom screening tool
(PSST), developed, validated, and adapted for use in adolescents by McMaster University, Canada.10 The PSST consists of 19 items, 14 premenstrual symptoms (13 mood-related symptoms + 1 physical symptom such as breast tenderness/headache/joint or muscle pain/bloating/weight gain) and 5 functional items (impact of PMS symptoms on daily activities), which could be self-graded as “not at all,” “mild,” “moderate,” or “severe.” As the study was designed before the implementation of DSM-5, we applied the DSM-IV criteria for PMS as follows: (1) at least 1 of 4 “core PMS symptoms as follows: anger/anxiety/sensitivity to rejection or depression,” rated either moderate or severe, (2) at least 4 additional PMS symptoms rated either moderate or severe, and (3) at least 1 of 5 “functional” items rated either moderate or severe. In case, the core PMS symptom and the functional item are graded “severe,” the condition is defined as PMDD. Reproductive history of HIV-positive participants and laboratory data from their medical records within 6 months of enrollment were collected as well. Data were analyzed by calculating median and interquartile range for quantitative characteristics and number and percentage for categorical characteristics using Stata version 11.2 (StataCorp LP, College Station, TX). Factors related to PMS/PMDD were assessed by univariate and multivariate logistic regression. Wilcoxon rank sum (Mann–Whitney) test was used to compare variables between study groups.
RESULTS Between June 2013 and August 2014, 73 perinatally HIV-infected girls (median = 19 years) and 87 healthy controls (median = 21 years) completed the PSST assessment. Baseline characteristics of the 2 groups are presented in Table 1. Most (95%) HIV-positive girls were on antiretrovirals, the median CD4 was 508 cells per cubic millimeter, and 73% had viral load (VL) ,1000 copies per milliliter. The differences between the groups in age, length of menstrual period, and education status were statistically significant. All PMS symptoms, assessed with the PSST, in the HIV-positive group were self-graded more often as not at all/mild;
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J Acquir Immune Defic Syndr Volume 70, Number 4, December 1, 2015
TABLE 1.
Letters to the Editor
Baseline Demographic, Medical, and Social Characteristics HIV+, median (IQR)/n (%)
Variable
n
Age, yrs Menarche, yrs Period length, d Route of HIV infection (perinatally) Currently studying Education #Primary .Primary to #secondary .Secondary Living with Both parents 1 parent only Relatives Partner/husband Alone Ever been pregnant Weight, kg Height, cm BMI VL, copies/mL ,40 ,1000 .1000, median = 37,355 (IQR: 13,875–241,000) CD4, cells/mm3 On ART EFV, as part of ART TDF, as part of ART Smoking Alcohol use Drug use (any) Sexual violence Forced sex Physical abuse by caregiver/partner Exchange money for sex PMS PMDD
73 73 73 73
19 13 4 73
65 63
38 (58)
(18–20) (12–15) (3–5) (100)
n
21 (20–22) 13 (12–14) 5 (5–7) NA
,0.001* 0.122 ,0.001*
87 87
87 (100)
,0.001*
0 0 87 (100) Not collected
69
71 73 73 73 71
P
87 80 77
9 (14) 38 (60) 16 (26) 10 11 24 15 9 21 47 154 19.6
HIV− (control), median (IQR)/n (%)
(14) (16) (35) (22) (13) (29) (43–50) (151–157) (17.9–21.2)
Not Not Not Not
collected collected collected collected NA
42 (59) 10 (14) 19 (27) 73 73 73 73 73 73 73 73 73 73 73 73 73
508 69 16 19 8 33 5 6 5 5 1 25 8
(347–742) (95) (22) (26) (11) (45) (7) (8) (7) (7) (1) (34) (11)
87 87
NA NA NA NA Not collected Not collected Not collected Not collected Not collected Not collected Not collected 42 (48) 10 (11)
0.074 0.915
*P , 0.05, statistically significant difference. BMI, body mass index; EFV, efavirenz; IQR, interquartile range; NA, not applicable; TDF, tenofovir.
in the control group, all symptoms were reported more often in moderate/severe grade. The impact of these symptoms on daily activities was milder in the HIVpositive group and more severe in the control group. Nevertheless, there was no statistically significant difference in the prevalence of PMS between the 2 groups (Table 1); 25 (34%) of HIV-positive adolescents met the criteria for PMS vs. 42 (48%) in the control group, P = 0.074. Eleven percent of the adolescents in each group met the PMDD criteria, P = 0.915.
In the HIV-positive group, PMS prevalence was positively associated in a univariate analysis with CD4 ,200 cells per cubic millimeter, VL .1000 copies per milliliter, history of physical abuse by caregiver or partner, and a longer duration of the menstrual period. However, neither of these relations was confirmed in the multivariate model, with an exception of a trend in case of a longer menstrual period (odds ratio = 1.3; 95% confidence interval: 0.95 to 1.88; P = 0.079).
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HIV-positive adolescents with a longer menstrual period were also more likely to have PMDD (odds ratio = 1.4; 95% confidence interval: 0.99 to 1.96; P = 0.044). No association was observed in the control group.
DISCUSSION We observed similar prevalence rates of PMS and PMDD in perinatally HIV-infected and healthy adolescents. About one-third of adolescents reported PMS, and one-tenth reported PMDD. These rates are within the wide range reported in the literature, from ,5% for severe forms up to 80% for all severity of PMS symptoms.11–16 There is a tendency for higher prevalence of PMS and PMDD in younger women, with considerable variations at an individual level.17 Earlier reports from Thailand in Thai nurses found about 25% prevalence for self-reported PMS, including PMDD, with higher rates in those below 30 years of age.18 PMS symptoms appear after ovulation and are related to the production of progesterone by the ovary7 and its interaction with the gamma-aminobutyric acid (GABAergic), the main inhibitor in the brain, and serotoninergic systems. In a similar way, PMS symptoms might be triggered by progestin components in hormonal contraceptives or hormone replacement therapy. The role of genetic influence is under study as well.19 Literature is conflicting whether HIV-positive women are less prone to PMS because of lower ovarian function. Shorter menstrual cycles, including amenorrhea, and lower rates of premenstrual symptoms such as breast tenderness and dysmenorrhea have been reported with severe HIV disease.5,20 Others have not found direct effects of HIV or immunosuppression on menstrual function.21–23 We observed a trend towards lower PMS prevalence in the HIV-positive group, but this did not reach statistical significance. Our patient population was relatively healthy with high CD4 counts and possibly had preserved ovarian function as illustrated by the onset of menarche at a similar age as those without HIV, followed by regular menstrual cycles. Most of the symptoms defining PMS are related to mood disorders. HIV-positive adolescents are generally at higher risk of mental health problems www.jaids.com |
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Letters to the Editor
in comparison with HIV-negative controls.24,25 Studies report on possible overlap between PMS and mental health disorders26–28 as well as the premenstrual state exacerbating mental health conditions.29–31 Here, we found a trend of higher PMS prevalence in HIV-positive adolescents with low CD4 and high VL, which could indicate poor adherence to ART, as well as in those with history of physical abuse by caregiver/partner. The latest relationship is explained by increased sensitivity to pain.32,33 The trend of lower PMS prevalence in the HIV-positive group may also be interpreted by a somewhat higher “resilience” in the positive group to natural “challenges.” HIV-positive adolescents with all their medical and social problems might not be unhappy to experience something, which symbolizes a normal physiological function, such as the menstrual cycle. In contrast, monthly menstrual cycle can be perceived as a much more disagreeable health/social condition by healthy first-year university students. Negative attitudes toward menstruation were associated with premenstrual symptoms and a desire for less frequent menstruation in several studies.19,34–37 Our study is limited by the small sample size and absence of complete match for age and social and educational status between the 2 groups. Nevertheless, the study provides a report on PMS prevalence in perinatally HIV-infected adolescents, using validated tools. The study also draws attention to important knowledge gaps in this field, such as a lack of a comprehensive characterization of ovarian function, as well as the lack of analysis of the complex relations between PMS and psychiatric mood disorders in perinatally HIV-infected female adolescents. In conclusion, with ART, perinatally HIV-infected children can survive, grow up, and have a development more comparable with that of the general population. Conditions, such as PMS, become common as well. The study highlights the importance of comprehensive care including clinical, reproductive health, and psychosocial support for this target population.37
ACKNOWLEDGMENTS The authors are grateful to all the study participants, as well as to the
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research and clinical staff and clients at the 5 sites of the study for their contribution to this assessment; more specifically, HIV-NAT: Amornrat Srimuan, Supalak Klungkang, Oratai Butterworth, Prapatsara Larpmahawong, Kanitta Pussadee, Ganon Yosphan, and Bencharat Thongpunchang; Khon Kaen: Chanasda Sopharak and Somjai Rattanamanee; Phetchaburi: Manee Yentang and Paweena Kaewdang; Chantaburi: Wanna Jamjumrus, Naulta Selawattanakul, and Chuleewan Siromkul; Chiangrai: Aree Sophradit, Benjamas Jongrungrotsakul, and Kannikar Saisawat. Nadia Kancheva Landolt, MD, PhD* Torsak Bunupuradah, MD* Jullapong Achalapong, MD† Pope Kosalaraksa, MD‡ Witaya Petdachai, MD§ Chaiwat Ngampiyaskul, MDk Chatsuda Auchieng, MBA, MECom* Jintanat Ananworanich, MD, PhD*¶#**†† Pongrak Boonyanurak, MD‡‡ on behalf of HIV-NAT 176 Study *The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand †Department of Obstetrics and Gynecology, Chiangrai Prachanukroh Hospital, Chiangrai, Thailand ‡Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand §Department of Pediatrics, Phra Chomklao Hospital, Phetchaburi, Thailand kDepartment of Pediatrics, Phrapokklao Hospital, Chanthaburi, Thailand ¶The Thai Red Cross AIDS Research Centre, Bangkok, Thailand #SEARCH, Bangkok, Thailand **Currently, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD ††Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD ‡‡Department of Obstetrics and Gynecology, Phra Mongkut Klao Hospital, Bangkok, Thailand
REFERENCES 1. Chokephaibulkit K, Kariminia A, Oberdorfer P, et al. Characterizing HIV manifestations and treatment outcomes of perinatally infected adolescents in Asia. Pediatr Infect Dis J. 2014;33:291–294.
2. Lolekha R, Boon-Yasidhi V, Leowsrisook P, et al. Knowledge, attitudes, and practices regarding antiretroviral management, reproductive health, sexually transmitted infections, and sexual risk behavior among perinatally HIV-infected youth in Thailand. AIDS Care. 2015;27:618–628. 3. Buchacz K, Rogol AD, Lindsey JC, et al. Delayed onset of pubertal development in children and adolescents with perinatally acquired HIV infection. J Acquir Immune Defic Syndr. 2003;33:56–65. 4. Williams PL, Abzug MJ, Jacobson DL, et al. Pubertal onset in children with perinatal HIV infection in the era of combination antiretroviral treatment. AIDS. 2013;27:1959–1970. 5. Massad LS, Evans CT, Minkoff H, et al. Effects of HIV infection and its treatment on selfreported menstrual abnormalities in women. J Womens Health (Larchmt). 2006;15:591–598. 6. Rapkin AJ, Mikacich JA. Premenstrual dysphoric disorder and severe premenstrual syndrome in adolescents. Paediatr Drugs. 2013; 15:191–202. 7. Rapkin AJ, Akopians AL. Pathophysiology of premenstrual syndrome and premenstrual dysphoric disorder. Menopause Int. 2012;18:52–59. 8. Cirillo PC, Passos RB, López JR, et al. Will the DSM-5 changes in criteria for premenstrual dysphoric disorder impact clinical practice? Rev Bras Psiquiatr. 2014;36:271. 9. American Psychiatric Association. Highlights of Changes from DSM-IV-TR to DSM-5; 2012. Available at: http://www.dsm5.org/Pages/ Default.aspx. Accessed January 1, 2015. 10. Steiner M, Peer M, Palova E, et al. The premenstrual symptoms screening tool revised for adolescents (PSST-A): prevalence of severe PMS and premenstrual dysphoric disorder in adolescents. Arch Womens Ment Health. 2011;14:77–81. 11. Yonkers KA, O’Brien PM, Eriksson E. Premenstrual syndrome. Lancet. 2008;371: 1200–1210. 12. Derman O, Kanbur NO, Tokur TE, et al. Premenstrual syndrome and associated symptoms in adolescent girls. Eur J Obstet Gynecol Reprod Biol. 2004;116:201–206. 13. Vichnin M, Freeman EW, Lin H, et al. Premenstrual syndrome (PMS) in adolescents: severity and impairment. J Pediatr Adolesc Gynecol. 2006;19:397–402. 14. Farrokh-Eslamlou H, Oshnouei S, Heshmatian B, et al. Premenstrual syndrome and quality of life in Iranian medical students. Sex Reprod Healthc. 2015;6:23–27. 15. Yang J, Joe SH, Lee MS, et al. Survey of premenstrual symptom severity and impairment in Korean adolescents: premenstrual dysphoric disorder, subthreshold premenstrual dysphoric disorder and premenstrual syndrome. Asia Pac Psychiatry. 2014;6:135–144. 16. Pal SA, Dennerstein L, Lehert P. Premenstrual symptoms in Pakistani women and their effect on activities of daily life. J Pak Med Assoc. 2011;61:763–768. 17. Ju H, Jones M, Mishra GD. Premenstrual syndrome and dysmenorrhea: symptom trajectories over 13 years in young adults. Maturitas. 2014;78:99–105. 18. Chayachinda C, Rattanachaiyanont M, Phattharayuttawat S, et al. Premenstrual syndrome
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towards long-cycle treatment with oral contraceptives. Contraception. 2004;69:37–42. 36. Lin K, Barnhart K. The clinical rationale for menses-free contraception. J Womens Health (Larchmt). 2007;16:1171–1180. 37. Lowenthal ED, Bakeera-Kitaka S, Marukutira T, et al. Perinatally acquired HIV infection in adolescents from sub-Saharan Africa: a review of emerging challenges. Lancet Infect Dis. 2014;14:627–639.
Preference for Condoms, Antiretroviral Preexposure Prophylaxis, or Both Methods to Reduce Risk for HIV Acquisition Among Uninfected US Black and Latino MSM To the Editors: Men who have sex with men (MSM) in the United States continue to be disproportionately affected by HIV, particularly those who are younger and African American/black and Latino MSM.1 Antiretroviral preexposure prophylaxis (PrEP) is an efficacious biomedical intervention for reducing HIV acquisition. An international study of MSM found PrEP efficacy levels to be 44% for the sample overall, 73% among men with good self-reported adherence, and 95% among men in which PrEP medication was detected in their blood.2 Although awareness of and access to PrEP is a concern,3 it is an additional option for reducing risk of HIV infection. This is particularly helpful since a recent study found only 70% effectiveness for condom use during anal sex among MSM.4 However, there are concerns Supported by the Secretary’s Minority AIDS Initiative Fund of the US Department of Health and Human Services and the Centers for Disease Control and Prevention under CDC research, contract no. 200-2012-53307. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. The authors have no conflicts of interest to disclose.
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Letters to the Editor
about potential “risk compensation,” wherein a large shift occurs from condom use to PrEP use, potentially resulting in little practical net benefit (or even net loss) in protection from HIV infection with less than good adherence to PrEP.5 As information about PrEP continues to reach populations that could benefit from its use, prevention practitioners must understand the potential for PrEP uptake and risk compensation. We analyzed data on behavioral intentions to use condoms, PrEP, or both methods among HIV-uninfected black and Latino MSM in the United States. Data are from Messages4Men, a 2014 cross-sectional study conducted to better understand preferences for new HIV prevention information and methods among black and Latino MSM in Chicago, Fort Lauderdale, and Kansas City. This analysis included HIV-uninfected (self-reported) black (n = 296) and Latino (n = 309) men who reported having sex with a man in the past year, recruited through online, agency, and street/venue outreach efforts. Demographic variables and anal sex without a condom in the previous 3 months were reported through computer assessment. After informing participants that a daily pill exists to prevent HIV infection (ie, PrEP) that was found to be 73% efficacious with good adherence2 and that condoms have been found to be 70% effective for anal use among MSM,4 participants were asked: If you had a choice of using condoms during anal sex or taking a pill every day to prevent HIV infection at no cost to you, which would you pick? Response options included condoms, PrEP, or both methods. Overall, 88% of the sample reported anal sex and 52% reported condomless anal sex in the past 3 months, which did not differ by race/ethnicity. More MSM preferred to use both prevention methods (43%) in the future than condoms (35%) and PrEP (22%) only. In bivariate analyses (Table 1), method preferences differed for men reporting recent behavioral risk, and by race/ethnicity, age group, and city (P , 0.05). Men who did not report recent anal sex without a condom were more likely to prefer condoms only or both methods compared with men who had risk behavior. Latino men were more www.jaids.com |
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13.
14.
15.
16.
17.
GeSida Study 8114. J Int AIDS Soc. 2014;17 (4 suppl 3):19795. Gantner P, Reinhart S, Partisani M, et al. Switching to emtricitabine, tenofovir and rilpivirine as single tablet regimen in virologically suppressed HIV-1-infected patients: a cohort study. HIV Med. 2014;16(2):132–136. Gazaignes S, Resche-Rigon M, Yang C, et al. Efficacy and safety of rilpivirine-based regimens in treatment-experienced HIV-1 infected patients: a prospective cohort study. J Int AIDS Soc. 2014;17(4 suppl 3): 19796. Wu PY, Cheng CY, Luo YZ, et al. Safety of rilpivirine plus nucleoside reversetranscriptase inhibitors in HIV-infected Taiwanese with a higher prevalence of hepatitis virus infection. J Int AIDS Soc. 2014;17(4 suppl 3):19580. Sax PE, DeJesus E, Mills A, et al; GS-US236-0102 Study Team. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks. Lancet. 2012;379: 2439–2448. Greig SL, Deeks ED. Abacavir/dolutegravir/ lamivudine single-tablet regimen: a review of its use in HIV-1 infection. Drugs. 2015;75(5): 503–514.
Premenstrual Disorders Among Perinatally HIV-Infected Adolescents To the Editors:
INTRODUCTION With antiretroviral therapy (ART), many children born with HIV survive and grow into adolescence. In some countries, over 30% of HIVpositive perinatally infected children are now above the age of 121,2 and about half of them are females.1 Girls with severe HIV disease can experience delayed onset of puberty.3,4 With earlier treatment, maturation timing seems to be normalized.4 Comparably, ART Supported by TREAT Asia/amfAR, The Foundation for AIDS Research, through a grant from ViiV Healthcare. The authors have no conflicts of interest to disclose. The views expressed are those of the authors and should not be construed to represent the positions of the US Army or the Department of Defense.
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use and higher CD4 counts have been linked to lower rates of persistent menstrual problems in behaviorally HIV-infected women.5 However, the presence of a regular menstrual cycle has been related to premenstrual syndrome (PMS) in women in the general population, with onset in the adolescent years.6 PMS is a group of physical, emotional, and behavioral symptoms in the luteal phase of the menstrual cycle, which interferes with the daily functioning of women.7 Premenstrual dysphoric disorder (PMDD), the most severe form of PMS, is included in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).6,8,9 Here, we report the prevalence of PMS and PMDD in a cohort of perinatally HIV-infected Thai adolescents compared with that of healthy controls. In addition, we evaluated factors associated with the prevalence of PMS in HIV-positive adolescents. To the best of our knowledge, this is the first report on PMS prevalence in perinatally HIVinfected adolescents.
METHODS We conducted a cross-sectional assessment of PMS in perinatally HIVinfected adolescents in 5 sites throughout Thailand: The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok; Faculty of Medicine, Khon Kaen; Phra Chomklao Hospital, Phetchaburi; Phrapokklao Hospital, Chanthaburi; and Chiangrai Prachanukroh Hospital, Chiangrai. To participate in the assessment, HIV-positive adolescents had to be between 12 and 24 years, perinatally infected, self-aware of HIV status, postmenarche, and not pregnant; all participants in the HIV-positive group were sexually active. Healthy controls, with no history of HIV infection, were enrolled from first-year university students in Bangkok. All participants (and their caregivers if younger than 18 years) gave consent. The study was approved by the Institutional Review Board of the Faculty of Medicine, Chulalongkorn University, Bangkok, and by the respective institutional review boards at each site. For evaluation of PMS/PMDD, with the permission of the university, we used a premenstrual symptom screening tool
(PSST), developed, validated, and adapted for use in adolescents by McMaster University, Canada.10 The PSST consists of 19 items, 14 premenstrual symptoms (13 mood-related symptoms + 1 physical symptom such as breast tenderness/headache/joint or muscle pain/bloating/weight gain) and 5 functional items (impact of PMS symptoms on daily activities), which could be self-graded as “not at all,” “mild,” “moderate,” or “severe.” As the study was designed before the implementation of DSM-5, we applied the DSM-IV criteria for PMS as follows: (1) at least 1 of 4 “core PMS symptoms as follows: anger/anxiety/sensitivity to rejection or depression,” rated either moderate or severe, (2) at least 4 additional PMS symptoms rated either moderate or severe, and (3) at least 1 of 5 “functional” items rated either moderate or severe. In case, the core PMS symptom and the functional item are graded “severe,” the condition is defined as PMDD. Reproductive history of HIV-positive participants and laboratory data from their medical records within 6 months of enrollment were collected as well. Data were analyzed by calculating median and interquartile range for quantitative characteristics and number and percentage for categorical characteristics using Stata version 11.2 (StataCorp LP, College Station, TX). Factors related to PMS/PMDD were assessed by univariate and multivariate logistic regression. Wilcoxon rank sum (Mann–Whitney) test was used to compare variables between study groups.
RESULTS Between June 2013 and August 2014, 73 perinatally HIV-infected girls (median = 19 years) and 87 healthy controls (median = 21 years) completed the PSST assessment. Baseline characteristics of the 2 groups are presented in Table 1. Most (95%) HIV-positive girls were on antiretrovirals, the median CD4 was 508 cells per cubic millimeter, and 73% had viral load (VL) ,1000 copies per milliliter. The differences between the groups in age, length of menstrual period, and education status were statistically significant. All PMS symptoms, assessed with the PSST, in the HIV-positive group were self-graded more often as not at all/mild;
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J Acquir Immune Defic Syndr Volume 70, Number 4, December 1, 2015
TABLE 1.
Letters to the Editor
Baseline Demographic, Medical, and Social Characteristics HIV+, median (IQR)/n (%)
Variable
n
Age, yrs Menarche, yrs Period length, d Route of HIV infection (perinatally) Currently studying Education #Primary .Primary to #secondary .Secondary Living with Both parents 1 parent only Relatives Partner/husband Alone Ever been pregnant Weight, kg Height, cm BMI VL, copies/mL ,40 ,1000 .1000, median = 37,355 (IQR: 13,875–241,000) CD4, cells/mm3 On ART EFV, as part of ART TDF, as part of ART Smoking Alcohol use Drug use (any) Sexual violence Forced sex Physical abuse by caregiver/partner Exchange money for sex PMS PMDD
73 73 73 73
19 13 4 73
65 63
38 (58)
(18–20) (12–15) (3–5) (100)
n
21 (20–22) 13 (12–14) 5 (5–7) NA
,0.001* 0.122 ,0.001*
87 87
87 (100)
,0.001*
0 0 87 (100) Not collected
69
71 73 73 73 71
P
87 80 77
9 (14) 38 (60) 16 (26) 10 11 24 15 9 21 47 154 19.6
HIV− (control), median (IQR)/n (%)
(14) (16) (35) (22) (13) (29) (43–50) (151–157) (17.9–21.2)
Not Not Not Not
collected collected collected collected NA
42 (59) 10 (14) 19 (27) 73 73 73 73 73 73 73 73 73 73 73 73 73
508 69 16 19 8 33 5 6 5 5 1 25 8
(347–742) (95) (22) (26) (11) (45) (7) (8) (7) (7) (1) (34) (11)
87 87
NA NA NA NA Not collected Not collected Not collected Not collected Not collected Not collected Not collected 42 (48) 10 (11)
0.074 0.915
*P , 0.05, statistically significant difference. BMI, body mass index; EFV, efavirenz; IQR, interquartile range; NA, not applicable; TDF, tenofovir.
in the control group, all symptoms were reported more often in moderate/severe grade. The impact of these symptoms on daily activities was milder in the HIVpositive group and more severe in the control group. Nevertheless, there was no statistically significant difference in the prevalence of PMS between the 2 groups (Table 1); 25 (34%) of HIV-positive adolescents met the criteria for PMS vs. 42 (48%) in the control group, P = 0.074. Eleven percent of the adolescents in each group met the PMDD criteria, P = 0.915.
In the HIV-positive group, PMS prevalence was positively associated in a univariate analysis with CD4 ,200 cells per cubic millimeter, VL .1000 copies per milliliter, history of physical abuse by caregiver or partner, and a longer duration of the menstrual period. However, neither of these relations was confirmed in the multivariate model, with an exception of a trend in case of a longer menstrual period (odds ratio = 1.3; 95% confidence interval: 0.95 to 1.88; P = 0.079).
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HIV-positive adolescents with a longer menstrual period were also more likely to have PMDD (odds ratio = 1.4; 95% confidence interval: 0.99 to 1.96; P = 0.044). No association was observed in the control group.
DISCUSSION We observed similar prevalence rates of PMS and PMDD in perinatally HIV-infected and healthy adolescents. About one-third of adolescents reported PMS, and one-tenth reported PMDD. These rates are within the wide range reported in the literature, from ,5% for severe forms up to 80% for all severity of PMS symptoms.11–16 There is a tendency for higher prevalence of PMS and PMDD in younger women, with considerable variations at an individual level.17 Earlier reports from Thailand in Thai nurses found about 25% prevalence for self-reported PMS, including PMDD, with higher rates in those below 30 years of age.18 PMS symptoms appear after ovulation and are related to the production of progesterone by the ovary7 and its interaction with the gamma-aminobutyric acid (GABAergic), the main inhibitor in the brain, and serotoninergic systems. In a similar way, PMS symptoms might be triggered by progestin components in hormonal contraceptives or hormone replacement therapy. The role of genetic influence is under study as well.19 Literature is conflicting whether HIV-positive women are less prone to PMS because of lower ovarian function. Shorter menstrual cycles, including amenorrhea, and lower rates of premenstrual symptoms such as breast tenderness and dysmenorrhea have been reported with severe HIV disease.5,20 Others have not found direct effects of HIV or immunosuppression on menstrual function.21–23 We observed a trend towards lower PMS prevalence in the HIV-positive group, but this did not reach statistical significance. Our patient population was relatively healthy with high CD4 counts and possibly had preserved ovarian function as illustrated by the onset of menarche at a similar age as those without HIV, followed by regular menstrual cycles. Most of the symptoms defining PMS are related to mood disorders. HIV-positive adolescents are generally at higher risk of mental health problems www.jaids.com |
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Letters to the Editor
in comparison with HIV-negative controls.24,25 Studies report on possible overlap between PMS and mental health disorders26–28 as well as the premenstrual state exacerbating mental health conditions.29–31 Here, we found a trend of higher PMS prevalence in HIV-positive adolescents with low CD4 and high VL, which could indicate poor adherence to ART, as well as in those with history of physical abuse by caregiver/partner. The latest relationship is explained by increased sensitivity to pain.32,33 The trend of lower PMS prevalence in the HIV-positive group may also be interpreted by a somewhat higher “resilience” in the positive group to natural “challenges.” HIV-positive adolescents with all their medical and social problems might not be unhappy to experience something, which symbolizes a normal physiological function, such as the menstrual cycle. In contrast, monthly menstrual cycle can be perceived as a much more disagreeable health/social condition by healthy first-year university students. Negative attitudes toward menstruation were associated with premenstrual symptoms and a desire for less frequent menstruation in several studies.19,34–37 Our study is limited by the small sample size and absence of complete match for age and social and educational status between the 2 groups. Nevertheless, the study provides a report on PMS prevalence in perinatally HIV-infected adolescents, using validated tools. The study also draws attention to important knowledge gaps in this field, such as a lack of a comprehensive characterization of ovarian function, as well as the lack of analysis of the complex relations between PMS and psychiatric mood disorders in perinatally HIV-infected female adolescents. In conclusion, with ART, perinatally HIV-infected children can survive, grow up, and have a development more comparable with that of the general population. Conditions, such as PMS, become common as well. The study highlights the importance of comprehensive care including clinical, reproductive health, and psychosocial support for this target population.37
ACKNOWLEDGMENTS The authors are grateful to all the study participants, as well as to the
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J Acquir Immune Defic Syndr Volume 70, Number 4, December 1, 2015
research and clinical staff and clients at the 5 sites of the study for their contribution to this assessment; more specifically, HIV-NAT: Amornrat Srimuan, Supalak Klungkang, Oratai Butterworth, Prapatsara Larpmahawong, Kanitta Pussadee, Ganon Yosphan, and Bencharat Thongpunchang; Khon Kaen: Chanasda Sopharak and Somjai Rattanamanee; Phetchaburi: Manee Yentang and Paweena Kaewdang; Chantaburi: Wanna Jamjumrus, Naulta Selawattanakul, and Chuleewan Siromkul; Chiangrai: Aree Sophradit, Benjamas Jongrungrotsakul, and Kannikar Saisawat. Nadia Kancheva Landolt, MD, PhD* Torsak Bunupuradah, MD* Jullapong Achalapong, MD† Pope Kosalaraksa, MD‡ Witaya Petdachai, MD§ Chaiwat Ngampiyaskul, MDk Chatsuda Auchieng, MBA, MECom* Jintanat Ananworanich, MD, PhD*¶#**†† Pongrak Boonyanurak, MD‡‡ on behalf of HIV-NAT 176 Study *The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand †Department of Obstetrics and Gynecology, Chiangrai Prachanukroh Hospital, Chiangrai, Thailand ‡Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand §Department of Pediatrics, Phra Chomklao Hospital, Phetchaburi, Thailand kDepartment of Pediatrics, Phrapokklao Hospital, Chanthaburi, Thailand ¶The Thai Red Cross AIDS Research Centre, Bangkok, Thailand #SEARCH, Bangkok, Thailand **Currently, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD ††Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD ‡‡Department of Obstetrics and Gynecology, Phra Mongkut Klao Hospital, Bangkok, Thailand
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2. Lolekha R, Boon-Yasidhi V, Leowsrisook P, et al. Knowledge, attitudes, and practices regarding antiretroviral management, reproductive health, sexually transmitted infections, and sexual risk behavior among perinatally HIV-infected youth in Thailand. AIDS Care. 2015;27:618–628. 3. Buchacz K, Rogol AD, Lindsey JC, et al. Delayed onset of pubertal development in children and adolescents with perinatally acquired HIV infection. J Acquir Immune Defic Syndr. 2003;33:56–65. 4. Williams PL, Abzug MJ, Jacobson DL, et al. Pubertal onset in children with perinatal HIV infection in the era of combination antiretroviral treatment. AIDS. 2013;27:1959–1970. 5. Massad LS, Evans CT, Minkoff H, et al. Effects of HIV infection and its treatment on selfreported menstrual abnormalities in women. J Womens Health (Larchmt). 2006;15:591–598. 6. Rapkin AJ, Mikacich JA. Premenstrual dysphoric disorder and severe premenstrual syndrome in adolescents. Paediatr Drugs. 2013; 15:191–202. 7. Rapkin AJ, Akopians AL. Pathophysiology of premenstrual syndrome and premenstrual dysphoric disorder. Menopause Int. 2012;18:52–59. 8. Cirillo PC, Passos RB, López JR, et al. Will the DSM-5 changes in criteria for premenstrual dysphoric disorder impact clinical practice? Rev Bras Psiquiatr. 2014;36:271. 9. American Psychiatric Association. Highlights of Changes from DSM-IV-TR to DSM-5; 2012. Available at: http://www.dsm5.org/Pages/ Default.aspx. Accessed January 1, 2015. 10. Steiner M, Peer M, Palova E, et al. The premenstrual symptoms screening tool revised for adolescents (PSST-A): prevalence of severe PMS and premenstrual dysphoric disorder in adolescents. Arch Womens Ment Health. 2011;14:77–81. 11. Yonkers KA, O’Brien PM, Eriksson E. Premenstrual syndrome. Lancet. 2008;371: 1200–1210. 12. Derman O, Kanbur NO, Tokur TE, et al. Premenstrual syndrome and associated symptoms in adolescent girls. Eur J Obstet Gynecol Reprod Biol. 2004;116:201–206. 13. Vichnin M, Freeman EW, Lin H, et al. Premenstrual syndrome (PMS) in adolescents: severity and impairment. J Pediatr Adolesc Gynecol. 2006;19:397–402. 14. Farrokh-Eslamlou H, Oshnouei S, Heshmatian B, et al. Premenstrual syndrome and quality of life in Iranian medical students. Sex Reprod Healthc. 2015;6:23–27. 15. Yang J, Joe SH, Lee MS, et al. Survey of premenstrual symptom severity and impairment in Korean adolescents: premenstrual dysphoric disorder, subthreshold premenstrual dysphoric disorder and premenstrual syndrome. Asia Pac Psychiatry. 2014;6:135–144. 16. Pal SA, Dennerstein L, Lehert P. Premenstrual symptoms in Pakistani women and their effect on activities of daily life. J Pak Med Assoc. 2011;61:763–768. 17. Ju H, Jones M, Mishra GD. Premenstrual syndrome and dysmenorrhea: symptom trajectories over 13 years in young adults. Maturitas. 2014;78:99–105. 18. Chayachinda C, Rattanachaiyanont M, Phattharayuttawat S, et al. Premenstrual syndrome
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Preference for Condoms, Antiretroviral Preexposure Prophylaxis, or Both Methods to Reduce Risk for HIV Acquisition Among Uninfected US Black and Latino MSM To the Editors: Men who have sex with men (MSM) in the United States continue to be disproportionately affected by HIV, particularly those who are younger and African American/black and Latino MSM.1 Antiretroviral preexposure prophylaxis (PrEP) is an efficacious biomedical intervention for reducing HIV acquisition. An international study of MSM found PrEP efficacy levels to be 44% for the sample overall, 73% among men with good self-reported adherence, and 95% among men in which PrEP medication was detected in their blood.2 Although awareness of and access to PrEP is a concern,3 it is an additional option for reducing risk of HIV infection. This is particularly helpful since a recent study found only 70% effectiveness for condom use during anal sex among MSM.4 However, there are concerns Supported by the Secretary’s Minority AIDS Initiative Fund of the US Department of Health and Human Services and the Centers for Disease Control and Prevention under CDC research, contract no. 200-2012-53307. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. The authors have no conflicts of interest to disclose.
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about potential “risk compensation,” wherein a large shift occurs from condom use to PrEP use, potentially resulting in little practical net benefit (or even net loss) in protection from HIV infection with less than good adherence to PrEP.5 As information about PrEP continues to reach populations that could benefit from its use, prevention practitioners must understand the potential for PrEP uptake and risk compensation. We analyzed data on behavioral intentions to use condoms, PrEP, or both methods among HIV-uninfected black and Latino MSM in the United States. Data are from Messages4Men, a 2014 cross-sectional study conducted to better understand preferences for new HIV prevention information and methods among black and Latino MSM in Chicago, Fort Lauderdale, and Kansas City. This analysis included HIV-uninfected (self-reported) black (n = 296) and Latino (n = 309) men who reported having sex with a man in the past year, recruited through online, agency, and street/venue outreach efforts. Demographic variables and anal sex without a condom in the previous 3 months were reported through computer assessment. After informing participants that a daily pill exists to prevent HIV infection (ie, PrEP) that was found to be 73% efficacious with good adherence2 and that condoms have been found to be 70% effective for anal use among MSM,4 participants were asked: If you had a choice of using condoms during anal sex or taking a pill every day to prevent HIV infection at no cost to you, which would you pick? Response options included condoms, PrEP, or both methods. Overall, 88% of the sample reported anal sex and 52% reported condomless anal sex in the past 3 months, which did not differ by race/ethnicity. More MSM preferred to use both prevention methods (43%) in the future than condoms (35%) and PrEP (22%) only. In bivariate analyses (Table 1), method preferences differed for men reporting recent behavioral risk, and by race/ethnicity, age group, and city (P , 0.05). Men who did not report recent anal sex without a condom were more likely to prefer condoms only or both methods compared with men who had risk behavior. Latino men were more www.jaids.com |
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