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Clinical manifestations of infection with human immunodeficiency virus among adolescents in Louisiana
J O U R N A L OF ADOLESCENT H E A L T H 1996;18:422-428
ORIGINAL ARTICLE
Clinical Manifestations of Infection with Human Immunodeficiency Virus Among Adolescents in Louisiana CRYSTAL FULLER, M.P.H., REBECCA A. CLARK, M.D., PH.D., PATRICIA KISSINGER, PH.D., AND SUE ELLEN ABDALIAN, M.D.
Purpose: There is limited information regarding the clinical manifestations of human immunodeficiency virus (HIV) infection among adolescents. To better define the clinical presentation and course of HIV disease in this population, a retrospective review of all HIV-infected persons age 13-21 years at entry into a public, inner-city HIV outpatient clinic in New Orleans, Louisiana, was undertaken. Results: A total of 141 adolescents were included in this study. The cohort was predominantly female (65%) and African-American (83%), and acquired HIV infection through sexual contact (89%). As many as 75% of the females and 48% of the males were diagnosed with at least one sexually transmitted disease (STD), respectively, and young African-American females with a C D 4 cell count > 5 0 0 / m m 3 w e r e at highest risk. The proportions of female adolescents having a gravida >_ 1 and 2 were 82% and 20%, respectively. A total of 55% of females were diagnosed with squamous intraepithelial lesions (SIL) at least once. Similar to adults, the majority of opportunistic processes occurred in adolescents with a C D 4 cell count < 2 0 0 / m m 3. Known HIV-related symptoms (oral hairy leukoplakia, thrush, and zoster) were significantly predictive (p < .0001) for HIV disease progression. Conclusions: Although HIV-related symptoms and infections do not appear to be unique in the adolescent population, it is clear that STDs and pregnancies are common among female adolescents. Our results empha-
From the HIV Outpatient Program, Medical Center of Louisiana at New Orleans, New Orleans, Louisiana. Address correspondence to: Rebecca A. Clark, M.D., Ph.D., Infectious Diseases Section, LSU Medical Center, 1542 Tulane Avenue, New Orleans, LA 70112. Manuscript accepted July 30, 1995. 1054-139X/96/$15.00 SSDI 1054-139X(95)00235-9
size the need for aggressive STD and contraceptive protection counseling, and surveillance screening for STDs and cervical dysplasia.
KEY WORDS:
HIV infection Acquired immunodeficiency syndrome Sexually transmitted diseases Opportunistic infections HW-related processes
H u m a n i m m u n o d e f i c i e n c y virus (HIV) infection is an i m p o r t a n t cause of m o r b i d i t y a n d mortality in adolescents as e v i d e n c e d b y the mortality statistics in the United States. The Centers for Disease Control (CDC) r e p o r t e d in 1992 that AIDS w a s the sixth leading cause of d e a t h a m o n g 15-24-year-olds in the United States a n d the fifth leading cause of d e a t h a m o n g African-Americans of the s a m e age g r o u p (1). As a result of the a v e r a g e 10-year incubation period of H I V prior to the onset of AIDS, the majority of p e r s o n s w i t h AIDS b e t w e e n the ages of 25 a n d 35 w e r e likely infected d u r i n g adolescence (2). Alt h o u g h adolescents h a v e c o m p r i s e d only a small p r o p o r t i o n (2%) of the total n u m b e r of AIDS cases (1), the c u m u l a t i v e n u m b e r of AIDS cases a m o n g 13-19-year-olds in the United States increased f r o m 127 (3) to 1,965 (4) f r o m J a n u a r y 1987 t h r o u g h D e c e m b e r 1994. In addition, 13-19-year-olds accounted for 27% of m a l e and 7% of female HIVinfected non-AIDS cases r e p o r t e d in 1994 (4). The seroprevalence of H I V infection has b e e n
© Society for Adolescent Medicine, 1996 Published by Elsevier Science Inc., 655 Avenue of the Americas, New York, NY 10010
June 1996
noted to be relatively high in four studies examining high-risk adolescent youth. The Job Corps, a federally funded job training program for youth lacking formal education and/or of low socioeconomic status, found that seroprevalence among 16-20-yearolds was 3.9/1,000 (5). Two sentinel hospitals chosen for HIV screening by the Centers for Disease Control as communities of high AIDS prevalence determined HIV seroprevalence ranged from 11-38/1,000 in adolescents 15-19 years of age (6). In a 5-year study conducted in Washington, DC, the seroprevalence among urban adolescents ranged from 4.03-19.94/ 1,000 between 1987 and 1992 (7). A recent analysis of demographic and geographic trends of HW infection among Job Corps students from January 1988 through December 1992 demonstrated that the seroprevalence of HIV infection for young men actually decreased from 3.6/1,000 in 1988 to 2.2/1,000 in 1992, but the seroprevalence for young women increased from 2.1/1,000 to 4.2/1,000 (8). At the beginning of the 2nd decade of HIV disease, little clinical research has been done on HIVinfected adolescents. Most of the literature reviews the epidemiology, attitude, and behaviors of HIVinfected adolescents (9,10). Only one prior study described clinical manifestations in an adolescent population evaluated through the New York AIDS Program at the Montefiore Medical Center (11). To better define the clinical presentation and course of HIV disease in this population, a retrospective review of all HIV-infected adolescents enrolled in a public inner-city HIV outpatient clinic in New Orleans, Louisiana, was undertaken.
Methods All HW-infected adolescents between the ages of 13 and 21 years entering the HW Outpatient Program (HOP) of the Medical Center of Louisiana at New Orleans (MCLNO) from November 1, 1989, through February 1, 1994, were included in the study. The cohort was followed through October 1, 1994. Data were retrospectively collected through medical chart review and the hospital laboratory data base. In addition to demographic information, extensive information on clinical processes common among HWinfected adolescents was collected. Routine semiannual evaluations included ascertainment of HIV-related symptomatology, directed physical examinations including pelvic or genitourinary examinations, performance of immunodefi-
HW INFECTIONAMONGADOLESCENTS
423
ciency panels (CD4 cell counts), Papanicolaou smear testing, and surveillance screening for Neisseria gonorrhoeae and Chlamydia trachomatis infections. Syphilis serology was done annually. The HIV disease status of adolescents with a CD4 cell count < 500/ mm a was evaluated more frequently. Pelvic examinations were performed between the semiannual evaluations if warranted by clinical symptoms such as a new vaginal discharge or lower abdominal pain. Neisseria gonorrhoeae and C. trachomatis were determined by culture and use of an enzyme-linked immunosorbent assay test for the Chlamydia antigen. Trichomoniasis was detected by visualization of motile trichomonads on vaginal secretion saline preparations or evidence on Papanicolaou smear results. Candida vulvovaginitis was diagnosed in female adolescents with a positive potassium hydroxide preparation and accompanying characteristic signs or symptoms. Bacterial vaginosis was detected by the presence of > 20% clue cells on the vaginal secretion saline preparation and a positive "whiff test." Health care providers diagnosed pelvic inflammatory disease (PID) by characteristic signs and symptoms, such as lower abdominal, adnexal, or cervical motion tenderness, purulent cervical discharge, and fever, in conjunction with positive studies for N. gonorrhoeae or C. trachomatis. Infection with human papiUomavirus (HPV) was determined by Papanicolaou smear results or clinical findings on physical examination (such as irregular, nonumbilicated, verrucous lesions; spiked lesions; broad based fiat lesions; and single or clusters of calfliflower-like masses). Surveillance screening for N. gonorrhoeae and C. trachomatis was performed in males having biannual screening urinalyses reveal positive white blood cell (WBC) esterase. Males were determined to have nongonococcal urethritis (NGU) if urethritis signs or symptoms were present and testing for N. gonorrhoeae was negative. We used BMDP software for analyses (BMDP Statistical Software, Chicago, IL). Chi-square methods were utilized for bivariate analyses, and logistic regression techniques were used for multivariate modeling. Using an outcome of a 1993 CDC AIDS documented incident defining opportunistic process, selected entry variables were examined for prognostic significance in Cox proportional hazard models. The cumulative risks for AIDS (as defined by a opportunistic process definition) in subpopulations stratified by selected variables were determined using Kaplan-Meier methods (12).
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Table 1. Demographic Characteristics of Adolescents Male (n = 50)
Female (n = 91)
38 (76%) 12 (24%)
79 (87%) 12 (13%)
~.10
13 (26%) 37 (74%)
50 (55%) 41 (45%)
~.001
29 (56%) 6 (12%) 3 (6%) 1 (2%) 12 (24%)
0 (0%) 8 (9%) 42 (46%) 1 (1%) 40 (44%)
~.11
437.0 (39 SE) 27 (55%) 22 (45%)
582.0 (40 SE) 31 (37%) 52 (62%)
p
Race
African-American White Age -<18 yr ->19 yr Mode of transmission Homosexual Injection drug use Heterosexual Hemophiliac/bloodexposure NIR Entry blood C D 4 / m m 3 (median, n = 132) K500/mm 3 ~500/mm 3
~.05
NIR = No identifiable risk.
Results A total of 141 adolescents were included in this study. The cohort was p r e d o m i n a n t l y female (65%) and African-American (83%), and acquired HIV infection t h r o u g h sexual contact (56% of males rep o r t e d h o m o s e x u a l transmission, 50% of the females reported heterosexual transmission). Females rep o r t e d no identifiable risk (44%) more often than males (24%). The majority of the males entered the clinic at the age of 19 years or older (74%), whereas most females entered the clinic at an age of 18 years or y o u n g e r (55%), and gravid (53%) (Table 1). Females were y o u n g e r and had less a d v a n c e d HIV disease as evidenced b y a higher m e d i a n CD 4 cell count and smaller p r o p o r t i o n defined with a 1993 AIDS opportunistic process (13) (Table 1). Mean individual follow-up times for male and female adolescents were 22.3 and 24.9 months, respectively. There was a high prevalence and incidence of STDs, particularly in females as s h o w n in Table 2. A total of 75% and 48% of the females and males were diagnosed with at least one STD at study entry or follow-up, respectively. Although not significant, y o u n g African-American adolescent females with a CD 4 cell count ~ 5 0 0 / m m 3 were most likely to be diagnosed with an incident STD, as s h o w n in Table 3. Gravida and p r i m a r y contraceptive m e t h o d were not associated with an STD, with one exception. Although females using a h o r m o n a l contraceptive m e t h o d were more frequently diagnosed with a STD, this was not significant. Abstinence was the only significantly associated m e t h o d demonstrating that
females opting for this m e t h o d were less likely to be diagnosed with an STD. The majority of females (55%) had at least one Papanicolaou smear demonstrating SIL, and nearly one third (29%) had clinical evidence of HPV infection. Race, age, pregnancy, CD 4 cell count K 500/ m m 3, and h o r m o n a l m e t h o d of contraception were not significantly associated with SIL in a logistic regression multivariate model. An HPV finding [relative risk (RR) 6.8, 95% confidence interval (CI) 1.7-26.9, p ~ .003] was the only factor significantly associated with SIL after adjustment for the abovelisted nonsignificant variables in the multivariate model. A 1993 CDC AIDS-defining process occurred pred o m i n a n t l y in i m m u n o c o m p r o m i s e d adolescents as evidenced by the low m e d i a n C D 4 cell count of 6 9 / m m 3. As s h o w n in Table 4, the majority of opportunistic processes occurred in adolescents with a CD 4 cell count ~ 2 0 0 / m m 3. Not surprisingly, k n o w n HIV-related s y m p t o m s [oral hairy leukoplakia (OHL), thrush, and zoster] were noted in adolescents with relatively low m e d i a n C D 4 cell counts (96-273/mm3). Conversely, adolescents diagnosed with c o m m o n infections (upper respiratory infections, bronchitis, pharyngitis, and otitis) probably not related to their HIV infection had higher CD 4 cell counts (400-454/mm3). Although the risk for dermatitis, sinusitis, and gingivitis m a y have been influenced by HIV infection, adolescents with these processes generally had a CD 4 cell count ~ 5 0 0 / m m 3, suggesting that it was unlikely that these s y m p t o m s
June 1996
HIV INFECTIONAMONG ADOLESCENTS
Table 2. Clinical and Laboratory Characteristics of
Adolescents
STD prevalence during study period* Neisseria gonorrhoeae Chlamydia trachomatis
Syphilis Trichomoniasis Pelvic inflammatory disease Herpes simplex virus Human papilloma virus (HPV) Nongonococcal urethritis Genital ulcer disease Incident STD+
Male (n = 50) 24 (48%)
Female (n = 91) 68 (75%)
5 (10%) 1 (2%) 8 (16%) 0 (0%) 8 (16%) 8 (16%)
38 (42%) 23 (25%) 21 (23%) 45 (50%) 7 (8%) 18 (20%) 40 (44%)
1 (2%) 2 (4%) 7 (14%)
1 (1%) 42 (38%)
Candida vulvovaginitis Bacterial vaginosis
39 (43%) 26 (29%)
Gravida ~1 Gravida ~2
75 (82%) 18 (20%)
Papanicolaou smear results (n = 58)* Ever atypia Ever HPV expression Ever low or high-grade squamous intraepithelial lesions
21 (36%) 17 (29%) 32 (55%)
AIDS defining opportunistic infection§
12 (24%)
10 (11%)
p <.001
<.001
<.04
* Defined by every having N. gonorrhoeae,C. trachomatis, syphilis, trichomoniasis, pelvic inflammatory disease, herpes simplex virus, human papilloma virus, nongonococcal urethritis, or genital ulcer disease at study entry or during the study period, p refers to the gender difference in overall STD prevalence. The gender differences for individual STDs were not tested. +Defined as having at least one incident case of N. gonorrhoeae, C. trachomatis, or syphilis after study entry. Prevalent results of Papanicolaou smear samples from 58 adolescent females who had three consecutive 6-month pelvic examinations. § AIDS-defining opportunistic infection according to the 1993 Centers for Disease Control definition.
w e r e associated with i m m u n o s u p p r e s s i o n in this population. Interestingly, the m e d i a n CD 4 cell count for adolescents diagnosed with c o m m u n i t y - a c q u i r e d pneumonia ( 2 7 0 / m m 3) was similar to that n o t e d in adults (14,15) and was relatively low, suggesting that pneumonia in adolescents was probably related to their HIV infection. H o w e v e r , unlike HIV-infected adult w o m e n (14), the m e d i a n CD 4 cell count of adolescents diagnosed with Candida vulvovaginitis and SIL was > 4 5 0 / m m 3, implying these processes occur
425
early in the course of HIV infection in this population. The majority of adolescents with a CD4 cell count < 5 0 0 / m m 3 (34 of 54 females and 29 of 33 males) were prescribed an antiretroviral agent at some time d u r i n g the study. Males were significantly m o r e likely to have used antiretrovirals (p < .02). Only 3 (2 females and 1 male) adolescents with all CD4 cell counts > 5 0 0 / m m 3 were prescribed antiretrovira! treatment d u r i n g the s t u d y period. The cumulative risk for a 1993 CDC AIDS-defining opportunistic process in the cohort was 11% and 29% at 12 and 48 months, respectively. As s h o w n in Table 5 and Figure 1, HIV-related s y m p t o m a t o l o g y was highly significant in predicting HIV disease progression (p < .001). The cumulative risk for AIDS in adolescents with these s y m p t o m s was dramatically increased (35% vs. 4% at 12 m o n t h s and 71% vs. 26% at 48 months), as s h o w n in Figure 1. A total of five adolescents in the cohort died d u r i n g the study. Four entered clinic care with a history of a 1993 AIDS-defining opportunistic process and the fifth was diagnosed with an o p p o r t u nistic process 9 m o n t h s later. The m e d i a n entry CD4 cell count of deceased adolescents was 1 5 5 / m m 3 (range 1 5 - 1 5 6 / m m 3) excluding the non-AIDS clinic entry adolescent w h o entered with a CD4 cell count of 8 5 9 / m m 3.
Discussion
Unlike the two prior reports (11,16) describing HIVinfected adolescents, the majority of adolescents in the N e w Orleans cohort w e r e female, p r o b a b l y as a result of the highly successful prenatal screening p r o g r a m based at the MCLNO. As implied b y the y o u n g e r age and higher entry CD4 cell count in the N e w Orleans female adolescents, infection with HIV in females m a y have been detected earlier than in males, which could also be d u e to the prenatal screening program. A g e n d e r age difference could also be explained if adolescent female acquired HIV infection t h r o u g h sexual initiation with older men. Demographic characteristics of the initial 605 adolescent cases of AIDS in the United States w e r e reported b y V e r m u n d et al. (16). A total of 16% of this early cohort w e r e injection d r u g users (IDU). The proportions of both the N e w Orleans cohort and NYC cohort r e p o r t e d to have acquired the infection b y injection d r u g use were lower (10 and 8%, respectively). The difference b e t w e e n these proportions suggests that either transmission of HIV infection
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T a b l e 3. G y n e c o l o g i c a n d R e p r o d u c t i v e C h a r a c t e r i s t i c s of F e m a l e A d o l e s c e n t s W i t h a n I n c i d e n t of T r a n s m i t t e d D i s e a s e (n = 91)
Race African-American White Age -<18 yr >-19 yr CD4/mm 3 at clinic entry (median, n = 83) <500/mm 3 >500/ram 3 AIDS defining opportunistic process* Gravida >-1 Gravida -<2 Primary mode of contraception (n = 83)* N o r p l a n t / d e p o provera/oral contraception Condom Tubal sterilization Abstinence
Incident STD (n - 38)*
No Incident STD (n = 53)
36 (95%) 2 (5%)
43 (81%) 10 (19%)
<.06
25 (66%) 13 (34%)
25 (47%) 28 (53%)
<.08
672.0 (62 SE) 10 (26%) 28 (74%) 5 (13%) 30 (79%) 8 (21%)
537.0 (46 SE) 21 (47%) 24 (53%) 5 (9%) 45 (85%) 10 (19%)
<.58 <.60 <.81
20 (59%) 12 (34%) 2 (6%) 1 (3%)
20 (41%) 10 (20%) 6 (12%) 11 (22%)
<.11 <.16 <.34 <.02
p
<.06
* Incident STD defined as having at least one incident case of Neisseria gonorrhoeae, Chlamydia
trachomatis, or syphilis after study entry. * AIDS-defining opportunistic process by the CDC 1993 definition. * Adolescents advised to use condoms in addition to primary method.
T a b l e 4. I n c i d e n t O p p o r t u n i s t i c I n f e c t i o n s a n d O t h e r C o m m o n P r o c e s s e s A m o n g Adolescents n (%) 1993 AIDS-defining processes Pneumocystis carnii pneumonia Candidiasis, esophageal Herpes simplex Dementia Cryptosporidiosis Cryptococcosis Wasting syndrome Probable HIV-related processes Oral hairy leukoplakia Thrush Zoster Possible HIV-related processes Pneumonia Dermatitis/folliculitis Sinusitis/rhinitis Gingivitis Probable non-HIV-related processes Upper-respiratory infection/bronchitis Pharyngitis/tonsillitis Otitis Female specific possible HIV-related processes Candida vulvovaginitis Squamous intraepithilial lesions
9 8 2 1 1 1 1
(6.4) (5.7) (1.4) (0.7) (0.7) (0.7) (0.7)
CD4/mm 3 Median (SE) 206.8 (190.9)* 206.2 (227.6)* 126.7 (146.0)* 250.5 (303.3)* Unknown 169 + 150' 36*
5 (4) 26 (18) 3 (2)
96 (82) 321 (309) 272 (344)
11 41 32 11
350 468 466 591
(8) (29) (23) (8)
(299) (293) (230) (320)
26 (18) 15 (11) 7 (5)
398 (275) 491 (275) 407 (289)
39 (43) 25 (37)
591 (304)* 549 (263)*
* CD4/mm 3 counts taken within 3 months of diagnosis; P. carnii pneumonia (n = 6), candidiasis, esophageal (n = 6), Herpes simplex (n = 2), Candida vulvovaginitis (n = 31), squamous intraepithileal lesions (n = 22). * CD4/mm 3 count taken more than 3 months prior to diagnosis; cryptosporidiosis (8 months prior), cryptococcosis (14 months prior).
June 1996
HIV INFECTION AMONG ADOLESCENTS
Table 5. Clinical Factors Associated With Having an Opportunistic Process (n = 132)
Hazard Ratio
95% C!
0.5 2.8 0.5
(0.2-1.3) (0.8-10.7) (0.1-1.7)
<0.15 <0.10 <0.28
2.6 7.8 0.5
(0.7-9.1) (2.8-21.7) (0.1-1.8)
<0.12 <.0001 <0.24
Female gender African-American Injection drug use a n d / o r street drug use C D 4 / m m 3 cell < 500 OHL/Thrush/Zoster* Antiretroviral use*
p
* Patient had either oral hairy leukoplakia(OHL)or thrush, or zoster, at study entry or during study period. *Use of antiretrovirals including zidovudine (AZT), didanosine (DDI),and zalcitabine (DDC) during study period.
through sexual contact is proportionally increasing or methods used in ascertaining mode of transmission are improving. Even though the vast majority of New Orleans female adolescents were documented to use condoms for contraception, the high incidence of STDs among New Orleans adolescents showed that STD protection was either inconsistently or inappropriately utilized. It is therefore probable that sexual transmission of HIV infection will continue to escalate among adolescents in the New Orleans area. Sexually transmitted diseases were more frequently detected in female adolescents in this study. Surveillance bias may have contributed to the significant gender differences for N. gonorrhoeae and C. trachomatis. Although testing for these infections were performed in symptomatic males (those with
427
signs or symptoms or positive WBC esterase on urinalyses), asymptomatic males did not undergo routine surveillance screening. Even though males with urethritis are believed to be generally symptomatic, one study found a chlamydial isolation rate over 11% in asyrnptomatic males (17). Syphilis infection frequencies were comparable between females (23% vs. 23%) and males (15% vs. 16%) in the NYC (11) and New Orleans cohorts, respectively. Neisseria gonorrhoeae and C. trachomatis cervicitis prevalence rates were noticeably higher among New Orleans females, but pelvic inflammatory disease occurred 3.6 times more frequently among NYC females (11). The reason for this discrepancy is unclear, because management protocols (i.e., surveillance screening every 6 months) and the ages of the females did not differ between the NYC and New Orleans studies. In addition to other STDs, HPV infections and SIL were common among both the NYC and New Orleans cohorts (11). Although thrush, a symptom known to be HIVrelated, occurred relatively frequently, other symptoms and opportunistic processes clearly associated with HIV immunosuppression were rare, which was probably due to the limited number of adolescents in the study with a CD 4 cell count < 200/mm 3. The most commonly diagnosed AIDS-defining processes were PCP and Candida esophagitis, and the median CD4 cell count of adolescents diagnosed with these infections was also analogous to the findings in adults (14,15). The highly significant predictive value of HIV-related signs and symptoms was also not surprising because of prior findings in adults (18,19).
- 80%
0
(n=32)
70% "o
. . . . . . . . . . . . . . . . . . . . . . . . . .
.~ 60%
. . . . . . . . . . . . . . . . . . . . . . /
=~50% "~. 40%
9
.
30%
.
.
.
.
........
.
.
.
. r
.
.
.
.
.
.
.
.
.
.
.
.
.
i
.
(n=109)
. . . . . . . . . . . . . . . .
>~ 20% ~= 10%
8 0% - ~ - + - - - - - ~ 0
6
12
18
24
30
36
42
48
Time from clinic entry to incident OI (months)
[~" HIV related t
process
Conclusions
ft ~
--No HIV related
process
I I
HIV related process=oral hairy leukoplakia/thrush/zoster Ol=Opportunistic Infections
Figure 1. The cumulative risk for being diagnosed with an AIDSdefining opportunistic process in H1V-infected adolescents (n = 141).
With the increasing number of adolescents becoming HIV-infected, development of strategies for early diagnosis and provision of comprehensive medical and psychosocial services are vitally important. The predominance of females in the New Orleans cohort demonstrates that prenatal screening programs can be very effective in the early detection of HIV infection in female adolescents, and demonstrates that HIV screening with appropriate counseling should be offered to all pregnant adolescents. Although HIV-related symptoms and infections do not appear to be unique in the adolescent population, it is clear that STDs are common. The results from both this study and the NYC study emphasize the need for aggressive STD and contraceptive protection counseling and frequent routine STD and
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FULLER ET AL.
cervical dysplasia screening among adolescents. HIV-infected adolescents present a challenge to clinicians because of the limited information and the medical, developmental, and psychosocial issues in this population. Future prospective studies are warranted to better define HIV-related manifestations in adolescents and assist in the development of primary care programs targeted for HIV-infected youth.
JOURNAL OF ADOLESCENT HEALTH Vol. 18, No. 6
lescents: A five-year study. Presented at the Annual Meeting of the Society for Adolescent Medicine; March 20, 1993; Chicago, IL. 8. Conway GA, Epstein MR, Hayman CR, et al. Trends in HIV prevalence among disadvantaged youth: Survey results from a national job training program, 1988 through 1992. JAMA 1993;269:2887-9. 9. Kipke MD, Hein K. Acquired immunodeficiency syndrome (AIDS) in adolescents. Adolescent Med. State Art Rev 1990;1: 429-49.
The authors acknowledge the adolescent patients enrolled into the HIV Outpatient Program (HOP) and the HOP personnel who facilitated data collection.
10. Anderson MM, Morris RE. HIV and adolescents. Pediatric A n n 1993;22:436-45.
References
12. BMDP Statistical Software, vol. 2. University of California, Berkeley, 1992.
1. Monthly Vital Statistics Report, 1994. Hyattsville, MD: CDC/ National Center for Health Statistics, 1994. (The advanced report of final mortality statistics; vol. 43, no. 6, suppl, December 1994). 2. U.S. Govermnent Printing Office, Superintendent of Documents, U.S. Department of Commerce, 1990. Springfield, VA: National Technical Information Service. (Selected behaviors that increase risk for HIV infection among high school stud e n t s - U n i t e d States, 1990; vol. 41, no. 14, April 1990). 3. Centers for Disease Control, 1987. Atlanta, GA: U.S. Department of Health and H u m a n Services, Public Health Service, 1987. (AIDS surveillance report; January 1987). 4. Centers for Disease Control, 1994. Atlanta, GA: U.S. Department of Health and H u m a n Services, Public Health Service. (HIV/AIDS surveillance report, January 1994). 5. St. Louis ME, Conway GA, Hayman CR, et al. HIV infection in disadvantaged adolescents in the US: Findings for the Job Corps screening program. JAMA 1991;266:2387-91. 6. St. Louis ME, Rauch KJ, Petersoen LR, et al. Seroprevalence rates of h u m a n immunodeficiency virus infection at sentinel hospitals in the United States. N Engl J Med 1990;323:213-8. 7. D'Angelo LJ, Getson PR, Brasseux CO, et al. The increasing prevalence of h u m a n immunodeficiency virus in urban ado-
11. Futterman D, Hein K, Reuben N, et al. H u m a n immunodeficiency virus-infected adolescents: The first 50 patients in a New York City program. Pediatrics 1993;91:730-5.
13. Centers for Disease Control. 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. Morb Mort Wkly Rep 1992;41:1-19. 14. Clark RA, Brandon W, Dumestre J, et al. Clinical manifestations of infection with the h u m a n immunodeficiency virus in women in Louisiana. Clin Infect Dis 1993;17:165-72. 15. Greenberg AE, Thomas PA, Landesman SH, et al. The spectrum of HIV-1 related disease among outpatients in New York City. AIDS 1992;6:849-59. 16. Vermund SH, Hein K, Gayle HD, et al. Acquired imrnunodeficiency syndrome among adolescents. Am J Dis Child 1989; 143:1220-5. 17. Podoore JK, Holmes KK, Alexander ER. Asymptomatic urethral infections due to Chlamydia trachomatis in male U.S. military personnel. J Infect Dis 1982;146:828. 18. Katz MH, Greenspan D, Westenhouse J, et al. Progression to AIDS in HIV infected homosexual and bisexual men with hairy leukoplakia and oral candidiasis. AIDS 1992;6:95-100. 19. Melbye M, Grissman RJ, Goedert JJ, et al. Risk of AIDS after Herpes zoster. Lancet 1987;1:728-30.
ORIGINAL ARTICLE
Clinical Manifestations of Infection with Human Immunodeficiency Virus Among Adolescents in Louisiana CRYSTAL FULLER, M.P.H., REBECCA A. CLARK, M.D., PH.D., PATRICIA KISSINGER, PH.D., AND SUE ELLEN ABDALIAN, M.D.
Purpose: There is limited information regarding the clinical manifestations of human immunodeficiency virus (HIV) infection among adolescents. To better define the clinical presentation and course of HIV disease in this population, a retrospective review of all HIV-infected persons age 13-21 years at entry into a public, inner-city HIV outpatient clinic in New Orleans, Louisiana, was undertaken. Results: A total of 141 adolescents were included in this study. The cohort was predominantly female (65%) and African-American (83%), and acquired HIV infection through sexual contact (89%). As many as 75% of the females and 48% of the males were diagnosed with at least one sexually transmitted disease (STD), respectively, and young African-American females with a C D 4 cell count > 5 0 0 / m m 3 w e r e at highest risk. The proportions of female adolescents having a gravida >_ 1 and 2 were 82% and 20%, respectively. A total of 55% of females were diagnosed with squamous intraepithelial lesions (SIL) at least once. Similar to adults, the majority of opportunistic processes occurred in adolescents with a C D 4 cell count < 2 0 0 / m m 3. Known HIV-related symptoms (oral hairy leukoplakia, thrush, and zoster) were significantly predictive (p < .0001) for HIV disease progression. Conclusions: Although HIV-related symptoms and infections do not appear to be unique in the adolescent population, it is clear that STDs and pregnancies are common among female adolescents. Our results empha-
From the HIV Outpatient Program, Medical Center of Louisiana at New Orleans, New Orleans, Louisiana. Address correspondence to: Rebecca A. Clark, M.D., Ph.D., Infectious Diseases Section, LSU Medical Center, 1542 Tulane Avenue, New Orleans, LA 70112. Manuscript accepted July 30, 1995. 1054-139X/96/$15.00 SSDI 1054-139X(95)00235-9
size the need for aggressive STD and contraceptive protection counseling, and surveillance screening for STDs and cervical dysplasia.
KEY WORDS:
HIV infection Acquired immunodeficiency syndrome Sexually transmitted diseases Opportunistic infections HW-related processes
H u m a n i m m u n o d e f i c i e n c y virus (HIV) infection is an i m p o r t a n t cause of m o r b i d i t y a n d mortality in adolescents as e v i d e n c e d b y the mortality statistics in the United States. The Centers for Disease Control (CDC) r e p o r t e d in 1992 that AIDS w a s the sixth leading cause of d e a t h a m o n g 15-24-year-olds in the United States a n d the fifth leading cause of d e a t h a m o n g African-Americans of the s a m e age g r o u p (1). As a result of the a v e r a g e 10-year incubation period of H I V prior to the onset of AIDS, the majority of p e r s o n s w i t h AIDS b e t w e e n the ages of 25 a n d 35 w e r e likely infected d u r i n g adolescence (2). Alt h o u g h adolescents h a v e c o m p r i s e d only a small p r o p o r t i o n (2%) of the total n u m b e r of AIDS cases (1), the c u m u l a t i v e n u m b e r of AIDS cases a m o n g 13-19-year-olds in the United States increased f r o m 127 (3) to 1,965 (4) f r o m J a n u a r y 1987 t h r o u g h D e c e m b e r 1994. In addition, 13-19-year-olds accounted for 27% of m a l e and 7% of female HIVinfected non-AIDS cases r e p o r t e d in 1994 (4). The seroprevalence of H I V infection has b e e n
© Society for Adolescent Medicine, 1996 Published by Elsevier Science Inc., 655 Avenue of the Americas, New York, NY 10010
June 1996
noted to be relatively high in four studies examining high-risk adolescent youth. The Job Corps, a federally funded job training program for youth lacking formal education and/or of low socioeconomic status, found that seroprevalence among 16-20-yearolds was 3.9/1,000 (5). Two sentinel hospitals chosen for HIV screening by the Centers for Disease Control as communities of high AIDS prevalence determined HIV seroprevalence ranged from 11-38/1,000 in adolescents 15-19 years of age (6). In a 5-year study conducted in Washington, DC, the seroprevalence among urban adolescents ranged from 4.03-19.94/ 1,000 between 1987 and 1992 (7). A recent analysis of demographic and geographic trends of HW infection among Job Corps students from January 1988 through December 1992 demonstrated that the seroprevalence of HIV infection for young men actually decreased from 3.6/1,000 in 1988 to 2.2/1,000 in 1992, but the seroprevalence for young women increased from 2.1/1,000 to 4.2/1,000 (8). At the beginning of the 2nd decade of HIV disease, little clinical research has been done on HIVinfected adolescents. Most of the literature reviews the epidemiology, attitude, and behaviors of HIVinfected adolescents (9,10). Only one prior study described clinical manifestations in an adolescent population evaluated through the New York AIDS Program at the Montefiore Medical Center (11). To better define the clinical presentation and course of HIV disease in this population, a retrospective review of all HIV-infected adolescents enrolled in a public inner-city HIV outpatient clinic in New Orleans, Louisiana, was undertaken.
Methods All HW-infected adolescents between the ages of 13 and 21 years entering the HW Outpatient Program (HOP) of the Medical Center of Louisiana at New Orleans (MCLNO) from November 1, 1989, through February 1, 1994, were included in the study. The cohort was followed through October 1, 1994. Data were retrospectively collected through medical chart review and the hospital laboratory data base. In addition to demographic information, extensive information on clinical processes common among HWinfected adolescents was collected. Routine semiannual evaluations included ascertainment of HIV-related symptomatology, directed physical examinations including pelvic or genitourinary examinations, performance of immunodefi-
HW INFECTIONAMONGADOLESCENTS
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ciency panels (CD4 cell counts), Papanicolaou smear testing, and surveillance screening for Neisseria gonorrhoeae and Chlamydia trachomatis infections. Syphilis serology was done annually. The HIV disease status of adolescents with a CD4 cell count < 500/ mm a was evaluated more frequently. Pelvic examinations were performed between the semiannual evaluations if warranted by clinical symptoms such as a new vaginal discharge or lower abdominal pain. Neisseria gonorrhoeae and C. trachomatis were determined by culture and use of an enzyme-linked immunosorbent assay test for the Chlamydia antigen. Trichomoniasis was detected by visualization of motile trichomonads on vaginal secretion saline preparations or evidence on Papanicolaou smear results. Candida vulvovaginitis was diagnosed in female adolescents with a positive potassium hydroxide preparation and accompanying characteristic signs or symptoms. Bacterial vaginosis was detected by the presence of > 20% clue cells on the vaginal secretion saline preparation and a positive "whiff test." Health care providers diagnosed pelvic inflammatory disease (PID) by characteristic signs and symptoms, such as lower abdominal, adnexal, or cervical motion tenderness, purulent cervical discharge, and fever, in conjunction with positive studies for N. gonorrhoeae or C. trachomatis. Infection with human papiUomavirus (HPV) was determined by Papanicolaou smear results or clinical findings on physical examination (such as irregular, nonumbilicated, verrucous lesions; spiked lesions; broad based fiat lesions; and single or clusters of calfliflower-like masses). Surveillance screening for N. gonorrhoeae and C. trachomatis was performed in males having biannual screening urinalyses reveal positive white blood cell (WBC) esterase. Males were determined to have nongonococcal urethritis (NGU) if urethritis signs or symptoms were present and testing for N. gonorrhoeae was negative. We used BMDP software for analyses (BMDP Statistical Software, Chicago, IL). Chi-square methods were utilized for bivariate analyses, and logistic regression techniques were used for multivariate modeling. Using an outcome of a 1993 CDC AIDS documented incident defining opportunistic process, selected entry variables were examined for prognostic significance in Cox proportional hazard models. The cumulative risks for AIDS (as defined by a opportunistic process definition) in subpopulations stratified by selected variables were determined using Kaplan-Meier methods (12).
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Table 1. Demographic Characteristics of Adolescents Male (n = 50)
Female (n = 91)
38 (76%) 12 (24%)
79 (87%) 12 (13%)
~.10
13 (26%) 37 (74%)
50 (55%) 41 (45%)
~.001
29 (56%) 6 (12%) 3 (6%) 1 (2%) 12 (24%)
0 (0%) 8 (9%) 42 (46%) 1 (1%) 40 (44%)
~.11
437.0 (39 SE) 27 (55%) 22 (45%)
582.0 (40 SE) 31 (37%) 52 (62%)
p
Race
African-American White Age -<18 yr ->19 yr Mode of transmission Homosexual Injection drug use Heterosexual Hemophiliac/bloodexposure NIR Entry blood C D 4 / m m 3 (median, n = 132) K500/mm 3 ~500/mm 3
~.05
NIR = No identifiable risk.
Results A total of 141 adolescents were included in this study. The cohort was p r e d o m i n a n t l y female (65%) and African-American (83%), and acquired HIV infection t h r o u g h sexual contact (56% of males rep o r t e d h o m o s e x u a l transmission, 50% of the females reported heterosexual transmission). Females rep o r t e d no identifiable risk (44%) more often than males (24%). The majority of the males entered the clinic at the age of 19 years or older (74%), whereas most females entered the clinic at an age of 18 years or y o u n g e r (55%), and gravid (53%) (Table 1). Females were y o u n g e r and had less a d v a n c e d HIV disease as evidenced b y a higher m e d i a n CD 4 cell count and smaller p r o p o r t i o n defined with a 1993 AIDS opportunistic process (13) (Table 1). Mean individual follow-up times for male and female adolescents were 22.3 and 24.9 months, respectively. There was a high prevalence and incidence of STDs, particularly in females as s h o w n in Table 2. A total of 75% and 48% of the females and males were diagnosed with at least one STD at study entry or follow-up, respectively. Although not significant, y o u n g African-American adolescent females with a CD 4 cell count ~ 5 0 0 / m m 3 were most likely to be diagnosed with an incident STD, as s h o w n in Table 3. Gravida and p r i m a r y contraceptive m e t h o d were not associated with an STD, with one exception. Although females using a h o r m o n a l contraceptive m e t h o d were more frequently diagnosed with a STD, this was not significant. Abstinence was the only significantly associated m e t h o d demonstrating that
females opting for this m e t h o d were less likely to be diagnosed with an STD. The majority of females (55%) had at least one Papanicolaou smear demonstrating SIL, and nearly one third (29%) had clinical evidence of HPV infection. Race, age, pregnancy, CD 4 cell count K 500/ m m 3, and h o r m o n a l m e t h o d of contraception were not significantly associated with SIL in a logistic regression multivariate model. An HPV finding [relative risk (RR) 6.8, 95% confidence interval (CI) 1.7-26.9, p ~ .003] was the only factor significantly associated with SIL after adjustment for the abovelisted nonsignificant variables in the multivariate model. A 1993 CDC AIDS-defining process occurred pred o m i n a n t l y in i m m u n o c o m p r o m i s e d adolescents as evidenced by the low m e d i a n C D 4 cell count of 6 9 / m m 3. As s h o w n in Table 4, the majority of opportunistic processes occurred in adolescents with a CD 4 cell count ~ 2 0 0 / m m 3. Not surprisingly, k n o w n HIV-related s y m p t o m s [oral hairy leukoplakia (OHL), thrush, and zoster] were noted in adolescents with relatively low m e d i a n C D 4 cell counts (96-273/mm3). Conversely, adolescents diagnosed with c o m m o n infections (upper respiratory infections, bronchitis, pharyngitis, and otitis) probably not related to their HIV infection had higher CD 4 cell counts (400-454/mm3). Although the risk for dermatitis, sinusitis, and gingivitis m a y have been influenced by HIV infection, adolescents with these processes generally had a CD 4 cell count ~ 5 0 0 / m m 3, suggesting that it was unlikely that these s y m p t o m s
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HIV INFECTIONAMONG ADOLESCENTS
Table 2. Clinical and Laboratory Characteristics of
Adolescents
STD prevalence during study period* Neisseria gonorrhoeae Chlamydia trachomatis
Syphilis Trichomoniasis Pelvic inflammatory disease Herpes simplex virus Human papilloma virus (HPV) Nongonococcal urethritis Genital ulcer disease Incident STD+
Male (n = 50) 24 (48%)
Female (n = 91) 68 (75%)
5 (10%) 1 (2%) 8 (16%) 0 (0%) 8 (16%) 8 (16%)
38 (42%) 23 (25%) 21 (23%) 45 (50%) 7 (8%) 18 (20%) 40 (44%)
1 (2%) 2 (4%) 7 (14%)
1 (1%) 42 (38%)
Candida vulvovaginitis Bacterial vaginosis
39 (43%) 26 (29%)
Gravida ~1 Gravida ~2
75 (82%) 18 (20%)
Papanicolaou smear results (n = 58)* Ever atypia Ever HPV expression Ever low or high-grade squamous intraepithelial lesions
21 (36%) 17 (29%) 32 (55%)
AIDS defining opportunistic infection§
12 (24%)
10 (11%)
p <.001
<.001
<.04
* Defined by every having N. gonorrhoeae,C. trachomatis, syphilis, trichomoniasis, pelvic inflammatory disease, herpes simplex virus, human papilloma virus, nongonococcal urethritis, or genital ulcer disease at study entry or during the study period, p refers to the gender difference in overall STD prevalence. The gender differences for individual STDs were not tested. +Defined as having at least one incident case of N. gonorrhoeae, C. trachomatis, or syphilis after study entry. Prevalent results of Papanicolaou smear samples from 58 adolescent females who had three consecutive 6-month pelvic examinations. § AIDS-defining opportunistic infection according to the 1993 Centers for Disease Control definition.
w e r e associated with i m m u n o s u p p r e s s i o n in this population. Interestingly, the m e d i a n CD 4 cell count for adolescents diagnosed with c o m m u n i t y - a c q u i r e d pneumonia ( 2 7 0 / m m 3) was similar to that n o t e d in adults (14,15) and was relatively low, suggesting that pneumonia in adolescents was probably related to their HIV infection. H o w e v e r , unlike HIV-infected adult w o m e n (14), the m e d i a n CD 4 cell count of adolescents diagnosed with Candida vulvovaginitis and SIL was > 4 5 0 / m m 3, implying these processes occur
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early in the course of HIV infection in this population. The majority of adolescents with a CD4 cell count < 5 0 0 / m m 3 (34 of 54 females and 29 of 33 males) were prescribed an antiretroviral agent at some time d u r i n g the study. Males were significantly m o r e likely to have used antiretrovirals (p < .02). Only 3 (2 females and 1 male) adolescents with all CD4 cell counts > 5 0 0 / m m 3 were prescribed antiretrovira! treatment d u r i n g the s t u d y period. The cumulative risk for a 1993 CDC AIDS-defining opportunistic process in the cohort was 11% and 29% at 12 and 48 months, respectively. As s h o w n in Table 5 and Figure 1, HIV-related s y m p t o m a t o l o g y was highly significant in predicting HIV disease progression (p < .001). The cumulative risk for AIDS in adolescents with these s y m p t o m s was dramatically increased (35% vs. 4% at 12 m o n t h s and 71% vs. 26% at 48 months), as s h o w n in Figure 1. A total of five adolescents in the cohort died d u r i n g the study. Four entered clinic care with a history of a 1993 AIDS-defining opportunistic process and the fifth was diagnosed with an o p p o r t u nistic process 9 m o n t h s later. The m e d i a n entry CD4 cell count of deceased adolescents was 1 5 5 / m m 3 (range 1 5 - 1 5 6 / m m 3) excluding the non-AIDS clinic entry adolescent w h o entered with a CD4 cell count of 8 5 9 / m m 3.
Discussion
Unlike the two prior reports (11,16) describing HIVinfected adolescents, the majority of adolescents in the N e w Orleans cohort w e r e female, p r o b a b l y as a result of the highly successful prenatal screening p r o g r a m based at the MCLNO. As implied b y the y o u n g e r age and higher entry CD4 cell count in the N e w Orleans female adolescents, infection with HIV in females m a y have been detected earlier than in males, which could also be d u e to the prenatal screening program. A g e n d e r age difference could also be explained if adolescent female acquired HIV infection t h r o u g h sexual initiation with older men. Demographic characteristics of the initial 605 adolescent cases of AIDS in the United States w e r e reported b y V e r m u n d et al. (16). A total of 16% of this early cohort w e r e injection d r u g users (IDU). The proportions of both the N e w Orleans cohort and NYC cohort r e p o r t e d to have acquired the infection b y injection d r u g use were lower (10 and 8%, respectively). The difference b e t w e e n these proportions suggests that either transmission of HIV infection
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T a b l e 3. G y n e c o l o g i c a n d R e p r o d u c t i v e C h a r a c t e r i s t i c s of F e m a l e A d o l e s c e n t s W i t h a n I n c i d e n t of T r a n s m i t t e d D i s e a s e (n = 91)
Race African-American White Age -<18 yr >-19 yr CD4/mm 3 at clinic entry (median, n = 83) <500/mm 3 >500/ram 3 AIDS defining opportunistic process* Gravida >-1 Gravida -<2 Primary mode of contraception (n = 83)* N o r p l a n t / d e p o provera/oral contraception Condom Tubal sterilization Abstinence
Incident STD (n - 38)*
No Incident STD (n = 53)
36 (95%) 2 (5%)
43 (81%) 10 (19%)
<.06
25 (66%) 13 (34%)
25 (47%) 28 (53%)
<.08
672.0 (62 SE) 10 (26%) 28 (74%) 5 (13%) 30 (79%) 8 (21%)
537.0 (46 SE) 21 (47%) 24 (53%) 5 (9%) 45 (85%) 10 (19%)
<.58 <.60 <.81
20 (59%) 12 (34%) 2 (6%) 1 (3%)
20 (41%) 10 (20%) 6 (12%) 11 (22%)
<.11 <.16 <.34 <.02
p
<.06
* Incident STD defined as having at least one incident case of Neisseria gonorrhoeae, Chlamydia
trachomatis, or syphilis after study entry. * AIDS-defining opportunistic process by the CDC 1993 definition. * Adolescents advised to use condoms in addition to primary method.
T a b l e 4. I n c i d e n t O p p o r t u n i s t i c I n f e c t i o n s a n d O t h e r C o m m o n P r o c e s s e s A m o n g Adolescents n (%) 1993 AIDS-defining processes Pneumocystis carnii pneumonia Candidiasis, esophageal Herpes simplex Dementia Cryptosporidiosis Cryptococcosis Wasting syndrome Probable HIV-related processes Oral hairy leukoplakia Thrush Zoster Possible HIV-related processes Pneumonia Dermatitis/folliculitis Sinusitis/rhinitis Gingivitis Probable non-HIV-related processes Upper-respiratory infection/bronchitis Pharyngitis/tonsillitis Otitis Female specific possible HIV-related processes Candida vulvovaginitis Squamous intraepithilial lesions
9 8 2 1 1 1 1
(6.4) (5.7) (1.4) (0.7) (0.7) (0.7) (0.7)
CD4/mm 3 Median (SE) 206.8 (190.9)* 206.2 (227.6)* 126.7 (146.0)* 250.5 (303.3)* Unknown 169 + 150' 36*
5 (4) 26 (18) 3 (2)
96 (82) 321 (309) 272 (344)
11 41 32 11
350 468 466 591
(8) (29) (23) (8)
(299) (293) (230) (320)
26 (18) 15 (11) 7 (5)
398 (275) 491 (275) 407 (289)
39 (43) 25 (37)
591 (304)* 549 (263)*
* CD4/mm 3 counts taken within 3 months of diagnosis; P. carnii pneumonia (n = 6), candidiasis, esophageal (n = 6), Herpes simplex (n = 2), Candida vulvovaginitis (n = 31), squamous intraepithileal lesions (n = 22). * CD4/mm 3 count taken more than 3 months prior to diagnosis; cryptosporidiosis (8 months prior), cryptococcosis (14 months prior).
June 1996
HIV INFECTION AMONG ADOLESCENTS
Table 5. Clinical Factors Associated With Having an Opportunistic Process (n = 132)
Hazard Ratio
95% C!
0.5 2.8 0.5
(0.2-1.3) (0.8-10.7) (0.1-1.7)
<0.15 <0.10 <0.28
2.6 7.8 0.5
(0.7-9.1) (2.8-21.7) (0.1-1.8)
<0.12 <.0001 <0.24
Female gender African-American Injection drug use a n d / o r street drug use C D 4 / m m 3 cell < 500 OHL/Thrush/Zoster* Antiretroviral use*
p
* Patient had either oral hairy leukoplakia(OHL)or thrush, or zoster, at study entry or during study period. *Use of antiretrovirals including zidovudine (AZT), didanosine (DDI),and zalcitabine (DDC) during study period.
through sexual contact is proportionally increasing or methods used in ascertaining mode of transmission are improving. Even though the vast majority of New Orleans female adolescents were documented to use condoms for contraception, the high incidence of STDs among New Orleans adolescents showed that STD protection was either inconsistently or inappropriately utilized. It is therefore probable that sexual transmission of HIV infection will continue to escalate among adolescents in the New Orleans area. Sexually transmitted diseases were more frequently detected in female adolescents in this study. Surveillance bias may have contributed to the significant gender differences for N. gonorrhoeae and C. trachomatis. Although testing for these infections were performed in symptomatic males (those with
427
signs or symptoms or positive WBC esterase on urinalyses), asymptomatic males did not undergo routine surveillance screening. Even though males with urethritis are believed to be generally symptomatic, one study found a chlamydial isolation rate over 11% in asyrnptomatic males (17). Syphilis infection frequencies were comparable between females (23% vs. 23%) and males (15% vs. 16%) in the NYC (11) and New Orleans cohorts, respectively. Neisseria gonorrhoeae and C. trachomatis cervicitis prevalence rates were noticeably higher among New Orleans females, but pelvic inflammatory disease occurred 3.6 times more frequently among NYC females (11). The reason for this discrepancy is unclear, because management protocols (i.e., surveillance screening every 6 months) and the ages of the females did not differ between the NYC and New Orleans studies. In addition to other STDs, HPV infections and SIL were common among both the NYC and New Orleans cohorts (11). Although thrush, a symptom known to be HIVrelated, occurred relatively frequently, other symptoms and opportunistic processes clearly associated with HIV immunosuppression were rare, which was probably due to the limited number of adolescents in the study with a CD 4 cell count < 200/mm 3. The most commonly diagnosed AIDS-defining processes were PCP and Candida esophagitis, and the median CD4 cell count of adolescents diagnosed with these infections was also analogous to the findings in adults (14,15). The highly significant predictive value of HIV-related signs and symptoms was also not surprising because of prior findings in adults (18,19).
- 80%
0
(n=32)
70% "o
. . . . . . . . . . . . . . . . . . . . . . . . . .
.~ 60%
. . . . . . . . . . . . . . . . . . . . . . /
=~50% "~. 40%
9
.
30%
.
.
.
.
........
.
.
.
. r
.
.
.
.
.
.
.
.
.
.
.
.
.
i
.
(n=109)
. . . . . . . . . . . . . . . .
>~ 20% ~= 10%
8 0% - ~ - + - - - - - ~ 0
6
12
18
24
30
36
42
48
Time from clinic entry to incident OI (months)
[~" HIV related t
process
Conclusions
ft ~
--No HIV related
process
I I
HIV related process=oral hairy leukoplakia/thrush/zoster Ol=Opportunistic Infections
Figure 1. The cumulative risk for being diagnosed with an AIDSdefining opportunistic process in H1V-infected adolescents (n = 141).
With the increasing number of adolescents becoming HIV-infected, development of strategies for early diagnosis and provision of comprehensive medical and psychosocial services are vitally important. The predominance of females in the New Orleans cohort demonstrates that prenatal screening programs can be very effective in the early detection of HIV infection in female adolescents, and demonstrates that HIV screening with appropriate counseling should be offered to all pregnant adolescents. Although HIV-related symptoms and infections do not appear to be unique in the adolescent population, it is clear that STDs are common. The results from both this study and the NYC study emphasize the need for aggressive STD and contraceptive protection counseling and frequent routine STD and
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FULLER ET AL.
cervical dysplasia screening among adolescents. HIV-infected adolescents present a challenge to clinicians because of the limited information and the medical, developmental, and psychosocial issues in this population. Future prospective studies are warranted to better define HIV-related manifestations in adolescents and assist in the development of primary care programs targeted for HIV-infected youth.
JOURNAL OF ADOLESCENT HEALTH Vol. 18, No. 6
lescents: A five-year study. Presented at the Annual Meeting of the Society for Adolescent Medicine; March 20, 1993; Chicago, IL. 8. Conway GA, Epstein MR, Hayman CR, et al. Trends in HIV prevalence among disadvantaged youth: Survey results from a national job training program, 1988 through 1992. JAMA 1993;269:2887-9. 9. Kipke MD, Hein K. Acquired immunodeficiency syndrome (AIDS) in adolescents. Adolescent Med. State Art Rev 1990;1: 429-49.
The authors acknowledge the adolescent patients enrolled into the HIV Outpatient Program (HOP) and the HOP personnel who facilitated data collection.
10. Anderson MM, Morris RE. HIV and adolescents. Pediatric A n n 1993;22:436-45.
References
12. BMDP Statistical Software, vol. 2. University of California, Berkeley, 1992.
1. Monthly Vital Statistics Report, 1994. Hyattsville, MD: CDC/ National Center for Health Statistics, 1994. (The advanced report of final mortality statistics; vol. 43, no. 6, suppl, December 1994). 2. U.S. Govermnent Printing Office, Superintendent of Documents, U.S. Department of Commerce, 1990. Springfield, VA: National Technical Information Service. (Selected behaviors that increase risk for HIV infection among high school stud e n t s - U n i t e d States, 1990; vol. 41, no. 14, April 1990). 3. Centers for Disease Control, 1987. Atlanta, GA: U.S. Department of Health and H u m a n Services, Public Health Service, 1987. (AIDS surveillance report; January 1987). 4. Centers for Disease Control, 1994. Atlanta, GA: U.S. Department of Health and H u m a n Services, Public Health Service. (HIV/AIDS surveillance report, January 1994). 5. St. Louis ME, Conway GA, Hayman CR, et al. HIV infection in disadvantaged adolescents in the US: Findings for the Job Corps screening program. JAMA 1991;266:2387-91. 6. St. Louis ME, Rauch KJ, Petersoen LR, et al. Seroprevalence rates of h u m a n immunodeficiency virus infection at sentinel hospitals in the United States. N Engl J Med 1990;323:213-8. 7. D'Angelo LJ, Getson PR, Brasseux CO, et al. The increasing prevalence of h u m a n immunodeficiency virus in urban ado-
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13. Centers for Disease Control. 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. Morb Mort Wkly Rep 1992;41:1-19. 14. Clark RA, Brandon W, Dumestre J, et al. Clinical manifestations of infection with the h u m a n immunodeficiency virus in women in Louisiana. Clin Infect Dis 1993;17:165-72. 15. Greenberg AE, Thomas PA, Landesman SH, et al. The spectrum of HIV-1 related disease among outpatients in New York City. AIDS 1992;6:849-59. 16. Vermund SH, Hein K, Gayle HD, et al. Acquired imrnunodeficiency syndrome among adolescents. Am J Dis Child 1989; 143:1220-5. 17. Podoore JK, Holmes KK, Alexander ER. Asymptomatic urethral infections due to Chlamydia trachomatis in male U.S. military personnel. J Infect Dis 1982;146:828. 18. Katz MH, Greenspan D, Westenhouse J, et al. Progression to AIDS in HIV infected homosexual and bisexual men with hairy leukoplakia and oral candidiasis. AIDS 1992;6:95-100. 19. Melbye M, Grissman RJ, Goedert JJ, et al. Risk of AIDS after Herpes zoster. Lancet 1987;1:728-30.