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Care for the HIV-Infected Female Adolescent

Updated March 2007 — Currently Under Revision

I. INTRODUCTION

This chapter is a supplement to the NYSDOH AI guidelines for the care of HIV-infected adolescents, entitled Ambulatory Care of HIV-Infected Adolescents, which includes recommendations for identifying HIV-infected adolescents; obtaining a baseline medical history; performing baseline and ongoing physical examinations, laboratory evaluations, and psychosocial interventions; and maximizing treatment adherence. This chapter discusses issues that may have particular diagnostic, preventive, or therapeutic implications for female adolescents, including epidemiology, pelvic examinations, reproductive health, contraception, and pregnancy.

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II. EPIDEMIOLOGY

The most common mode of female HIV acquisition is through heterosexual sex. In New York State, female adolescents aged 13 to 24 accounted for 42% of the adolescents living with HIV/AIDS in 2005.1 Nationwide, it is estimated that 63% and 82% of new AIDS cases among younger (13 to 19 years) and older (20 to 24 years) adolescent females, respectively, are from heterosexual transmission.2

Sexually active adolescent females may be particularly vulnerable to acquiring HIV infection for the following reasons3:

  • An adolescent’s immature cervix contains more single-layer columnar cells that may be more vulnerable to infection.
  • Females are more likely than males to experience asymptomatic STIs, and the presence of STIs may enhance transmission of HIV infection.
  • HIV infection is more easily transmitted from male to female than female to male because 1) the susceptible surface area of the female (cervical epithelium and the mucosal area of the vagina and rectum) is larger than that of the male (urethral meatus) and 2) semen can remain in the vagina, cervix, and rectum for hours to days after sexual intercourse, making the period of HIV exposure much longer for a female than a male.

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III. IDENTIFICATION OF A SUPPORTIVE ADULT

Recommendation:

Clinicians should identify a supportive adult to whom the adolescent can safely disclose HIV-related information and discuss reproductive health issues.

HIV infection and reproductive health issues are often difficult topics for many HIV-infected adolescents to discuss. Some adolescents are comfortable discussing these subjects with parents/guardians, while others are not. A supportive adult with whom the adolescent can comfortably discuss HIV-related information and reproductive health care should be identified. The medical team should encourage the adolescent to involve this person in discussions concerning her care. This person may or may not be a parent or legal guardian but should be someone with whom the adolescent feels comfortable sharing personal information.

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IV. HUMAN PAPILLOMAVIRUS VACCINE

Recommendations:

Clinicians should offer the HPV vaccine to HIV-infected females between the ages of 9 and 26 years.

Clinicians should continue to obtain cervical Pap tests on the recommended schedule in HIV-infected women who have been vaccinated with HPV vaccine (see Table 2). Vaginal and vulvar visual inspection should be continued at regularly scheduled pelvic examinations.

HPV typing prior to administering the vaccine is not recommended.

In June 2006, the Food and Drug Administration (FDA) approved the release of a quadrivalent HPV vaccine (Gardasil) that protects against disease caused by HPV types 6, 11, 16, and 18. These HPV types are associated with 70% of cervical cancers (HPV 16 and 18) and 90% of genital warts (HPV 6 and 11) in non-HIV-infected women.4 The pivotal clinical trials showed that the vaccine prevented precancerous vulvar, vaginal, and cervical lesions caused by these HPV types for up to 36 months. Most studies have shown a high prevalence of HPV infections in HIV-infected individuals.5

The vaccine is FDA-approved for administration to females between the ages of 9 and 26 years.6 It is administered as a three-dose regimen over a 6-month period (0, 2, and 6 months). The full regimen must be completed to confer protection. HPV vaccine has been demonstrated to provide high levels of neutralizing antibody for 5 years; the full length of its protection has not been established.

The HPV vaccine is preventive, but not therapeutic. Current studies demonstrate that the preventive efficacy of the HPV vaccine is greatest in women who are not yet sexually active and thus have not been exposed to HPV. However, HPV testing is not required before administration of the vaccine, and most women, regardless of sexual activity status, may benefit from vaccination. In the pivotal clinical trials, only 1 in a 1,000 women showed evidence of having been exposed to all four types of HPV prevented by the vaccine. Gardasil may also provide some cross-protection against HPV genotypes other than 6, 11, 16, and 18. However, additional data are required before the vaccine can be recommended for the prevention of cross-reactive HPV types.

Most of the data regarding HPV vaccine safety and efficacy are derived from studies in non-HIV-infected females. HIV-infected women may have reduced antibody response to the immunization because women who are immune suppressed have an impaired ability to mount an immune response. Studies are currently underway to provide more extensive data regarding the safety and efficacy of the vaccine in the HIV-infected population. There currently are no recommendations to vaccinate males against HPV.

Clinicians should continue to perform regular cervical screening with Pap tests and visual inspection of the vulva and vagina during annual pelvic examinations in women who have received the HPV vaccine because the vaccine does not protect against the 25% to 30% of lesions and genital cancers caused by other HPV types. Females who have not engaged in vaginal or anal penetrative sex but who have participated in sexual activity with direct genital contact should be evaluated for vulvar lesions because the virus can be passed through direct contact.

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V. SEXUAL RISK ASSESSMENT AND RISK-REDUCTION COUNSELING

Recommendations:

Clinicians should obtain a sexual risk assessment during the baseline examination and during routine visits (see Table 1).

The clinician should routinely discuss sexuality, personal relationships, birth control, safe sex, and partner disclosure with patients. Clinicians should discuss partner disclosure prior to the onset of the adolescent’s sexual activity.

Clinicians should inquire about physical and sexual abuse and sexual assault and should refer patients for counseling when indicated.

Clinicians should recommend consistent and correct use of latex condoms to prevent pregnancy, acquisition of STIs, transmission of HIV/STIs, and superinfection. For patients with a latex allergy, clinicians should recommend polyurethane condoms. Clinicians should advise HIV-infected adolescents to avoid using lambskin condoms or condoms that are lubricated with nonoxynol-9. For adolescents with same-sex partners, the use of dental dams during oral sex and safe use of sex toys should be discussed to prevent disease transmission.

Clinicians should use a model to demonstrate to adolescents the correct way to use a condom.

Clinicians who are not comfortable discussing sexual practices with adolescents should consult with clinicians who have experience in risk-reduction counseling for adolescents or seek training to enhance their comfort level.

Sexuality and sexual practices should be addressed during the initial visit and during routine clinical visits. Adolescents may choose not to disclose all important personal information during the first visit. Some adolescents are comfortable discussing sexual activity and reproductive health with their providers with whom they have had a long-term relationship, in some cases since childhood; however, other adolescents may feel more comfortable discussing their sexual activity with a different provider or a same-sex provider. Clinicians who are nonjudgmental when interacting with patients may establish a trusting bond with the adolescent which will facilitate discussion of sensitive issues.

The purpose of the sexual history and risk behavior assessment is to enable the clinician to provide appropriate risk-reduction counseling. This counseling should include safer-sex practices, including strongly advising continued use of condoms to prevent superinfection with an HIV-infected partner or transmitting HIV/STIs to their sexual partners. Clinicians who are not comfortable discussing different sexual behaviors and ways to reduce the risk of sexually transmitting HIV should seek training to enhance their comfort level. Consultation with clinicians who have experience in risk-reduction counseling for adolescents may also be beneficial.

Table 1: Elements of a Sexual Risk Assessment for HIV-Infected Female Adolescents
  • Whether patient is sexually active or has plans to initiate sexual activity
  • Age at initiation of sexual intercourse
  • Number of sexual partners
  • Gender(s) and ages of partners,* length of relationships
  • HIV and STI status of partners
  • Disclosure to partner(s) of HIV status†
  • History of STIs and treatment
  • Sexual practices (oral, anal, vaginal, digital, use of sex toys) with and without protection
  • Contraceptive history and current practices, specifying frequency and condom use
  • Self-assessment of safer-sex practices
  • Pregnancy history
  • Sexual abuse (personal or family)
  • History of exchanging sex for housing, food, money, or drugs
  • Drug or alcohol use
* Inquiring about the age of partners may be useful when obtaining a sexual risk assessment because it is often more difficult for younger
women to be assertive regarding safe-sex practices with older partners.
† If HIV status has not yet been disclosed to partner(s), the clinician should offer assistance with partner disclosure.



Use of alcohol and marijuana is significant among HIV-infected adolescents. Although their use is not a direct risk for HIV transmission, they cause disinhibition which can result in sexual risk taking. Intoxication from these substances impairs the adolescent’s judgment and ability to negotiate condom use and sexual activities with partners. This not only increases the risk of pregnancy and other STIs, but also increases the risk of transmitting HIV infection. Referrals should be made for counseling for patients who indicate risky substance use.

For further information about female substance users, see Medical Care of the HIV-Infected Substance-Using Woman.

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VI. PERFORMING GYNECOLOGIC EXAMINATIONS

Recommendations:

At baseline and as part of the annual comprehensive physical examination, clinicians should obtain a menstrual, gynecologic, and sexual history as well as examine the external genitalia, anus, perineal area, breasts, and axilla using the Tanner rating scale for sexual maturity.

The clinician should educate the patient about the importance of periodic pelvic examinations, STI screening, and Pap tests.

Clinicians should perform the first gynecologic examination when any of the following occur:

  • the patient reports sexual activity;
  • the patient requests a pelvic examination;
  • the patient presents with any gynecologic symptom for which a pelvic examination would assist in a differential diagnosis, e.g., pelvic pain or new onset menstrual irregularity;
  • the patient presents with symptoms of an STI or sexual activity;
  • the patient reaches age 14—however, if the inspection reveals an intact hymen or no likely sexual activity, the speculum examination and the Pap test should be deferred until age 18 or until the patient is sexually active, whichever occurs first.

Before performing a first-time pelvic examination in a patient, the clinician should explain the various steps and components involved in the examination, including a review of basic genital anatomy, the instruments used for the examination, and the purpose of the examination. Clinicians should use the smallest speculum available for a first-time examination, even in sexually active adolescents.

Patients should be asked if they would prefer having a female provider perform the examination. During the examination, an additional female member of the medical staff should be present as a chaperone.

Primary care clinicians who do not directly provide gynecologic care should obtain a menstrual, gynecologic, and sexual history and then refer the patients to gynecologic providers with experience providing examinations to adolescents.

Adolescent or young adult female patients who have not had a previous gynecologic examination, who have had previous “bad experiences” with pelvic examinations, or who are victims of past sexual assault may require extra time and explanation during their first examination. New York State law requires clinicians to report cases of suspected child abuse or neglect to the New York State Central Registry at 1-800-635-1522. More than one visit may be necessary for these patients before a comprehensive gynecologic examination can be completed.

If the clinician is performing the patient’s first pelvic examination, he/she should take time to explain the various steps and components involved in a pelvic examination, show the patient the instruments that will be used, and explain how the instruments function. Well-informed patients may feel more comfortable during examinations, which may then encourage the patient to be proactive in obtaining future routine pelvic examinations. The use of demonstration models or pictures can alleviate concerns about what to expect during a pelvic examination. The smallest speculum available should be used for a first-time examination, even in sexually active adolescents. For some adolescents, a nasal speculum may be needed.

Key Point:

Adolescents may require additional time during clinical visits to become comfortable with the idea of receiving a pelvic examination. Additional time may be needed when scheduling these appointments.

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VII. EVALUATIONS FOR SEXUALLY ACTIVE HIV-INFECTED FEMALE ADOLESCENTS

Recommendations:

At baseline and as part of the annual comprehensive physical examination, clinicians should examine the anogenital area, including the vulva and vagina, to assess for visible ulcerative lesions.

Clinicians should perform the laboratory tests listed in Table 2 for HIV-infected females who are sexually active.

Table 2: Laboratory Tests for Sexually Active HIV-Infected Adolescent Females
Test Frequency
Cervical Pap test Baseline, 6 months after baseline, then annually, as long as results are normala,b
Culture, nucleic acid amplification test (NAT), or urine test for gonorrheac,d Baseline and every 6 months
RPR or VDRL for syphilise Baseline and at least annually
Immunofluorescence or DNA amplification test for Chlamydia

Urine testing for chlamydia

Baseline and every 6 months
 

At 6-month evaluations when a pelvic examination is not performed

Herpes simplex virus serology

Herpes cultures

Baseline

When symptoms are present

Pregnancy test Baseline and when: 1) the adolescent requests one, 2) menses change in pattern or flow, 3) timing of unprotected sex concerns the patient or provider, or 4) prior to starting teratogenic medication (e.g., efavirenz)
a Colposcopy should be performed for all HIV-infected women with abnormal Pap tests. Follow-up would then vary on a case-by-case basis. Abnormal Pap tests should be repeated every 3 to 6 months thereafter until there have been two successive normal cervical Pap tests. Women with cervical HSIL also should be referred for high-resolution anoscopy and/or examination with biopsy of abnormal tissue.
b Annual anal cytology should be obtained from patients with a history of anogenital condyloma or abnormal cervical/vulvar histology.
c Urine screening should not preclude performing a pelvic examination because other visible STI lesions may be missed (HPV, HSV, etc.).
d Depending on the sexual behaviors reported or suspected, oral and anal cultures may be indicated as well as cervical or urethral cultures.
e Positive test verified by confirmatory FTA-Abs or MHA-TP.

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VIII. CONTRACEPTION

Recommendations:

Clinicians should counsel patients about contraceptive options. If necessary, patients should be referred to a family planning provider for contraceptive counseling.

Clinicians should recommend the simultaneous use of a condom and an additional method of contraception (dual method use) in the event of condom breakage or slippage.

When prescribing hormonal contraceptives, clinicians should consider, on a case-by-case basis, drug interactions between HIV-related medications and hormonal contraceptives, the patient’s adherence patterns to medications, and the side effect profile of the hormonal contraceptives. Clinicians should also reinforce the importance of using condoms in addition to hormonal contraception.

Clinicians should counsel HIV-infected adolescents about the interactions between ARV medications and oral contraceptives, specifically lopinavir/ritonavir, nelfinavir, nevirapine, ritonavir, saquinavir, and tipranavir, because contraception protection may be reduced.

Clinicians should strongly recommend the use of contraception for HIV-infected adolescent females of childbearing age who are receiving efavirenz or combination pills containing efavirenz.

Rates of unintended pregnancy are higher among adolescent and young adult females than among older females; therefore, it is essential that clinicians clearly address reproductive health issues and contraception with HIV-infected adolescents. Clinicians prescribing contraceptives should be cognizant of adolescent adherence patterns, which may be poor. Many adolescent healthcare clinicians offer younger patients contraception in the form of a shot (Depo-Provera), vaginal ring (Nuvaring), or patch (Ortho-Evra) to reduce inconsistent contraceptive use, which may be encountered with oral contraceptives. However, use of any hormonal contraception is often accompanied by a decrease in use of condoms during sex. Patients should be strongly advised to continue using condoms simultaneously with hormonal contraceptives to avoid superinfection with an HIV-infected partner or transmitting HIV/STIs to their sexual partners.

Key Point:

Correct and consistent use of routine contraception may be challenging for adolescents. A reliable contraceptive method that does not require daily use may be more successful in this population.



Injectable progesterone (depot medroxyprogesterone acetate, Depo-Provera) is an efficacious contraceptive; however, current data suggest that Depo-Provera can cause bone demineralization when used for prolonged periods. For this reason, the Food and Drug Administration recommends that providers limit the use of Depo-Provera to 2 continuous years followed by an interruption of its use.7 Recent data suggest that after 2 years of discontinued use of Depo-Provera, bone mineral density returns; however, these studies have not been performed in adolescents with or without HIV infection.

If efavirenz is used, or combination pills containing efavirenz, female adolescents should be informed of the possible risk to an unborn fetus and should be strongly advised to use effective birth control or choose an alternative medication. Many HIV providers prefer not to use efavirenz in this population because of teratogenicity concerns; efavirenz is contraindicated during the first trimester of pregnancy.

For more detailed information about contraception, including interactions with ARV medications, see Contraception and the HIV-Infected Woman.

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IX. REPRODUCTIVE HEALTH COUNSELING

Recommendations:

Clinicians should provide reproductive health counseling to HIV-infected female adolescents (see Table 3). As part of reproductive health counseling, clinicians should educate female adolescents about the importance of maintaining their own health should they wish to become pregnant in the future.

Clinicians should recommend prenatal vitamins and folic acid for adolescents who wish to become pregnant or who are not taking action to prevent pregnancy.

For patients of childbearing age, clinicians should discuss the following concerning ARV medications:

  • Efavirenz and combination pills containing efavirenz should be avoided in adolescents of childbearing age and adolescents who are in their first trimester of pregnancy. These patients should receive an alternative regimen if possible.
    • If there are no alternatives for efavirenz, clinicians should strongly advise the use of effective contraception and should obtain a pregnancy test before initiation.
    • If pregnancy is discovered during the second trimester, an alternative regimen should be offered but can be continued if the benefits outweigh the risks.
    • For adolescents receiving efavirenz and expressing a desire to have children, efavirenz should be discontinued 2 months before stopping contraception.
  • Amprenavir oral solution is contraindicated.
  • Stavudine/didanosine combination should be avoided and only be used when no other combinations are feasible (See Management of HIV-infected Pregnant Women Including Prevention of Perinatal Transmission for more information)
  • Nelfinavir should not be given to pregnant adolescents or to those who anticipate pregnancy, if other treatment options are available. In pregnant adolescents receiving nelfinavir, nelfinavir should be substituted for another ARV agent.

Clinicians should consider pregnancy in all adolescents of childbearing age when prescribing medications that are known to be harmful to the fetus. Selection of drugs for the ARV regimen should be guided by available data.

Upon learning of their HIV infection, many HIV-infected adolescents think that they may not live long enough to bear children or may never be able to bear non-HIV-infected children. Many young women view pregnancy as a “rite of passage” and may feel deprived of this “rite.” Perinatally infected female adolescents may develop strong desires to become pregnant in an effort to be connected to a family of their own or to be “normal.” Their motivations may be to be like their peers or, as a result of their fear of mortality; they may want to have children to leave behind in the event of their own premature death.

Key Point:

Clinicians providing HIV care to adolescents may be the only source of medical information for these patients. Female adolescents may not be as successful as older women in navigating the healthcare system to obtain reproductive health care and information.



Clinicians providing HIV care to younger female patients need to proactively counsel patients about future reproductive options. Explicit guidance about how to increase the chances of delivering a healthy, non-HIV-infected infant when the patient is ready to become pregnant should be outlined during this counseling. Topics such as those shown in Table 3 should be discussed. For patients who are already receiving ARV medications, adherence to the drug regimen should be emphasized. The clinician also should explain to the patient that a planned pregnancy which occurs when the patient is in her best physical condition is one that has the greatest chance of resulting in a healthy, non-HIV-infected infant and a healthy mother.

Table 3: Elements of Reproductive Health Counseling for HIV-Infected Adolescent Females
General Concerns
  • Effect of HIV on pregnancy
  • Effect of pregnancy on HIV
  • Future reproductive concerns and options
Contraception
  • Routine contraception
    • use of dual contraceptive methods
  • Emergency contraception
  • Effect of ARV drugs on oral contraceptive pills
ARV Medications
  • Potential for maternal and fetal/neonatal toxicity
  • Effect on pregnancy outcome
  • Role in preventing perinatal transmission
  • Importance of adherence to the ARV regimen, especially for patients already receiving ARV medications
Routine Prenatal Care
  • Vitamin and folic acid supplementation
  • Smoking cessation
  • Healthy nutrition
Perinatal HIV Transmission
  • Risk of transmission and risk-prevention
  • Mode of delivery (cesarean vs vaginal)
  • Avoiding breastfeeding
Parenting Responsibilities
  • Housing/food
  • Childcare
  • Medical care and pediatric care
  • Continuing education

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X. PROVIDING CARE FOR PREGNANT ADOLESCENTS

Recommendations:

Clinicians should consider the likelihood of pregnancy when selecting specific HAART medications for HIV-infected adolescents because some adolescents may not inform the clinician about a pregnancy for significant periods of time.

Clinicians should discuss options with patients who are making decisions about carrying pregnancy to term or terminating pregnancy. For adolescents who are not comfortable discussing pregnancy with their long-term provider, other trained professionals should be accessible.

Clinicians should educate pregnant adolescents who choose to carry pregnancy to term about the role of ARV therapy in optimizing maternal health and reducing the likelihood of perinatal transmission.

Clinicians should use the three-part zidovudine regimen for all HIV-infected pregnant adolescents, regardless of whether or not they are receiving HAART, unless a specific contraindication to zidovudine is known, such as a history of a severe adverse effect of zidovudine, severe anemia, or the need for an antagonistic medication such as stavudine.

The clinician should consult with an HIV Specialist to devise prenatal HAART regimens for perinatally infected adolescents.

Primary care clinicians should have referral agreements with obstetrical services that can provide care to HIV-infected females during pregnancy.

Clinicians should refer adolescent patients to supportive services available at prenatal clinics.

The adolescent’s clinician should work in conjunction with the infant’s pediatrician to provide the adolescent with access to training to improve parenting skills and other necessary services.

Pregnancy is often the time when heterosexually infected females are identified as being HIV-infected. The recommendation for universal counseling with recommended testing of all pregnant women, either prenatally or through expedited perinatal testing, has facilitated the identification of HIV infection in adolescents who become pregnant.

Optimal care of HIV-infected pregnant adolescents includes ARV treatment to reduce mother-to-child HIV-1 transmission and maintenance of general health for the pregnant adolescent. Providers face the difficult task of maximally suppressing the virus while avoiding or minimizing potential toxicities to the mother and fetus. To prevent perinatal HIV transmission, a three-part zidovudine regimen is recommended for all HIV-infected pregnant women, regardless of whether or not they are receiving HAART, unless a specific contraindication to zidovudine is known, such as a history of a severe adverse effect of zidovudine, severe anemia, or the need for an antagonistic medication such as stavudine. Factors associated with higher rates of transmission include ruptured membranes for more than 4 hours, advanced maternal disease, high maternal viral load, low maternal CD4 cell count, and concomitant infections, including hepatitis C. Cesarean delivery prior to the onset of labor and ruptured membranes can significantly reduce the risk of transmission. Guidelines for the use of ARV therapy during pregnancy, routine monitoring of HIV-infected pregnant women, and labor and newborn management are included in Management of HIV-Infected Pregnant Women Including Prevention of Perinatal HIV Transmission.

Key Point:

Although HIV-infected pregnant adolescents will be referred to obstetrical care services that can provide care to HIV-infected pregnant women, the clinician may want to remain the primary care provider for the adolescent during the pregnancy.



Clinicians should consider the likelihood of pregnancy when considering specific HAART medications, such as efavirenz or combination pills containing efavirenz, because some adolescent patients may be pregnant for a significant amount of time without informing their HIV providers. Devising prenatal HAART regimens for pregnant, perinatally infected females is often difficult because the patients are frequently more advanced in their clinical disease state and may be resistant to many ARV medications. Clinicians should consult with an HIV Specialist when developing a prenatal HAART regimen for this population. Treatment during adolescent pregnancy raises multiple issues and should be provided by a clinician experienced in caring for HIV-infected pregnant patients.

Pregnant adolescents may benefit from supportive services to help prepare them for parenthood. Adolescent patients should be referred to supportive services that are often provided at prenatal clinics that encourage a healthy outcome for adolescent patients during their pregnancy and delivery. Supportive services may include prenatal, postpartum, and infant development education; nutrition education for mother and child; parenting skills training; child care support; and counseling, whether group or individual.

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XI. RESOURCES FOR CONSULTATION

Clinicians who need additional information concerning care for female adolescents can refer to the following websites:

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REFERENCES

1. NYSDOH. NYS HIV/AIDS surveillance semiannual report for cases diagnosed through 2005. Available at: http://www.health.state.ny.us/diseases/aids/statistics/semiannual/2005/surveillance_semiannual_report_2005_june.pdf

2. Kaiser Family Foundation. Women and HIV/AIDS in the United States. HIV/AIDS Policy Fact Sheet. February 2006. Available at: http://www.kff.org/hivaids/upload/6092-03.pdf

3. Futterman D. HIV and AIDS in adolescents. Adolesc Med Clin 2004;15:369-391. Review.

4. Centers for Disease Control and Prevention. Quadrivalent Human Papillomavirus Vaccine – Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2007;56:1-24. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr56e312a1.htm

5. Clifford GL, Goncalves MA, Franceschi S for the HPV and HIV Study Group. Human papillomavirus types among women infected with HIV: a meta-analysis. AIDS 2006;20:2337-2344.

6. Food and Drug Administration. Product Approval Information – Licensing Action. Available at: http://www.fda.gov/CBER/products/hpvmer060806.htm

7. Food and Drug Administration. Black Box Warning Added Concerning Long-Term Use of Depo-Provera Contraceptive Injection. November 17, 2004. Available at: http://www.fda.gov/bbs/topics/ANSWERS/2004/ANS01325.html

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