INFECTION: WOMEN AT RISK
| HIV INFECTION AND GYNECOLOGIC CARE —Noe B. Mateo, MD, Infectious Diseases Consultant, HealthPartners Medical Group and Clinics, Regions Hospital, St. Paul |
| Prognostic factors: CD4 T-cell count—indicates how well immune system functioning; count >500 cells/mm3 indicates immune system functioning as normal as someone HIV-negative; risk of developing opportunistic and gynecologic infections with count <200 cells/mm3 ; viral load (VL), RNA polymerase chain reaction (PCR), and branched-chain DNA—indicate how actively virus multiplying; poor prognosis with high number; weight and hemoglobin other prognostic factors; HIV infection risk factor for reactivation and rapid progression of other infections; highly active antiretroviral therapy (HAART)—2 (typically 3 or 4) medications used simultaneously |
| Complications: Pneumocystis carinii pneumonia (PCP), cytomegalovirus retinitis, and disseminated macular infection less common because of HAART; more common complications include hepatitis C and B, metabolic disorders (eg, lipodystrophy, atherosclerosis, accelerated osteopenia), body habitus changes, and malignancies; infection occurs in separate and discrete compartments; VL measurement and CD4 count estimate of what is occurring at tissue level; central nervous system (CNS) sanctuary site; prevention of CNS infection purpose of drug therapy; reproductive tract separate sanctuary site; adequate control of HIV infection in blood does not ensure control in reproductive tract; local infection in reproductive tract predisposes patient to increase in VL in that area alone and increases chances for transmission; consequences of failed therapy—viral resistance; virus resistant to one antiretroviral drug becomes resistant to other agents in same class |
| Menstrual abnormalities: currently not enough data to support HIV infection as sole cause of premature ovarian failure; work-up of amenorrhea in HIV-positive women similar to that of general population |
| Lower genital tract neoplasia: human papillomavirus (HPV) detected more frequently in HIV-positive women, more persistent, and more difficult to treat than in HIV-negative women; squamous intraepithelial lesion (SIL)—three quarters of coinfection attributable to HPV and one fifth attributable to HIV; invasive cervical squamous cell carcinoma AIDS-defining illness since 1993; data show prevalence of SIL-positive cytology 17% to 18% in HIV-positive women, compared to 3% to 5% in HIV-negative women; incidence of new histologically confirmed lesions 20% in HIV-positive women, compared to 5% in HIV-negative women over 3-yr period; infection with high-risk HPV DNA types and multiple HPV types occurs more frequently in HIV-positive women; guidelines recommend repeating Papanicolaou (Pap) test and pelvic examination 6 mo after initial examination; if normal, conduct evaluation annually; refer patient for colposcopy if test indicates atypical squamous cells of undetermined significance (ASCUS), low-grade SIL, or high-grade SIL; if verified, proceed with standard therapy; progression rate from low-grade SIL to high-grade SIL higher in HIV-positive women; higher prevalence of vulvar, vaginal, and anal intraepithelial neoplasias in HIV-positive women, therefore colposcopy and biopsy of any abnormalities warranted; HPV infection unlikely cleared in woman with CD4 count <200 cells/mm3 ; 39% to 62% of HIV-positive women have post treatment SIL recurrences, compared to 9% to 18% in HIV-negative women; chronic persistent disease found in 45% of HIV-positive women, compared with 5% in HIV-negative women; adjunctive therapy—HAART, oral isotretinoic acid, and topical 5-fluorouracil; mucosal microbicides and HPV vaccine currently in research and development |
| Genital tract infections: vulvovaginal candidiasis—most common gynecologic infection in HIV-positive women; typically recurrent or chronic disease; repeated azole therapy can lead to resistance or overgrowth of non-albicans Candida; bacterial vaginosis—occurs more frequently in HIV-positive women; associated with higher HIV VL in female genital tract; trichomoniasis—frequently elicits vigorous inflammatory and local immune response, causing punctate mucosal hemorrhages; HIV-positive women can have higher VL and can transmit virus more easily, whether symptomatic or not; cells susceptible to HIV infection increased in vaginal tract of HIV-negative woman with Trichomonas vaginitis; ulcerative sexually transmitted viruses—promote HIV transmission; HIV immunosuppression can make STDs more subtle in early presentation, more aggressive in progression, more difficult to diagnose and treat, and more prone to recurrence or persistence; acyclovir-resistant herpes simplex virus (HSV) that develops after repeated therapy can be treated with intravenous (IV) foscarnet or topical cidofovir; foscarnet can alter electrolyte balance; neurosyphilis can occur as early as 2 to 3 yr after untreated infection in HIV-positive host; higher rate of tubo-ovarian abscess in HIV-positive women, however, good response possible with antibiotic therapy that targets anaerobes and Mycoplasma |
| Contraception: condoms—3% pregnancy rate even with perfect use; do not prevent transmission of HPV infection; intrauterine device (IUD)—not good choice because of slight inflammatory environment and increase in local VL; diaphragm, cervical cap, and sponge—do not prevent transmission or acquisition of HIV; oral contraceptives (OCs)— can lead to cervical ectopy, predisposing woman to infection; associated with nonuse of condoms; potential for drug interactions (because of estrogen contained in OCs); protease inhibitors and nonnucleoside reverse transcriptase inhibitors heavily metabolized by hepatic cytochrome P450 (CYP450) system; tubal ligation—associated with decreased condom use |
| Adherence and psychosocial issues: anemia major side effect of all therapies; fatigue more prominent when anemia worsened by blood loss and drug interactions or side effects; socioeconomic factors affect women disproportionately more than men, and may affect access to appropriate therapy and decision to start therapy; reasons for nonadherence to therapy— complicated treatment regimens, side effects, social relationships, lack of confidence in therapy, busy daily schedules, and treatment-induced changes in body habitus; poor rates of adherence among women raising small children; refer patient with negative psychosocial history to appropriate health care resource |
| VIRAL INFECTIONS IN PREGNANCY AND TOXOPLASMOSIS —Ernest M. Graham, MD, Assistant Professor of Gynecology and Obstetrics, John Hopkins University School of Medicine; Director, Perinatal Services, Howard County General Hospital, Columbia, Maryland |
| Rubella: 6% to 25% of women susceptible to german measles; rubella vaccination—attenuated live virus vaccine; not given 1 mo before pregnancy or postpartum; vaccination during pregnancy not indication for termination; can be given while breast-feeding; congenital rubella syndrome—100% of neonates have some clinical features if infection occurs before 11th week; 54% at 13 to 14 wk; at 15 to 16 wk, only one quarter of exposed fetuses show some features; clinical manifestations—heart defects, cataracts, deafness, CNS defects, intrauterine growth retardation, thrombocytopenia, liver problems, bone changes, pneumonitis, chromosomal abnormalities; infected baby sheds virus and should be isolated; diagnostic tests—cordocentesis not useful in proving first trimester infection; fetal immunoglobulin production usually not detectable in first trimester; chorionic villus sampling proposed as diagnostic test because rubella causes certain cytopathic effects in placental cells; amniocentesis culture can be obtained for rubella virus; ultrasonography (US) best test to determine if serious fetal injury has occurred |
| Cytomegalovirus (CMV): ubiquitous double-stranded DNA virus; eventually infects most humans; most common perinatal infection (2% of neonates CMV-positive at birth); most maternal infections asymptomatic; 15% of infected mothers develop mononucleosis-like syndrome; clinical features—low birth weight, microcephaly, intracranial calcifications, chorioretinitis, mental and motor retardation, sensorineural deficits, hepatosplenomegaly, jaundice, hemolytic anemia; immunity present in 85% of lower socioeconomic groups and 55% of higher-income groups; 1% to 4% risk for seroconversion during pregnancy; 40% of women with primary CMV infection during pregnancy transmit virus to fetus; ≈90% of infected neonates asymptomatic; 10% show signs of infection at birth, probably 90% develop sequelae (neurologic deficits); treatment—no effective therapy; serologic screening not recommended; no accurate predictability of sequelae of primary infection; no vaccine; 1% to 2% of all infants excrete CMV; ≈10% of pregnant women excrete CMV, but most have recurrent infections that are low risk for fetus; primary infection diagnosed by 4-fold increase in paired acute and convalescent IgG titers or presence of IgM antibodies; US findings—microcephaly, ventriculomegaly, cerebral calcifications, hyperechoic bowel; PCR used to detect DNA in amniotic fluid |
| Herpes simplex virus: type 1—associated with oral lesions; about one third associated with genital lesions; type 2— predominantly genital tract lesions; both types distinct serotypes, but share antigenic features; patient can have antibodies to one type, but get infected with other type; primary infection—indicates no previous antibodies to either type; nonprimary first episode—newly acquired HSV-2 infection with preexisting HSV-1 cross-reacting antibodies; recurrent infection—reactivation of previous HSV-2 infection in presence of HSV-2 antibodies; lowest risk of having symptoms in mother or having infectious problems in fetus; signs and symptoms—incubation period generally 3 to 6 days; paresthesias or tingling with lesions; prodromal symptoms; urinary retention from pain associated with lesions; lesions generally disappear within 2 to 4 wk; subclinical cervical and vulvar shedding occurs in ≈2.3% of women with HSV-2 and <1% of women with HSV-1; tissue culture used to document; virus detectable in ≈80% of patients with primary and nonprimary first-episode ulcers and ≈40% of patients with crusted-over lesions; Tzanck and Pap tests not accurate screening tests for HSV (maximum sensitivity 70%); antiviral therapy—acyclovir, famciclovir, and valacyclovir used to treat active lesions or for suppression during pregnancy; start patient at 36 wk and continue therapy to term; class 3 drugs teratogenic; early reports of increased risk for first trimester spontaneous abortion but later report stated unlikely; neonatal infection—can be localized, asymptomatic, or disseminated; most infected neonates have localized mild skin, eye, and mouth disease; ≈50% risk for neonatal infection with primary maternal infection (no antibodies and new-onset disease); ≈33% risk for neonatal infection if mother has antibodies to HSV-1 and develops primary lesion; ≈5% risk for neonatal infection with recurrent infection; disseminated infection—associated with 60% mortality, even with treatment; cesarean delivery—indicated if woman has active genital lesion, prodrome of impending outbreak, or ruptured membranes; no evidence that ruptured membranes places baby at risk; cesarean delivery with evidence of active lesion, regardless of duration of ruptured membranes; separating mother with herpetic lesions not necessary, and breast-feeding not contraindicated |
| Varicella zoster: DNA herpesvirus; remains latent in dorsal root ganglia; may reactivate to cause herpes zoster or shingles; ≈95% of adults immune; 50% of varicella deaths occur in 5% of population that is varicella-negative; adults infected with varicella more likely to develop varicella pneumonia; aggressive follow-up warranted for pregnant woman complaining of cough; varicella zoster immunoglobulin—prevents or attenuates varicella infection in susceptible patients if given within 96 hr of exposure; serologic testing warranted if woman uncertain whether she had varicella; 80% to 90% of patients immune; Varivax—attenuated live virus vaccine; approved for use in 1995; 1 dose for children 1 to 12 yr of age; 2 doses 4 to 8 wk apart for adolescents and adults; not recommended for pregnant women; congenital malformations— chorioretinitis, cerebrocortical atrophy, hydronephrosis, cutaneous and bony leg defects, and liver calcifications; most serious malformations occur 13 to 20 wk into pregnancy; infections occurring at >20 wk not linked to specific problems; exposure within 5 days of delivery serious threat to fetus (antibodies from mother have not crossed to fetus) |
| Parvovirus: small virus; makes small number of proteins; has predisposition for erythroblast precursors; transmitted by respiratory droplets; incubation period 4 to 20 days; erythema infectiosum or fifth disease—characteristic rash; 50% risk of baby developing hydrops from in utero parvovirus infection; serology—IgM-specific antibody positive within 7 days and lasts 120 days; IgG appearing after that point persists for life; US—most valuable diagnostic test; incubation period <20 days (may be longer in fetus); serial US examination for 8 to 10 wk after acute illness recommended to look for signs of hydrops; repeat serology in 3 wk if patient susceptible to check for seroconversion; no antiviral agent or vaccine available for treatment; patient with transient aplastic crisis may require transfusion during acute phase of illness; unfavorable reports about long-term development in surviving infants |
| Influenza virus: does not cause in utero infection; vaccination recommended for women after first trimester; vaccine made from activated virus; amantadine antiviral agent with specific activity against influenza; prophylactic amantadine reserved for unimmunized woman at high risk for influenza complications; neuraminidase inhibitors effective in treating symptoms |
| Toxoplasmosis: cat only host for oocyst; oocysts formed in cat intestine and excreted in feces; cows ingest oocysts, and animals’ intestines release invasive trophozoite; infection can occur from eating infected meat, gardening, or handling cat litter boxes; maternal immunity protects against fetal infection; ≈40% to 50% of women in the United States have antibodies; American College of Obstetricians and Gynecologists (ACOG) does not recommend routine screening for pregnant women with HIV infection; most infections asymptomatic; generally, patients with severe illness immunocompromised; serologic tests—that suggest acute infection include detection of IgM or extremely high IgG titers; serologic assays not well standardized; PCR assay used to detect virus in amniotic fluid; confirm positive result with reference laboratory; clinical features—periventricular calcifications, chorioretinitis; usually asymptomatic or self-limited illness in immunocompetent adult; treatment—pyrimethamine, sulfonamides, and spiramycin (experimental drug); infected baby treated for ≈1 yr after birth; counsel patients to—avoid contact with stray cats or cat litter, wash hands after preparing meat, never eat rare or raw meat; wash fruits and vegetables to remove possible contamination by oocysts |
Educational Objectives
| The goal of this program is to educate the listener about gynecologic issues in the HIV-positive woman and viral infections and toxoplasmosis in pregnancy After hearing and assimilating this program, the clinician will be better able to: |
 | 1. List surrogate markers of HIV infection and the spectrum of complications associated with HIV infection. |
| 2. Recognize gynecologic complications of HIV infection. |
| 3. Discuss the role of contraception in the HIV-positive woman as well as psychosocial barriers to obtaining treatment. |
| 4. Determine the appropriate screening modality for detecting rubella virus, cytomegalovirus, herpes simplex virus, varicella zoster virus, and parvovirus. |
| 5. Counsel patients about prevention of toxoplasmosis. |
Discussed on This Program
Acyclovir (acycloguanosine) [Zovirax] Cidofovir [Forvade (investigational), Vistide] Enfuvirtide (T-20) [Fuzeon] Famciclovir [Famvir] Fluconazole [Diflucan] Fluorouracil (5-fluorouracil, 5-FU) [Adrucil, Carac, Efudex, Fluoroplex] Foscarnet sodium (phosphonoformic acid; PFA) [Foscavir] Isotretinoin (13-cis-retinoic acid) [Accutane] Levofloxacin [Levaquin, Quixin] Metronidazole [Flagyl, others] Miconazole nitrate [several trade names] Moxifloxacin HCl [Avelox, Avelox I.V., Vigamox] Terconazole [Terazol 3, Terazol 7] Valacyclovir HCl [Valtrex] Varicella virus vaccine [Varivax]
Suggested Reading
Biggers SB: The need to revolutionize our approach to women coinfected with HIV and HPV. AIDS Read 10(12):692, 2000, Boyer KM et al: Risk factors for Toxoplasma gondii infection in mothers of infants with congenital toxoplasmosis: Implications for prenatal management and screening. Am J Obstet Gynecol 192(2):564, 2005; Cejtin HE: Gynecologic issues in the HIV-infected woman. Obstet Gynecol Clin North Am 30(4):711, 2003; Conley LJ et al: HIV-1 infection and risk of vulvovaginal and perianal condylomata acuminata and intraepithelial neoplasia: a prospective cohort study. Lancet 359(9301):108, 2002; Jay N: Human papillomavirus infections in women with HIV disease: prevalence, risk, and management. AIDS Read 10(11):659, 2000; Schrag SJ et al: Prenatal screening for infectious diseases and opportunities for prevention. Obstet Gynecol 102(4):753, 2003; Sheffield JS et al: Acyclovir prophylaxis to prevent herpes simplex virus recurrence at delivery: a systematic review. Obstet Gynecol 102(6):1396, 2003; Williams AB: Gynecologic are for women with HIV infection. J Obstet Gynecol Neonatal Nurs 32(1):87, 2003; Helfgott A et al: Vaginal infections in human immunodeficiency virus-infected women. Am J Obstet Gynecol 183(2):347, 2000; Sorvillo F et al: Trichomonas vaginalis, HIV, and African-Americans. Emerg Infect Dis 7(6):927, 2001; Wilson TE et al: Sexually transmitted disease among women with HIV infection: a missed opportunity for intervention. AIDS Read 9(8):573, 1999; Squires KE: Treating HIV infection and AIDS in women. AIDS Read 13(5):228, 2003.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship with the manufacturer or provider of any commercial product or service discussed. The following has been disclosed: Dr. Mateo has received honoraria from Bristol-Myers Squibb and GlaxoSmithKline in connection with their antiretroviral medications.
Dr. Mateo was recorded at the 23rd Annual OB/GYN Update, sponsored by HealthPartners Department of Obstetrics and Gynecology and HealthPartners Institute for Medical Education, Center for Continuing Professional Development, and held on April 14-15, 2005, in Minneapolis. Dr. Graham was recorded at the 46th Emil Novak Memorial Course: An Update in Gynecology and Obstetrics, sponsored by the Office of Continuing Medical Education at the Johns Hopkins University School of Medicine, and held on September 29 to October 2, 2004, in Baltimore. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
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