Pharmacokinetics of tenofovir during pregnancy and postpartum.

OBJECTIVES: Tenofovir disoproxil fumarate (TDF) is increasingly used in the highly active antiretroviral therapy (HAART) regimens of pregnant women, but limited data exist on the pregnancy pharmacokinetics of chronically dosed TDF. This study described tenofovir pharmacokinetics during pregnancy and postpartum. METHODS: International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) P1026s is a prospective, nonblinded pharmacokinetic study of HIV-infected pregnant women that included a cohort receiving 300 mg TDF once daily. Steady-state 24-hour pharmacokinetic profiles were measured at the second and third trimesters, postpartum, and in maternal and umbilical cord samples collected at delivery. Tenofovir was measured by liquid chromatography-mass spectrometry (LC-MS). The target area under the concentration versus time curve from time 0 to 24 h post dose (AUC) was ≥ 1.99 µg h/mL (nonpregnant historical control 10th percentile). RESULTS: The median tenofovir AUC was decreased during the second (1.9 µg h/mL) and third (2.4 µg h/mL; P = 0.005) trimesters versus postpartum (3.0 µg h/mL). Tenofovir AUC exceeded the target for two of four women (50%) in the second trimester, 27 of 37 women [73%; 95% confidence interval (CI) 56%, 86%] in the third trimester, and 27 of 32 women (84%; 95% CI 67%, 95%) postpartum (P > 0.05). Median second/third-trimester troughs were lower (39/54 ng/mL) than postpartum (61 ng/mL). Median third-trimester weight was greater for subjects below the target AUC versus those above the target (97.9 versus 74.2 kg, respectively; P = 0.006). The median ratio of cord blood to maternal concentrations was 0.88. No infants were HIV infected. CONCLUSIONS: This study found lower tenofovir AUC and troughs during pregnancy. Transplacental passage with chronic TDF use during pregnancy was high. Standard TDF doses appear to be appropriate for most HIV-infected pregnant women but therapeutic drug monitoring with dose adjustment should be considered in pregnant women with high weight (> 90 kg) or inadequate HIV RNA response.

Predictors of adverse pregnancy outcomes in women infected with HIV in Latin America and the Caribbean: a cohort study.

OBJECTIVE: To examine maternal characteristics associated with adverse pregnancy outcomes among women infected with HIV. DESIGN: Prospective cohort study. SETTING: Multiple sites in Latin America and the Caribbean. POPULATION: Women infected with HIV enrolled in the Perinatal (2002-2007) and the Longitudinal Study in Latin American Countries (LILAC; 2008-2012) studies of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) International Site Development Initiative (NISDI). METHODS: Frequencies of adverse pregnancy outcomes assessed among pregnancies. Risk factors investigated by logistic regression analysis. MAIN OUTCOME MEASURES: Adverse pregnancy outcomes, including preterm delivery (PT), low birthweight (LBW), small for gestational age (SGA), stillbirth (SB), and neonatal death. RESULTS: Among 1512 women, 1.9% (95% confidence interval, 95% CI, 1.3-2.7) of singleton pregnancies resulted in a stillbirth and 32.9% (95% CI 30.6-35.4) had at least one adverse pregnancy outcome. Of 1483 singleton live births, 19.8% (95% CI 17.8-21.9) were PT, 14.2% (95% CI 12.5-16.1) were LBW, 12.6% (95% CI 10.9-14.4) were SGA, and 0.4% (95% CI 0.2-0.9) of infants died within 28 days of birth. Multivariable logistic regression modelling indicated that the following risk factors increased the probability of having one or more adverse pregnancy outcomes: lower maternal body mass index at delivery (odds ratio, OR, 2.2; 95% CI 1.4-3.5), hospitalisation during pregnancy (OR 3.3; 95% CI 2.0-5.3), hypertension during pregnancy (OR 2.7; 95% CI 1.5-4.8), antiretroviral use at conception (OR 1.4; 95% CI 1.0-1.9), and tobacco use during pregnancy (OR 1.7; 95% CI 1.3-2.2). The results of fitting multivariable logistic regression models for PT, LBW, SGA, and SB are also reported. CONCLUSIONS: Women infected with HIV had a relatively high occurrence of adverse pregnancy outcomes, and some maternal risk factors were associated with these adverse pregnancy outcomes. Interventions targeting modifiable risk factors should be evaluated further.

Treatment interruption after pregnancy: effects on disease progression and laboratory findings.

OBJECTIVE: To assess clinical progression and inflammatory markers among women stopping or continuing antiretroviral therapy (ART) after pregnancy. METHODS: ART-naïve women with CD4+ lymphocyte counts >350 cells/uL initiating ART during pregnancy had clinical events and laboratory markers compared over one year postpartum between those stopping (n = 59) or continuing (n = 147) ART. RESULTS: Slopes in CD4 count and HIV RNA did not differ between groups overall and in subsets of ZDV or combination therapy. The hazard ratio (HR) of a new class B event was 2.09 (95% CI 0.79-5.58) among women stopping ART, 1.24 (0.31-4.95) in those stopping ZDV, and 2.93 (0.64-13.36) among those stopping combination therapy. Women stopping ART had increased immune activation. No significant differences were seen in C-reactive protein, lipids, leptin, or interleukin-6. CONCLUSIONS: While changes in CD4 and HIV RNA levels over one year were similar between women stopping or continuing ART postpartum, higher immune activation among women stopping therapy requires further study.

Pharmacokinetics and safety of nelfinavir when used in combination with zidovudine and lamivudine in HIV-infected pregnant women: Pediatric AIDS Clinical Trials Group (PACTG) Protocol 353.

BACKGROUND: Combination antiretroviral regimens including nelfinavir (NFV) are commonly used in pregnancy. We studied the safety, antiviral effect, and pharmacokinetics of NFV and its M8 metabolite with two dosing regimens in combination with zidovudine (ZDV) and lamivudine (3TC) in HIV-infected pregnant women. METHOD: HIV-infected pregnant women between 14 and 34 weeks gestation received NFV (Cohort 1: 750 mg tid, n = 10; Cohort 2: 1250 mg bid, n = 23) with ZDV and 3TC. Serial blood sampling for NFV concentrations was performed antepartum (AP) and 6 weeks postpartum (PP). Maternal and cord blood samples were also obtained at delivery. NFV and M8 levels were determined by high-performance liquid chromatography. The pharmacokinetic (PK) target was an extrapolated NFV AUC0-24 > 30 mug . h/mL. Mothers were followed frequently for potential clinical and laboratory toxicity. RESULTS: Overall, NFV in combination with ZDV and 3TC was well tolerated. The PK target was met in 3/8 AP and 5/7 PP in Cohort 1 and 17/21 AP and 16/17 PP in Cohort 2. When Cohort 2 NFV PK parameters AP and PP were compared, median Cmax (3.90 microg/mL vs. 5.01 microg/mL, p < .05) and AUC0-24 (56.6 vs. 86.8 microg . h/mL, p < .05) were increased PP and oral clearance (Cl/F; 44.2 vs. 28.8 L/h, p < .05) was decreased PP. The average M8/NFV ratio was increased PP compared to AP (0.085 vs. 0.29, p < .001). Placental transfer of NFV was low with a median cord blood:maternal plasma ratio at delivery of 0.05. Maternal mean CD4+ T cell counts increased significantly and plasma HIV-1 RNA levels decreased from entry to delivery and 6 to 12 weeks postpartum. CONCLUSION: NFV used in combination with ZDV and 3TC was well tolerated in pregnant HIV-infected women and produced a significant improvement in HIV disease parameters. NFV drug exposure is inadequate in most pregnant women receiving 750 mg tid but is much improved with 1250 mg bid. NFV crosses the placenta poorly. The AP increase in NFV oral clearance and decrease in M8/NFV ratio suggest that CYP3A activity increases relative to CYP2C19 activity during pregnancy.

Depo-medroxyprogesterone in women on antiretroviral therapy: effective contraception and lack of clinically significant interactions.

We conducted an open-label, steady-state pharmacokinetic (PK) study of drug interactions among HIV-infected women treated with depo-medroxyprogesterone acetate (DMPA) while on nucleoside analogues plus nelfinavir (N=21), efavirenz (N=17), or nevirapine (N=16); or nucleosides only or no antiretroviral therapy as a control group (N=16). PK parameters were estimated using non-compartmental analysis, with between-group comparisons of medroxyprogesterone acetate (MPA) PKs and within-subject comparisons of ARV PKs before and 4 weeks after DMPA dosing. Plasma progesterone levels were measured at baseline and at 2, 4, 6, 8, 10, and 12 weeks after DMPA dosing. There were no significant changes in MPA area under the concentration curve, peak or trough concentrations, or apparent clearance in the nelfinavir, efavirenz, or nevirapine groups compared to the control group. Minor changes in nelfinavir and nevirapine drug exposure were seen after DMPA, but were not considered clinically significant. Suppression of ovulation was maintained.

Histologic endometritis in asymptomatic human immunodeficiency virus-infected women: characterization and effect of antimicrobial therapy.

OBJECTIVE: To estimate the prevalence, risk factors, clinical symptoms and signs, and response to antimicrobial therapy of histologic endometritis in human immunodeficiency virus (HIV)-infected women without clinical salpingitis. METHODS: This was a cross-sectional study of 42 HIV-infected women enrolled from a single clinic. Subjects underwent standardized history, examination, and laboratory determinations, including endometrial biopsy. Women with suspected pelvic inflammatory disease were excluded. All women were given antibiotics and repeat evaluation in 5-7 weeks. Histologic endometritis was defined by at least one stromal plasma cell per 120x field and five or more surface polymorphonuclear leukocytes per 400x field. Chi-square and Fisher exact tests were used as appropriate. RESULTS: Histologic endometritis was present among 16 (38%) of 42 evaluable HIV-infected women, none of whom had Chlamydia trachomatis or Neisseria gonorrhoeae. Douching three or more times per month, history of ectopic pregnancy, and two or more prior urinary tract infections were associated with endometritis, as was elevated erythrocyte sedimentation rate (P < or = .05). Physical examination findings and mean CD4+ lymphocyte count were similar among those with and without endometritis. In the nine HIV-infected women with a repeat biopsy, endometritis decreased from four (44%) to two (22%) after treatment (P = .30). CONCLUSION: The prevalence of histologic endometritis in HIV-infected women was high despite few examination findings and no demonstrated pathogens. Endometritis in HIV-infected women might be related to pathogens not evaluated, to prior infection, or to reduced immunity from HIV.

The effect of highly active antiretroviral therapy on cervical cytologic changes associated with oncogenic HPV among HIV-infected women.

OBJECTIVE: Cervical intraepithelial neoplasia (CIN), a common condition among HIV-infected women, has been linked to HIV load and immune status. Highly active antiretroviral therapy (HAART) improves immunologic and virologic status. This study was undertaken to determine the relationship between HAART use and CIN. DESIGN: Cohort study. The Women's Interagency HIV Study (WIHS) in five cities in the USA (Bronx/Manhattan, New York; Brooklyn, New York; Chicago, Illinois; Los Angeles, California; San Francisco Bay area, California; Washington, District of Columbia). METHODS: HIV-infected women were followed every 6 months with Papanicolaou smears and cervicovaginal lavage for human papillomavirus (HPV) DNA testing. To characterize exposures that changed over time and to capture the dynamic nature of cytologic changes, Papanicolaou smear findings from each participant's consecutive visits were defined as a pair. We determined the proportion of all pairs that exhibited either regression or progression, according to HAART exposure, HPV results and Papanicolaou smear status. As participants could contribute multiple pairs, inferences were based on robust methods to adjust for correlated observations. RESULTS: Women with persistent HPV infection were more likely to have progression of their lesions. After adjustment for CD4 cell count and Papanicolaou smear status, women on HAART were 40% (95% confidence interval, 4-81%) more likely to demonstrate regression and less likely (odds ratio, 0.68; 95% confidence interval, 0.52-0.88) to demonstrate progression CONCLUSIONS: HAART altered the course of HPV disease in HIV-infected women, reducing progression and increasing regression. As HPV disease is a common sex-specific manifestation of HIV disease this effect of HAART would be a major additional benefit from this modality of therapy.

Hormonal levels among HIV-1-seropositive women compared with high-risk HIV-seronegative women during the menstrual cycle. Women's Health Study (WHS) 001 and WHS 001a Study Team.

There is a paucity of normative data on hormonal levels among HIV-infected women. Hormonal levels may influence fertility and HIV-related immunological and virological factors. The objective of this study was to determine progesterone and estradiol levels during the menstrual cycle in HIV-seropositive women compared with high-risk seronegative women. The study enrolled 55 HIV-infected and 10 high-risk uninfected women with self-reported regular menstrual cycles (25-30-day cycles). Progesterone and estradiol levels were determined on a weekly basis for 8 weeks. The analysis included evaluations from the first complete menstrual cycle for the 54 HIV-infected and 9 uninfected women who had at least one complete cycle. The median age was 35 years for HIV-infected women and 36 years for uninfected women. The median CD4+ count for HIV-seropositive women was 210 cells/mm3. The median menstrual cycle length was 28 days (range 22-49 days) for HIV-infected women and 25 days (range 24-44 days) for uninfected women. The maximum progesterone level during the luteal phase was normal (>3.0 ng/ml) for 52 (96%) of 54 HIV-seropositive women and 7 (78%) of 9 HIV-seronegative women (p = 0.09, Fisher's exact test). The median maximum progesterone level was 12.2 ng/ml in HIV-seropositive women and 7.2 ng/ml in HIV-seronegative women (p = 0.07, Wilcoxon test). The median maximum estradiol value during the follicular phase was 148 pg/ml for HIV-seropositive women and 111 pg/ml for HIV-seronegative women (p = 0.04, Wilcoxon test). Among HIV-infected women, there were no significant differences in progesterone and estradiol levels by antiretroviral therapy, baseline plasma viral load, or median CD4+ cell count. We conclude that HIV-infected women with self-reported normal menstrual cycles have normal levels of progesterone and estradiol during the menstrual cycle.

Maternal and neonatal outcomes after induction of labor without an identified indication.

OBJECTIVE: This study was undertaken to examine associations between induction of labor and maternal and neonatal outcomes among women without an identified indication for induction. STUDY DESIGN: This was a population-based cohort study of 2886 women with induced labor and 9648 women with spontaneous labor who were delivered at 37 to 41 weeks' gestation, all without identified medical and obstetric indications for induction. RESULTS: Among nulliparous women 19% of women with induced labor versus 10% of those with spontaneous labor underwent cesarean delivery (adjusted relative risk, 1.77; 95% confidence interval, 1.50-2.08). No association was seen in multiparous women (relative risk, 1.07; 95% confidence interval, 0. 81-1.39). Among all women induction was associated with modest increases in instrumental delivery (19% vs 15%; relative risk, 1.20; 95% confidence interval, 1.09-1.32) and shoulder dystocia (3.0% vs 1. 7%; relative risk, 1.32; 95% confidence interval, 1.02-1.69). CONCLUSION: Among women who lacked an identified indication for induction of labor, induction was associated with increased likelihood of cesarean delivery for nulliparous but not multiparous women and with modest increases in the risk of instrumental delivery and shoulder dystocia for all women.

Complications according to mode of delivery among human immunodeficiency virus-infected women with CD4 lymphocyte counts of < or = 500/microL.

OBJECTIVE: We sought to describe rates of and risk factors for complications by delivery mode among human immunodeficiency virus-infected women with CD4 counts of < or = 500/microL. STUDY DESIGN: Complication rates were calculated by delivery mode, as follows: planned cesarean delivery performed without labor or rupture of membranes, other cesarean delivery performed after labor or rupture of membranes, or vaginal delivery. Risk factors were evaluated. RESULTS: Major complications in the planned cesarean delivery (n = 37), other cesarean delivery (n = 95), and vaginal delivery (n = 365) groups were amnionitis or endometritis (16%, 27%, and 7%, respectively), wound infection (5%, 8%, and <1%, respectively), and transfusion (8%, 6%, and 3%, respectively). Any peripartum infection occurred among 16 (18%) of those with a CD4 count of <200/microL and 43 (13%) with a CD4 count of > or =200/microL (P =.17). On multivariate analyses, factors associated with amnionitis-endometritis were cesarean delivery and African American race, and a factor associated with transfusion was third-trimester anemia. CONCLUSION: Endometritis and wound infection occurred more frequently among human immunodeficiency virus-infected women after cesarean than among women undergoing vaginal delivery; however, complication rates overall were within the range reported in human immunodeficiency virus-negative women. Measures to decrease complications in human immunodeficiency virus-infected women, such as greater use of prophylactic antibiotics, should be assessed.

Risk factors for preterm birth, low birth weight, and intrauterine growth retardation in infants born to HIV-infected pregnant women receiving zidovudine. Pediatric AIDS Clinical Trials Group 185 Team.

OBJECTIVE: To evaluate independent contributions of maternal factors to adverse pregnancy outcomes (APO) in HIV-infected women receiving antiretroviral therapy (ART). DESIGN: Risk factors for preterm birth (< 37 weeks gestation), low birth weight (LBW) (< 2500 g), and intrauterine growth retardation (IUGR) (birth weight < 10th percentile for gestational age) examined in 497 HIV-infected pregnant women enrolled in PACTG 185, a perinatal clinical trial. METHODS: HIV RNA copy number, culture titer, and CD4 lymphocyte counts were measured during pregnancy. Information collected included antenatal use of cigarettes, alcohol, illicit drugs; ART; obstetric history and complications. RESULTS: Eighty-six percent were minority race/ethnicity; 86% received antenatal monotherapy, predominantly zidovudine (ZDV), and 14% received combination antiretrovirals. Preterm birth occurred in 17%, LBW in 13%, IUGR in 6%. Risk of preterm birth was independently associated with prior preterm birth [odds ratio (OR) 3.34; P < 0.001], multiple gestation (OR, 6.02; P = 0.011), antenatal alcohol use (OR, 1.91; P = 0.038), and antenatal diagnosis of genital herpes (OR, 0.24; P = 0.022) or pre-eclampsia (OR, 6.36; P = 0.025). LBW was associated with antenatal diagnosis of genital herpes (OR, 0.08; P = 0.014) and pre-eclampsia (OR, 5.25; P = 0.049), and baseline HIV culture titer (OR, 1.41; P = 0.037). IUGR was associated with multiple gestation (OR, 8.20; P = 0.010), antenatal cigarette use (OR, 3.60; P = 0.008), and pre-eclampsia (OR, 12.90; P = 0.007). Maternal immune status and HIV RNA copy number were not associated with APO. CONCLUSIONS: Risk factors for APO in antiretroviral treated HIV-infected women are similar to those reported for uninfected women. These data suggest that provision of prenatal care and ART may reduce APO.

Vaginal 5-fluorouracil for high-grade cervical dysplasia in human immunodeficiency virus infection: a randomized trial.

OBJECTIVE: To compare the efficacy and toxicity of topical vaginal 5-fluorouracil (5-FU) maintenance therapy against the effects of observation after standard treatment for high-grade cervical dysplasia in human immunodeficiency virus (HIV)-infected women and to evaluate the association between baseline CD4 count and time to recurrence. METHODS: In a phase III unmasked, randomized, multicenter, outpatient clinical trial, 101 HIV-positive women either received 6 months of biweekly treatment with vaginal 5-FU cream (2 g) or underwent 6 months of observation after standard excisional or ablative cervical treatment for cervical intraepithelial neoplasia (CIN). Papanicolaou smears and colposcopy were scheduled at regular intervals during the ensuing 18 months, with the primary end point being the time at which CIN of any grade recurred. RESULTS: Thirty-eight percent of women developed recurrence: 14 (28%) of 50 in the 5-FU therapy group and 24 (47%) of 51 in the observation group. Treatment with 5-FU was significantly associated with prolonged time to CIN development (P = .04). Observation subjects were more likely to have high-grade recurrences, with 31% developing CIN 2-3 compared with 8% in the 5-FU treatment arm (P = .014), and disease recurred more quickly in observation subjects as well. Baseline CD4 count was related significantly to time to recurrence (P = .04), with 46% of subjects with CD4 counts less than 200 cells/mm3 developing recurrence compared with 33% of subjects with CD4 counts at least 200 cells/mm3. Disease recurred more slowly in subjects who had received antiretroviral therapy than in antiretroviral therapy-naive subjects. There were no instances of grade 3 or 4 toxicity, and compliance with 5-FU treatment was generally good. CONCLUSION: Adjunctive maintenance intravaginal 5-FU therapy after standard surgery for high-grade lesions safely and effectively reduced recurrence of cervical intraepithelial neoplasia in HIV-infected women.

The effects of three nonoxynol-9 preparations on vaginal flora and epithelium.

To evaluate the effects of nonoxynol-9 (N-9) on the vaginal flora and epithelium, 48 women (16 in each group) were evaluated by use of quantitative vaginal cultures and colposcopy. at baseline and at 0.5, 4, 24, 48, and 72 h after insertion of one of three N-9 preparations (4% gel [Conceptrol], 3.5% gel [Advantage-24], or a 28% vaginal contraceptive film). The proportion positive for H2O2+ or H2O2- lactobacilli did not change significantly with any of the preparations, but lactobacilli concentrations decreased transiently. Both the proportion of women with Gardnerella vaginalis and the concentration of G. vaginalis decreased transiently. The proportion of women with Escherichia coli increased with the 4% gel, and the concentration increased with all preparations. The number with anaerobic gram-negative rods increased, although the concentrations decreased. Symptoms and colposcopic abnormalities were rare. Changes in levels of vaginal bacteria were transient after single applications of N-9, but adverse effects may be enhanced with frequent, chronic use.

A matched prospective study of human immunodeficiency virus serostatus, human papillomavirus DNA, and cervical lesions detected by cytology and colposcopy.

OBJECTIVE: To compare the prevalence and type of human papillomavirus (HPV) infections in the genital tract of human-immunodeficiency-virus- (HIV) seropositive and -seronegative women matched for cytology and to examine prospectively the relationship of HPV DNA, colposcopic findings and cervical squamous intraepithelial lesions (SIL) in these matched seropositive and seronegative cohorts. METHODS: A matched prospective study of HIV-seropositive and -seronegative women undergoing cytologic screening, colposcopy, and testing for HPV DNA and other infections at each visit. RESULTS: Twenty-three HIV-seropositive women were matched with 23 seronegative women by cervical cytology reading, lifetime number of sexual partners, age, and follow-up length. Fourteen pairs of these women had follow-up visits every 4 months, for 56 and 53 total visits in seropositive and seronegative women, respectively. After matching, the groups had a similar overall prevalence of HPV DNA and of HPV oncogenic (high risk) types at baseline. On follow up, HIV-seropositive women were more likely than seronegative women to develop SIL (38% vs. 10%), less likely to have negative cytology (34% vs. 60%, overall P = 0.03), more visits with HPV DNA detected (68% vs. 40% P = 0.04), and more visits with multiple HPV DNA types detected (18% vs. 0%, P = 0.02). Colposcopic lesions in the seropositive women were more likely to have sharp borders or mosaicism or to be thick white (P = 0.009). CONCLUSIONS: After matching for baseline Papanicolaou smear readings, these data suggest that over time seropositive women have more visits that yield abnormal cytology, more persistent HPV DNA detection, and more colposcopic abnormalities than seronegative women.

Comparison of gynecologic history and laboratory results in HIV-positive women with CD4+ lymphocyte counts between 200 and 500 cells/microl and below 100 cells/microl.

OBJECTIVE: To assess rates of sexual activity, contraceptive use, genital infections and dysplasia, and other gynecologic symptoms among well-characterized populations of HIV-seropositive women enrolled in two Adult AIDS Clinical Trials Group (AACTG) randomized studies. METHODS: Gynecologic data were collected using standardized interview and examination forms from women enrolled in two protocols: ACTG 175, an antiretroviral trial (CD4+ lymphocyte counts 200-500 cells/microl) and ACTG 196, a Mycobacterium avium complex prophylaxis trial (CD4+ counts < or =100 cells/microl). RESULTS: Women enrolled in the two studies were similar in age, race, weight, and history of illicit or injection drug use, but women in ACTG 196 (n = 67) had lower median CD4+ counts (median, 35 cells/microl; range, 0-135 cells/microl versus median, 356 cells/microl; range, 131-620 cells/microl; p < .0005), were less likely to be antiretroviral naive (6% versus 38%; p < .0005), and were more likely to have a Karnofsky score <80 (28% versus 5%; p < .0001) than women in ACTG 175 (n = 185) at baseline. Recent changes in menstrual cycle were not different between groups. Women enrolled in ACTG 196 were less likely to be sexually active (40% versus 61%; p < .005), but both groups reported high levels of contraceptive use. Papanicolaou smear results in ACTG 196 and ACTG 175 respectively, were: normal, 38% and 50%, atypia, 24% and 39%, low-grade squamous intraepithelial lesions (SIL), 27% and 10%, and high-grade SIL, 11% and 0.7% (p < .001). CONCLUSIONS: Gynecologic complications are common among HIV-seropositive women with CD4+ lymphocyte counts < 500 cells/microl and are more common and severe among those with more advanced immunosuppression.

Lactobacilli and vaginal host defense: activation of the human immunodeficiency virus type 1 long terminal repeat, cytokine production, and NF-kappaB.

Lactobacilli, a component of the normal vaginal flora, can activate the human immunodeficiency virus (HIV)-1 long terminal repeat (LTR) in the Jurkat T lymphocyte and THP-1 macrophage cell lines. Activation of the LTR in Jurkat cells was strongly enhanced by vanadate and inhibited by catalase, implicating H2O2. In contrast, activation in THP-1 cells occurred in the absence of vanadate and was unaffected by catalase. The active material partitioned into the phenol layer on hot aqueous phenol extraction. Lactobacilli also increased tumor necrosis factor-alphaand interleukin-1betaproduction and activated NF-kappaB in THP-1 cells and increased tumor necrosis factor-alphaproduction by human monocytes. Human vaginal fluid specimens had comparable properties, which correlated with their bacterial content. These findings suggest the presence in vaginal fluid of agent(s) derived from indigenous bacteria that can activate the HIV-1 LTR, cytokine production, and NF-kappaB in cells of macrophage lineage, with possible influence on vaginal physiology and host defense.

Pregnant adolescents in chemical dependency treatment. Description and outcomes.

This study examines the treatment, maternal and infant outcomes of pregnant adolescents (16-19 years) enrolled in an adult perinatal chemical dependency treatment program. Twenty-one adolescent subjects were compared to 323 adult women (mean age, 27.4 years) after enrollment into a randomized treatment trial consisting of intensive outpatient or short-term residential conditions. The results show a similar treatment retention rate. Adolescents differed from adult women on marital status, drugs of choice (alcohol, marijuana vs. opiates and cocaine) and method of administration, with no injection drug users in the adolescent cohort. Tobacco use was high (> 85%) in both groups. Obstetric, maternal, and infant outcomes to 1 year were comparable. Older adolescents who are chemically dependent and pregnant have treatment needs similar to adult women and can benefit from programs designed to treat older women. Recruitment difficulties for adolescents in need of treatment is discussed.

PIP: This study describes a sample of 21 pregnant women aged 16-19 years in treatment for substance abuse through the MOMS Project in Seattle, Washington, during 1991-94 who were followed for at least 90 days after the beginning of treatment with regard to a number of variables. The treatment, maternal, and infant outcomes of these pregnant adolescents enrolled in an adult perinatal chemical dependency treatment program are compared with like outcomes for 323 randomized adults of mean age 27.4 years in the program. The randomized treatment trial involved either intensive outpatient or short-term residential conditions. 27% of adolescents and 32% of adults remained in treatment for longer than 90 days, a statistically nonsignificant difference. The adolescents did, however, differ from adult women on marital status, preferred drugs, and the method of drug administration, with no IV drug users among the adolescents. A larger proportion of the adolescents drank alcohol compared to the adults. More than 85% of the women in both groups smoked cigarettes. Obstetric, maternal, and infant outcomes to 1 year were comparable. These findings demonstrate that older adolescents who are chemically dependent and pregnant have treatment needs similar to adult women and can benefit from programs designed to treat older women.

Maternal physical activity in pregnancy and infant size for gestational age.

PURPOSE: To estimate the effect of several types of maternal physical activity in pregnancy on size for gestational age and length of gestation. METHODS: Telephone interviews, birth certificates, and medical records provided data on physical activity and other factors for a random sample of 291 Colorado residents. Backward polychotomous logistic regression modeling yielded estimates of the odds ratios for size for gestational age (appropriate versus small or large) and length of gestation (term versus pre-term or post-term) in relation to second and third trimester maternal physical activity. RESULTS: Performance of any moderate or vigorous physical activity for two hours per week or more in any month was associated with a decreased risk of large infant size for gestational age (LGA; odds ratio = 0.3, 95% confidence interval = 0.2, 0.7), but had no significant effect on risk of small infant size for gestational age (SGA; odds ratio (OR) = 0.8, 95% confidence interval (CI) = 0.3, 2.3). Length of gestation was not affected by prenatal physical activity. CONCLUSIONS: These results suggest that prenatal physical activity may decrease risk of LGA, as might be expected given its salutary effects on glucose tolerance.

Prevention of chickenpox in reproductive-age women: cost-effectiveness of routine prenatal screening with postpartum vaccination of susceptibles.

OBJECTIVE: To evaluate economic and clinical outcomes of a program of routine prenatal serotesting for varicella and postpartum vaccination of seronegative women. METHODS: An analytic cost-effectiveness model was constructed to compare the current strategy of no serotesting with 1) selective serotesting of pregnant women without a prior history of chickenpox and 2) serotesting of all pregnant women. In both serotesting strategies, seronegative women were vaccinated postpartum. The model followed a hypothetical cohort of 4 million women over 20 years. Costs and chickenpox disease outcomes during and outside of subsequent pregnancies were considered. The incremental cost-effectiveness (cost per adult chickenpox case prevented) of selective serotesting compared with the current strategy was measured. RESULTS: Compared to no testing, selective serotesting would prevent 43% (48,577 of 112,654) of adult chickenpox cases, save $21.8 million in discounted medical and work loss costs from the societal perspective, and cost $1126 per case prevented from the health payer's perspective (medical costs only). The model was sensitive to varicella seroprevalence and incidence of chickenpox among susceptible women but was relatively insensitive to the cost of serologic testing and vaccination. Compared with selective serotesting, the serotest-all strategy would prevent an additional 15,645 cases, at a societal cost of $7653 per additional case prevented. CONCLUSION: The selective serotesting strategy could prevent nearly half of chickenpox cases among this cohort and is cost-saving from the societal perspective. From the health payer's perspective, it compares favorably with other generally accepted preventive practices. It should be considered for prevention of chickenpox among women of childbearing age.