Oral zidovudine during labor to prevent perinatal HIV transmission, Bangkok: tolerance and zidovudine concentration in cord blood. Bangkok Collaborative Perinatal HIV Transmission Study Group.

OBJECTIVES: To evaluate tolerance for the oral administration of zidovudine (ZDV) during labor and measure the resulting ZDV concentrations in umbilical cord blood. DESIGN: A cross-sectional study of women in a placebo-controlled trial of short-course ZDV (twice a day from 36 weeks' gestation until labor and every 3 h during labor) to prevent perinatal HIV transmission in Bangkok. METHODS: Umbilical cord blood was collected. Sixty control specimens and specimens from 372 women (182 in the ZDV group, 190 in the placebo group) were tested for ZDV by radioimmunoassay (lower detection limit < 1 ng/ml). RESULTS: All women in the ZDV group took one or more labor dose, 170 (93%) took their last dose within 3 h of delivery, and only five (3%) experienced nausea or vomiting, a proportion similar to the placebo group. The median concentration of ZDV in the cord blood in the ZDV group was 252 ng/ml (range, < 1-1133 ng/ml); 31 (17%) specimens were less than 130 ng/ml (0.5 microM), the concentration thought to be active against HIV in vitro. Median concentrations were 189 ng/ml in specimens from women taking one or two labor doses, 290 ng/ml in those taking three or four doses, and 293 ng/ml in those taking more than four doses (P < 0.01). The ZDV concentration was not associated with time since the last dose, body weight, or perinatal transmission. CONCLUSION: Oral intrapartum ZDV was feasible and well tolerated. Most ZDV concentrations in the cord blood after oral dosing during labor were at therapeutic concentrations but were lower than those reported after continuous intravenous administration. Although concentrations were not associated with perinatal transmission, these data do not exclude the possibility that intrapartum and neonatal chemoprophylaxis is effective.

Short-course zidovudine for perinatal HIV-1 transmission in Bangkok, Thailand: a randomised controlled trial. Bangkok Collaborative Perinatal HIV Transmission Study Group.

BACKGROUND: Many developing countries have not implemented the AIDS Clinical Trials Group 076 zidovudine regimen for prevention of perinatal HIV-1 transmission because of its complexity and cost. We investigated the safety and efficacy of short-course oral zidovudine administered during late pregnancy and labour. METHODS: In a randomised, double-blind, placebo-controlled trial, HIV-1-infected pregnant women at two Bangkok hospitals were randomly assigned placebo or one zidovudine 300 mg tablet twice daily from 36 weeks' gestation and every 3 h from onset of labour until delivery. Mothers were given infant formula and asked not to breastfeed. The main endpoint was babies' HIV-1-infection status, tested with HIV-1-DNA PCR at birth, 2 months, and 6 months. We measured maternal plasma viral concentrations by RNA PCR. FINDINGS: Between May, 1996, and December, 1997, 397 women were randomised; 393 gave birth to 395 live-born babies. Median duration of antenatal treatment was 25 days, and median number of doses during labour was three. 99% of women took at least 90% of scheduled antenatal doses. Adverse events were similar in the study groups. Of 392 babies with at least one PCR test, 55 tested positive: 18 in the zidovudine group and 37 in the placebo group. The estimated transmission risks were 9.4% (95% CI 5.2-13.5) on zidovudine and 18.9% (13.2-24.2) on placebo (p=0.006; efficacy 50.1% [15.4-70.6]). Between enrolment and delivery, women in the zidovudine group had a mean decrease in viral load of 0.56 log. About 80% of the treatment effect was explained by lowered maternal viral concentrations at delivery. INTERPRETATION: A short course of twice-daily oral zidovudine was safe and well tolerated and, in the absence of breastfeeding, can lessen the risk for mother-to-child HIV-1 transmission by half. This regimen could prevent many HIV-1 infections during late pregnancy and labour in less-developed countries unable to implement the full 076 regimen.

Maternal viral load and timing of mother-to-child HIV transmission, Bangkok, Thailand. Bangkok Collaborative Perinatal HIV Transmission Study Group.

OBJECTIVES: To determine the proportion of HIV-1-infected infants infected in utero and intrapartum, the relationship between transmission risk factors and time of transmission, and the population-attributable fractions for maternal viral load. DESIGN: Prospective cohort study of 218 formula-fed infants of HIV-1-infected untreated mothers with known infection outcome and a birth HIV-1-positive DNA PCR test result. METHODS: Transmission in utero was presumed to have occurred if the birth sample (within 72 h of birth) was HIV-1-positive by PCR; intrapartum transmission was presumed if the birth sample tested negative and a later sample was HIV-1-positive. Two comparisons were carried out for selected risk factors for mother-to-child transmission: infants infected in utero versus all infants with a HIV-1-negative birth PCR test result, and infants infected intrapartum versus uninfected infants. RESULTS: Of 49 infected infants with an HIV-1 birth PCR result, 12 (24.5%) [95% confidence interval (CI), 14 -38] were presumed to have been infected in utero and 37 (75.5%) were presumed to have been infected intrapartum. The estimated absolute overall transmission rate was 22.5%; this comprised 5.5% (95% CI, 3-9) in utero transmission and 18% (95% CI, 13-24) intrapartum transmission. Intrapartum transmission accounted for 75.5% of infections. High maternal HIV-1 viral load (> median) was a strong risk factor for both in utero [adjusted odds ratio (AOR) 5.8 (95% CI, 1.4-38.8] and intrapartum transmission (AOR, 4.4; 95% CI, 1.9-11.2). Low birth-weight was associated with in utero transmission, whereas low maternal natural killer cell and CD4(+) T-lymphocyte percentages were associated with intrapartum transmission. The population-attributable fraction for intrapartum transmission associated with viral load > 10 000 copies/ml was 69%. CONCLUSIONS: Our results provide further evidence that most perinatal HIV-1 transmission occurs during labor and delivery, and that risk factors may differ according to time of transmission. Interventions to reduce maternal viral load should be effective in reducing both in utero and intrapartum transmission.

Maternal virus load and perinatal human immunodeficiency virus type 1 subtype E transmission, Thailand. Bangkok Collaborative Perinatal HIV Transmission Study Group.

To determine the rate and risk factors for human immunodeficiency virus (HIV)-1 subtype E perinatal transmission, with focus on virus load, pregnant HIV-infected women and their formula-fed infants were followed prospectively in Bangkok. Of 281 infants with known outcome, 68 were infected (transmission rate, 24.2%; 95% confidence interval, 19.3%-29.6%). Transmitting mothers had a 4.3-fold higher median plasma HIV RNA level at delivery than did nontransmitters (P<.001). No transmission occurred at <2000 copies/mL. On multivariate analysis, prematurity (adjusted odds ratio [AOR], 4.5), vaginal delivery (AOR, 2.9), low NK cell percentage (AOR, 2.4), and maternal virus load were associated with transmission. As RNA quintiles increased, the AOR for transmission increased linearly from 4.5 to 24.8. Two-thirds of transmission was attributed to virus load>10,000 copies/mL. Although risk is multifactorial, high maternal virus load at delivery strongly predicts transmission. This may have important implications for interventions designed to reduce perinatal transmission.

Differences in sexual behaviour between HIV-infected pregnant women and their husbands in Bangkok, Thailand.

In a Bangkok antenatal clinic, we interviewed 102 HIV-infected pregnant women and their husbands, 30% of whom were HIV-negative. We evaluated these data by matched and unmatched analysis, compared men and women in stable couple relationships on a number of sociodemographic and risk factor indicators and investigated further whether there were any differences in sociodemographic or risk factor profiles between HIV-serodiscordant couples and seroconcordant couples. When compared to wives, more of the husbands were working (p = 0.001), earning more money (p = 0.001), had had more than two sex partners (p = 0.001) and had had syphilis (p = 0.001). Serodiscordant couples did not differ greatly from seroconcordant couples except that women married to HIV-negative men were more likely to have been divorced or separated than their husbands which was not the case for women married to HIV-positive men (p = 0.02). There was poor agreement between husband and wife reports of husband risk behaviour and this did not differ between concordant and discordant couples. These findings suggest that assessment of risk and counselling of Thai women is incomplete without information on the HIV status and risk behaviour of her partner. Prevention strategies to decrease heterosexual transmission among couples need to target both the man and the woman.

PIP: This study compared the sexual behaviors of HIV-infected pregnant women and their husbands in Bangkok, Thailand. Researchers interviewed a total of 102 HIV-infected pregnant women and their husbands (30% of whom were HIV-negative). Using matched and unmatched analysis, sociodemographic and risk factor indicators among men and women in stable couple relationships were compared. Differences in sociodemographic or risk factor profiles between HIV-serodiscordant couples and seroconcordant couples were also investigated. Results revealed that income discrepancy between husbands and wives was smaller in discordant than in concordant couples, but the difference did not reach significance. Variables such as jobs, income, number of sexual partners, and presence of syphilis were noted to be much higher among husbands than wives. Men, regardless of HIV status, had consistently higher levels of risk behavior than their female partners. Moreover, women partnered with HIV-negative men, unlike women partnered with HIV-positive men, were infected outside the current relationship. Divorce or separation from a previous husband, younger age at first sex, and a higher number of sexual partners on the part of the wife were predictive of her husband being seronegative. The findings confirm the existence of a gender dichotomy in sexual behavior in Thailand, which is characterized by frequent partner change in males and female monogamy.

Impact of HIV on families of HIV-infected women who have recently given birth, Bangkok, Thailand.

The objective of this study was to assess changes in the family situation of HIV-infected women who have recently given birth. As part of a prospective perinatal HIV transmission study, interviews were conducted with a subset of HIV-infected women at 18 to 24 months postpartum, and answers were compared with baseline information obtained during pregnancy. Standardized scales were used to assess levels of psychosocial functioning. A convenience sample of 129 HIV-infected women enrolled during pregnancy was interviewed at 18 to 24 months postpartum. At delivery, the women were young (median age, 22 years), primiparous (57%), and asymptomatic (93%). When baseline and follow-up data were compared, more women were living alone (1% versus 6%; p = 0.03), fewer women were living with their partners (98% versus 73%; p < 0.001), and 30% of families had reduced incomes. At follow-up, 10% of partners had died, and more partners than wives had become ill or died (21% versus 4%; p = 0.02). Most children (78%) were living with their mothers, but only 57% of the HIV-infected women were the primary caretakers. Fewer women had disclosed their HIV status to others (e.g., family, friends) than to their partners (34% versus 84%; p < 0.001), largely because of fear of disclosure. The women appeared to have high levels of depression and worry. The women's greatest worries were about their children's health and the family's future. Within 2 years after childbirth, substantial change within the families of HIV-infected women was evident. These were manifest by partner illness or death, family separation, reduced family income, shifting responsibilities for child care, and signs of depression and isolation. Providing family support is a major challenge in Thailand as the perinatal HIV epidemic progresses.

PIP: As part of a larger prospective perinatal HIV transmission study in Bangkok, Thailand (1992-94), interviews were conducted with a subset of 129 HIV-infected women 18-24 months after delivery and the results were compared with data obtained from these women during pregnancy. The median age of women at delivery was 22 years; 57% were primiparous and 93% were asymptomatic at delivery. 25 infants (19.4%) had confirmed HIV infection and 2 had died by the time of the follow-up interview. By follow up, 21% of male partners had died or developed HIV-related functional impairments. The proportion of women living alone rose from 1% at baseline to 6% at follow up, while the proportion living with their partner declined from 98% to 73%. 30% of families had reduced incomes at follow-up compared with baseline. Although 78% of infants were living with their mothers, they were the primary caretakers in only 57% of families. Only 34% of HIV-infected mothers had disclosed their HIV status to friends or family other than their partner. 43% of women scored above the cut-off on the depression scale. Mothers worried extensively about their child's health and their family's future. However, only 37% believed they could find someone to talk to about their feelings related to HIV. 58% were interested in joining a support group for women with HIV. These findings of family disruption, reduced family income, shifting responsibilities for child care, depression, and isolation indicate an urgent need for increased social support for HIV-infected mothers in Thailand.

Chlamydial and gonococcal cervicitis in HIV-seropositive and HIV-seronegative pregnant women in Bangkok: prevalence, risk factors, and relation to perinatal HIV transmission.

OBJECTIVES: To determine the prevalence and risk factors associated with cervicitis caused by Chlamydia trachomatis and Neisseria gonorrhoeae in human immunodeficiency virus (HIV) type 1-seropositive and HIV-seronegative pregnant women in Bangkok, and the relation to perinatal HIV transmission. METHODS: As part of a multicenter perinatal HIV transmission study in an antenatal population with 2% HIV seroprevalence, endocervical swabs obtained at mid-pregnancy from a consecutive sample of 222 HIV-seropositive and 219 HIV-seronegative pregnant women at two large hospitals in Bangkok were tested for the presence of C. trachomatis and N. gonorrhoeae by DNA hybridization probe (Gen-Probe). Clinical risk factors and DNA probe results were analyzed in relation to the women's and newborns' HIV infection status. RESULTS: The prevalence of C. trachomatis was 16.2% in HIV-seropositive pregnant women and 9.1% in HIV-seronegative pregnant women (P = 0.03). The prevalence of N. gonorrhoeae was 2.7% in HIV-seropositive pregnant women and 1.4% in HIV-seronegative pregnant women (P = 0.5). The overall population prevalence estimate was 9.2% for C. trachomatis and 1.4% for N. gonorrhoeae. Women with gonococcal infection were more likely to be positive for C. trachomatis (RR(MH) = 5.2, P < 0.01). Young age (<21 years) and primigravid status were associated with C. trachomatis infection among HIV-seropositive women; history of multiple sex partners (>1) were associated with C. trachomatis infection among HIV-seronegative women. For HIV-seropositive women, primigravida status also was associated with C. trachomatis infection. The perinatal HIV transmission rates were similar for those with and without C. trachomatis (24.1% and 23.2%, P = 0.9) and among those with and without N. gonorrhoeae (20% and 23.5%, P = 1.0). CONCLUSIONS: Among pregnant women in Bangkok, C. trachomatis infection was considerably more common than N. gonorrhoeae infection and was associated with HIV infection, young age and first pregnancy (HIV-seropositive women), and multiple partners (HIV-seronegative women). Our data do not suggest an association between perinatal HIV transmission and maternal C. trachomatis or N. gonorrhoeae infection identified and treated during pregnancy. The high prevalence of C. trachomatis found using a test not readily available in Thailand emphasizes the need for improved, inexpensive ways to screen for and diagnose these sexually transmitted infections in developing countries.

PIP: Numerous studies have suggested that Chlamydia trachomatis and Neisseria gonorrhoeae facilitate heterosexual HIV transmission; the impact of these sexually transmitted diseases (STDs) on perinatal HIV transmission is unknown, however, due to the expense of routine screening for STDs during pregnancy in developing countries. As part of a multicenter perinatal HIV transmission study, 222 HIV-positive and 219 HIV-negative women presenting for prenatal care at 2 hospitals in Bangkok, Thailand, during 1993-94 were enrolled. At mid-pregnancy, endocervical swabs were obtained and tested for the presence of C. trachomatis and N. gonorrhoeae by DNA hybridization probe. There were 36 cases (16.2%) of C. trachomatis infection among HIV-positive women and 20 cases (9.1%) among HIV-negative women. There were 6 cases (2.7%) of N. gonorrhoeae among HIV-positive women and 3 cases (1.4%) among HIV-negative women. Based on an estimated antenatal HIV seroprevalence of 2%, these findings imply a general antenatal prevalence of 9.2% for C. trachomatis and 1.4% for N. gonorrhoeae. Women with gonococcal infection were more likely (relative risk, 5.2) to be positive for C. trachomatis as well. C. trachomatis infection among HIV-infected pregnant women was associated with age under 21 years and primigravidity. The overall perinatal HIV transmission rate was 24.2%, with no significant difference according to STD infection status. However, since all women diagnosed with STDs received treatment by the mid-third trimester of pregnancy, it remains possible that untreated STDs facilitate perinatal HIV transmission. The high prevalence of C. trachomatis detected in this study through use of a test not readily available in Thailand emphasizes the need for inexpensive, reliable methods to screen for STDs among pregnant women in developing countries.

Rapid eradication of trichomonads by single-dosed nimorazole.

Previous in vitro studies demonstrated the rapidity of trichomonacidal action of nimorazole (Naxogin 500) which was twice that of metronidazole and many times that of tinidazole. Since rapid eradication of parasites can lead to a significant decrease in transmission rate, and hence, a lower prevalence of this sexually transmitted disease, a pilot study was designed to investigate the in vivo speed of action of nimorazole. Twenty females with positive wet smears for trichomonas vaginalis were treated with a single 2 gram-dose of nimorazole orally. Without any antiseptics, specimens of vaginal discharge were collected at 0 hour (before treatment), 3, 24 and 72 hours for parasite count and culture. After a single treatment with 2 g of nimorazole the cure rate was 65 per cent at 3 hours and 100 per cent at all points thereafter. The result of this pilot study supports previous in vitro findings that nimorazole rapidly eradicates vaginal parasites.