HIV seroconversion during pregnancy and risk for mother-to-infant transmission.

Pregnant women infected with HIV-1 were enrolled in a prospective mother-to-infant transmission study from 1992 through 1994 in Bangkok. In participating hospitals, voluntary HIV testing was routinely offered at the beginning of antenatal care and again in the middle of the third trimester of pregnancy. Women who seroconverted to HIV during pregnancy were compared with women who had tested positive on their first antenatal test. Maternal HIV RNA levels were determined during pregnancy, at delivery, and postpartum using RNA polymerase chain reaction (PCR), and infection status in infants was determined by DNA PCR. No infants were breast-fed, but prophylactic antiretroviral therapy was not yet used in Thailand to prevent transmission from mother to infant. Among enrolled women, 16 who seroconverted during pregnancy and 279 who were HIV-1-seropositive at their first antenatal test gave birth. Median plasma RNA levels at delivery were similar for the two groups (17,505 and 20,845 copies/ml, respectively; p =.8). Two (13.3%) of 15 infants born to women who seroconverted and 66 (24.8%) of 266 infants born to previously HIV-seropositive women were infected with HIV (p =.5). There was no increased risk for mother-to-infant HIV transmission and no significant difference in viral load at delivery between HIV-infected women who seroconverted to HIV during pregnancy and those who were HIV-seropositive when first tested.

Virological, immunological and host factors in HIV-1 discordant couples in Thailand.

The potential factors of resistance to HIV-1 infection were investigated in 23 HIV discordantly infected couples, of each, one partner had HIV infection and the matched spouse was not infected. Both partners of the HIV discordant couples possessed comparable number of CD4+ cells expressing CCR5. Our study demonstrated that resistance to HIV-1 infection was not due to low level of HIV viral load in their infected-matched spouses. In addition, selective biological phenotype of HIV clinical isolates, which is indicative for risk of transmission, could not be determined in this study. However, we have demonstrated that the unknown genetic factor(s), and neutralizing antibody of broad and high activity could be taken into an account for resistance to HIV infection in the HIV discordant couples.

Diversity of HIV-1 subtype E in semen and cervicovaginal secretion.

OBJECTIVES: To characterize human immunodeficiency virus type 1 (HIV-1) subtype E variants in blood and genital fluid of infected Thai couples. STUDY DESIGN/METHODS: Blood and genital fluid were collected from 30 asymptomatic healthy HIV-1 subtype E infected couples from Bangkok, Thailand from 1995 to 1998. RESULTS: All 60 viruses in blood samples were identified as subtype E by heteroduplex mobility assay. The biotype of viruses founded in blood was syncytium-inducing (SI), whereas M-tropic and non-syncytium-inducing (NSI) isolates were predominantly detected in genital fluid. HIV-1 proviral DNA was detected in 43.33% and 56.67%, and viral RNA was detected in 93.33% and 56.67%, of semen (n = 30) and cervicovaginal secretion (n = 30) samples tested, respectively. A higher intersample genetic distance and more positive charge of the V3 loop were found in blood strains composed of genital fluid strains (22.30 +/- 5.92% and 17.96 +/- 6.3%), which was statistically significant (P = 0.003). The env V1-V4 intraperson variation of the HIV-1 subtype E in the blood and genital fluid of each individual was in the range 3.0%-5.7%. We also determined the intrasample variation of HIV-1 from blood and genital fluid by heteroduplex mobility assay. The mean heteroduplex mobility of the HIV-1, V1-V4 region of env gene, in blood (n = 8) and genital fluid (n = 8) was 0.59 +/- 0.06 and 0.74 +/- 0.11 (t test, p = 0.001), respectively. CONCLUSIONS: There was genetic and phenotypic compartmentalization of HIV-1 subtype E in blood and genital fluid with the presence of SI and NSI phenotypic variants as a common property of subtype E isolates from blood and genital fluid, respectively.

Update on perinatal HIV transmission.

Over the past decade, much progress has been made in understanding the risk factors and timing of perinatal HIV transmission. Even more impressive have been the successful clinical trials with antiretrovirals, such as ZDV, ZDV-3TC, and nevirapine, that demonstrated significant reductions in the risk for infant infection. Within the United States and Europe, these trial results have led to rapid implementation and dramatic decreases in new perinatal HIV cases since 1994. An immediate challenge is to rapidly translate the short-course antiretroviral trial results with ZDV and nevirapine into public health policy and practice in resource-poor settings, where almost 600,000 neonates continue to become infected by mother-infant HIV transmission each year. Physicians must also test strategies to further decrease the risk for infant HIV infection during the breast-feeding period.

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.

The use of lenograstim (Granocyte) in chemotherapy for ovarian cancer.

We have conducted an open, controlled study on the febrile neutropenia effects by Lenograstim (Granocyte) therapy following cytotoxic chemotherapy of cisplatinum and cyclophosphamide in patients with primary advanced epithelial ovarian cancer. Eligible patients (n = 17) were divided into 2 groups receiving a combined chemotherapy of intravenous cisplatinum (70 mg/m2) and cyclophosphamide (700 mg/m2) with or without the addition of Lenograstim. Subcutaneous administration of Lenograstim (100 micrograms/day) for 7 consecutive days was given from day 8 to day 14 of the 3rd to the 5th cycle of chemotherapy in Lenograstim treated patients. After 3 cycles of treatment, Lenograstim treated patients (group 1, n = 10) showed a significant improvement in white blood cell (WBC) count as compared with group 2 (control) of 7 patients (p = 0.00002). Group 1 patients also showed an increased C-reactive protein, though of no significance. There were no significant differences among the 2 groups regarding ESR, hematocrit, platelet counts and blood chemistry profiles. This preliminary data encourages more study of the benefits of Lenograstim in the treatment of ovarian cancer.

HIV prevalence, risk, and partner serodiscordance among pregnant women in Bangkok. Bangkok Collaborative Perinatal HIV Transmission Study Group.

CONTEXT: Most prior studies of the human immunodeficiency virus (HIV) epidemic in Thailand have focused on commercial sex encounters; however, because the epidemic increasingly concerns stable heterosexual relationships, determining risk factors for this form of transmission is warranted. OBJECTIVES: To determine temporal trends in HIV prevalence, risk factors for HIV seropositivity, and rates of partner serodiscordance for pregnant women in Bangkok, Thailand. DESIGN: Retrospective review of hospital antenatal clinic HIV test results from 1991 through 1996. Baseline demographic and behavioral risk factors for HIV were assessed for subjects enrolled from November 1992 through March 1994. SETTING: Two Bangkok hospitals with routine antenatal clinic HIV counseling and testing. PARTICIPANTS: The HIV-positive pregnant women enrolled in a perinatal HIV transmission study and their partners and HIV-negative pregnant controls. RESULTS: From 1991 through 1996, antenatal clinic HIV seroprevalence increased from 1.0% to 2.3%. On multivariate analysis of data from 342 HIV-positive and 344 HIV-negative pregnant women, more than 1 lifetime sex partner, history of a sexually transmitted disease, and a high-risk sex partner were the most important factors for seropositivity (all P<.001). Twenty-six percent of partners of HIV-positive women were HIV negative. Women reporting more than 1 lifetime sex partner were more likely to have an HIV-negative partner than women reporting only 1 (45% vs 8%; relative risk, 5.5; 95% confidence interval, 3.2-9.5; P<.001); women reporting no high-risk behaviors were less likely to have an HIV-negative partner (10% vs 44%; relative risk, 0.2; 95% confidence interval, 0.1-0.4; P<.001). CONCLUSIONS: Prevalence of HIV in pregnant women has increased steadily in Bangkok from 1991 through 1996. Sex with current partners was the only identified risk exposure for about half (52%) of the HIV-positive women. Although few HIV-positive pregnant women reported high-risk behaviors, more than 1 lifetime partner and a partner with high-risk behavior were strong risk factors for seropositivity. Together with the unexpected finding that one fourth of partners of seropositive pregnant women were seronegative, these data emphasize that women in the general population are at risk for HIV because of the risk behavior of both current and previous partners.

Prevalence of herpes simplex virus infection in patients suspected of genital herpes; and virus typing by type specific fluorescent monoclonal antibodies.

During the period between April 1994 and February 1996, a total of 154 female patients who attended the Clinic of Female Sexually Transmitted Diseases, Siriraj Hospital with clinical symptoms suspected of genital herpes were investigated for herpes simplex virus (HSV) infection by the virus isolation method in Vero cell cultures. Swabs from external genital lesions and the cervix from each patient were collected separately and used as the clinical specimens for isolation of HSV. The virus isolates were identified by indirect immunofluorescence (IIF) staining of the infected cell cultures using polyclonal HSV-2 specific antiserum which was reactive to common HSV antigens for both types of viruses. Typing of HSV was performed by direct IF using monoclonal antibody specific to HSV-1 or HSV-2. HSV was isolated from 78.6 per cent (121 of 154) of the cases studied; and among the infected cases, there were 47.9 per cent (58 of 121) in whom the infection involved both external genital lesions and cervixes, and 50.4 per cent (61) in whom the infection was limited to external genital lesions only. There were 2 cases (1.7%) in whom HSV was isolated from cervixes but not external genital lesions. Seventy-five HSV isolates were further subjected to typing. The present study showed that HSV-1 was accounted for 18.7 per cent (14 isolates), while HSV-2 took the remaining part of 81.3 per cent (61 isolates). The data demonstrated an increase in the prevalence of HSV-1 in genital herpes in our people.

Comparison between virus isolation method, Papanicolaou stain, immunoperoxidase stain and polymerase chain reaction in the diagnosis of genital herpes.

Papanicolaou (Pap) stain, immunoperoxidase (IP) stain and polymerase chain reaction (PCR) were evaluated against the virus isolation method for their sensitivity and specificity in the diagnosis of herpes simplex virus (HSV) infection in 96 women who were suspected of genital herpes. The result showed that the sensitivity of PCR, IP and Pap stain was 100, 92.0 and 62.7%, respectively, while the specificity was 76.2, 66.7 and 81.0%, respectively. PCR was even more sensitive than the virus isolation technique. As Pap stain is the technique routinely performed for diagnosing genital herpes in most of the hospitals in Thailand, its low sensitivity should be taken into consideration. Based on the investigation by all four techniques together, HSV infection was diagnosed in 91.6% of the cases suspected of genital herpes which reflected higher precision of the clinical diagnosis over Pap stain.

Shedding of HIV-1 subtype E in semen and cervico-vaginal fluid.

The uneven expansion of HIV-1 subtypes in each transmitted group raises the possibility that some viruses have less/more potential by qualitative/quantitative for heterosexual transmission compared to others. In Thailand, HIV-1 subtype E is mainly spread via heterosexual route and accounts for about 95 per cent of the infected cases. To determine whether high sexual infectivity of HIV-1 subtype E is due to the presence of a virus in genital fluid, we conducted a study to characterize shedding of HIV-1 in seminal and cervico-vaginal fluids of 30 HIV-1 subtype E infected Thai couples by PCR and virus isolation methods. All subjects had no HIV-associated diseases and other sexually transmitted diseases. HIV-1 subtype E DNA was detected in 22/30 (77.33%) of cervico-vaginal and also 22/30 (77.33%) of seminal fluid samples. The isolation rate of HIV-1 from semen and cervico-vaginal secretion was 36.67 per cent and 16.67 per cent, respectively. Number of HIV-1 subtype E DNA copies in the blood is reversely correlated with the number of blood CD4+ T cells, while that in genital fluid was not related to CD4+ T cell count. An increase in shedding of HIV- DNA subtype E in female genital tract compared to other HIV subtypes reported by other investigators might be one reason to explain the rapid spread of subtype E by heterosexual transmission in Thailand.

PIP: Preliminary evidence suggests that HIV subgroups differ in both their transmissibility and virulence. In Thailand, HIV-1 subtype E (accounting for almost 95% of total HIV cases) is transmitted primarily through heterosexual sex, with a predominance of female-to-male infection. This study characterized virus shedding patterns in seminal and cervico-vaginal fluids from 30 asymptomatic husband-wife pairs from Bangkok, Thailand, known to be infected with HIV-1 subtype E. HIV-1 subtype E was detected in 22 (77.3%) cervico-vaginal and 22 (77.3%) seminal fluid samples. HIV-1 subtype B, in contrast, is found in only 30-50% of cervico-vaginal specimens; detection of subtype B in seminal specimens (70-80%) is comparable to that identified for subtype E in the present study. The isolation rate of HIV-1 was 36.67% from semen and 16.67% from cervico-vaginal secretions. The number of HIV-1 subtype E DNA copies in blood--but not in genital fluids--was inversely correlated with the number of blood CD4+ T cells. The increased shedding of HIV-1 DNA subtype E compared with other subtypes in the female genital tract presumably accounts for the rapid spread of subtype E among heterosexuals in Thailand.

Detection of HIV-1 proviral DNA by polymerase chain reaction: a preliminary study in Bangkok.

Nested polymerase chain reaction (nested PCR) was used to separately amplify part of gag, pol, and env genes of human immunodeficiency virus type 1 (HIV-1) to evaluate that primer specific to either gag (SK380/390&SK38/39), pol (JA17/18&JA19/20), or env (JA9/10&JA11/12) genes is suitable for HIV-1 PCR based diagnosis in Thailand. The positive PCR results in 70 HIV-1 infected adults are 100, 97, 89 per cent and in 75 HIV-1 infected infants are 100, 94, 74 per cent by gag, pol, env primer, respectively. The specificity of all three primer sets is 100 per cent. The unamplified samples by pol and env primers were identified as HIV-1 subtype E by PELISA method. False negative in HIV-1 PCR based diagnosis caused by high genetic variation of HIV-1 can be overcome by using several primer sets as shown in this study.

Carpal tunnel syndrome during pregnancy: prevalence and blood level of pyridoxine.

The prevalence of CTS in third trimester pregnant women in the study in 28 per cent. With the use of NCS it was able to detect nearly 80 per cent of them who had no symptoms or signs. There was no association between the level of vitamin B6 or B6 deficiency and CTS. Since CTS may result in a permanent disability if undiagnosed or left untreated it is essential to make an early diagnosis and treat it especially older women and those who are edematous.

The study of HCV antibody and serologic tests for syphilis in Thai patients with gynecologic disorders.

Investigation for prevalence of antibodies to hepatitis C virus (HCV) and to Treponema pallidum was conducted in 883 females with gynecologic disorders who were admitted to the gynecological ward of the Department of Obstetrics and Gynecology, Siriraj Hospital during April to August 1991. The study population consisted of 678 patients with malignancies and 205 patients with benign diseases. Anti-HCV antibody was found in 3.1% of the cases with malignancies and 1.46% of those with benign diseases. Among the gynecologic malignant group, the patients with carcinoma of cervix had the highest prevalence of HCV antibody (3.6%). The positive serologic tests for syphilis in patients with carcinoma of cervix (9.8%) were significantly higher from those in patients with ovarian carcinoma (3.75%) (p < 0.01). There were 3 cases with carcinoma of cervix who were simultaneously sero-positive for both HCV and syphilis.

Itraconazole in the treatment of acute vaginal candidosis.

An open non-comparative multicenter study of Itraconazole (Sporal) 400 mg as a single day therapy for vaginal candidosis was carried out at Siriraj Hospital and Chulalongkorn Hospital from 1st November 1988 to 31st August, 1989. Fifty-nine female out patients with vaginal candidosis were included in the study after excluding pregnancy, lactation, mixed vaginal infection and prior antimycotic therapy. Two capsules of 100 mg Itraconazole were given b.i.d. as a single day 400 mg dose. The patients were evaluated at the beginning prior to treatment for physical signs and symptoms, direct microscopic examination, and culture of vaginal fluid. The first and second follow-up were arranged at the end of one week and one month after therapy. The evaluations were the same as in the first visit. The clinical cure rate was 89 and 90 per cent at first and second follow-up respectively. The mycological cure rates were 83.3 and 69.57 per cent at the first and second follow-up respectively. There was one case of Torulopsis glabarta at the second follow-up.

Risk factors in puerperal infection.

Puerperal infection is one of the most common obstetric complications which leads to certain serious sequelas for those parturients. The study of 92 postpartum women at Siriraj Hospital from April 1, 1980 to March 1, 1983 was conducted to investigate the risk factors of puerperal infection. All 92 cases were diagnosed for puerperal infection according to the criteria of the Joint Committee on Maternal Welfare. Irregular antenatal care or no antenatal care, sexual intercourse during the last week before delivery and pelvic examination during pregnancy were found to be important predisposing factors in the antepartum period. Pelvic examination during labor accounted for 78 per cent of the patients and played an important role, while operative obstetrics (30%) and concomitant diseases during pregnancy (27%) were the next significant factors.

Causative organisms in puerperal infection.

Ninety-two postpartum women who had been admitted to Siriraj Hospital from April 1, 1980 to March 1, 1983 were studied for the causative organisms of puerperal infection. Cervical and intrauterine swab & smear-gram stain as well as cultures were performed. Hemocultures were done in some cases. Only 50 per cent of all cases had positive cervical and intrauterine swab smears which showed different kinds of micro-organisms, 78 per cent were gram-positive cocci, gram-negative rod was found in 4 specimens, 2 specimens of gonococcal smears, one for trichomonads. Cervical and intrauterine swab cultures were positive in only 31.5 per cent. E. Coli was the most common and Staphylococci & Streptococci were the second most common.

Treatment of puerperal infection.

Ninety-two patients with puerperal infection admitted to Siriraj Hospital from April 1, 1980 to March 1, 1983 were studied. The treatment in this study was both medical and surgical, blood transfusion was given in some cases with low hematocrit level. The medical treatment alone was based on the causative organisms which were detected by cervical & intrauterine swab, smear & gram stain and cultures. PGS & Kanamycin were the most frequently used antibiotics which were intended to treat both gram-positive and gram-negative bacteria and adjunctive chloramphenicol for anaerobes. The surgical procedures which were performed in combination with medical treatment included total abdominal hysterectomy, uterine curettage, appendectomy and drainage of subdiaphragmatic abscess. The result of the treatment was satisfactory, 96.7 per cent improved after therapy with slight morbidity in some patients.