High mortality among women with HIV-1 infection in Thailand.
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Adolescent↗
Biomedical subjects
T D Mastro
Publications and source records attributed to T D Mastro.
Early diagnosis of HIV-1-infected infants in Thailand using RNA and DNA PCR assays sensitive to non-B subtypes.
OBJECTIVES: To evaluate the sensitivity and specificity of RNA and DNA polymerase chain reaction (PCR) for early diagnosis of perinatal HIV-1 infection and to investigate early viral dynamics in infected infants. DESIGN: A cohort study of 395 non-breastfed infants born to HIV-infected mothers in a randomized clinical trial of short-course antenatal zidovudine. METHODS: Infant venous blood specimens collected at birth, 2 months, and 6 months of age were tested by qualitative DNA and quantitative RNA PCR (Roche Amplicor). To determine sensitivity and specificity of DNA and RNA PCR, results were compared with later DNA PCR results and to antibody results at 18 months. The HIV-1 subtype of the mother's infection was determined by peptide serotyping. RESULTS: In the study, 92% of mothers were infected with subtype E. DNA PCR sensitivity was 38% (20 of 53) at birth, and 100% at 2 months (53 of 53) and 6 months (47 of 47). RNA PCR sensitivity was 47% (25 of 53) at birth and 100% (53 of 53) at 2 months. All samples that tested DNA-positive tested RNA-positive. Specificity was 100% for both DNA and RNA testing at all timepoints. For infected infants, the median viral load of RNA-positive specimens was 407,000 copies/ml (5.6 log10) at birth, 3, 700,000 copies/ml (6.6 log10) at 2 months, and 1,700,000 copies/ml (6.2 log10) at 6 months. Infant RNA levels at 2 and 6 months did not differ by maternal zidovudine exposure, or RNA level at birth. CONCLUSION: This RNA PCR assay performed well for diagnosing perinatal HIV subtype E infection, detecting nearly half of infected infants at birth, and 100% at 2 and 6 months, with 100% specificity. Infected infant viral RNA levels were very high at 2 and 6 months, and were unaffected by maternal zidovudine treatment.
Age Factors↗
Implementing short-course zidovudine to reduce mother-infant HIV transmission in a large pilot program in Thailand.
OBJECTIVES: To describe a pilot mother-infant HIV prevention program started by the Ministry of Public Health of Thailand in July 1998 and to report on the first year of its implementation. DESIGN: Analysis of monthly summaries of data from project logbooks, simple data forms in antenatal clinics and delivery rooms, site visits and workshops, mail survey. SETTING: All 89 public hospitals in seven north-eastern provinces of Thailand. PARTICIPANTS: Childbearing women, program officials. INTERVENTIONS: Counseling and HIV testing for pregnant women, short-course antenatal zidovudine for HIV-infected pregnant women, and infant formula for their children. MAIN OUTCOME MEASURES: Proportion of women with HIV test, proportion of HIV-infected women receiving zidovudine. RESULTS: Of 75,308 women who gave birth between July 1998 and June 1999, 74,511 (98.9%) had antenatal care, 51,492 (69.1%) in the same district and 23,019 (30.9%) outside the district where they gave birth. HIV test results were available at delivery for 46,648 (61.9%) women, 410 (0.9%) of whom tested positive. Of these HIV-infected women, 259 (63.2%) participated in the zidovudine program and 6 (1.5%) received zidovudine from other sources. The proportion of women whose HIV test results were known and proportion of HIV-infected women who received zidovudine increased significantly during the year. CONCLUSIONS: A mother-infant HIV prevention program using short-course antenatal zidovudine was quickly implemented in a large region of Thailand with moderate HIV prevalence. This successful experience is leading to national implementation of a perinatal HIV prevention program in Thailand and may prompt other developing countries to start similar programs.
Adolescent↗
Genetic characterization of incident HIV type 1 subtype E and B strains from a prospective cohort of injecting drug users in Bangkok, Thailand.
We obtained specimens from 128 HIV-1 seroconverters identified from 1995 through 1998 in a prospective cohort study of 1,209 HIV-negative injecting drug users (IDUs) in Bangkok, Thailand. Epidemiologic data indicated that parenteral transmission accounted for nearly all infections. HIV-1 DNA from the C2-V4 env region was sequenced, and phylogenetic analyses determined that 102 (79.7%) of the specimens were subtype E and 26 (20.3%) subtype B strains. All subtype B strains clustered with strains often referred to in previous studies as Thai B or B'. The interstrain nucleotide distance (C2-V4) within subtype E strains was low (mean, 6.8%), and pairwise comparisons with a prototype subtype E strain, CM244, showed limited divergence (mean, 5.6%). The subtype B stains showed greater interstrain divergence (mean, 9.2%) and were significantly divergent from the prototype B strain HIV-MN (mean, 13.0%; p < 0.0001). The subtype E strains had significantly lower mean V3 loop charge than did subtype B strains (p = 0.017) and, on the basis of analysis of amino acid sequences, were predicted to be predominantly (91%) non-syncytium-inducing (NSI), chemokine coreceptor CCR5-using (CCR5+) viruses. The subtype B strains had a higher mean V3 loop charge, and a smaller proportion (23%) were predicted to be NSI/CCR5+ viruses. This study demonstrates that most incident HIV1 infections among Bangkok IDUs are due to subtype E viruses, with a narrow spectrum of genetic diversity. The characterization of incident HIV-1 strains from 1995 to 1998 will provide important baseline information for comparison with any breakthrough infections that occur among IDUs in Bangkok who are participating in an HIV-1 vaccine efficacy trial initiated in 1999.
Amino Acid Sequence↗
Lack of association between human immunodeficiency virus type 1 antibody in cervicovaginal lavage fluid and plasma and perinatal transmission, in Thailand.
To determine the association between human immunodeficiency virus type 1 (HIV)-specific antibody and RNA levels in cervicovaginal lavage (CVL) samples and plasma, zidovudine treatment, and perinatal transmission, HIV subtype E gp160-specific IgG and IgA were serially measured in a subset of 74 HIV-infected women in a placebo-controlled trial of zidovudine, beginning at 36 weeks of gestation. HIV IgG was detected in 100% of plasma and 97% of CVL samples; HIV IgA was consistently detected in 62% of plasma and 31% of CVL samples. Antibody titers in CVL samples correlated better with the RNA level in CVL samples than with plasma antibody titers. Zidovudine did not affect antibody titers. Perinatal HIV transmission was not associated with antibody in CVL samples or plasma. HIV-specific antibody is present in the cervicovaginal canal of HIV-infected pregnant women; its correlation with the RNA level in CVL fluid suggests local antibody production. However, there was no evidence that these antibodies protected against perinatal HIV transmission.
Acquired Immunodeficiency Syndrome↗
Disease progression and survival with human immunodeficiency virus type 1 subtype E infection among female sex workers in Thailand.
This study describes rates and correlates of disease progression and survival among 194 female sex workers in northern Thailand who were infected with human immunodeficiency virus type 1 (HIV-1; 96% with subtype E). The median rate of CD4 T lymphocyte decline (3.9 cells/microL/month), median time from infection to <200 CD4 T lymphocytes/microL (6.9 years), and time to 25% mortality (6.0 years) were similar to those found in studies performed in Western countries before highly active antiretroviral therapy was available to populations infected with HIV-1 subtype B. Mortality rates among women with >100,000 HIV-1 RNA copies/mL were 15.4 times higher (95% confidence interval, 5.2-45.2) than among women with <10,000 copies. Initial CD4 T lymphocyte counts and serum virus load were independently strong predictors of survival. These results can help in assessing the effects of the epidemic in Thailand and in determining the prognoses for individual patients.
Adult↗
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.
Administration, Oral↗
Short-course antenatal zidovudine reduces both cervicovaginal human immunodeficiency virus type 1 RNA levels and risk of perinatal transmission. Bangkok Collaborative Perinatal HIV Transmission Study Group.
Human immunodeficiency virus (HIV) levels in cervicovaginal lavage (CVL) and plasma samples were evaluated in relation to perinatal transmission in a randomized placebo-controlled trial of brief antenatal zidovudine treatment. Samples were collected at 38 weeks' gestation from 310 women and more frequently from a subset of 74 women. At 38 weeks, after a 2-week treatment period, CVL HIV-1 was quantifiable in 23% and 52% of samples in the zidovudine and placebo groups, respectively (P<.001). The perinatal transmission rate was 28.7% among women with quantifiable CVL HIV-1 and high plasma virus levels (>10,000 copies/mL) and 1% among women without quantifiable CVL HIV-1 and with low plasma virus levels (P<.001). A 1-log increase in plasma HIV-1 increased the transmission odds 1.8 and 6.1 times (95% confidence interval, 0.9-3.5 vs. 2.4-15.4) for women with and without quantifiable CVL HIV-1, respectively (P=.03). CVL HIV-1 is an independent risk factor for perinatal HIV-1 transmission.
Cervix Uteri↗
Analysis of genetic variability within the immunodominant epitopes of envelope gp41 from human immunodeficiency virus type 1 (HIV-1) group M and its impact on HIV-1 antibody detection.
The serodiagnosis of human immunodeficiency virus type 1 (HIV-1) infection primarily relies on the detection of antibodies, most of which are directed against the immunodominant regions (IDR) of HIV-1 structural proteins. Among these, the N-terminal region of gp41 contains cluster I (amino acids [aa] 580 to 623), comprising the cytotoxic T-lymphocyte epitope (AVERYLKDQQLL) and the cysteine loop (CSGKLIC), and cluster II (aa 646 to 682), comprising an ectodomain region (ELDKWA). To delineate the epitope diversity within clusters I and II and to determine whether the diversity affects serologic detection by U.S. Food and Drug Administration (FDA)-licensed enzyme immunoassay (EIA) kits, gp41 Env sequences from 247 seropositive persons infected with HIV-1 group M, subtypes A (n = 42), B (n = 62), B' (n = 13), C (n = 38), D (n = 41), E (n = 18), F (n = 27), and G (n = 6), and 6 HIV-1-infected but persistently seronegative (HIPS) persons were analyzed. While all IDR were highly conserved among both seropositive and HIPS persons, minor amino acid substitutions (<20% for any one residue, mostly conservative) were observed for all subtypes, except for B', in comparison with the consensus sequence for each subtype. Most importantly, none of the observed substitutions among the group M plasma specimens affected antibody detection, since all specimens (n = 152) tested positive with all five FDA-licensed EIA kits. Furthermore, all specimens reacted with a group M consensus gp41 peptide (WGIKQLQARVLAVERYLKDQQLLGIWGCSGKLICTTAVPWNASW), and high degrees of cross-reactivity (>80%) were observed with an HIV-1 group N peptide, an HIV-1 group O peptide, and a peptide derived from the homologous region of gp41 from simian immunodeficiency virus from chimpanzee (SIVcpz). Taken together, these data indicate that the minor substitutions observed within the IDR of gp41 of HIV-1 group M subtypes do not affect antibody recognition and that all HIV-1-seropositive specimens containing the observed substitutions react with the FDA-licensed EIA kits regardless of viral genotype and geographic origin.
AIDS Serodiagnosis↗
Human immunodeficiency virus-related tuberculosis and primary drug resistance in Bangkok, Thailand.
SETTING: Central Chest Hospital, a 500-bed referral hospital near Bangkok with a large out-patient department. OBJECTIVES: To determine human immunodeficiency virus (HIV) seroprevalence among patients with pulmonary tuberculosis (TB), and compare HIV-positive and HIV-negative TB patients. DESIGN: From July 1995 through June 1996, a cross-sectional study was conducted of newly registered adults (> or =16 years old) with suspected pulmonary TB. RESULTS: Of 2587 newly registered patients with suspected pulmonary TB, 2019 (78%) received HIV pretest counseling and 1816 (90%) consented to testing. Of these, 364 (20%) were HIV-seropositive. Among 1091 patients with bacteriologically confirmed TB, HIV seroprevalence was 22%. HIV-positive patients were more likely to be young, unemployed, single men and to have a history of injection drug use. HIV-positive patients with first-episode TB were more likely to have Mycobacterium tuberculosis strains resistant to isoniazid (10.9% vs 3.5%; P < 0.001), rifampicin (9.4% vs 2.9%; P < 0.001), and at least isoniazid and rifampicin (multidrug-resistant TB [MDR-TB]; 5.2% vs 0.4%; P < 0.001). CONCLUSIONS: HIV prevalence is high among TB patients at this Bangkok hospital and is associated with drug resistance, including a 12 times higher risk of MDR-TB. These findings underscore the urgent need to assure adherence to complete, effective TB treatment regimens for all patients, including persons who are potentially difficult to manage such as injection drug users.
AIDS-Related Opportunistic Infections↗
Clinical disease associated with HIV-1 subtype B' and E infection among 2104 patients in Thailand.
BACKGROUND: Two HIV-1 envelope subtypes have accounted for virtually all infections in Thailand: subtype B' (Thai B), found mainly in injection drug users (IDU), and subtype E, found in over 90% of sexually infected persons and an increasing proportion of IDU in recent years. It remains unclear whether there are differences in pathogenesis associated with these HIV-1 subtypes. METHODS: From November 1993 to June 1996, demographic, risk, clinical, and laboratory data were collected by enhanced surveillance from HIV-infected inpatients (> or =14 years) at an infectious disease hospital near Bangkok. HIV-1 subtype was determined by V3-loop peptide enzyme immunoassay (EIA). Because of confounding, multivariate analyses were stratified by risk category and controlled for sex and age. RESULTS: The infecting HIV-1 subtype was determined for 2104 (94.9%) of 2217 HIV-infected patients with complete data: 284 (13.5%) were subtype B', 1820 (86.5%) were E. Specimens from 113 (5.1%) patients were non-reactive or dually reactive on peptide EIA and were excluded. Among IDU, 199 (67.2%) had subtype B', and 97 (32.7%) had E. IDU accounted for 70.1% (199/284) of patients with subtype B' and 5.3% (97/1820) of those with E. Patients infected with HIV-1 subtypes B' or E had similar spectrums of opportunistic infections (OI), levels of immunosuppression, and in-hospital mortality rates. Of patients who did not inject drugs, more patients infected with subtype E had extrapulmonary cryptococcosis than those with subtype B' (adjusted odds ratio, 2.6; 95% confidence interval, 1.28-5.37). CONCLUSION: HIV-1 subtypes B' and E seem to be associated with similar degrees of immunosuppression and, with one exception, with similar OI patterns. These data do not suggest an association between HIV-1 subtype and differences in pathogenicity.
Adolescent↗
Role of maternal humoral immunity in vertical transmission of HIV-1 subtype E in Thailand.
The significance of the maternal humoral immune response in relation to vertical transmission of HIV-1 was investigated in 123 mothers infected with subtype E from Thailand. Antibody binding titers to HIV-1 env domains (monomeric gp120, the CD4/gp120 binding site [BS], V3 loop, and gp41) and antibody-mediated neutralization of primary and T-cell line-adapted (TCLA) subtypes B and E HIV-1 isolates were investigated. No correlation between maternal anti HIV-1 antibodies at delivery and vertical transmission of HIV-1 subtype E was found. However, a trend to higher titer antibody-mediated cross-neutralization of a heterologous subtype B TCLA isolate, HIV-1MN, was observed in nontransmitting mothers postpartum. The HIV-1-specific antibody titers in these infected mothers increased significantly from delivery to 6 months postpartum (p < .05), but this was only partially attributable to hemodilution and an additional factor or factors appear to affect humoral immunity to HIV-1 during late pregnancy.
Adult↗
Seroprevalence of HIV among female sex workers in Bangkok: evidence of ongoing infection risk after the "100% condom program" was implemented.
BACKGROUND: After implementation in 1991 of a nationwide campaign to promote condom use during commercial sex, HIV-1 seroprevalence among young men began to decrease in 1994. However, it is unknown to what degree female sex workers (FSWs) have been protected from infection. METHODS: FSWs attending a government clinic in Bangkok in 1997 and 1998 were interviewed, counseled, and tested for evidence of prior syphilis by Treponema pallidum hemagglutination assay (TPHA) and for HIV-1 antibodies. RESULTS: Among the 500 participants, women who began sex work more recently reported less risky sex behavior when they were first potentially exposed to HIV infection, and TPHA reactivity rates were lower among these women. However, their HIV infection rates were higher. HIV seroprevalence was 5.5% among 91 women who began sex work before 1989, 8.0% among 87 women who began during 1990 to 1993, and 12.5% among 322 women who had begun since 1994. CONCLUSIONS: Although condom use is critical to HIV prevention, women in this study who began sex work after the condom promotion campaign was implemented were still at high risk for HIV infection. Additional measures are needed to prevent HIV infection among the many young women who initiate or continue to engage in commercial sex.
Adult↗
Clinical presentation of hospitalized adult patients with HIV infection and AIDS in Bangkok, Thailand.
OBJECTIVE: To characterize the clinical spectrum of disease and immune status of adult HIV-1-infected patients in Bangkok. DESIGN: Cross-sectional survey of hospital admissions. METHODS: From November 1993 through June 1996, demographic, clinical, and laboratory data were collected from HIV-infected inpatients (> or =14 years old) at an infectious diseases hospital. RESULTS: Of 16,717 persons admitted, 3112 (18.6%) were HIV-seropositive, 2261 of whom were admitted for the first time. Of 2261, 1926 (85.2%) were male, 1942 (85.9%) had been infected heterosexually or by means not related to drug use, 319 (14.1%) were injection drug users (IDUs), and 1553 (68.7%) had AIDS. The most common AIDS-defining conditions were extrapulmonary cryptococcosis (EPC; 38.4%), tuberculosis (TB; 37.4%), and wasting syndrome (WS; 8.1%). IDUs were more likely (p < .05) to have TB or WS but less likely (p < .05) to have EPC or Pneumocystis carinii pneumonia than patients with no history of injection drug use. Lymphocyte counts were measured for 2047 (90.5%) patients; 81.8% had < or =1500 lymphocytes/microl. CONCLUSION: These HIV-infected patients were admitted with severe immunosuppression. Cryptococcosis and TB are major problems and differ in prevalence among IDUs and persons infected sexually. Clinical and immunologic information is critical in improving the lives of HIV-infected persons in Asia through prevention, treatment, and prophylaxis.
AIDS-Related Opportunistic Infections↗
Willingness of injection drug users to participate in an HIV vaccine efficacy trial in Bangkok, Thailand.
We assessed willingness to participate in an HIV recombinant gp120 bivalent subtypes B/E candidate vaccine efficacy trial among 193 injection drug users (IDUs) attending drug treatment clinics in Bangkok, Thailand. IDUs previously enrolled in a prospective cohort study were invited to group sessions describing a potential trial, then completed questionnaires assessing comprehension and willingness to participate. A week later, they completed a follow-up questionnaire that again assessed comprehension and willingness to participate, as well as barriers to and positive motives for participation, with whom (if anyone) they talked about the information, and whether others thought participation was a good, bad, or neutral idea. At baseline, 51% were definitely willing to participate, and at follow-up 54%; only 3% were not willing to participate at either time. Comprehension was high at baseline and improved at follow-up. Participants who viewed altruism, regular HIV tests, and family support for participation as important were more willing to volunteer. Frequency of incarceration and concerns about the length of the trial, possible vaccine-induced accelerated disease progression, and lack of family support were negatively associated with willingness. Overall, IDUs comprehended the information needed to make a fully informed decision about participating in an rgp120 vaccine efficacy trial and expressed a high level of willingness to participate in such a trial.
AIDS Vaccines↗
HIV-1 seroprevalence among childbearing women in northern Thailand: monitoring a rapidly evolving epidemic.
OBJECTIVES: To describe trends in prevalence of HIV-1 infection among women giving birth at Chiang Rai Hospital (CRH) and to assess risk factors associated with HIV infection in this population. DESIGN: Analysis of hospital registry data for all deliveries at CRH from 1990 to mid-1997. METHODS: From 1990 to mid-1997, women giving birth at CRH were tested for HIV-1 infection using enzyme immunoassay (EIA); positive sera were confirmed using a different manufacturer's EIA. Demographic and clinical data were abstracted from delivery-ward log books. RESULTS: Data from 40723 deliveries indicated that overall HIV-1 seroprevalence increased sharply, from 1.3% in 1990 to a peak of 6.4% in 1994, and then declined to 4.6% in the first 6 months of 1997. Prevalence was highest, at 7.0%, among young (age < or = 24 years) primigravidas, compared with 2.4% among older (age > or = 25 years) multigravidas. When we controlled for age, prevalence declined 40% from 1994 to 1997 among young primigravidas (95% confidence interval for percentage reduction, 16-57). Amongst older multigravid women, prevalence was consistently lower but increased steadily from 2.7% in 1994 to 3.4% in 1997. CONCLUSIONS: A rapid rise in HIV prevalence in childbearing women was followed by a sharp decline among young primigravidas. In each year, the prevalence was highest among young primigravidas. They may be the best subgroup of pregnant women for monitoring HIV epidemic trends, but they also represent a challenging prevention priority that will require its own targeted interventions.
Adolescent↗
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.
Administration, Oral↗
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.
Cohort Studies↗