Timing of breast milk HIV-1 transmission: a meta-analysis.

OBJECTIVE: To define the frequency and timing of breast milk transmission of HIV-1. DESIGN: Meta-analysis of data abstracted from published literature. SUBJECTS: Participants in prospective cohort studies of MTCT of HIV-1. Cohorts were separated on the basis of breast feeding duration. INTERVENTIONS: None. MAIN OUTCOME MEASURES: HIV-1 transmission rates. RESULTS: Two thousand three hundred and seventy five HIV-1 infected women and their infants, 499 of whom breast fed, the estimated risk of breast milk HIV-1 transmission was 16% (95% CI: 9, 22%). Among breastfeeding infants, forty seven per cent of HIV-1 infections were attributable to breast feeding. Breast milk transmission risk was 21% (95% CI: 10, 33%) in cohorts with mean/median duration of breast feeding > or = 3 months and 13% (95% CI: 4, 21%) in cohorts with median duration of breast feeding < 2 months. In a separate analysis of 702 infants with prolonged duration of breast feeding, the risk of late postnatal transmission (infection occurring later than three to six months of age) was four per cent (95% CI 2, 5%). CONCLUSIONS: This analysis suggests that breast milk transmission of HIV-1 is substantial and continues throughout the postnatal period. Early cessation of breast feeding at six months would avert some but not most infant HIV-1 infections due to breast feeding. While recently published studies showing some effectiveness of antiretrovirals early during the breast feeding period are encouraging, prevention of breast milk HIV-1 transmission needs to remain a high research priority.

Hormonal contraception and risk of sexually transmitted disease acquisition: results from a prospective study.

OBJECTIVES: To examine the relationship between use of oral contraceptive pills or depot medroxyprogesterone acetate and sexually transmitted disease acquisition. STUDY DESIGN: Prospective cohort included 948 Kenyan prostitutes. Multivariate Andersen-Gill proportional hazards models were constructed, adjusting for sexual behavioral and demographic variables. RESULTS: When compared with women who were using no contraception, users of oral contraceptive pills were at increased risk for acquisition of chlamydia (hazard ratio, 1.8; 95% confidence interval, 1.1-2.9) and vaginal candidiasis (hazard ratio, 1.5; 95% confidence interval, 1.2-1.9) and at decreased risk for bacterial vaginosis (hazard ratio, 0.8; 95% confidence interval, 0.7-1.0). Women using depot medroxyprogesterone acetate had significantly increased risk of chlamydia infection (hazard ratio, 1.6; 95% confidence interval, 1.1-2.4) and significantly decreased risk of bacterial vaginosis (hazard ratio, 0.7; 95% confidence interval, 0.5-0.8), trichomoniasis (hazard ratio, 0.6; 95% confidence interval, 0.4-1.0), and pelvic inflammatory disease (hazard ratio, 0.4; 95% confidence interval, 0.2-0.7). Consistent condom use was associated with significantly decreased risk of gonorrhea, chlamydia, genital ulcer disease, bacterial vaginosis, and pelvic inflammatory disease. CONCLUSIONS: The use of oral or injectable hormonal contraception altered susceptibility to sexually transmitted diseases, which may in turn influence transmission of human immunodeficiency virus type 1. Consistent condom use was protective with regards to sexually transmitted disease and should be encouraged for the prevention of sexually transmitted disease and human immunodeficiency virus type 1 among women who use hormonal contraception.

Evaluation of a low-dose nonoxynol-9 gel for the prevention of sexually transmitted diseases: a randomized clinical trial.

BACKGROUND: Low-dose nonoxynol-9 products have a potential advantage of reduced toxicity. However, little is known about their efficacy in reducing the incidence of sexually transmitted diseases (STDs). GOAL: To determine the effect that an intravaginal gel containing 52.5 mg of nonoxynol-9 has on the acquisition of STDs in a cohort of HIV-1-seronegative female sex workers in Mombasa, Kenya. STUDY DESIGN: A randomized double-blind placebo controlled trial was performed. RESULTS: In this study, 139 women were randomized to the nonoxynol-9 group and 139 to the placebo group. No significant differences were found between the two study groups in terms of safety outcomes and reported symptoms, except for a lower incidence of vaginal erythema in the nonoxynol-9 group. There was a significantly higher incidence of gonorrhea in the nonoxynol-9 group than in the placebo group. No significant differences were observed between the groups for acquisition of Candida, trichomonas, bacterial vaginosis, C trachomatis, syphilis, or HIV-1, although the statistical power to detect differences for some of these STDs was limited. CONCLUSIONS: In this randomized placebo-controlled trial of a low-dose nonoxynol-9 gel, a significantly higher incidence of gonorrhea was found in the nonoxynol-9 group, but no significant differences between the groups were found for Candida, trichomonas, bacterial vaginosis, C trachomatis, syphilis, or HIV-1.

Impact of an alarm device on medication compliance in women in Mombasa, Kenya.

A randomized controlled clinical trial was conducted to determine the efficacy and acceptability of an alarm device for improving medication compliance among women in resource poor countries. Study participants were given a one-month supply of daily multi-vitamins in an electronic medication vial. Women randomly received either an alarmed vial or a non-alarmed vial. Sixty per cent of women had good compliance (defined as 95% > or = of pills ingested). Women randomized to use the alarmed vial were significantly more likely to have good compliance than those in the non-alarmed control group (82% vs. 36%, P < 0.001). Vial acceptability was high and 99% of participants said they would choose to use the vial again. In conclusion, the alarm device was found to significantly improve medication adherence rates and may be particularly beneficial for improving adherence to antiretroviral therapy among HIV-1 infected persons in developing countries.

Selenium deficiency is associated with shedding of HIV-1--infected cells in the female genital tract.

OBJECTIVE: To assess the relation between selenium deficiency and vaginal or cervical shedding of HIV-1-infected cells. DESIGN: Cross-sectional study of 318 HIV-1 seropositive women in Mombasa, Kenya. METHODS: Vaginal and cervical swab specimens were tested for the presence of HIV-1 DNA by polymerase chain reaction. Multivariate logistic regression models, adjusting for CD4 count and vitamin A deficiency, were used. RESULTS: Selenium deficiency (defined as levels <85 microg/L) was observed in 11% of the study population. In unstratified multivariate analyses, there was no significant association between selenium deficiency and vaginal or cervical shedding. In stratified analyses, however, significant associations became apparent after excluding women with predictors of shedding with strong local effects on the genital tract mucosa. Among women who did not use oral contraceptives and who did not have vaginal candidiasis, selenium deficiency was significantly associated with vaginal shedding (adjusted odds ratio [AOR] 2.9, 95% confidence interval [CI] 1.0--8.8, p =.05). Effect modification was also observed in the relation between selenium deficiency and cervical shedding, with a significant association seen among those women who were not using oral contraceptive pills or depot medroxyprogesterone acetate and who did not have Neisseria gonorrhoeae infection (AOR 2.8, 95% CI 1.1--7.0, p =.02). CONCLUSIONS: We found selenium deficiency to be associated with a nearly threefold higher likelihood of genital mucosal shedding of HIV-1--infected cells, suggesting that deficiency may increase the infectiousness of women with HIV-1. Nutritional interventions to prevent HIV-1 transmission warrant investigation.

The effect of treatment of vaginal infections on shedding of human immunodeficiency virus type 1.

To assess the effect of treatment of vaginal infections on vaginal shedding of cell-free human immunodeficiency virus type 1 (HIV-1) and HIV-1-infected cells, HIV-1-seropositive women were examined before and after treatment of Candida vulvovaginitis, Trichomonas vaginitis, and bacterial vaginosis. For Candida (n=98), vaginal HIV-1 RNA decreased from 3.36 to 2.86 log(10) copies/swab (P<.001), as did the prevalence of HIV-1 DNA (36% to 17%; odds ratio [OR], 2.8; 95% confidence interval [CI], 1.3-6.5). For Trichomonas vaginitis (n=55), HIV-1 RNA decreased from 3.67 to 3.05 log(10) copies/swab (P<.001), but the prevalence of HIV-1 DNA remained unchanged (22%-25%; OR, 0.8; 95% CI, 0.3-2.2). For bacterial vaginosis (n=73), neither the shedding of HIV-1 RNA (from 3.11 to 2.90 log(10) copies/swab; P=.14) nor the prevalence of DNA (from 21% to 23%; OR, 0.8; 95% CI, 0.3-2.0) changed. Vaginal HIV-1 decreased 3.2- and 4.2-fold after treating Candida and Trichomonas, respectively. These data suggest that HIV-1 transmission intervention strategies that incorporate diagnosis and treatment of these prevalent infections warrant evaluation.

Validation of a modified commercial enzyme-linked immunoassay for detection of human immunodeficiency virus type 1 immunoglobulin G antibodies in saliva.

This study was performed to evaluate the performance of a saliva collection device (OmniSal) and an enzyme-linked immunoassay (EIA) designed for use on serum samples (Detect HIV1/2) to detect human immunodeficiency virus type 1 (HIV-1) antibodies in the saliva of high-risk women in Mombasa, Kenya. The results of the saliva assay were compared to a "gold standard" of a double-EIA testing algorithm performed on serum. Individuals were considered HIV-1 seropositive if their serum tested positive for antibodies to HIV-1 by two different EIAs. The commercial serum-based EIA was modified to test the saliva samples by altering the dilution and lowering the cutoff point of the assay. Using the saliva sample, the EIA correctly identified 102 of the 103 seropositive individuals, yielding a sensitivity of 99% (95% confidence interval [CI], 94 to 100%), and 96 of the 96 seronegative individuals, yielding a specificity of 100% (95% CI, 95 to 100%). In this high-risk population, the positive predictive value of the assay was 100% and the negative predictive value was 99%. We conclude that HIV-1 antibody testing of saliva samples collected with this device and tested by this EIA is of sufficient sensitivity and specificity to make this protocol useful in epidemiological studies.

Treatment of cervicitis is associated with decreased cervical shedding of HIV-1.

OBJECTIVE: To determine whether cervical mucosal shedding of HIV-1 RNA and HIV-1 infected cells decreases following successful treatment of cervicitis. DESIGN: Prospective interventional study. SETTING: Sexually Transmitted Infections Clinic, Coast Provincial General Hospital, Mombasa, Kenya. PARTICIPANTS: Thirty-six HIV-1 seropositive women with cervicitis: 16 with Neisseria gonorrhoeae, seven with Chlamydia trachomatis, and 13 with non-specific cervicitis. INTERVENTIONS: Treatment of cervicitis. MAIN OUTCOME MEASURES: Levels of total (cell-free and cell-associated) HIV-1 RNA and presence of HIV-1 DNA (a marker for infected cells) in cervical secretions before and after resolution of cervicitis. RESULTS: After treatment of cervicitis, the median HIV-1 RNA concentration in cervical secretions was reduced from 4.05 to 3.24 log10 copies/swab (P = 0.001). Significant decreases in cervical HIV-1 RNA occurred in the subgroups with N. gonorrhoeae (3.94 to 3.28 log10 copies/swab; P = 0.02) and C. trachomatis (4.21 to 3.19 log10 copies/swab; P = 0.02). Overall, the prevalence of HIV-1 infected cells in cervical secretions also decreased after treatment, from 67% to 42% (odds ratio, 2.8; 95% confidence interval, 1.3-6.0; P = 0.009). Detection of infected cells was associated with higher mean HIV-1 RNA levels (4.04 versus 2.99 log10 copies/swab; P< 0.0001). CONCLUSIONS: Effective treatment of cervicitis resulted in significant decreases in shedding of HIV-1 virus and infected cells in cervical secretions. Treatment of sexually transmitted diseases may be an important means of decreasing the infectivity of HIV-1 seropositive women by reducing exposure to HIV-1 in genital secretions.

Correlates of mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission: association with maternal plasma HIV-1 RNA load, genital HIV-1 DNA shedding, and breast infections.

To determine the effects of plasma, genital, and breast milk human immunodeficiency virus type 1 (HIV-1) and breast infections on perinatal HIV-1 transmission, a nested case-control study was conducted within a randomized clinical trial of breast-feeding and formula feeding among HIV-1-seropositive mothers in Nairobi, Kenya. In analyses comparing 92 infected infants with 187 infants who were uninfected at 2 years, maternal viral RNA levels >43,000 copies/mL (cohort median) were associated with a 4-fold increase in risk of transmission (95% confidence interval [CI], 2.2-7.2). Maternal cervical HIV-1 DNA (odds ratio [OR], 2.4; 95% CI, 1.3-4.4), vaginal HIV-1 DNA (OR, 2.3; 95% CI, 1.1-4.7), and cervical or vaginal ulcers (OR, 2.7; 95% CI, 1.2-5.8) were significantly associated with infant infection, independent of plasma virus load. Breast-feeding (OR, 1.7; 95% CI, 1.0-2.9) and mastitis (relative risk [RR], 3.9; 95% CI, 1.2-12.7) were associated with increased transmission overall, and mastitis (RR, 21.8; 95% CI, 2.3-211.0) and breast abscess (RR, 51.6; 95% CI, 4.7-571.0) were associated with late transmission (occurring >2 months postpartum). Use of methods that decrease infant exposure to HIV-1 in maternal genital secretions or breast milk may enhance currently recommended perinatal HIV-1 interventions.

Cervical shedding of herpes simplex virus and cytomegalovirus throughout the menstrual cycle in women infected with human immunodeficiency virus type 1.

OBJECTIVE: Our purpose was to evaluate the frequency and patterns of the shedding of herpes simplex virus and cytomegalovirus in the female genital tract throughout the menstrual cycle. STUDY DESIGN: Seventeen women, all seropositive for herpes simplex virus types 1 and 2, cytomegalovirus, and human immunodeficiency virus type 1, underwent daily evaluation of cervical viral shedding for the duration of 1 menstrual cycle (21-31 visits per woman). Serum estradiol and progesterone levels were monitored 3 times weekly. RESULTS: Overall, herpes simplex virus deoxyribonucleic acid was detected in 43 (10%) of 450 cervical swabs, and cytomegalovirus deoxyribonucleic acid was detected in 232 (52%) of 450 cervical swabs. For individual women there was considerable variability in the percentage of days on which virus was detected, ranging from 0% to 33% for herpes simplex virus and from 20% to 97% for cytomegalovirus. Shedding of herpes simplex virus did not vary significantly with menstrual cycle; however, shedding of cytomegalovirus was significantly more frequent in the luteal phase (odds ratio, 1.9; 95% confidence interval, 1.1-3.4). A CD4(+) lymphocyte count <200/microL was associated with increased frequency of the detection of herpes simplex virus (odds ratio, 5.7; 95% confidence interval, 1.1-29.4). CONCLUSIONS: Asymptomatic cervical shedding of both herpes simplex virus and cytomegalovirus occurs very frequently in women infected with human immunodeficiency virus type 1. The risk of transmitting these viruses to sexual partners and neonates may be higher than previously recognized.

Trends in HIV-1 incidence in a cohort of prostitutes in Kenya: implications for HIV-1 vaccine efficacy trials.

BACKGROUND: Accurate predictions of HIV-1 incidence in potential study populations are essential for designing HIV-1 vaccine efficacy trials. Little information is available on the estimated incidence of HIV-1 in such populations, especially information on incidence over time and incidence while participating in risk-reduction programs. OBJECTIVES: To examine time trends in HIV-1 incidence in a vaccine preparedness cohort. DESIGN: Prospective cohort study of female prostitutes in Mombasa, Kenya. METHODS: HIV-1 incidence was determined using open and closed cohort designs. Generalized estimating equations were used to model HIV-1 and sexually transmitted disease (STD) incidence and sexual risk behaviors over time. RESULTS: When analyzed as a closed cohort, HIV-1 incidence declined 10-fold during 3 years of follow-up (from 17.4 to 1.7 cases/100 person-years; p <.001). More than 50% of the cases of HIV-1 occurred during the first 6 months after enrollment, and 73% during the first 12 months. When analyzed as an open cohort, HIV-1 incidence density fell during the first 4 calendar years, influenced by accumulation of lower risk participants and variations in study recruitment. Significant declines occurred in both STD incidence and high-risk sexual behaviors during follow-up. CONCLUSIONS: This study documents a dramatic decline in the risk of HIV-1 infection while participating in a prospective cohort, with most seroconversions occurring within 1 year of enrollment. Variations in HIV-1 incidence within high-risk populations should be anticipated during the design of vaccine trials.

Evaluation of performance of the Gen-Probe human immunodeficiency virus type 1 viral load assay using primary subtype A, C, and D isolates from Kenya.

Accurate and sensitive quantification of human immunodeficiency virus type 1 (HIV-1) RNA has been invaluable as a marker for disease prognosis and for clinical monitoring of HIV-1 disease. The first generation of commercially available HIV-1 RNA tests were optimized to detect the predominant HIV-1 subtype found in North America and Europe, subtype B. However, these tests are frequently suboptimal in detecting HIV-1 genetic forms or subtypes found in other parts of the world. The goal of the present study was to evaluate the performance of a new viral load assay with non-subtype B viruses. A transcription-mediated amplification method for detection and quantitation of diverse HIV-1 subtypes, called the Gen-Probe HIV-1 viral load assay, is under development. In this study we examined the performance of the Gen-Probe HIV-1 viral load assay relative to that of the commonly used commercial HIV-1 RNA assays using a panel of primary isolates from Kenya. For comparison, we included several subtype B cloned viruses, and we quantified each virus using an in-house quantitative-competitive reverse transcriptase PCR (QC-RT-PCR) method and gag(p24) antigen capture. The Gen-Probe HIV-1 viral load assay and a version of the Roche AMPLICOR HIV-1 MONITOR test (version 1.5) that was designed to detect a broader range of subtypes were both sensitive for the quantification of Kenyan primary isolates, which represented subtype A, C, and D viruses. The Gen-Probe HIV-1 viral load assay was more sensitive for the majority of viruses than the Roche AMPLICOR HIV-1 MONITOR test version 1.0, the Bayer Quantiplex HIV RNA 3.0 assay, or a QC-RT-PCR method in use in our laboratory, suggesting that it provides a useful method for quantifying HIV-1 RNAs from diverse parts of the world, including Africa.

Maternal SDF1 3'A polymorphism is associated with increased perinatal human immunodeficiency virus type 1 transmission.

Genetic polymorphisms in chemokine and chemokine receptor genes influence susceptibility to human immunodeficiency virus type 1 (HIV-1) infection and disease progression, but little is known regarding the association between these allelic variations and the ability of the host to transmit virus. In this study, we show that the maternal heterozygous SDF1 genotype (SDF1 3'A/wt) is associated with perinatal transmission of HIV-1 (risk ratio [RR], 1.8; 95% confidence interval [CI], 1.0 to 3.3) and particularly postnatal breastmilk transmission (RR, 3.1; 95% CI, 1.1 to 8.6). In contrast, the infant SDF1 genotype had no effect on mother-to-infant transmission. These data suggest that SDF1, which is a ligand for the T-tropic HIV-1 coreceptor CXCR4, may affect the ability of a mother to transmit the virus to her infant. This suggests that a genetic polymorphism in a gene encoding a chemokine receptor ligand may be associated with increased infectivity of the index case and highlights the importance of considering transmission as well as clinical outcome in designing chemokine-based therapies for HIV-1.

Gender differences in HIV-1 diversity at time of infection.

To develop an HIV-1 vaccine with global efficacy, it is important to identify and characterize the viruses that are transmitted, particularly to individuals living in areas of high incidence. Several studies have shown that virus from the blood of acutely infected adults was homogeneous, even when the virus population in the index case was genetically diverse. In contrast to those results with mainly male cohorts in America and Europe, in several cases a heterogeneous virus population has been found early in infection in women in Africa. Thus, we more closely compared the diversity of transmitted HIV-1 in men and women who became infected through heterosexual contact. We found that women from Kenya were often infected by multiple virus variants, whereas men from Kenya were not. Moreover, a heterogeneous virus was present in the women before their seroconversion, and in each woman it was derived from a single index case, indicating that diversity was most likely to be the result of transmission of multiple variants. Our data indicate that there are important differences in the transmitted virus populations in women and men, even when cohorts from the same geographic region who are infected with the same subtypes of HIV-1 are compared.

Cervical shedding of herpes simplex virus in human immunodeficiency virus-infected women: effects of hormonal contraception, pregnancy, and vitamin A deficiency.

Genital shedding of herpes simplex virus (HSV) results in frequent transmission of infection to sexual partners and neonates. In a cross-sectional study, cervical shedding of HSV DNA was detected in 43 (17%) cervical swab samples from 273 women seropositive for HSV-1, HSV-2, and human immunodeficiency virus type 1 (HIV-1). Cervical shedding of HSV was significantly associated with oral contraception (adjusted odds ratio [aOR], 4.5; 95% confidence interval [CI], 1.7-12.2), use of depo-medroxyprogesterone acetate (aOR, 3.2; 95% CI, 1.3-7.7), and pregnancy (aOR, 7.9; 95% CI, 2.0-31.7). In the subgroup of women who were not pregnant and not using hormonal contraception (n=178), serum vitamin A was highly predictive of cervical HSV shedding: concentrations indicating severe deficiency, moderate deficiency, low-normal, and high-normal status were associated with 29%, 18%, 8%, and 2% prevalences of cervical HSV shedding, respectively (linear trend, P=.0002). Several factors appear to influence HSV reactivation in HIV-1 seropositive women.

Effect of intrauterine device use on cervical shedding of HIV-1 DNA.

OBJECTIVE: Hormonal contraception has been associated with an increased prevalence of cervical shedding of HIV-1 DNA among infected women. We conducted this study to evaluate the effect of the use of an intrauterine device (IUD) on the detection of HIV-1 DNA in cervical secretions. DESIGN: A prospective study of HIV-1-seropositive women undergoing IUD insertion at two public family planning clinics in Nairobi, Kenya. METHODS: Cervical swab samples were collected before IUD insertion and approximately 4 months thereafter for the detection of HIV-1-infected cells using polymerase chain reaction (PCR) amplification of HIV-1 gag DNA sequences. RESULTS: Ninety-eight women were enrolled and followed after IUD insertion. The prevalence of HIV-1 DNA cervical shedding was 50% at baseline and 43% at follow-up [odds ratio (OR) 0.8, 95% confidence interval (CI) 0.5-1.2]. There was no statistically significant difference between the baseline and follow-up shedding rates in a multivariate model that controlled for previous hormonal contraceptive use, condom use, cervical ectopy, friable cervix, cervical infections at an interim visit, and CD4 lymphocyte levels (OR 0.6, 95% CI 0.3-1.1). CONCLUSION: The insertion of an IUD did not significantly alter the prevalence of cervical shedding of HIV-1-infected cells. The use of IUDs, in conjunction with condoms, may be an appropriate method of contraception for HIV-1-infected women from the standpoint of potential infectivity to the male partner through exposure to genital HIV-1.

Cervical shedding of cytomegalovirus in human immunodeficiency virus type 1-infected women.

Cervical shedding of cytomegalovirus (CMV) is important in transmission of CMV to exposed sexual partners and neonates. We evaluated prevalence and correlates of CMV DNA shedding in cervical secretions from a large cohort of HIV-1-seropositive women. Using polymerase chain reaction (PCR) assays, CMV DNA was detected in 183 (59%) cervical swab samples from 311 women. Cervical shedding of CMV DNA was significantly associated with shedding of HIV-1 DNA (odds ratio 1.8; 95% confidence interval 1.1-2.8). CMV shedding was also more frequent in women with Neisseria gonorrhoeae and Trichomonas vaginalis infections, but these associations were not statistically significant. Cervical shedding of CMV in HIV-1-infected women is very frequent and may reflect higher risk of transmission to sexual partners and neonates than previously appreciated.

Effect of circumcision on incidence of human immunodeficiency virus type 1 and other sexually transmitted diseases: a prospective cohort study of trucking company employees in Kenya.

To determine the effect of circumcision status on acquisition of human immunodeficiency virus (HIV) type 1 and other sexually transmitted diseases, a prospective cohort study of 746 HIV-1-seronegative trucking company employees was conducted in Mombasa, Kenya. During the course of follow-up, 43 men acquired HIV-1 antibodies, yielding an annual incidence of 3.0%. The annual incidences of genital ulcers and urethritis were 4.2% and 15.5%, respectively. In multivariate analysis, after controlling for demographic and behavioral variables, uncircumcised status was an independent risk factor for HIV-1 infection (hazard rate ratio [HRR=4.0; 95% confidence interval [CI], 1.9-8.3) and genital ulcer disease (HRR=2.5; 95% CI, 1.1-5.3). Circumcision status had no effect on the acquisition of urethral infections and genital warts. In this prospective cohort of trucking company employees, uncircumcised status was associated with increased risk of HIV-1 infection and genital ulcer disease, and these effects remained after controlling for potential confounders.

Risk of HIV infection in oral contraceptive pill users: a meta-analysis.

OBJECTIVE: To review the literature and present a summary estimate of the association between HIV-1 acquisition or HIV-1 serostatus and oral contraceptives. DATA SOURCES: MEDLINE database (January 1986-October 1997), AIDSLINE database (January 1980-October 1997), bibliographies of identified articles, and experts in the field of heterosexual HIV transmission. STUDY SELECTION: In all, 591 articles were examined. Twenty-eight studies provided adequate data to calculate a risk estimate for the association of HIV-1 serostatus or HIV-1 seroconversion with oral contraceptives and were selected for inclusion. RESULTS: The overall summary odds ratio (OR) for the association between seroprevalent or seroincident HIV-1 infection and use of oral contraceptives in the 28 studies was 1.19 (95% confidence interval [CI], 0.99-1.42). The summary OR for 21 cross-sectional studies was 1.21 (95% CI, 1.01-1.44), whereas the summary relative risk for seven prospective studies was 1.32 (95% CI, 1.12-1.57). Study quality was assessed by applying a scale reflecting study design, measurement of exposure, ability to assess confounding, and publication status. The summary OR for the eight best studies was 1.60 (95% CI, 1.05-2.44). When analysis was limited to studies conducted in Africa, the summary OR was 1.45 (95% CI, 1.15-1.83) for the 14 studies overall, and 1.65 (95% CI, 1.09-2.52) for the seven best studies. CONCLUSION: This meta-analysis found a significant association between oral contraceptive use and HIV-1 seroprevalence or seroincidence. For women at risk of HIV-1 infection, oral contraceptive use for prevention of pregnancy should be accompanied by condom use for prevention of HIV-1 infection.