Search

Background: Studies of the effect of hormonal contraceptive use on the risk of HIV-1 acquisition have generated conflicting results. A recent study from Uganda and Zimbabwe found that women using hormonal contraception were at increased risk for HIV-1 if they were seronegative for herpes simplex virus type 2 (HSV-2), but not if they were HSV-2 seropositive., Objective: To explore the effect of HSV-2 infection on the relationship between hormonal contraception and HIV-1 in a high-risk population. Hormonal contraception has previously been associated with increased HIV-1 risk in this population., Methods: Data were from a prospective cohort study of 1206 HIV-1 seronegative sex workers from Mombasa, Kenya who were followed monthly. Multivariate Cox proportional hazards analyses were used to adjust for demographic and behavioral measures and incident sexually transmitted diseases., Results: : Two hundred and thirty-three women acquired HIV-1 (8.7/100 person-years). HSV-2 prevalence (81%) and incidence (25.4/100 person-years) were high. In multivariate analysis, including adjustment for HSV-2, HIV-1 acquisition was associated with use of oral contraceptive pills [adjusted hazard ratio (HR), 1.46; 95% confidence interval (CI), 1.00-2.13] and depot medroxyprogesterone acetate (adjusted HR, 1.73; 95% CI, 1.28-2.34). The effect of contraception on HIV-1 susceptibility did not differ significantly between HSV-2 seronegative versus seropositive women. HSV-2 infection was associated with elevated HIV-1 risk (adjusted HR, 3.58; 95% CI, 1.64-7.82)., Conclusions: In this group of high-risk African women, hormonal contraception and HSV-2 infection were both associated with increased risk for HIV-1 acquisition. HIV-1 risk associated with hormonal contraceptive use was not related to HSV-2 serostatus.

Background: Bacterial vaginosis (BV) is highly prevalent among African women and has been associated with adverse pregnancy outcomes, sexually transmitted diseases, and HIV-1., Goal: The goal of this study was to analyze the relationship among intravaginal practices, bathing, and BV., Study Design: The authors conducted a cross-sectional study of HIV-1-seronegative Kenyan female sex workers without symptoms of vaginal infections., Results: Of 237 women enrolled, 206 (87%) reported vaginal washing using either a finger or cloth. Increasing frequency of vaginal washing was associated with a higher likelihood of BV (chi(2) test for trend, P = 0.05). In multivariate analysis, vaginal lubrication with petroleum jelly (odds ratio [OR] = 2.8, 95% confidence interval [CI] = 1.4-5.6), lubrication with saliva (OR = 2.3, 95% CI = 1.1-4.8), and bathing less than the median for the cohort (14 times/week; OR = 4.6, 95% CI = 1.2-17.5) were associated with a significantly higher likelihood of BV., Conclusions: Modification of intravaginal and general hygiene practices should be evaluated as potential strategies for reducing the risk of BV.

We investigated the effect of human immunodeficiency virus type 1 (HIV-1) subtype on disease progression among 145 Kenyan women followed from the time of HIV-1 acquisition. Compared with those infected with subtype A, women infected with subtype D had higher mortality (hazard ratio, 2.3 [95% confidence interval, 1.0-5.6]) and a faster rate of CD4 cell count decline (P=.003). The mortality risk persisted after adjustment for plasma HIV-1 load. There were no differences in plasma viral load by HIV-1 subtype during follow-up. HIV-1 subtype D infection is associated with a >2-fold higher risk of death than subtype A infection, in spite of similar plasma HIV-1 loads.

Few data are available on genital tract viral replication early after HIV-1 acquisition, when infectivity is high. We compared cervical HIV-1 RNA from 60 women with paired samples from within 90 days after HIV-1 acquisition and at viral setpoint (4-24 months). Cervical HIV-1 was higher in early compared with setpoint samples (mean 3.43 versus 2.85 log10 copies/swab, P < 0.001). After adjusting for HIV-1-plasma RNA, cervical HIV-1 RNA from 30 days or less after infection was increased by 0.45 log10 copies/swab (P = 0.006).

Background: There is limited information on the natural history of human immunodeficiency virus type 1 (HIV-1) infection in Africa, especially from individuals with well-defined dates of infection. We used data from a prospective cohort study of female sex workers in Mombasa, Kenya, who were followed up monthly from before the date of HIV-1 infection., Methods: Antiretroviral-naive women who had a well-defined date of HIV-1 infection were included in this analysis. The effects of set point plasma viral load (measured 4-24 months after infection), early CD4+ cell count, and symptoms of acute HIV-1 infection on mortality were assessed using Cox proportional hazards analysis., Results: Among 218 women, the median duration of follow-up after HIV-1 infection was 4.6 years. Forty women died, and at 8.7 years (the time of the last death), the cumulative survival rate was 51% by Kaplan-Meier analysis. Higher set point viral load, lower early CD4+ cell count, and more-symptomatic acute HIV-1 illness each predicted death. In multivariate analysis, set point viral load (hazard ratio [HR], 2.28 per 1 log10 copies/mL increase; P=.001) and acute HIV-1 illness (HR, 1.14 per each additional symptom; P=.05) were independently associated with higher mortality., Conclusion: Among this group of African women, the survival rate was similar to that for HIV-1-infected individuals in industrialized nations before the introduction of combination antiretroviral therapy. Higher set point viral load and more-severe acute HIV-1 illness predicted faster progression to death. Early identification of individuals at risk for rapid disease progression may allow closer clinical monitoring, including timely initiation of antiretroviral treatment.

Background: Sexually transmitted diseases (STDs) enhance human immunodeficiency virus (HIV)-1 susceptibility, but few studies have examined the reciprocal effect of HIV-1 on STD acquisition., Methods: Data from a prospective cohort study conducted among female sex workers in Mombasa, Kenya between 1993 and 2003 were used to determine the effect of HIV-1 infection on STD susceptibility. The cohort included 1215 HIV-1-seronegative women who underwent monthly HIV-1 and STD screening, of whom 238 experienced seroconversion to HIV-1 during follow-up. Andersen-Gill proportional-hazards models were used to compare the incidence rates for genital-tract infections (syphilis, genital ulcer disease [GUD], Neisseria gonorrhoeae infection, Chlamydia trachomatis infection, Trichomonas vaginalis infection, vulvovaginal candidiasis, and bacterial vaginosis) in HIV-1-seropositive versus HIV-1-seronegative women, after controlling for sexual behavior and other potential confounding factors., Results: HIV-1 infection was associated with a significantly higher incidence of GUD (hazard ratio [HR], 2.8; 95% confidence interval [CI], 2.0-3.9), gonorrhea (HR, 1.6; 95% CI, 1.1-2.2), and vulvovaginal candidiasis (HR, 1.5; 95% CI, 1.3-1.8). The risks of GUD and vulvovaginal candidiasis increased with progressive levels of immunosuppression., Conclusions: The increased incidence of genital-tract infections among HIV-1-seropositive women could promote the spread of both HIV-1 and other STDs, particularly in areas where these conditions are highly prevalent.

Objective: To evaluate the relationship between hormonal contraceptive use and the acquisition of cervical sexually transmitted infections (STI) among HIV-1-infected women., Design: A prospective cohort study of 242 commercial sex workers in Mombasa, Kenya, followed from the time of HIV-1 infection., Methods: At monthly follow-up visits, sexual behavior and contraceptive use were recorded, and laboratory screening for STI was performed. Multivariate Andersen-Gill proportional hazards models were constructed to examine the association between the use of hormonal contraception and the occurrence of cervical STI., Results: The median duration of follow-up after HIV-1 acquisition was 35 months, and 799 person-years of follow-up were accrued. After adjustment for demographic factors and sexual behavior, women using the injectable contraceptive depot medroxyprogesterone acetate were at increased risk of Chlamydia trachomatis infection [hazard ratio (HR) 3.1, 95% confidence interval (CI) 1.0-9.4, P = 0.05] and cervicitis (HR 1.6, 95% CI 1.0-2.3, P = 0.03) compared with women using no contraception. The use of oral contraceptive pills was associated with an increased risk of cervicitis (HR 2.3, 95% CI 1.4-3.8, P = 0.001). Hormonal contraception was not associated with an increased risk of infection with Neisseria gonorrhoeae., Conclusion: The use of hormonal contraception by HIV-1-infected women was associated with an increased risk of cervicitis and cervical chlamydia infection. HIV-1-seropositive women using hormonal contraception should be counseled about the importance of consistent condom use to prevent both STI and HIV-1 transmission.

Prevalence of placental malaria in human immunodeficiency virus (HIV) type 1-infected and -uninfected women and the effect of placental malaria on genital shedding and perinatal transmission of HIV-1 were examined. Genital samples for HIV-1 DNA RNA were collected during labor. Infants were tested for HIV-1 at 1 day and 6 weeks postpartum. Placental malaria was diagnosed by histopathological examination: 372 placentas of HIV-1-infected women and 277 of HIV-1-uninfected women were processed. A higher prevalence of placental malaria was seen in HIV-1-infected women. No association was found between placental malaria and either maternal virus load, genital HIV-1 DNA, or HIV-1 RNA. Placental malaria did not correlate with in utero or peripartal transmission of HIV-1.

Although several virologic and immunologic factors associated with an increased risk of perinatal human immunodeficiency virus type 1 (HIV-1) transmission have been described, the mechanism of mother-to-child transmission is still unclear. More specifically, the question of whether selective pressures influence the transmission remains unanswered. The aim of this study was to assess the genetic diversity of the transmitted virus after in utero transmission and after peripartum transmission and to compare the viral heterogeneity in the child with the viral heterogeneity in the mother. To allow a very accurate characterization of the viral heterogeneity in a single sample, limiting-dilution sequencing of a 1016-bp fragment of the env gene was performed. Thirteen children were tested, including 6 with in utero infections and 7 with peripartum infections. Samples were taken the day after birth and at the ages of 6 and 14 weeks. A homogeneous virus population was seen in six (46.2%) infants, of whom two were infected in utero and four were infected peripartum. A more heterogeneous virus population was detected in seven infants (53.8%), four infected in utero and three infected peripartum. The phylogenetic trees of the mother-child pairs presented a whole range of different tree topologies and showed infection of the child by one or more maternal variants. In conclusion, after HIV-1 transmission from mother to child a heterogeneous virus population was detected in approximately one-half of the children examined. Heterogeneous virus populations were found after peripartum infection as well as after in utero infection. Phylogenetic tree topologies argue against selection processes as the major mechanism driving mother-to-child transmission but support the hypothesis that virus variability is mainly driven by the inoculum level and/or exposure time.

The effect of placental membrane inflammation on mother-to-child transmission (MTCT) of HIV-1 is reported. Placentas from HIV-1-infected women were examined as part of a perinatal HIV-1 project in Mombasa, Kenya. Polymerase chain reaction analysis was used to test for HIV-1 in the infants at birth and at 6 weeks. The maternal HIV-1 seroprevalence was 13.3% (298 of 2,235). The overall rate of MTCT of HIV-1 was 25.4%; polymerase chain reaction analysis revealed that of the 201 infants 6.0% (12) were already HIV-1-positive at birth (intrauterine transmission) and 19.4% (39) were infected during the peripartum period or in early neonatal life (perinatal transmission). The prevalence of acute chorioamnionitis was 8.8%, that of deciduitis was 10.8%, and that of villitis was 1.6%. Acute chorioamnionitis was independently associated with peripartum HIV-1 transmission but not with in utero MTCT (17.9% vs. 6.7%, respectively; adjusted odds ratio, 3.9; 95% confidence interval, 1.2-12.5; p =.025). Other correlates of perinatal MTCT were presence of HIV in the genital tract and in the baby's oral cavity and a high maternal viral load in peripheral blood. The adjusted population attributable fraction of 12.8% (95% confidence interval, 1.5%-22.8%) indicated that approximately 3% of MTCT could be prevented if acute chorioamnionitis was eliminated. We suggest that further research on the role of antimicrobial treatment in the prevention of chorioamnionitis and the reduction of peripartum MTCT needs to be performed.

Objectives: To evaluate the effect of vaginal lavage with diluted chlorhexidine on mother-to child transmission of HIV (MTCT) in a breastfeeding population., Methods: This prospective clinical trial was conducted in a governmental hospital in Mombasa, Kenya. On alternating weeks, women were allocated to non-intervention or to intervention consisting of vaginal lavage with 120 ml 0.2% chlorhexidine, later increased to 0.4%, repeated every 3 h from admission to delivery. Infants were tested for HIV by DNA polymerase chain reaction within 48 h and at 6 and 14 weeks of life., Results: Enrolment and follow-up data were available for 297 and 309 HIV-positive women, respectively, in the non-lavage and the lavage groups. There was no evidence of a difference in intrapartum MTCT (17.2 versus 15.9%, OR 0.9, 95% CI 0.6-1.4) between the groups. Lavage solely before rupture of the membranes tended towards lower MTCT with chlorhexidine 0.2% (OR 0.6, 95% CI 0.3-1.1), and even more with chlorhexidine 0.4% (OR 0.1, 95% CI 0.0-0.9)., Conclusion: The need remains for interventions reducing MTCT without HIV testing, often unavailable in countries with a high prevalence of HIV. Vaginal lavage with diluted chlorhexidine during delivery did not show a global effect on MTCT in our study. However, the data suggest that lavage before the membranes are ruptured might be associated with a reduction of MTCT, especially with higher concentrations of chlorhexidine.

This article aimed to examine the association between maternal and infant HIV infection and low birth weight (LBW <2500 grams). Data from 8563 singleton liveborns in Mombasa, Kenya, were analysed. Maternal HIV infection was found in 14.1% of the women and 9.6% of neonates had a birth weight of <2500 grams. In multivariate analysis, maternal HIV infection was independently associated with LBW (RR=1.46, 95% CI=1.20-1.79, P =0.0002). Maternal age, primiparity, sex of the baby, religion, syphilis infection, anaemia and previous history of stillbirth were also independently associated with LBW (RR: 1.32, 2.19, 1.44, 1.56, 1.61, 1.31 and 1.69, respectively). The rate of intra-uterine HIV transmission was 5.1% and 20.1% of the exposed infants were infected during the intrapartum period. Intrapartum infected infants had a relative risk of LBW of 1.95 (95% CI=1.18-2.87, P <0.01) compared to uninfected children, whereas the birth weight of infants infected in utero was not different from uninfected infants (RR=1.18, 95% CI=0.56-2.60, P=0.630). HIV infected mothers are more likely to have small babies, even after controlling for possible confounding factors. Low birth weight babies were more at risk for peripartum HIV transmission, but further research is needed to study mechanisms of transmission in relation to birth weight.

Background: The correlation between the presence of HIV-1 in maternal cervicovaginal secretions and in the infant's oro-pharyngal secretions at birth, and mother-to-child HIV transmission (MTCT) were examined to obtain a better understanding of its mechanism., Methods: Women without medical and obstetrical complications, living within a reasonable distance of the government hospital in Mombasa, Kenya, were recruited after informed consent. Maternal and infant characteristics were collected. Polymerase chain reaction was used to detect HIV-1 in cervico-vaginal and oro-pharyngal secretions. Infants were tested for HIV-1 by polymerase chain reaction within 48 h and at 6 weeks after delivery., Results: Between April 1998 and April 1999, 228 woman-infant pairs were included in the study. HIV-1 DNA in cervico-vaginal secretions was independently associated with HIV-1 maternal viral load and with infant birth-weight, whereas HIV-1 RNA was associated with maternal viral load and maternal age. HIV-1 DNA in the oropharyngal secretions was also independently associated with maternal viral load. MTCT rate at the age of 6 weeks was 23.6%. Intrapartum and early postpartum HIV transmission was independently associated with maternal viral load [adjusted odds ratio (OR), 1.6; 95% confidence interval (CI),1.0-2.7], detection of HIV-1 RNA in cervico-vaginal secretions (adjusted OR, 3.2; 95% CI, 1.5-7.3) and of HIV-1 DNA in oro-pharyngeal secretions (adjusted OR, 3.2; 95% CI, 1.1-9.0)., Discussion: As far as is known, this is the first study showing that infant exposure to HIV-1 in the birth canal and the presence of HIV-infected cells in the infant's oropharyngeal cavity are independently associated with intrapartum and early postpartum MTCT. It supports the hypothesis that MTCT could occur through the oral route.

Objectives: To determine the incidence of hospital admissions for adverse events related to drug therapy, and to assess whether these drug-related admissions (DRAs) could have been reasonably prevented., Setting: A tertiary teaching hospital., Design and Patients: Prospective assessment of all admissions through the emergency department and resulting in a stay of more than 24 hours during 30 consecutive days in November and December 1994 to determine if the admission was related to drug therapy. Cases of intentional overdose were excluded., Main Outcome Measures: The number, type, causality and avoidability of drug-related admissions., Results: Of 965 admissions, 55 (5.7%) were assessed as being drug-related. Drug-related admissions (DRAs) were designated possibly (38%), probably (46%) or definitely (16%) drug-related; caused by prescribing factors (26%), patient noncompliance (27%) and adverse drug reactions (47%); and classified as definitely (5.5%), possibly (60.0%) and not (34.5%) avoidable. The estimated annual cost to the hospital for all DRAs was $3,496,956 and for unavoidable DRAs was $1,629,494., Conclusion: The DRA rate we found lies around the middle of the range of other published rates. Few DRAs were judged definitely avoidable and over one-third were unavoidable. Nevertheless, the largest proportion were judged possibly avoidable. As the drugs identified in this study are clearly needed in the community, efforts to reduce DRAs must concentrate on education, counselling and monitoring of drug therapy.