Breastfeeding in women with HIV
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Biomedical subjects
Publications and source records attributed to J Kreiss.
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CONTEXT: Transmission of human immunodeficiency virus type 1 (HIV-1) is known to occur through breastfeeding, but the magnitude of risk has not been precisely defined. Whether breast milk HIV-1 transmission risk exceeds the potential risk of formula-associated diarrheal mortality in developing countries is unknown. OBJECTIVES: To determine the frequency of breast milk transmission of HIV-1 and to compare mortality rates and HIV-1-free survival in breastfed and formula-fed infants. DESIGN AND SETTING: Randomized clinical trial conducted from November 1992 to July 1998 in antenatal clinics in Nairobi, Kenya, with a median follow-up period of 24 months. PARTICIPANTS: Of 425 HIV-1-seropositive, antiretroviral-naive pregnant women enrolled, 401 mother-infant pairs were included in the analysis of trial end points. INTERVENTIONS: Mother-infant pairs were randomized to breastfeeding (n = 212) vs formula feeding arms (n = 213). MAIN OUTCOME MEASURES: Infant HIV-1 infection and death during the first 2 years of life, compared between the 2 intervention groups. RESULTS: Compliance with the assigned feeding modality was 96% in the breastfeeding arm and 70% in the formula arm (P<.001). Median duration of breastfeeding was 17 months. Of the 401 infants included in the analysis, 94% were followed up to HIV-1 infection or mortality end points: 83% for the HIV-1 infection end point and 93% to the mortality end point. The cumulative probability of HIV-1 infection at 24 months was 36.7% (95% confidence interval [CI], 29.4%-44.0%) in the breastfeeding arm and 20.5% (95% CI, 14.0%-27.0%) in the formula arm (P = .001). The estimated rate of breast milk transmission was 16.2% (95% CI, 6.5%-25.9%). Forty-four percent of HIV-1 infection in the breastfeeding arm was attributable to breast milk. Most breast milk transmission occurred early, with 75% of the risk difference between the 2 arms occurring by 6 months, although transmission continued throughout the duration of exposure. The 2-year mortality rates in both arms were similar (breastfeeding arm, 24.4% [95% CI, 18.2%-30.7%] vs formula feeding arm, 20.0% [95% CI, 14.4%-25.6%]; P = .30). The rate of HIV-1-free survival at 2 years was significantly lower in the breastfeeding arm than in the formula feeding arm (58.0% vs 70.0%, respectively; P = .02). CONCLUSIONS: The frequency of breast milk transmission of HIV-1 was 16.2% in this randomized clinical trial, and the majority of infections occurred early during breastfeeding. The use of breast milk substitutes prevented 44% of infant infections and was associated with significantly improved HIV-1-free survival.
The occurrence of clinical manifestations associated with primary human immunodeficiency virus type 1 (HIV-1) infection was evaluated in a prospective cohort study of female sex workers in Mombasa, Kenya. Among 103 women who seroconverted to HIV-1, fever, vomiting, diarrhea, headache, arthralgia, myalgia, skin rash, swollen lymph nodes, extrainguinal lymphadenopathy, inguinal lymphadenopathy, and vaginal candidiasis were noted significantly more frequently at visits in which seroconversion first became evident. Eighty-one percent of seroconverting women had >/=1 of these 11 symptoms or signs. Among 44% of the women, the acute illness was severe enough to prevent them from working. Having >/=2 of 6 selected symptoms and signs yielded a sensitivity of 51%, specificity of 83%, positive likelihood ratio of 3.2, and negative likelihood ratio of 0.5 for acute HIV-1 infection. The recognition of primary HIV-1-infection illness in high-risk populations and subsequent risk-reduction counseling could potentially reduce secondary HIV-1 transmission during this highly infectious period.
OBJECTIVE: To determine the prevalence, incidence, and correlates of HIV-1 infection in a cohort of east African trucking company employees. METHODS: HIV-1-seronegative trucking company employees were enrolled in a prospective cohort study and evaluated at 3 monthly intervals for HIV-1 seroconversion, sexually transmitted diseases, and sexual behavior. RESULTS: The baseline seroprevalence of HIV-1 among 1500 trucking company employees was 17.8%. Among 752 HIV-1-seronegative men who were followed, the HIV-1 annual seroincidence was 3.1%. In univariate analysis, HIV-1 acquisition was associated with age under 25 years, 10 years or less of sexual activity, occupation as a driver/driver's assistant, occupational travel for more than 14 days per month, religion other than Christian or Muslim, uncircumcised status, sex with a prostitute, sex with a girlfriend/casual partner, extramarital sex, and enrollment seropositivity to Treponema pallidum, Haemophilus ducreyi, and Herpes simplex virus type 2 (all P values < or = 0.05). Using multivariate analysis, HIV-1 acquisition was independently associated with 10 years or less of sexual activity (hazard rate ratio (HRR) 2.0, 95% confidence interval (CI) 1.0-4.3), occupation as a driver/driver's assistant (HRR 3.9, 95% CI 1.7-9.0), religion other than Christian or Muslim (HRR 6.1, 95% CI 1.4-25.7), uncircumcised status (HRR 2.3, 95% CI 1.0-5.0), and unprotected sex with a prostitute (HRR 2.8, 95% CI 1.1-7.0). CONCLUSIONS: Trucking company employees had a high HIV-1 seroprevalence rate at enrollment and a high HIV-1 seroincidence during follow-up. Risk factors for HIV-1 seroconversion included years of sexual activity, occupation, religion, uncircumcised status, and unprotected sex with a prostitute. This population is an appropriate target for HIV-1 prevention trials and behavioral interventions.
OBJECTIVE: This study was undertaken to determine the effects of human immunodeficiency virus 1 infection on the clinical presentation, severity, causal organisms, and response to ambulatory therapy of pelvic inflammatory disease. STUDY DESIGN: Women 18 to 40 years old with lower abdominal pain for <1 month were recruited. Participants underwent a standardized questionnaire, physical examination, screening for human immunodeficiency virus 1 and other sexually transmitted infections, and endometrial biopsy to detect plasma cell endometritis. Reevaluations were performed at 1 and 4 weeks to assess response to therapy. RESULTS: Among 162 women with adequate endometrial biopsy specimens 63 (39%) had histologically confirmed endometritis. Endometritis was more frequent among women who were seropositive for human immunodeficiency virus 1 than among women who were seronegative (odds ratio, 3.0; 95% confidence interval, 1.5-5.9). Infections with either Neisseria gonorrhoeae or Chlamydia trachomatis, or both, were least common and bacterial vaginosis was most common among human immunodeficiency virus 1-infected women with CD4 T-lymphocyte counts <400 cells/microL (P <. 04, P <.03, respectively). After oral antibiotic therapy, similar proportions of both women who were seropositive and women who were seronegative for human immuno-deficiency virus 1 had a >/=75% reduction in clinical severity score (81% vs 86%). CONCLUSION: Outpatient treatment of pelvic inflammatory disease was successful regardless of human immunodeficiency virus 1 serostatus.
If human immunodeficiency virus type 1 (HIV-1) vaccines are to be highly effective, it is essential to understand the virologic factors that contribute to HIV-1 transmission. It is likely that transmission is determined, in part, by the genotype or phenotype (or both) of infectious virus present in the index case, which in turn will influence the quantity of virus that may be exchanged during sexual contact. Transmission may also depend on the fitness of the virus for replication in the exposed individual, which may be influenced by whether a virus encounters a target cell that is susceptible to infection by that specific variant. Of interest, our data suggest that the complexity of the virus that is transmitted may be different in female and male sexual exposures.
A prospective cohort study was conducted to examine the relationship between vaginal colonization with lactobacilli, bacterial vaginosis (BV), and acquisition of human immunodeficiency virus type 1 (HIV-1) and sexually transmitted diseases in a population of sex workers in Mombasa, Kenya. In total, 657 HIV-1-seronegative women were enrolled and followed at monthly intervals. At baseline, only 26% of women were colonized with Lactobacillus species. During follow-up, absence of vaginal lactobacilli on culture was associated with an increased risk of acquiring HIV-1 infection (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.2-3.5) and gonorrhea (HR, 1.7; 95% CI, 1.1-2.6), after controlling for other identified risk factors in separate multivariate models. Presence of abnormal vaginal flora on Gram's stain was associated with increased risk of both HIV-1 acquisition (HR, 1.9; 95% CI, 1.1-3.1) and Trichomonas infection (HR, 1.8; 95% CI, 1.3-2.4). Treatment of BV and promotion of vaginal colonization with lactobacilli should be evaluated as potential interventions to reduce a woman's risk of acquiring HIV-1, gonorrhea, and trichomoniasis.
PCR is a highly sensitive method for the detection of human immunodeficiency virus type 1 (HIV-1) nucleic acids in blood mononuclear cells and plasma. However, blood separation techniques require extensive laboratory support systems and are difficult when a limited volume of blood is available, which is often the case for infants. The use of blood samples stored on filter paper has many advantages for the detection of perinatal HIV-1 infection, but current methods require extraction and purification of target DNA prior to PCR amplification. We report a highly sensitive and rapid method for the extraction and detection of HIV-1 DNA in infant blood samples stored on filter papers. Because this rapid protocol does not involve steps for the removal of potential inhibitors of the PCR, the highest sensitivity is achieved by testing the filter paper lysate in quadruplicate. Assays for HIV-1 DNA were done by using nested PCR techniques that amplify HIV-1 gag DNA from blood spot samples on filter paper and from corresponding viably frozen mononuclear cells separated from venous blood samples obtained from 111 infants born to HIV-1-seropositive mothers. PCR results with blood from filter papers showed 100% specificity (95% confidence internal [CI] 93.1 to 100%) and 96% (95% CI, 88.65 to 98.9%) and 88% (95% CI, 79.2 to 94.5%) sensitivity (for quadruplicate and duplicate tests, respectively) compared to PCR results with blood mononuclear cells. Moreover, this method could detect HIV-1 sequences of multiple subtypes.
To determine the effect of human immunodeficiency virus type 1 (HIV-1) infection upon pelvic inflammatory disease (PID), a laparoscopic study of acute PID was conducted in Nairobi, Kenya. Subjects underwent diagnostic laparoscopy, HIV-1 serology, and testing for sexually transmitted diseases. Of the 133 women with laparoscopically verified salpingitis, 52 (39%) were HIV-1-seropositive. Tubo-ovarian abscesses (TOA) were found in 33% of HIV-1-infected and 15% of HIV-1-uninfected women (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.2-6.5). Among seropositive women, TOA was found in 55% of those with CD4 cell percent <14% vs. 28% with CD4 cell percent>14% (OR 3.1, 95% CI 0.6-15.3). Neisseria gonorrhoeae was detected in 37 women (28%) and Chlamydia trachomatis in 12 (9%); neither was significantly related to HIV-1 seropositivity. Length of hospitalization was not affected by HIV-1 serostatus overall but was prolonged among HIV-1-infected women with CD4 cell percent <14%. Among patients with acute salpingitis, likelihood of TOA was related to HIV-1 infection and advanced immunosuppression. In general, HIV-1-seropositive women with acute salpingitis responded well to treatment.
To examine associations between method of contraception, sexually transmitted diseases (STDs), and incident human immunodeficiency virus type 1 (HIV-1) infection, a prospective observational cohort study was done among female sex workers attending a municipal STD clinic in Mombasa, Kenya. Demographic and behavioral factors significantly associated with HIV-1 infection included type of workplace, condom use, and parity. In multivariate models, vulvitis, genital ulcer disease, vaginal discharge, and Candida vaginitis were significantly associated with HIV-1 seroconversion. Women who used depo medroxyprogesterone acetate (DMPA) had an increased incidence of HIV-1 infection (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.4-3.4). In a multivariate model controlling for demographic and exposure variables and biologic covariates, the adjusted HR for HIV-1 infection among DMPA users was 2.0 (CI, 1.3-3.1). There was a trend for an association between use of high-dose oral contraceptive pills and HIV-1 acquisition (HR, 2.6; CI, 0.8-8.5).
OBJECTIVES: To assess low abdominal pain, yellow vaginal discharge, other symptoms and signs, and demographic and behavioural variables as predictors for cervical or vaginal infection. METHODS: A cross sectional study of women attending gynaecology and family planning clinics in Lima, Peru was undertaken. 630 consecutive eligible female patients with chief or elicited complaints of yellow vaginal discharge, low abdominal pain, or both were interviewed and examined, together with a comparable reference group without these complaints. Vaginal specimens were tested for trichomoniasis and bacterial vaginosis. Endocervical specimens were tested for Neisseria gonorrhoeae and Chlamydia trachomatis using the ligase chain reaction. RESULTS: Infections found included chlamydial infection in 69 women (10.9%), gonorrhoea in 10 (1.6%), and either infection in 77 (12.2%); trichomoniasis in 46 (7.3%), bacterial vaginosis in 189 (30%), and either infection in 209 (33.2%). Cervical infection with C trachomatis and/or N gonorrhoeae was independently associated with history of a new sex partner within the last 3 months, more than one sex partner within the last year, use of condoms never or in less than 50% of sex acts, history of sex partner with STD within the last year; with symptoms of persistent low abdominal pain and of yellow vaginal discharge; and with signs of profuse and yellow vaginal discharge, cervical ectopy, easily induced endocervical bleeding, or brown cervical secretion. Using these findings, an algorithm was created that had a positive predictive value (PPV) of 36% for cervical infection among women reporting chief or elicited complaint of this abnormal vaginal discharge and a PPV of 25% among those without a complaint. A chief complaint of yellow vaginal discharge had a PPV of 50% for trichomoniasis or bacterial vaginosis. Among women without a chief complaint of yellow vaginal discharge, clinical findings of yellow vaginal discharge had a PPV of 55%. CONCLUSIONS: Where economic and technical constraints preclude testing, clinical findings and risk assessment are helpful in detecting vaginal and cervical infections. Several demographic, behavioural, clinical, and laboratory variables were predictive of infection in this population.
An estimated one-third to one-half of vertical transmission of human immunodeficiency virus type 1 (HIV-1) worldwide is due to breastfeeding. The exact frequency of breast milk HIV-1 transmission is unknown, but it has been estimated to be 14% in the setting of established maternal HIV-1 infection and 29% in the setting of acute maternal infection. The timing of breast milk transmission during the course of lactation also remains unknown, but two studies have found an association between duration of breastfeeding and risk of infant infection. In one such study, prolonged breastfeeding for 15 months or longer was associated with a twofold increased transmission risk. Human immunodeficiency virus type 1 DNA can be detected in over 50% of breast milk samples and is correlated with CD4 depletion and vitamin A deficiency. The presence of breast milk HIV-1 provirus is associated with increased transmission risk. Many current intervention strategies to prevent vertical transmission of HIV-1 are aimed at in utero or perinatal transmission. In developing countries in which breastfeeding by HIV-1 infected women is recommended practice, additional intervention strategies to reduce breast milk transmission warrant evaluation.
A great deal of progress has been made in our understanding of mother-to-child transmission of HIV-1. Standardization of case definitions and transmission rate calculation methodologies, and a broader array of diagnostic options for detection of infant HIV-1 infection, will enhance our ability to evaluate and compare cohorts worldwide. In the next decade, several intervention studies should be completed. Carefully designed intervention studies have the potential both to determine which interventions are effective as well as to add to our understanding of vertical transmission of HIV-1. Regional differences in vertical transmission rates reflect a variety of viral, host, and obstetric factors. Intervention strategies will probably need to be regionally designed, taking into consideration these factors. Further research on timing and correlates of vertical transmission is necessary to determine the extent to which specific clinical trials can be extrapolated to public health policy.
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BACKGROUND: A cross-sectional survey was performed to determine the seroprevalence and correlates of human immunodeficiency virus (HIV) infection among long-distance truck drivers in Kenya. METHODS: Truck drivers along the Mombasa-Nairobi highway were enrolled at a roadside research clinic. A standardized interview and serologic evaluation for HIV and syphilis were conducted. RESULTS: We enrolled 970 truck drivers and their assistants of whom 257 (27%) had HIV antibodies. In univariate analysis, HIV infection was correlated with older age, non-Kenyan nationality, Christian religion, longer duration of truck driving, travel outside of Kenya, less frequent visits to wives, and more frequent visits to prostitutes. Uncircumcised status, history of genital ulcer disease or urethritis during the previous 5 years, and a positive Treponema pallidum hemagglutination assay for syphilis were each associated with positive HIV serostatus. Univariate correlates of uncircumcised status included younger age, non-Kenyan nationality, Christian religion, travel outside of Kenya, and less frequent visits to prostitutes. There was a significant association between uncircumcised status and 5-year history of genital ulcer disease or serologic evidence of syphilis, but not with 5-year history of urethritis. In multivariate analysis, HIV infection was independently associated with uncircumcised status (adjusted odds ratio [OR], 4.9; 95% confidence interval [CI], 2.8 to 8.4), history of genital ulcer disease (adjusted OR, 2.4; 95% CI, 1.5 to 4.1), history of urethritis (adjusted OR, 1.8; 95% CI, 1.1 to 2.9), more frequent sex with prostitutes (more than once per month; adjusted OR, 1.7; 95% CI, 1.1 to 2.8), and positive T pallidum hemagglutination assay (adjusted OR, 1.2; 95% CI, 1.0 to 1.4). The attributable risk percentage for the association between HIV and uncircumcised status was 70%, and the population attributable risk was 25%. CONCLUSIONS: Truck drivers in east Africa are at high risk of HIV infection. The strongest correlates of HIV seropositivity were uncircumcised status and history of both ulcerative and nonulcerative sexually transmitted diseases.
Four hundred female sex workers attending a sexually transmitted disease clinic in Lima, Peru, were interviewed for demographic information and medical, contraceptive, and sexual practice histories. Cervical cultures were done for Neisseria gonorrhoeae and Chlamydia trachomatis, and serum was tested for antibodies to human immunodeficiency virus, human T cell lymphotropic virus type I (HTLV-I), Treponema pallidum, C. trachomatis, herpes simplex virus type 2 (HSV-2), and Haemophilus ducreyi. The prevalence of HTLV-I increased with duration of prostitution from 3.6% (< 3 years) to 9.3% (3-6 years) to 15.9% (> 6 years; P < .01). After adjustment for duration of prostitution, reduced risk of HTLV-I was significantly correlated with condom use for more than half of all sexual exposures for > 3 years (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.13-0.89). Further adjusting for condom use, HTLV-I seropositivity was associated with C. trachomatis (OR, 3.7; 95% CI, 1.4-13.2) and with antibody to HSV-2 (OR, 3.7; 95% CI, 0.5-29.6). Thus, duration of prostitution, lack of consistent condom use, and past infection with C. trachomatis were significantly associated with HTLV-I seropositivity.
A cross-sectional study was conducted among prostitutes in Nairobi, Kenya, to determine the prevalence and correlates of cervical human immunodeficiency virus (HIV) DNA. Ninety-two HIV-seropositive prostitutes were evaluated during 137 clinic visits. Cervical HIV DNA was detected by polymerase chain reaction assay in 36 (39%) women at initial visits and in 40 (44%) women at any visit. There was a significant correlation between cervical HIV and microscopic evidence of cervical inflammation (odds ratio [OR], 7.2; 95% confidence interval [CI], 2.1-24.6). Using multivariate analysis to adjust for possible confounding, the adjusted OR for the association between cervical inflammation and cervical HIV DNA was 8.7 (95% CI, 2.0-37.2). Conditions associated with cervical inflammation are associated with the detection of HIV proviral DNA. Whether such conditions lead to increased infectivity remains to be proven.