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Barbra A Richardson

Publications and source records attributed to Barbra A Richardson.

At least 19 recordsLinked to original sources
PubMed2007

Statistical methods for determining the accuracy of quantitative polymerase chain reaction-based tests.

Quantitative polymerase chain reaction (PCR)-based tests are used in several different scientific fields to determine levels of a target DNA sequence of interest (the target molecule). The accuracy of quantitative PCR-based tests can be assessed by using the assay to determine the number of copies of the target molecule in a sample with a known concentration of the target molecule. For example, a sample with a known concentration of a target DNA sequence is serially diluted into replicate aliquots and these are tested to determine if the observed quantity of the target is close to the expected quantity (given the concentration in the original sample and the dilution). Statistical methods that are conventionally used to assess the accuracy of these assays do not take into account the variability in the number of target molecules in each aliquot from the original sample. We develop methods that take into account this extra variation and which determine the accuracy of quantitative PCR-based tests in estimating the number of target molecules based on a set of assays of serial dilutions from an original sample with a known concentration of target molecules. These methods are applied to data from an experiment to test the accuracy of a real-time PCR assay at low HIV-1 DNA copy levels.

DNA, Viral↗
PubMed2007

Hormonal contraception and the risk of HIV acquisition.

BACKGROUND: Combined oral contraceptives (COC) and depot-medroxyprogesterone acetate (DMPA) are among the most widely used family planning methods; their effect on HIV acquisition is not known. OBJECTIVE: To evaluate the effect of COC and DMPA on HIV acquisition and any modifying effects of other sexually transmitted infections. METHODS: This multicenter prospective cohort study enroled 6109 HIV-uninfected women, aged 18-35 years, from family planning clinics in Uganda, Zimbabwe and Thailand. Participants received HIV testing quarterly for 15-24 months. The risk of HIV acquisition with different contraceptive methods was assessed (excluding Thailand, where there were few HIV cases). RESULTS: HIV infection occurred in 213 African participants (2.8/100 woman-years). Use of neither COC [hazard ratio (HR), 0.99; 95% confidence interval (CI), 0.69-1.42] nor DMPA (HR, 1.25; 95% CI, 0.89-1.78) was associated with risk of HIV acquisition overall, including among participants with cervical or vaginal infections. While absolute risk of HIV acquisition was higher among participants who were seropositive for herpes simplex virus 2 (HSV-2) than in those seronegative at enrolment, among the HSV-2-seronegative participants, both COC (HR, 2.85; 95% CI, 1.39-5.82) and DMPA (HR, 3.97; 95% CI, 1.98-8.00) users had an increased risk of HIV acquisition compared with the non-hormonal group. CONCLUSIONS: No association was found between hormonal contraceptive use and HIV acquisition overall. This is reassuring for women needing effective contraception in settings of high HIV prevalence. However, hormonal contraceptive users who were HSV-2 seronegative had an increased risk of HIV acquisition. Additional research is needed to confirm and explain this finding.

Adult↗
PubMed2007

Associations between intravaginal practices and bacterial vaginosis in Kenyan female sex workers without symptoms of vaginal infections.

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.

Adult↗
PubMed2006

HIV-1 disease progression in breast-feeding and formula-feeding mothers: a prospective 2-year comparison of T cell subsets, HIV-1 RNA levels, and mortality.

BACKGROUND: There is conflicting evidence regarding the effects of breast-feeding on maternal mortality from human immunodeficiency virus type 1 (HIV-1) infection, and little is known about the effects of breast-feeding on markers of HIV-1 disease progression. METHODS: HIV-1-seropositive women were enrolled during pregnancy and received short-course zidovudine. HIV-1 RNA levels and CD4 cell counts were determined at baseline and at months 1, 3, 6, 12, 18, and 24 postpartum and were compared between breast-feeding and formula-feeding mothers. RESULTS: Of 296 women, 98 formula fed and 198 breast-fed. At baseline, formula-feeding women had a higher education level and prevalence of HIV-1-related illness than did breast-feeding women; however, the groups did not differ with respect to CD4 cell counts and HIV-1 RNA levels. Between months 1 and 24 postpartum, CD4 cell counts decreased 3.9 cells/ microL/month (P<.001), HIV-1 RNA levels increased 0.005 log(10) copies/mL/month (P=.03), and body mass index (BMI) decreased 0.03 kg/m(2)/month (P<.001). The rate of CD4 cell count decline was higher in breast-feeding mothers (7.2 cells/ microL/month) than in mothers who never breast-fed (4.0 cells/ microL/month) (P=.01). BMI decreased more rapidly in breast-feeding women (P=.04), whereas HIV-1 RNA levels and mortality did not differ significantly between breast-feeding and formula-feeding women. CONCLUSIONS: Breast-feeding was associated with significant decreases in CD4 cell counts and BMI. HIV-1 RNA levels and mortality were not increased, suggesting a limited adverse impact of breast-feeding in mothers receiving extended care for HIV-1 infection.

Adult↗
PubMed2006

High levels of cervical HIV-1 RNA during early HIV-1 infection.

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).

Cervix Uteri↗
PubMed2006

Evidence for persistent, occult infection in neonatal macaques following perinatal transmission of simian-human immunodeficiency virus SF162P3.

To model human immunodeficiency virus (HIV) perinatal transmission, we studied infection of simian-human immunodeficiency virus (SHIV) SF162P3 in 10 pregnant Macaca nemestrina females and their offspring. Four of nine infants born to and suckled by these dams had evidence of infection, a transmission rate of 44.4% (95% confidence interval, 13.7% to 78.8%). We quantified transplacentally acquired and de novo Env-specific immunoglobulin G (IgG), IgM, and neutralizing antibodies in newborns. Transmission of escape variants was confirmed. In utero infection (n = 1) resulted in high viremia, depletion of peripheral CD4+ T cells, and rapid evolution of env in blood and tissues. Peripartum or postpartum SHIV infection (n = 3) resulted in postacute viral control that was undetectable by very sensitive multiplex PCR, despite increasing antibodies. Seropositive infants with highly controlled viremia had homogeneous peripheral blood env sequences, and their tissues had <3 copies per million cells. A high incidence of seropositive virus-low or -negative SHIV infection in infant macaques has implications for HIV type 1 perinatal transmission and detection.

Animals↗
PubMed2006

Quantification of genital human immunodeficiency virus type 1 (HIV-1) DNA in specimens from women with low plasma HIV-1 RNA levels typical of HIV-1 nontransmitters.

Studies of human immunodeficiency virus type 1 (HIV-1) transmission suggest that genital HIV-1 RNA and DNA may both be determinants of HIV-1 infectivity. Despite its potential role in HIV-1 transmission, there are limited quantitative data on genital HIV-1 DNA. Here we validated an in-house real-time PCR method for quantification of HIV-1 DNA in genital specimens. In reactions with 100 genomes to 1 genome isolated from a cell line containing one HIV-1 provirus/cell, this real-time PCR assay is linear and agrees closely with a commercially available real-time PCR assay specific for a cellular housekeeping gene. In mock genital samples spiked with low numbers of HIV-1-infected cells such that the expected HIV-1 DNA copy number/reaction was 100, 10, or 5, the average copy number/reaction was 80.2 (standard deviation [SD], 28.3), 9.1 (SD, 5.4), or 3.1 (SD, 2.1), respectively. We used this method to examine genital HIV-1 DNA levels in specimens from women whose low plasma HIV-1 RNA levels are typical of HIV-1 nontransmitters. The median HIV-1 DNA copy number in endocervical secretions from these women (1.8 HIV-1 DNA copies/10,000 cells) was lower than that for women with higher plasma HIV-1 RNA levels (16.6 HIV-1 DNA copies/10,000 cells) (P=0.04), as was the median HIV-1 DNA copy number in vaginal secretions (undetectable versus 1.0 HIV-1 DNA copies/10,000 cells). These data suggest that women with low plasma HIV-1 RNA and thus a predicted low risk of HIV-1 transmission have low levels of genital HIV-1 cell-associated virus. The assay described here can be utilized in future efforts to examine the role of cell-associated HIV-1 in transmission.

Adult↗
PubMed2006

HIV-1 acquisition and disease progression are associated with decreased high-risk sexual behaviour among Kenyan female sex workers.

BACKGROUND: Changes in sexual risk behaviour may occur following HIV-1 infection. OBJECTIVE: To test the hypothesis that HIV-1 seroconversion and disease progression are associated with changes in risk behaviours, using data from a cohort of Kenyan female sex workers (FSWs). METHODS: HIV-1-seronegative FSWs were enrolled in a prospective cohort study of risk factors for HIV-1 acquisition. At monthly visits, standardized interviews were conducted to assess sexual risk behaviour and HIV-1 serologic testing was performed. Seroconverters were invited to continue with follow-up. Between 1993 and 2004 (when antiretroviral therapy was introduced in the cohort), 265 women seroconverted for HIV-1 (incidence 7.7/100 person-years) and were included in this analysis. RESULTS: Unprotected intercourse was reported at 546/2037 (27%) pre-seroconversion visits versus 557/3732 (15%) post-seroconversion visits (P < 0.001). These findings remained significant after adjustment for potential confounding factors [adjusted odds ratio (AOR) 0.69; 95% confidence interval (CI), 0.55-0.86]. Compared with HIV-1-seronegative women, there was a progressive stepwise decrease in unprotected intercourse among HIV-1-seropositive women with CD4 cell counts > or = 500 (AOR, 0.93; 95% CI, 0.62-1.39), 200-499 (AOR, 0.58; 95% CI, 0.41-0.82) and < 200 cells/microl (AOR, 0.45; 95% CI, 0.25-0.82). Decreases in unprotected intercourse reflected increases in both abstinence and 100% condom use. Women also reported fewer partners and fewer episodes of intercourse after HIV-1 seroconversion. CONCLUSIONS: HIV-1 seroconversion and disease progression were associated with decreases in sexual risk behaviour among Kenyan FSWs.

AIDS Serodiagnosis↗
PubMed2006

Domestic violence and prevention of mother-to-child transmission of HIV-1.

OBJECTIVES: To determine the prevalence of life-time domestic violence by the current partner before HIV-1 testing, its impact on the uptake of prevention of mother-to-child transmission (PMTCT) interventions and frequency after testing. DESIGN: A prospective cohort. METHODS: Antenatally, women and their partners were interviewed regarding physical, financial, and psychological abuse by the male partner before HIV-1 testing and 2 weeks after receiving results. RESULTS: Before testing, 804 of 2836 women (28%) reported previous domestic violence, which tended to be associated with increased odds of HIV-1 infection [univariate odds ratio (OR) 1.7, 95% confidence interval (CI) 1.3-2.2; P < 0.0001, adjusted OR 1.2, 95% CI 0.9-1.6; P = 0.1], decreased odds of coming with partners for counseling (adjusted OR 0.7, 95% CI 0.5-1.0; P = 0.04), and decreased odds of partner notification (adjusted OR 0.7, 95% CI 0.5-1.1; P = 0.09). Previous domestic violence was not associated with a reduced uptake of HIV-1 counseling, HIV-1 testing, or nevirapine. After receiving results, 15 out of 1638 women (0.9%) reported domestic violence. After notifying partners of results, the odds of HIV-1-seropositive women reporting domestic violence were 4.8 times those of HIV-1-seronegative women (95% CI 1.4-16; P = 0.01). Compared with women, men reported similar or more male-perpetrated domestic violence, suggesting a cultural acceptability of violence. CONCLUSION: Domestic violence before testing may limit partner involvement in PMTCT. Although infrequent, immediate post-test domestic violence is more common among HIV-1-infected than uninfected women. Domestic violence prevention programmes need to be integrated into PMTCT, particularly for HIV-1-seropositive women.

Child↗
PubMed2006

A comparison of genital HIV-1 shedding and sexual risk behavior among Kenyan women based on eligibility for initiation of HAART according to WHO guidelines.

BACKGROUND: Guidelines for initiating antiretrovirals are based on markers of advanced disease and are not directly linked to markers of HIV-1 transmission such as viral shedding. METHODS: We evaluated genital HIV-1 shedding and risk behavior among 650 antiretroviral-naïve women stratified by WHO criteria for initiating antiretrovirals based on CD4 count and symptoms. RESULTS: Genital HIV-1 concentrations increased in stepwise fashion with declining CD4 counts and the presence of symptoms. Compared with the reference group (asymptomatic with CD4 >350 cells/microL), those with advanced immunosuppression (CD4 <200 cells/microL) had significantly higher cervical HIV-1 RNA concentrations (2.4 log10 copies/swab vs. 3.8 log10 copies/swab, P < 0.001). However, women with CD4 counts <200 cells/microL were also less likely than the reference group to report intercourse during the past week (58% vs. 26%, P < 0.001). CONCLUSIONS: Antiretroviral guidelines focusing on individuals with the most advanced immunosuppression will target those with the highest genital HIV-1 concentrations. However, individuals with less advanced immunosuppression also have high levels of genital HIV-1 and may be more sexually active. The effect of increased antiretroviral availability on the spread of HIV-1 might be enhanced by extending treatment, in addition to other risk reduction services, to those with less advanced disease.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Higher set point plasma viral load and more-severe acute HIV type 1 (HIV-1) illness predict mortality among high-risk HIV-1-infected African women.

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.

Adult↗
PubMed2006

HIV-1 infection alters the retinol-binding protein:transthyretin ratio even in the absence of the acute phase response.

The ratio of retinol-binding protein (RBP) to transthyretin (TTR) has been proposed as an indirect method with which to assess vitamin A status in the context of inflammation. Few studies have been conducted among adults, and none examined the effect of HIV-1 infection. Our goal was to assess the RBP:TTR ratio among adults, including the effects of HIV-1 and the acute phase response. We used data from a cross-sectional study of 600 Kenyan women, of whom 400 had HIV-1. The effect of vitamin A supplementation among the HIV-1-infected participants was subsequently assessed in a randomized trial. Among HIV-1-uninfected women without an acute phase response, a RBP:TTR cut-off value of 0.25 had approximately 80% sensitivity and specificity to detect vitamin A deficiency (retinol <0.70 micromol/L). No RBP:TTR cut-off value demonstrated both high sensitivity and specificity among HIV-1 infected women without evidence of inflammation. HIV-1 infection and advanced HIV-1 disease were associated with higher RBP:TTR ratios. The effect of HIV-1 was independent of the acute phase response, which also increased the RBP:TTR ratio. Serum retinol increased with vitamin A supplementation among those with a low RBP:TTR ratio, although the effect was small and was not present among those with concurrent inflammation. Thus, the RBP:TTR ratio has modest ability to predict vitamin A deficiency among healthy adults, but HIV-1 infection alters the ratio, even in the absence of the acute phase response. Our results raise questions about the utility of this measurement given the high prevalence of HIV-1 infection in areas where vitamin A deficiency is common.

Acute-Phase Reaction↗
PubMed2006

Neutralization escape variants of human immunodeficiency virus type 1 are transmitted from mother to infant.

Maternal passive immunity typically plays a critical role in protecting infants from new infections; however, the specific contribution of neutralizing antibodies in limiting mother-to-child transmission of human immunodeficiency virus type 1 is unclear. By examining cloned envelope variants from 12 transmission pairs, we found that vertically transmitted variants were more resistant to neutralization by maternal plasma than were maternal viral variants near the time of transmission. The vertically transmitted envelope variants were poorly neutralized by monoclonal antibodies b12 [corrected] 2G12, 2F5, and 4E10 individually or in combination. Despite the fact that the infant viruses were among the most neutralization resistant in the mother, they had relatively few glycosylation sites. Moreover, the transmitted variants elicited de novo neutralizing antibodies in the infants, indicating that they were not inherently difficult to neutralize. The neutralization resistance of vertically transmitted viruses is in contrast to the relative neutralization sensitivity of viruses sexually transmitted within discordant couples, suggesting that the antigenic properties of viruses that are favored for transmission may differ depending upon mode of transmission.

Antibodies, Monoclonal↗
PubMed2005

Breast milk HIV-1 suppression and decreased transmission: a randomized trial comparing HIVNET 012 nevirapine versus short-course zidovudine.

OBJECTIVE: To compare the effect of perinatal regimens of short-course nevirapine (HIVNET 012) and zidovudine [Thai-Centers for Disease Control and Prevention (CDC) regimen] on breast milk viral shedding and perinatal transmission during the first 6 weeks postpartum in a randomized clinical trial. DESIGN: Randomized clinical trial. METHODS: Pregnant HIV-1 seropositive women in Nairobi, Kenya who planned to breastfeed were randomized to HIVNET 012 or Thai-CDC regimens. Two to four breast milk samples were collected each week between delivery and 6 weeks postpartum. Breast milk HIV-1 RNA was quantified using the Gen-Probe TMA assay. Infants were tested for HIV-1 DNA at birth and 6 weeks. RESULTS: From March to October 2003, 76 women were enrolled and 795 breast milk samples were collected from 60 women who were randomized and followed after delivery. Between 3 and 21 days postpartum, nevirapine was associated with significantly greater suppression of breast milk log10 HIV-1 RNA: days 3 to 7 (1.98 versus 2.42, P = 0.1); days 8 to 14 (1.78 versus 2.48, P = 0.005); days 15 to 21 (1.90 versus 2.97, P = 0.003). At 6 weeks, the HIV-1 perinatal transmission rate was significantly lower among those who took nevirapine than zidovudine (6.8% versus 30.3%, P = 0.02). CONCLUSIONS: Compared to a peripartum zidovudine regimen, nevirapine was significantly more likely to decrease HIV-1 RNA in breast milk during the first week and through the third week postpartum following single-dose administration, and corresponded with decreased transmission risk at 6 weeks. Sustained breast milk HIV-1 suppression may contribute to the ability of nevirapine to decrease perinatal transmission of HIV-1.

Adult↗
PubMed2005

Subtype C Is associated with increased vaginal shedding of HIV-1.

The prevalence of human immunodeficiency virus (HIV)-1-infected cells and HIV-1 RNA levels in genital secretions and breast milk and the risk of mother-to-child transmission of HIV-1 were compared among subtypes A, C, and D in a Kenyan cohort. Pregnant women infected with subtype C were significantly more likely to shed HIV-1-infected vaginal cells than were those infected with subtype A or D (odds ratio [OR], 3.6 [95% confidence interval {CI}, 1.4-8.8]; P = .006). This relationship held after adjusting for age, CD4 cell count, and plasma HIV-1 RNA load (OR, 3.1 [95% CI, 1.1-8.6]; P = .03). These observations suggest that HIV-1 subtype influences mucosal shedding of HIV-1.

Colostrum↗
PubMed2005

Methods for assessing the accuracy of PCR-based tests: comparisons and extensions.

Polymerase chain reaction (PCR) based tests are commonly used to diagnose various infections. Such tests are assumed to be highly 'sensitive', however, no consensus definition of, or method for estimating, sensitivity exists. Hughes and Totten proposed that sensitivity be defined as a function of the number of target DNA molecules in the sample with specificity corresponding to the case where there is no target DNA molecule present. They then developed parametric, non-parametric and semi-parametric models for estimating the sensitivity curve. In this paper a general model is proposed that yields their three models as special cases when specificity is assumed to be 1.0. We also extend the general model to incorporate covariates. Simulation studies are used to compare the different estimators. The methods are applied to data from a PCR-based test for Mycoplasma genitalium.

Algorithms↗
PubMed2005

Female-to-male infectivity of HIV-1 among circumcised and uncircumcised Kenyan men.

BACKGROUND: A lack of male circumcision has been associated with increased risk of human immunodeficiency virus type 1 (HIV-1) acquisition in a number of studies, but questions remain as to whether confounding by behavioral practices explains these results. The objective of the present study was to model per-sex act probabilities of female-to-male HIV-1 transmission (i.e., infectivity) for circumcised and uncircumcised men, by use of detailed accounts of sexual behavior in a population with multiple partnerships. METHODS: Data were collected as part of a prospective cohort study of HIV-1 acquisition among 745 Kenyan truck drivers. Sexual behavior with wives, casual partners, and prostitutes was recorded at quarterly follow-up visits. Published HIV-1 seroprevalence estimates among Kenyan women were used to model HIV-1 per-sex act transmission probabilities. RESULTS: The overall probability of HIV-1 acquisition per sex act was 0.0063 (95% confidence interval, 0.0035-0.0091). Female-to-male infectivity was significantly higher for uncircumcised men than for circumcised men (0.0128 vs. 0.0051; P=.04). The effect of circumcision was robust in subgroup analyses and across a wide range of HIV-1 prevalence estimates for sex partners. CONCLUSIONS: After accounting for sexual behavior, we found that uncircumcised men were at a >2-fold increased risk of acquiring HIV-1 per sex act, compared with circumcised men. Moreover, female-to-male infectivity of HIV-1 in the context of multiple partnerships may be considerably higher than that estimated from studies of HIV-1-serodiscordant couples. These results may explain the rapid spread of the HIV-1 epidemic in settings, found throughout much of Africa, in which multiple partnerships and a lack of male circumcision are common.

Adult↗