B Richardson

Comparison of Human Immunodeficiency Virus Type 1 Viral Loads in Kenyan Women, Men, and Infants during Primary and Early Infection

ABSTRACT Steady-state levels of human immunodeficiency virus type 1 (HIV-1) RNA in plasma reached at approximately 4 months postinfection are highly predictive of disease progression. Several studies have investigated viral levels in adults or infants during primary and early infection. However, no studies have directly compared these groups. We compared differences in peak and set point plasma HIV-1 RNA viral loads among antiretrovirus-naive Kenyan infants and adults for whom the timing of infection was well defined. Peak and set point viral loads were significantly higher in infants than in adults. We did not observe any gender-specific differences in viral set point in either adults or infants. However, infants who acquired HIV-1 in the first 2 months of life, either in utero, intrapartum, or through early breast milk transmission, had significantly higher set point HIV-1 RNA levels than infants who were infected after 2 months of age through late breast milk transmission or adults who were infected through heterosexual transmission.

Human Herpesvirus 8: Seroprevalence and Correlates in Prostitutes in Mombasa, Kenya

Human herpesvirus 8 (HHV-8) infection is very prevalent in sub-Saharan Africa, but the role of sexual transmission has not been well characterized. HHV-8 seroprevalence and correlates were evaluated in a cohort of female prostitutes in Mombasa, Kenya. Between February 1993 and January 2000, stored plasma samples taken from 736 women were tested, by whole-virus ELISA assay, for the presence of HHV-8 antibodies; of these 736 women, 633 were included in the analysis of correlates of HHV-8 infection; and, of these 633, 44.1% were seropositive for HHV-8 antibodies. In univariate analysis, age, years of education, years of prostitution, workplace, hormonal contraception, intrauterine-device use, alcohol consumption, syphilis, and gonorrhea were all significantly associated with the presence of HHV-8 antibodies. In a multivariate model, older age, fewer years of education, and 2 markers of high-risk sexual behavior-namely, alcohol consumption and gonorrhea-were each independently associated with HHV-8 seropositivity. These results suggest that heterosexual transmission may contribute to acquisition of HHV-8 infections in this African population of prostitutes.

Infant feeding practices of women in a perinatal HIV-1 prevention study in Nairobi, Kenya.

ObjectiveTo determine feeding practices and nutritional status of infants born to HIV-1–infected women. MethodsFeeding plans and practices were evaluated by questionnaires and focus group discussions. Infants were weighed at 1 and 6 weeks and tested for HIV-1 at 6 weeks. ResultsOf 128 women seen after delivery, 111 completed the study. Mothers who planned to breast feed were more likely to feed their infants as planned (86% vs. 55%; P < 0.001). Women opted to breast feed due to financial constraints, partner influence, and fear of losing confidentiality. Women who reported that their partners were willing to have HIV-1 testing were less likely to be breast feeding at 6 weeks (odds ratio [OR] = 0.3, 95% confidence interval [CI]: 0.1–0.8; P = 0.01). At 6 weeks, more infants were mixed fed (31% vs. 21%; P = 0.05) than at 1 week. Lower infant weight at 6 weeks was associated with not breast feeding (P = 0.001), HIV-1 infection (P = 0.05), birth weight <3000 g (P = 0.01), maternal employment (P = 0.02), and paying <

P3.090 Bacterial Vaginosis and the Risk of Trichomonas Vaginalis Acquisition Among HIV-1 Negative Women

12.5 per month in house rent (among infants not breast fed; P = 0.05). ConclusionsReplacement feeding was difficult, particularly without partner support in HIV-1 testing. Mixed feeding was common and increased by 6 weeks. Mothers of low socioeconomic status who opt not to breast feed require support to avoid nutritional compromise of infants.

Infants with late breast milk acquisition of HIV-1 generate interferon-gamma responses more rapidly than infants with early peripartum acquisition

Background The vaginal microbiota may play a role in mediating susceptibility to sexually transmitted infections, including Trichomonas vaginalis (TV). This analysis evaluated the association between bacterial vaginosis (BV) and incident TV among women enrolled in a biomedical HIV prevention trial. Methods Data were analysed from HIV-1 seronegative women participating in HIV Prevention Trials Network Protocol 035. At quarterly visits for up to 30 months, participants completed structured interviews and specimens were collected for genital tract infection testing. TV was detected by saline microscopy. BV was characterised by Gram stain using the Nugent score (BV = 7–10; intermediate = 4–6; normal = 0–3 [reference group]). Cox proportional hazards models stratified by study site were used to assess the association between BV at the prior quarterly visit and TV acquisition. Participants were censored at their first TV infection or if they became pregnant or HIV-infected. Results This secondary analysis included 2,804 participants from Malawi, South Africa, USA, Zambia and Zimbabwe who contributed 13,977 follow-up visits. BV was detected at 5,184 (37.1%) visits and TV was detected at 352 (2.5%) visits. After adjusting for age, marital status, hormonal contraceptive use, sexual activity and TV at baseline, intermediate microbiota and BV at the prior visit were independently associated with an increased risk of TV (intermediate microbiota: adjusted hazard ratio [aHR] = 1.74, 95% confidence interval [CI] 1.22, 2.47; BV: aHR = 3.25, 95% CI 2.53–4.17). TV at baseline was also associated with an increased risk of TV (aHR = 2.54; 95% CI 1.91, 3.36). Sensitivity analyses excluding 202 women with baseline TV showed similar results (BV: aHR = 3.18; 95% CI 2.42 – 2.19). Conclusions Women with a Nugent score > 3 were at an increased risk of acquiring TV. If this relationship is causal, interventions that decrease the incidence of BV and promote a normal vaginal microbiota could potentially contribute to reductions in TV incidence.

Association between Cellular Immune Activation, Target Cell Frequency, and Risk of Human Immunodeficiency Virus Type-1 Superinfection

Infants infected with HIV‐1 after the first month of life have a lower viral set‐point and slower disease progression than infants infected before 1 month. We investigated the kinetics of HIV‐1‐specific CD8+ T lymphocyte secretion of interferon (IFN)‐γ in infants infected before 1 month of life compared with those infected between months 1 and 12 (late infection). HIV‐1 infection was assessed at birth and at months 1, 3, 6, 9 and 12 and timing of infection was determined by HIV‐1 gag DNA from dried blood spots and verified by plasma HIV‐1 RNA levels. HIV‐1 peptide‐specific IFN‐γ responses were measured by enzyme‐linked immunospot at months 1, 3, 6, 9 and 12. Timing of development of IFN‐γ responses was compared using the log–rank test and Kaplan–Meier survival curves. Infants infected late developed HIV‐1‐specific CD8+ T cell responses 2·8 months sooner than infants infected peripartum: 2·3 versus 5·1 months after HIV‐1 infection (n = 52, P = 0·04). Late‐infected infants had more focused epitope recognition than early‐infected infants (median 1 versus 2 peptides, P = 0·03); however, there were no differences in the strength of IFN‐γ responses. In infants infected with HIV‐1 after the first month of life, emergence of HIV‐1‐specific CD8+ IFN‐γ responses is coincident with the decline in viral load, nearly identical to what is observed in adults and more rapid than in early‐infected infants.

The post-trial effect of oral periodic presumptive treatment for vaginal infections on the incidence of bacterial vaginosis and Lactobacillus colonization

ABSTRACT We performed a case-control study of women at risk of HIV-1 superinfection to understand the relationship between immune activation and HIV-1 acquisition. An increase in the frequency of HIV-1 target cells, but not in other markers of T cell activation, was associated with a 1.7-fold increase in the odds of superinfection. This suggests that HIV-1 acquisition risk is influenced more by the frequency of target cells than by the generalized level of immune activation.

Primary CMV infection: a co-factor HIV-1 disease progression in African infants?

Background Bacterial vaginosis (BV) is a highly prevalent infection that frequently recurs following standard treatment. In a randomised controlled trial (RCT) of oral periodic presumptive treatment (PPT) to reduce vaginal infections among Kenyan women, we observed a decrease in BV and an increase in Lactobacillus colonisation among women randomised to receive 2 g metronidazole +150 mg fluconazole monthly for 12 months. After the trial, women were invited to continue follow-up in an open cohort study. These post-trial data were analysed to test the hypothesis that the treatment effect would persist in the absence of PPT. Methods Data were obtained from women who completed all 12 RCT visits and attended ≥1 cohort study visit within 120 days of their final RCT visit. We used Andersen-Gill proportional hazards models to estimate the post-trial effect of the intervention vs placebo on the incidence of BV by Gram stain (Nugent score ≥7) and Lactobacillus species by culture on Rogosa agar. Results The RCT enrolled 310 subjects (155 per arm), of whom 165 (83 active and 82 placebo) were included in this analysis. Included subjects were slightly older (median (IQR): 33 years (29–39) vs 30 years (26–35); p<0.001) and reported a longer duration of sex work (median (IQR): 6 years (2–11) vs 3 years (1–6); p<0.001) compared to those excluded. At the final RCT visit, which represented the baseline visit for this analysis, demographic and behavioural characteristics were similar by arm. The prevalence of BV at the final RCT visit was 16% in the active arm and 43% in the placebo arm (p<0.001). The post-trial incidence of BV was 260/100 person-years (p-yrs) in the active arm vs 358/100 p-yrs in the placebo arm (HR=0.76; 95% CI: 0.51% to 1.12%). The prevalence of Lactobacillus colonisation at the final RCT visit was 17% in the active arm and 18% in the placebo arm (p=0.81). The post-trial incidence of Lactobacillus colonisation was 180/100 p-yrs in the active arm vs 127/100 p-yrs in the placebo arm (HR=1.42; 95% CI: 0.85% to 2.71%). Conclusions Despite a decrease in BV and an increase in Lactobacillus colonisation during the RCT, the effect of PPT was not sustained during the 120 days following cessation of the intervention. New interventions that reduce BV recurrence and promote long-term Lactobacillus colonisation without the need for ongoing PPT or suppressive therapy are needed.

Maternal highly active antiretroviral therapy reduces vertical CMV transmission but not maternal breast milk CMV levels

not submitted for publication from Fourth Dominique Dormont International Conference. Host-Pathogen Interactions in Chronic Infections Paris, France. 13-15 December 2007 Published: 9 April 2008 Retrovirology 2008, 5(Suppl 1):O23 doi:10.1186/1742-4690-5-S1-O23 Maternal chronic viral infections transmitted to infants: from mechanisms to prevention and care Meeting abstracts A single PDF containing all abstracts in this Supplement is available here . http://www.biomedcentral.com/content/pdf/1742-4690-5-S1-info.pdf This abstract is available from: http://www.retrovirology.com/content/5/S1/O23

Impact of vaginal washing on the vaginal microbiota

Abstract To evaluate the impact of highly active antiretroviral therapy (HAART) on CMV transmission and breast milk level in the context of maternal HIV. Specimens from a randomized trial conducted in Nairobi, Kenya between 2003–2005 were used to compare CMV transmission and breast milk levels between mother-infant pairs randomized to HAART versus short-course antenatal zidovudine plus single-dose nevirapine (ZDV/sdNVP) for prevention of mother-to-child HIV transmission (PMTCT). Fifty-one antiretroviral-naive women ≤32 weeks gestation, and CD4 between 200–500 cells/mm3 were randomized at 34 weeks to begin either antenatal ZDV/sdNVP, or HAART through 6 months postpartum. Mean breast milk CMV levels and transmission were compared between arms. Age, sociodemographics, CD4%, and HIV plasma RNA viral load were similar between arms at baseline. CMV viral loads were measured from 243 infant plasma and 185 breast milk specimens during the first year postpartum. The probability of infant CMV infection at 12 months...