G de Bruyn

Unreported antiretroviral use by HIV-1-infected participants enrolling in a prospective research study

The concentration of viral RNA in plasma is the primary risk factor for sexual transmission of HIV-1 [1–3], and reductions in plasma HIV-1 RNA levels due to antiretroviral therapy (ART) result in marked decreases in HIV-1 transmission risk [4,5]. Results from studies of HIV-1 transmission and disease progression may be more difficult to interpret if a substantial proportion of HIV-1 infected partners have low or undetectable viral loads on ART, and thus, ART use at study enrollment is often an exclusion factor.

The relative contribution of viral and bacterial sexually transmitted infections on HIV acquisition in southern African women in the Methods for Improving Reproductive Health in Africa study.

We assess the relative contribution of viral and bacterial sexually transmitted infections (STIs) on HIV acquisition among southern African women in a nested case-control study within the Methods for Improving Reproductive Health in Africa (MIRA) trial. Cases were women with incident HIV infection; controls were HIV-uninfected at the time of case seroconversion selected in a 1 to 3 case to control ratio (risk-set sampling), matched on study site and time of follow-up. Conditional logistic regression models were used to calculate adjusted odds ratios (AORs) and population-attributable fractions (PAF). Among 4948 enrolled women, we analysed 309 cases and 927 controls. The overall HIV incidence rate was 4.0 per 100 women-years. The incidence of HIV infection was markedly higher in women who had prevalent Herpes simplex virus type 2 (HSV-2) (AOR: 2.14; 95% confidence interval [CI]: 1.55–2.96), incident HSV-2 (AOR: 4.43; 95% CI: 1.77–11.05) and incident Neisseria gonorrhoeae (AOR: 6.92; 95% CI: 3.01–15.90). The adjusted PAF of HIV incidence for prevalent HSV-2 was 29.0% (95% CI: 16.8–39.3), for incident HSV-2 2.1% (95% CI: 0.6–3.6) and for incident N. gonorrhoeae 4.1% (95% CI: 2.5–5.8). Womens greatest risk factors for HIV acquisition were incident bacterial and viral STIs. Women-centred interventions aimed at decreasing HIV incidence in young African women need to address these common co-morbid conditions.

Changes in Lectin-Binding Patterns during Late Fetal Development of the Rat Colon

Lectin-binding and histochemical studies were integrated with a morphological description of colon development in rat fetuses to determine whether changes in glycoprotein sugars could be identified with stages of colon organogenesis. At 16 days gestation the colon consisted of a minute lumen surrounded by 3-5 layers of cuboidal, stratified epithelium, a basement membrane and undifferentiated mesenchyme. As development proceeded, epithelial spaces eventually fused with the main lumen, and fingers of mesenchyme, with a basement membrane and epithelial mantle, formed the walls of crypts lined with simple to stratified columnar cells. Goblet cells and mucin production appeared only on the 20th-21st day of gestation. Mesenchyme differentiation to a circular muscle band, the prospective tunica muscularis, occurred on days 17-18, and vascularization of the lamina propria was first detected on day 19. Wheat germ agglutinin (WGA) lectin bound avidly to sugar residues in the mesenchyme matrix from day 16 but weakened as the tissue differentiated, particularly into smooth muscle. Alcian blue staining of the matrix, also weakening with time, confirmed the sialic acid nature of binding sites for WGA on matrix acid mucopolysaccharides. Under controlled conditions, WGA also detected N-acetylglucosamine-binding sites on brush borders as they developed on the apical surface of primitive enterocytes. Ulex lectin bound to fucose residues of Alcian-blue-positive, PAS-positive mucin from the first appearance of goblet cells. Concanavalin A and glycine max lectins bound only to blood group substances on both nucleated red cells between days 16 and 19 and anucleate red cells from day 19.(ABSTRACT TRUNCATED AT 250 WORDS)

P15-08. Did unblinding affect HIV risk behaviour and risk perception in the HVTN503/Phambili study?

Address: 1Perinatal HIV Research Unit, Soweto, South Africa, 2Desmond Tutu HIV Foundation, Cape Town, South Africa, 3Aurum Institute for Health Research, Cape Town, South Africa, 4Medunsa HIV Clinical Research Unit (MeCRU), Tswane, South Africa, 5Centre for the AIDS Programme for Research in South Africa (CAPRISA), Durban, South Africa, 6Statistical Center for HIV/AIDS Research and Prevention, FHCRC, Seattle, WA, USA, 7National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD USA and 8HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center, Seattle, WA, USA * Corresponding author

P1-S5.25 Acyclovir and transmission of HSV-2 from HSV-2/HIV-1 dually infected persons

Background Daily suppressive therapy with valacyclovir reduces the risk of sexual transmission of HSV-2 in healthy HSV-2 serodiscordant heterosexual couples by 48%. Whether suppressive therapy reduces HSV-2 transmission from persons who have both HIV-1 and HSV-2 is unknown. Methods Within a randomised trial of daily acyclovir 400 mg bid in African HIV-1 serodiscordant couples, in which the HIV-1 infected partner was HSV-2 seropositive, we identified partnerships in which the HIV-1 susceptible partners were HSV-2 seronegative. Cox proportional hazards analysis was used. Results We followed 911 HIV-1 and HSV-2 serodiscordant couples for a median of 18 months (IQR 3, 24). For 112 couples (12%), the HIV-1/HSV-2 infected partner was male, of whom 37% (34/91) were circumcised. 68 HSV-2 seroconversions were observed (an incidence of 5.1 per 100 person-years): 40 in the acyclovir group and 28 in the placebo group (HR 1.4, 95% CI 0.8 to 2.2; p=0.2). In a multivariate analysis of HSV-2 susceptible women, hormonal contraception (HR 3.84, 95% CI 1.32 to 11.14, p=0.013) and having an uncircumcised male partner (HR 8.91, 95% CI 1.17 to 67.85, p=0.035) were significant risk factors for HSV-2 acquisition. Among HSV-2 susceptible men, younger age was the only significant HSV-2 risk factor (p=0.014). Conclusions Suppressive acyclovir therapy did not decrease the risk of HSV-2 transmission within HSV-2-serodiscordant couples in which the HSV-2-seropositive partner also had HIV-1 infection. Hormonal contraceptive use and lack of male circumcision in the HIV-1/HSV-2 dually infected male partners increased the risk of HSV-2 acquisition among initially HSV-2 seronegative women.

P15-13. HVTN 503(Phambili) trial discontinuation of enrolment/vaccination: the impact on trial participant attitudes to vaccine trials and scientific research

Address: 1Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa, 2Perinatal HIV Research Unit, University of Witwatersrand, Johannesburg, South Africa, 3CAPRISA, University of KwaZulu-Natal, Durban, South Africa, 4Medunsa Clinical Research Unit, University of Limpopo, Pretoria, South Africa, 5Aurum Institute for Health Research, Johannesburg, South Africa, 6HIV Vaccine Trials Network, Seattle, WA, USA and 7DAIDS, NIAID, NIH, Bethesda, MD, USA * Corresponding author

Discrepancies in diagnosis of incident HIV infection between antibody- and DNA-based tests in a phase III prevention trial in southern Africa

Dried blood spots (DBS) are widely used to test for HIV in a variety of research and service delivery settings; however, uniform guidelines regarding collection, storage and DNA extraction processes have neither been developed nor evaluated. Previously published reports suggested DBS may be stored at room temperature for up to 60 days, and intensive stability tests have shown that DBS can withstand high temperatures, humidity and freeze–thawing. During the implementation of a large randomized controlled trial (RCT) in southern Africa, with HIV acquisition as the primary endpoint, we observed 65 instances when DBS samples collected from the same day as a positive HIV antibody test yielded negative DNA polymerase chain reaction (PCR) results. The source of this discrepancy may have been due to inadequate specimen volume, filter paper or DNA extraction procedures, but were most likely due to storage conditions that have been reported as acceptable in other settings.

OA04-04. Perceived parental willingness for their adolescents to participate in future HIV prevention trials: a survey conducted amongst adolescents in Soweto

Background Following the high HIV prevalence rates in Sub-Saharan Africa, several target specific interventions have been put in place with varying degrees of success. In implementing these interventions, adolescents have become a crucial target group. This study specifically examines perceived parental willingness for their adolescent to participate in HIV prevention trials by taking parent-adolescent communication into account.

P14-07. Offering new prevention modalities in HIV vaccine trials: experience with male circumcision in the Phambili trial

Address: 1Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa, 2Centre for the AIDS Programme of Research in South Africa, Congella, South Africa, 3Statistical Center for HIV/AIDS Research and Prevention, Seattle, WA, USA, 4Aurum Institute for Health Research, Johannesburg, South Africa, 5Medunsa Clinical Research Unit, Tshwane, South Africa, 6Desmond Tutu HIV Foundation, University of Cape Town, Cape Town, South Africa, 7Center for the AIDS Programme of Research in South Africa, Congella, South Africa and 8Fred Hutchinson Cancer Research Center, Seattle, USA * Corresponding author

S03-05 OA. A less differentiated memory phenotype of Gag-specific CD4+ T-cells during primary HIV infection associates with viral control at 12 months

Methods We examined a cohort of 15 subtype C HIV-infected subjects identified during primary HIV-1 infection (PHI). Polychromatic flow cytometry was used to simultaneously analyze activation and memory maturation profiles in total and antigen-specific CD4+ T cells. Isolated PBMC from each subject were stimulated for 6 h with Gag, CMV (pp65) or Ad5 Hexon peptide pools and labeled with a cocktail of monoclonal antibodies to CD3, CD4, CD8, CD45RO, CD27, HLA-DR, CD38, Ki-67, IFNγ and IL-2.