New Pharmacogenomics Research Network: An Open Community Catalyzing Research and Translation in Precision Medicine.

The goal of pharmacogenomics research is to discover genetic polymorphisms that underlie variation in drug response. Increasingly, pharmacogenomics research involves large numbers of patients and the application of new technologies and methodologies to enable discovery. The Pharmacogenomics Research Network (PGRN) has become a community-driven network of investigators spanning scientific and clinical disciplines. Here, we highlight the activities and types of resources that enable PGRN members to enhance and drive basic and translational research in pharmacogenomics.

Lack of protection against HIV-1 infection among women with HIV-2 infection.

OBJECTIVE: To assess whether HIV-2 infection protects against HIV-1 infection by comparing the rate of HIV-1 seroconversion among HIV-negative and HIV-2-seropositive women followed in a cohort study in Abidjan, Côte d'Ivoire. DESIGN: Prospective cohort study METHODS: HIV seroconversion was assessed in 266 HIV-seronegative, 129 HIV-1-seropositive, and 127 HIV-2-seropositive women participating in a closed cohort study of mother-to-child transmission of HIV conducted during 1990-1994. Participants were seen every 6 months, and blood samples were obtained. All blood samples were screened for HIV antibodies by enzyme immunoassay (EIA) and confirmed by line immunoassay (LIA) and Western blot. Among women who were HIV-seronegative at enrolment, seroconversion was defined as new EIA-reactivity confirmed on LIA and Western blot. Among HIV-1- or HIV-2-seropositive women, seroconversion to dual reactivity was defined as new dual reactivity on the LIA that was confirmed by reactivity on both HIV-1- and HIV-2-monospecific EIA. RESULTS: Five HIV-seronegative women became HIV-1-seropositive [seroconversion rate, 1.1 per 100 person-years; 95% confidence interval (CI), 0.3-2.5), and none became HIV-2-seropositive. No HIV-1-seropositive women became HIV-1/2 dually reactive, whereas six HIV-2-seropositive women acquired HIV-1 seroreactivity and thus became HIV-1/2 dually reactive (seroconversion rate 2.9 per 100 person-years; 95% CI, 1.1-6.3). HIV-2-seropositive women were more likely to acquire HIV-1 seroreactivity than were HIV-seronegative women (rate ratio, 2.7; 95% CI, 0.7-11.2), but this difference was not statistically significant (P>0.15). CONCLUSION: HIV-2 infection does not appear to protect against HIV-1 infection.

Late postnatal mother-to-child transmission of HIV-1 in Abidjan, Côte d'Ivoire.

BACKGROUND: HIV-1 can be transmitted from an infected mother to her infant through breastfeeding, although the precise risk of transmission by this route is unknown. A long-term follow-up of children born to HIV-infected women in Abidjan, Côte d'Ivoire, has enabled us to estimate this risk. METHODS: Children born to 138 HIV-1-seropositive women, 132 HIV-2-seropositive women, 69 women seroreactive to both HIV-1 and HIV-2, and 274 HIV-seronegative women were enrolled at birth and followed up for as long as 48 months. All children were breastfed (median duration 20 months). Blood samples for either or both HIV PCR and HIV serology were obtained at 1, 2, and 3 months of age, and every 3 months thereafter. Early HIV infection was defined as a positive HIV-1 PCR result obtained in the first 6 months of life. Late postnatal transmission was diagnosed when a child had a negative PCR at 3 or 6 months of age, followed by either or both a positive HIV-1 PCR at 9 months or older, or persistently positive HIV-1 serology at 15 months or older. FINDINGS: 82 children born to HIV-1-seropositive mothers and 57 children born to mothers seropositive for both HIV-1 and HIV-2 had PCR results for samples taken within the first 6 months. By 6 months of age, 23 (28%; 95% CI 19-39) of the 82 children born to HIV-1-seropositive mothers and ten (18%; 95% CI 9-30) of the 57 children born to dually seropositive mothers were HIV-1 infected. Among children whose PCR results were negative at or before age 6 months, and who were followed up beyond 6 months, an additional four (9%) of the 45 children born to HIV-1-seropositive mothers and two (5%) of the 39 children born to dually seropositive mothers became HIV infected. The estimated rates of late postnatal transmission, with account taken of loss to follow-up and the observed pattern of weaning, were 12% (95% CI 3-23) and 6% (0-14), respectively. One of the five children whose mothers seroconverted from HIV-negative to HIV-1, and one of seven children whose mothers seroconverted from HIV-2 to dual reactivity, became HIV-1 positive. No case of late postnatal transmission occurred in children born to HIV-2-positive or persistently HIV-negative mothers. INTERPRETATION: Breastfed children born to mothers seropositive for HIV-1 alone or seropositive for HIV-1 and HIV-2 in Abidjan are at substantial risk of late postnatal transmission. Early cessation of breastfeeding at 6 months of age should be assessed as a possible intervention to reduce postnatal transmission of HIV.

Television violence--reactions from physicians, advertisers and the networks.

In response to our call for letters on television violence we received more than 1500 letters from readers of the Journal. Seventy-two per cent of the leading television advertisers responded to a subsequent letter requesting a description of their policies regarding content of the programs they sponsor. Their responses included exculpating factors such as lack of control over programming, the limited amount of available advertising time and censorship. We presented these responses to network representatives. They commented on the difficulty in defining violence, the current decrease in the amount of violence shown and their activities in response to this issue. We maintain that the burden of proof that television violence does not harm lies with those who introduce it into society. Advertisers and networks will respond, we believe, to the problem of television violence if continuous public pressure is maintained.