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“If we want to stop the HIV epidemic, then we must know the mechanisms by which HIV uses human sex to spread,” said principal investigator Davey Smith, MD, MAS, associate professor of medicine in UCSD’s Division of Infectious Diseases and in the Veterans Affairs San Diego Healthcare System, and director of the CFAR Viral Pathogenesis Core.

It is known that most HIV infections worldwide result from exposure to the HIV virus in semen, made up of seminal cells and the fluid around these calls, called seminal plasma. HIV virus particles contain RNA and exist in the plasma, while infected seminal cells contain HIV DNA.

Using a method of comparing genetic characteristics, called phylogenetic analysis, the researchers studied a group of men who had sexually transmitted their HIV virus to other men. Phylogenetic models allow researchers to estimate the dates of origin of various groups of viruses; in this way the team was able to determine the source of rapidly mutating HIV viruses by analyzing the viral sequences extracted from the blood and semen of HIV transmitting partners. The team found that recipients shared a more recent common ancestor with virus from the seminal plasma than with virus found in the seminal cells of their source partner.

“Until now, it had not been established whether HIV RNA or DNA is transmitted during sex,” said Smith. “By analyzing the genetic differences between these two forms and the virus that was ultimately transmitted to newly infected individuals we found that it was the HIV RNA form present in seminal plasma that was transmitted.”

“The findings from this study will help direct prevention strategies to address the virus in the seminal plasma,” Smith said. “By knowing the origin of the transmitted virus, scientists may be able to develop new vaccines, vaginal microbicides and drugs to prevent the spread of sexually transmitted HIV.”

Smith notes that because the study involved pairs of men who have sex with men, the findings do not comment directly on HIV transmission to women. “Since the vast majority of women are infected with HIV by exposure to the virus in semen, HIV RNA in the seminal plasma is the likely culprit, but this needs to be confirmed,” he said.

The results of this paper, “HIV and Tuberculosis Co-infection Among Hispanics in Southern California: An Increasing Health Disparity,” will appear in the February edition of the American Journal of Public Health.

“While the overall numbers are modest, our study shows that what used to be mostly a disease of white and black patients in San Diego is now largely a disease of Hispanics,” said Timothy Rodwell MD, PhD, MPH, associate physician/fellow in the Division of Global Public Health at UC San Diego. “This indicates that the benefits of prevention and treatment of TB and HIV over the last decade have been uneven in the different ethnic/racial groups in this region.”

HIV is a potent risk factor for TB disease. It increases the risk of latent TB infection reactivation, the rate of disease progression and the risk of new infections. TB also accelerates HIV disease progression, increasing infectivity and reducing HIV treatment efficacy.

“The synergy of TB and HIV has created a worldwide public health crisis and has significantly complicated attempts to eliminate TB in both the industrialized and developing worlds,” noted Rodwell.

Rodwell’s team analyzed San Diego County TB surveillance data from 1993 through 2007, grouping cases by HIV status: positive, negative or unknown. Of the 5,172 TB cases analyzed, 8.8 percent were also infected with HIV. The number of new co-infected cases did not change significantly during this period, but the proportion of cases among Hispanics did increase significantly, while the proportion of cases among non-Hispanic white and black patients decreased.

Hispanics now account for more than 80 percent of all TB–HIV co-infection cases in the county, further widening existing health disparities in this region. Co-infected patients are significantly more likely to be Hispanic 30 to 49 year-old male injection drug users than any other patient group. Researchers recommend that since the burden of TB and HIV in San Diego has shifted to Hispanics, the disparity must be addressed with focused binational TB and HIV prevention efforts.

Rodwell explained, “With more than 40,000 people crossing the border between Mexico and San Diego on a daily basis, and our finding that the majority of new TB–HIV co-infection cases occurred among Hispanics that were born in Mexico, it is clear that future interventions to address this health disparity will need to be binational in nature.”

Published in the January/February 2010 issue of the journal Child Development, the study was conducted by scientists at Leiden University in the Netherlands. One of the researchers, doctoral student Natasha Dobrova-Krol, is of Ukrainian origin.

The researchers sought to examine the effects of HIV infection and being raised in institutions on the development of 58 infected and uninfected Ukrainian 4-year-olds. Some of the children lived in institutions from shortly after birth, while others lived with their biological families.

The study found that the quality of the relationships between the children and their caregivers had a bigger impact on children’s physical growth and cognitive performance than the presence of the HIV infection or the quality of the physical environment. In addition, the study found that for both children with and without HIV, family care, even when it was compromised, was better for children than institutional care.

“This study underscores efforts to strengthen the quality of children’s relationship with caregivers as important for children infected with HIV,” suggests Marinus H. van IJzendoorn, professor of child and family studies at Leiden University, who worked on the study.

“Because HIV-infected children are the least-preferred candidates for adoption or foster care, many of them will remain in rather low-quality institutions. Renovating the premises and giving them toys and learning materials has become a popular form of intervention in Eastern Europe, and it is certainly valuable. But our study shows that interventions should focus on more stable and sensitive relationships between children and their caregivers.”

The researchers suggest that changing the work schedules of part-time workers enhances caregiver stability. They also developed a training program for caregivers and parents, based on feedback of videotaped interactions between adults and children, that was effective in promoting basic parenting skills and, they suggest, should be tried out in orphanages.

The study, conducted by the Partners in Prevention HSV/HIV Transmission Study, was released by the New England Journal of Medicine in its online edition Jan. 20 and will follow in the print edition Feb. 4.

The largest risk group worldwide, but particularly in Africa and Asia, for contracting HIV is stable, heterosexual couples where only one partner is infected. Among those infected, about 90 percent also have a herpes simplex virus-2 (HSV-2), the most common cause of genital herpes, said study co-author Kenneth H. Fife, M.D., Ph.D., professor of medicine in the Division of Infectious Diseases at the Indiana University School of Medicine.

“Logic indicated that outbreaks of HSV-2 sores could enhance the transmission of HIV,” said Dr. Fife. “This is the first comprehensive study to look at the potential for reducing the transmission of HIV through treatment of the herpes virus.”

Multiple studies have shown that frequent genital herpes recurrences increase the amount of HIV in the blood and genital tract. It is known that HIV virus is shed through genital herpes ulcers and people with those ulcers transmit HIV to other more efficiently.

Five preliminary studies showed that it is possible to decrease the amount of HIV in the blood and genital tract through treatment to suppress HSV-2. However, those studies did not measure whether there also was a reduction in HIV transmission.

The study found that acyclovir reduced the occurrence of HSV-2 genital ulcers by 73 percent and thus the amount of HIV present in the blood and genital tract decreased twofold.

In spite of the reduction of HIV present in blood levels, the researchers found there was no significant difference in the transmission of HIV. Laboratory testing showed there were 41 infections in the group taking acyclovir and 43 in the placebo group.