Unprotected Sex Between HIV-Infected Partners Keeps Immune Responses Activated

Nice article on the health benefits of sero-sorting for HIV-positive men via IRMA Blog -


By Charlene Crabb
AIDS. 23(11):N7, July 17, 2009.

HIV acts as a ‘natural immunogen’, keeping anti-HIV-1 immune responses boosted in HIV-infected male couples who have unprotected sex, say University of California San Francisco researchers [original article from UCSF researchers: PLoS Pathog 2008; 4:e1000185].

Until now, little has been reported on the consequences of continued exposure to HIV in people who are already infected. But serosorting, the practice of identifying sexual partners based on their HIV status, is a growing trend. It often leads to unprotected sex between HIV infected individuals, which poses the risk of acquiring a drug-resistant strain of the virus.

To shed light on the immunological consequences of continued exposure to HIV, Christian Willberg and colleagues studied 49 men, from a San Francisco prospective cohort of couples in long-term relationships, who were suppressing their virus below the detection level (50RNAcopies/ml) with HAART. Twenty-nine men had partners whose virus was also in check due to antiviral therapy, whereas 20 men had viremic partners whose viral loads were more than 90 000RNAcopies/ml.

Using enzyme-linked immunosorbent spot (ELISPOT) assay to compare HIV-1-specific T-cell responses between the two groups, the researchers found significantly stronger (P¼0.001) responses against HIV-1 protease, reverse transcriptase, and integrase peptides in the men with viremic partners. The magnitude of their responses correlated with a greater frequency of unprotected sex, and in particular with the frequency of exposure through receptive (versus insertive) anal sex. No similar correlations were found in the men with nonviremic partners.

‘Rather than losing responses because their own virus has been suppressed by antiviral therapy,’ explains Willberg, ‘we found that the men are maintaining a response because they are constantly being exposed to their partner’s virus.’

That the amount of exposure drives the boosted HIV-1- specific immune responses was also illustrated in three individuals from the viremic partner group whose T-cell responses dropped significantly a year later. Two had partners who started antiretroviral therapy and were suppressing their viral loads. The third had reduced his exposure. (Seven individuals from the viremic partner group had blood samples available froma 1-year followup.)

The researchers note that superinfection is the most likely mechanism to maintain or boost the HIV-1 immune responses. However, HIV-1 sequencing of all participants in the study found no evidence of superinfection at the systemic level in which a new virus overgrows the existing strain. Willberg, who is now at Oxford University, cautions that the study’s phylogenetic analysis does not rule out localized superinfections in the gut, most likely the rectum.

Furthermore, no one knows whether maintaining a high T-cell response is good or bad. Willberg says that keeping an active HIV-1 immune response might help control viral rebound in a person when antiviral therapy fails for some reason, or it could indicate a compartmentalized superinfection and the increased risk of acquiring a drug-resistant strain. ‘It could be a double-edged sword,’ he says.

Love, AIDS and Aging

Living on golden time

A really incredible, touching, REAL accounting of the toll of AIDS on a long-term gay couple, via The Story [American Public Media].

LifeLube found itself nodding in recognition, holding back tears...

Drugs that combat HIV have prolonged millions of lives. But for some older people, these drugs are also making them age faster.

Larry Gibson and Dennis Golay are in their 60s. They've been together for 27 years, and both have felt the side effects from their medications. Dennis lost his teeth, had a heart attack and developed a humped back. Larry's skull protruded outwards and he's undergone numerous facial injections. Despite their wavering health, Larry and Dennis have outlived 60 of their closest friends.

They talk with Dick Gordon about how they maintain their optimism - and how a pact they made two decades ago keeps them moving forward.

Listen to their story. [you must]

Read Dennis and Larry's article "With HIV, growing older faster."

Learn more about the Desert AIDS Project.

Study examines repeated exposure to HIV in treatment-suppressed HIV patients

A new study looking at unprotected intercourse within gay couples when each partner has established HIV-infection found a correlation between anti-HIV immune response and sexual activity.

Study results showed that individuals who had regular unprotected receptive anal intercourse with partners with significant levels of HIV in their blood showed a stronger anti-HIV immune response. In addition, the magnitude of anti-HIV specific immune response correlated with their exposure to HIV through sex.

Published in the October 24th, 2008 issue of PLoS Pathogens, "Immunity to HIV-1 Is Influenced by Continued Natural Exposure to Exogenous Virus," is authored by a research team from UCSF and the Gladstone Institute for Virology and Immunology.

The researchers found no evidence of systemic superinfection (re-infection with another strain of HIV) in the receptive partners, whose virus had been successfully suppressed through antiretroviral therapy for at least five months. In a comparison group of HIV-infected couples in which both partners' viruses had been suppressed by therapy, researchers did not find the same strength of immune responses correlations or the same correlations with sexual exposure.

"We found HIV-specific immune responses in the treatment-suppressed partners that correlated with the level and route of exposure. The individuals with no detectable virus who were on antiretroviral
therapy and who were exposed to HIV through receptive intercourse with a partner with detectable virus, had the stronger anti-HIV immune responses in comparison to individuals exposed to partners whose virus was also suppressed by antiretroviral therapy, where no effect was seen," said study lead author, Christian B. Willberg, PhD, post- doctoral fellow in the UCSF Division of Experimental Medicine.

Notwithstanding the intriguing HIV specific findings, the findings also reveal an important general mechanism occurring in infectious diseases.

"We found that immune responses to chronic viral infections are influenced not only by the chronic infection existing in an individual or host, but also by exposures to exogenous virus from outside the individual or host," said study co-senior author, Douglas F. Nixon, MD, PhD, professor of medicine in the UCSF Division of Experimental Medicine.

The investigators were unable to determine from these findings whether there is any benefit from this type of repeated exposure to HIV—i.e., a type of therapeutic vaccination for HIV-infected patients with suppressed virus. Some HIV patients on antiretroviral regimens lose many of their HIV-specific immune responses over time due to the successful suppression of viral replication by therapy.

"Indeed, our hypothesis had been that in the context of these waning anti-HIV responses among the suppressed partners and the expected level of exposure from repeated unprotected receptive intercourse, we would find evidence of superinfection. While we did not find systemic super-infection, we cannot exclude limited or localized superinfections in the gut. And, antiretroviral therapy may have been the factor that prevented superinfection in these patients," said study co-senior author Robert M. Grant, MD, MPH, senior investigator at the Gladstone Institute of Virology and Immunology and associate professor of medicine at UCSF.

The study involved 49 HIV-infected gay men from the San Francisco Positive Partners Program study—a cohort of couples in which both partners are HIV-positive that began enrolling participants in 2000. Viral suppression in this study meant viral loads less than 50 copies. Among those participants whose virus had not been suppressed, the lowest viral load was 9,420 copies.

The team that designed this study benefited from its unique multidisciplinary composition. Immunologists working with social researchers were able to design a study that managed to distinguish between different levels of viral suppression and different patterns of sexual contacts and correlate the immunological aspects with the behavioral variables.

"We call the interaction between these two scientific communities together: 'social immunology'. It may be true that patterns of social activities shape immune responses generally, as we observed for people with HIV having contact with other HIV infected persons. Obviously more study is needed and we would like to see whether social immunology will continue to offer important insights," said Grant.

"While we have not found a case of superinfection in our cohort of chronically infected HIV couples, a handful of cases of superinfection verified by linkage to a known partner's virus have been reported in chronically infected HIV patients. It is also important to stress, these findings do not address the negative consequences of acquiring other sexually transmitted diseases through engaging in unprotected sex or the potentially positive consequences that unprotected sex may have in partnerships where both individuals are HIV-positive," said study co-author, J. Jeff McConnell, MA, director of the Positive Partners study at the Gladstone Institute for Virology and Immunology.

Read the paper here.

Doctors Miss Early HIV Symptoms

BBC (originally posted 07.22.08)

Almost half of all early-stage HIV infections in the United Kingdom are being missed, the National AIDS Trust (NAT) said recently. Approximately 7,000 new HIV cases occur annually in Britain, and as many as 50 percent are believed to be transmitted by people who are in the early stages of their own infection.

The first few weeks of infection are often marked by severe flu-like symptoms such as sore throat, fever, and rashes. After about six weeks, these symptoms typically recede and the infected person will feel normal again, even though he or she has HIV. People seeking medical treatment for these symptoms are often told they have a trivial viral infection and to return if they see no improvement, said NAT.

A study in Brighton found that 48 percent of HIV patients who had sought medical attention for their early symptoms were not diagnosed with HIV during that appointment.

"It is very worrying that [general practitioners] and other health care professionals are often missing the signs and symptoms of HIV infection," said NAT CEO Deborah Jack. "This can mean they become seriously ill in the longer term and respond less well to treatment. It also means they are likely to be putting partners at risk of infection as they may live undiagnosed for a number of years."

"HIV testing needs to be more widespread and routine," said Dr. Martin Fisher, a consultant in HIV medicine. The symptoms that accompany early infection represent a "golden opportunity" to spot new cases, he said.

Recreational drug use does not adversely affect CD4 cell counts

[via aidsmap]

Use of the recreational drugs, cannabis, cocaine, poppers, or amphetamines, does not adversely affect the number or percentage of CD4 or CD8 cells in either HIV-positive or HIV-negative gay men, according to data from the Multicenter AIDS Cohort Study (MACS) published online on January 3^rd in the journal Drug and Alcohol Dependence. However, the investigators did not measure the quality or function of these cells.

Animal and test tube studies have previously shown that recreational drugs such as cannabis (smoked as marijuana), cocaine, poppers, and amphetamines may adversely affect animal and human T cell responses.

Notably, cocaine given to HIV-infected mice greatly increased HIV levels and reduced CD4 cell counts to one ninth of the levels of the mice in the control group.

However, studies examining the impact of these recreational drugs on CD4 and CD8 T-cells in real life have reported inconsistent and conflicting findings, possibly due to confounding factors such as antiretroviral drug use, injecting drug use, and differences in the level and frequency of recreational drugs used over time.

Read the rest.

HPV therapeutic vaccine stimulates immune response in people with HIV

by Liz Highleyman for aidsmap

A new therapeutic vaccine for human papillomavirus (HPV), a sexually transmitted virus that can cause anal and genital cancer, appears safe and stimulates an immune response in HIV-positive people, according to a poster presented Monday at the Fourth International AIDS Society Conference on HIV Treatment, Pathogenesis and Prevention in Sydney.

Although two HPV preventive vaccines have now been approved in Europe, it is unclear if those vaccines will have any impact on the incidence of anal or cervical cancer in HIV-positive people already infected with HPV.

An analysis of the FUTURE 1 study of the approved Gardasil HPV vaccine found a 73% efficacy rate against the development of anogenital warts or pre-cancerous or cancerous cell changes in the anus in women during four years of follow-up. However the investigators stressed that the study did not include HIV-positive people, and the protective effect of the vaccine in people with HIV remains unclear.

A therapeutic vaccine against cancer-causing HPV type 16 is being developed by the Australian company CSL. It is designed to prevent the development of neoplasia (pre-cancerous cell changes) by stimulating cellular immune responses to this type of HPV.

The manufacturer chose to test the vaccine in HIV-positive people in order to determine whether it would induce immune responses to HPV in people with moderate immune suppression.

Read the rest.

Lancet study reports that HIV treatment can "normalize" CD4 counts

AIDS Action Committee's blog analyzes Reuters article reporting that people with HIV can build "normal" immune strength...

Click here to read the post.