Sexual Seroadaptation: Lessons for Prevention and Sex Research from a Cohort of HIV-Positive Men Who Have Sex with Men

BACKGROUND: Surveillance data on sexually transmitted infections (STIs) and behavioral characteristics identified in studies of the risk of seroconversion are often used as to track sexual behaviors that spread HIV. However, such analyses can be confounded by "seroadaptation"--the restriction of unprotected anal intercourse (UAI), especially unprotected insertive UAI, to seroconcordant partnerships. METHODS: We utilized sexual network methodology and repeated-measures statistics to test the hypothesis that seroadaptive strategies reduce the risk of HIV transmission despite numerous partnerships and frequent UAI. PRINCIPAL FINDINGS: In a prospective cohort study of HIV superinfection including 168 HIV-positive men who have sex with men (MSM), we found extensive seroadaptation. UAI was 15.5 times more likely to occur with a positive partner than a negative one (95% confidence interval [CI], 9.1-26.4). Receptive UAI was 4.3 times more likely in seroconcordant partnerships than with negative partners (95% CI, 2.8-6.6), but insertive UAI was 13.6 times more likely with positives (95% CI, 7.2-25.6). Our estimates suggest that seroadaptation reduced HIV transmissions by 98%. CONCLUSION: Potentially effective HIV prevention strategies, such as seroadaptation, have evolved in communities of MSM before they have been recognized in research or discussed in the public health forum. Thus, to be informative, studies of HIV risk must be designed to assess seroadaptive behaviors rather than be limited to individual characteristics, unprotected intercourse, and numbers of partners. STI surveillance is not an effective indicator of trends in HIV incidence where there are strong patterns of seroadaptation

Immunity to HIV-1 Is Influenced by Continued Natural Exposure to Exogenous Virus

Unprotected sexual intercourse between individuals who are both infected with HIV-1 can lead to exposure to their partner's virus, and potentially to super-infection. However, the immunological consequences of continued exposure to HIV-1 by individuals already infected, has to our knowledge never been reported. We measured T cell responses in 49 HIV-1 infected individuals who were on antiretroviral therapy with suppressed viral loads. All the individuals were in a long-term sexual partnership with another HIV-1 infected individual, who was either also on HAART and suppressing their viral loads, or viremic (>9000 copies/ml). T cell responses to HIV-1 epitopes were measured directly ex-vivo by the IFN-γ enzyme linked immuno-spot assay and by cytokine flow cytometry. Sexual exposure data was generated from questionnaires given to both individuals within each partnership. Individuals who continued to have regular sexual contact with a HIV-1 infected viremic partner had significantly higher frequencies of HIV-1-specific T cell responses, compared to individuals with aviremic partners. Strikingly, the magnitude of the HIV-1-specific T cell response correlated strongly with the level and route of exposure. Responses consisted of both CD4+ and CD8+ T cell subsets. Longitudinally, decreases in exposure were mirrored by a lower T cell response. However, no evidence for systemic super-infection was found in any of the individuals. Continued sexual exposure to exogenous HIV-1 was associated with increased HIV-1-specific T cell responses, in the absence of systemic super-infection, and correlated with the level and type of exposure

A-Kinase Anchoring in Dendritic Cells Is Required for Antigen Presentation

BACKGROUND: Dendritic cells (DC) are the most potent antigen presenting cells (APC) of the immune system. Prostaglandin E(2), cyclic AMP, and protein kinase A (PKA) have all been shown to regulate DC maturation and activity. In other cells, the ability of these molecules to convey their signals has been shown to be dependent on A-kinase anchoring proteins (AKAPs). Here we present evidence for the existence and functional importance of AKAPs in human DC. METHODOLOGY/PRINCIPAL FINDINGS: Using immunofluorescence and/or western analyses we identify AKAP79, AKAP149, AKAP95, AKAP LBC and Ezrin. We also demonstrate by western analysis that expression of AKAP79, AKAP149 and RII are upregulated with DC differentiation and maturation. We establish the functional importance of PKA anchoring in multiple aspects of DC biology using the anchoring inhibitor peptides Ht31 and AKAP-IS. Incubation of protein or peptide antigen loaded DC with Ht31 or AKAP-IS results in a 30-50% decrease in antigen presentation as measured by IFN-gamma production from antigen specific CD4(+) T cells. Incubation of LPS treated DC with Ht31 results in 80% inhibition of TNF-alpha and IL-10 production. Ht31 slightly decreases the expression of CD18 and CD11a and CD11b, slightly increases the basal expression of CD83, dramatically decreases the LPS stimulated expression of CD40, CD80 and CD83, and significantly increases the expression of the chemokine receptor CCR7. CONCLUSIONS: These experiments represent the first evidence for the functional importance of PKA anchoring in multiple aspects of DC biology

Sexual seroadaptation: lessons for prevention and sex research from a cohort of HIV-positive men who have sex with men.

BackgroundSurveillance data on sexually transmitted infections (STIs) and behavioral characteristics identified in studies of the risk of seroconversion are often used as to track sexual behaviors that spread HIV. However, such analyses can be confounded by "seroadaptation"--the restriction of unprotected anal intercourse (UAI), especially unprotected insertive UAI, to seroconcordant partnerships.MethodsWe utilized sexual network methodology and repeated-measures statistics to test the hypothesis that seroadaptive strategies reduce the risk of HIV transmission despite numerous partnerships and frequent UAI.Principal findingsIn a prospective cohort study of HIV superinfection including 168 HIV-positive men who have sex with men (MSM), we found extensive seroadaptation. UAI was 15.5 times more likely to occur with a positive partner than a negative one (95% confidence interval [CI], 9.1-26.4). Receptive UAI was 4.3 times more likely in seroconcordant partnerships than with negative partners (95% CI, 2.8-6.6), but insertive UAI was 13.6 times more likely with positives (95% CI, 7.2-25.6). Our estimates suggest that seroadaptation reduced HIV transmissions by 98%.ConclusionPotentially effective HIV prevention strategies, such as seroadaptation, have evolved in communities of MSM before they have been recognized in research or discussed in the public health forum. Thus, to be informative, studies of HIV risk must be designed to assess seroadaptive behaviors rather than be limited to individual characteristics, unprotected intercourse, and numbers of partners. STI surveillance is not an effective indicator of trends in HIV incidence where there are strong patterns of seroadaptation

A network “sexiogram” differentiates sexual linkages that may or may not have caused new infections.

<p>The individuals represented by the labels A–B and C–D were couples enrolled in the study. The other nodes are sexual partners described by the enrollees. The partnerships were not necessarily concurrent and included all those reported during the 3 months before A's enrollment and those of D, who enrolled 6 months later. Thus, the partnerships spanned a 9-month interval altogether. In some analyses, all partnerships of these HIV-positive individuals known to practice UAI would be counted as potential transmission linkages. This diagram illustrates the preponderance of low-risk partnerships (solid lines) compared with potential transmission linkages (broken lines).</p

General estimating equation models predicting UAI in partnerships.

<p>The HIV-positive status of partner was a strong predictor of sexual practices in partnerships and for individual episodes of intercourse; partners of unknown status were not treated very differently from HIV-negative partners. The analysis also revealed strategic positioning by showing that positive participants were several times more likely to practice insertive rather than receptive UAI in serodiscordant partnerships. ^A HIV-negative partners are the reference group in all cases. ^B Designates the sexual position of the HIV-positive participant.</p

Changes in seroadaptive practices from before to after diagnosis of recent HIV infection among men who have sex with men.

We assessed changes in sexual behavior among men who have sex with men (MSM), before and for several years after HIV diagnosis, accounting for adoption of a variety of seroadaptive practices.We collected self-reported sexual behavior data every 3 months from HIV-positive MSM at various stages of HIV infection. To establish population level trends in sexual behavior, we used negative binomial regression to model the relationship between time since diagnosis and several sexual behavior variables: numbers of (a) total partners, (b) potentially discordant partners (PDP; i.e., HIV-negative or unknown-status partners), (c) PDPs with whom unprotected anal intercourse (UAI) occurred, and (d) PDPs with whom unprotected insertive anal intercourse (uIAI) occurred.A total of 237 HIV-positive MSM contributed 502 interviews. UAI with PDPs occurred with a mean of 4.2 partners in the 3 months before diagnosis. This declined to 0.9 partners/3 months at 12 months after diagnosis, and subsequently rose to 1.7 partners/3 months at 48 months, before falling again to 1.0 partners/3 months at 60 months. The number of PDPs with whom uIAI occurred dropped from 2.4 in the pre-diagnosis period to 0.3 partners/3 months (an 87.5% reduction) by 12 months after enrollment, and continued to decline over time.Within months after being diagnosed with HIV, MSM adopted seroadaptive practices, especially seropositioning, where the HIV-positive partner was not in the insertive position during UAI, resulting in a sustained decline in the sexual activity associated with the highest risk of HIV transmission