Inferring HIV Transmission Dynamics from Phylogenetic Sequence Relationships

New insights into HIV transmission dynamics, say the authors, are likely to come from analyzing the viral sequence information that is being routinely collected during HIV genotyping

Adjusting for sampling variability in sparse data: geostatistical approaches to disease mapping

Abstract Background Disease maps of crude rates from routinely collected health data indexed at a small geographical resolution pose specific statistical problems due to the sparse nature of the data. Spatial smoothers allow areas to borrow strength from neighboring regions to produce a more stable estimate of the areal value. Geostatistical smoothers are able to quantify the uncertainty in smoothed rate estimates without a high computational burden. In this paper, we introduce a uniform model extension of Bayesian Maximum Entropy (UMBME) and compare its performance to that of Poisson kriging in measures of smoothing strength and estimation accuracy as applied to simulated data and the real data example of HIV infection in North Carolina. The aim is to produce more reliable maps of disease rates in small areas to improve identification of spatial trends at the local level. Results In all data environments, Poisson kriging exhibited greater smoothing strength than UMBME. With the simulated data where the true latent rate of infection was known, Poisson kriging resulted in greater estimation accuracy with data that displayed low spatial autocorrelation, while UMBME provided more accurate estimators with data that displayed higher spatial autocorrelation. With the HIV data, UMBME performed slightly better than Poisson kriging in cross-validatory predictive checks, with both models performing better than the observed data model with no smoothing. Conclusions Smoothing methods have different advantages depending upon both internal model assumptions that affect smoothing strength and external data environments, such as spatial correlation of the observed data. Further model comparisons in different data environments are required to provide public health practitioners with guidelines needed in choosing the most appropriate smoothing method for their particular health dataset

Efficient Identification of HIV Serodiscordant Couples by Existing HIV Testing Programs in South Brazil.

ObjectiveTo examine the feasibility of identifying HIV negative at risk individuals in HIV serodiscordant couples, during voluntary HIV testing in South Brazil.MethodsWe surveyed HIV testers at 4 public testing sites in Rio Grande do Sul. We obtained information on risk behaviors and sexual partnerships. HIV testing and testing for recent infection were performed; HIV prevalence and risk behaviors were assessed among subjects who reported having a steady partner who was HIV positive (serodiscordant group) and compared with the general testing population.ResultsAmong 3100 patients, 490 (15.8%) reported being in a steady relationship with an HIV positive partner. New HIV infections were diagnosed in 23% of the serodiscordant group (vs. 13% in the general population, p = 0.01); among newly positive subjects, recent HIV infections were more frequent (23/86, 26.7%) among testers with positive partners than among the general testing group (52/334; 15.6%; p = 0.016). Less than half of the serodiscordant testers reported having used a condom during the last sexual intercourse with their HIV-positive partner. Participants with inconsistent condom use with steady partner were four times more likely to test positive for HIV compared to those who reported always using condoms with the steady partner (OR: 4.2; 95% CI: 2.3 to 7.5).ConclusionIt is highly feasible to identify large numbers of HIV susceptible individuals who are in HIV serodiscordant relationships in South Brazil testing sites. Condom use within HIV serodiscordant couples is low in this setting, suggesting urgent need for biomedical prevention strategies to reduce HIV transmission

Leveraging a Rapid, Round-the-Clock HIV Testing System to Screen for Acute HIV Infection in a Large Urban Public Medical Center

Methods The hospital laboratory performed round-the-clock rapid HIV antibody testing on venipuncture specimens from patients undergoing HIV testing in hospital and community clinics, inpatient settings, and the emergency department. For patients with negative results, a public health laboratory conducted pooled HIV RNA testing for acute HIV infection. The laboratories communicated positive results from the hospital campus to a linkage team. Linkage was defined as one outpatient HIV-related visit. Results Among 7,927 patients, 8,550 rapid tests resulted in 137 cases of HIV infection (1.7%, 95% CI 1.5%–2.0%), of whom 46 were new HIV diagnoses (0.58%, 95% CI 0.43%–0.77%). Pooled HIV RNA testing of 6,704 specimens (78.4%) resulted in 3 cases of acute HIV infection (0.05%, 95% CI 0.01%–0.14) and increased HIV case detection by 3.5%. Half of new HIV diagnoses and 2/3 of acute infections were detected in the emergency department and urgent care clinic. Rapid test sensitivity was 98.9% (95% CI 93.8%– 99.8%); specificity was 99.9% (95% CI 99.7%–99.9%). Over 95% of newly diagnosed and out-of-care HIV-infected patients were linked to care. Conclusions Patients undergoing HIV testing in emergency departments and urgent care clinics may benefit from being simultaneously screened for acute HIV infection

How can we better identify early HIV infections?

Detection of early HIV infections (EHIs), including acute HIV infection (AHI), is important for individual health, prevention of HIV transmission, and measurement of HIV incidence. We describe markers of EHI, diagnostic strategies for detecting these markers, and ways to incorporate these strategies into diagnostic and HIV incidence algorithms

Performance of Risk-Based Criteria for Targeting Acute HIV Screening in San Francisco

Federal guidelines now recommend supplemental HIV RNA testing for persons at high risk for acute HIV infection. However, many rapid HIV testing sites do not include HIV RNA or p24 antigen testing due to concerns about cost, the need for results follow-up, and the impact of expanded venipuncture on clinic flow. We developed criteria to identify patients in a municipal STD clinic in San Francisco who are asymptomatic but may still be likely to have acute infection.Data were from patients tested with serial HIV antibody and HIV RNA tests to identify acute HIV infection. BED-CEIA results were used to classify non-acute cases as recent or longstanding. Demographics and self-reported risk behaviors were collected at time of testing. Multivariate models were developed and preliminarily evaluated using predictors associated with recent infection in bivariate analyses as a proxy for acute HIV infection. Multivariate models demonstrating ≥70% sensitivity for recent infection while testing ≤60% of patients in this development dataset were then validated by determining their performance in identifying acute infections.From 2004-2007, 137 of 12,622 testers had recent and 36 had acute infections. A model limiting acute HIV screening to MSM plus any one of a series of other predictors resulted in a sensitivity of 83.3% and only 47.6% of patients requiring testing. A single-factor model testing only patients reporting any receptive anal intercourse resulted in 88.9% sensitivity with only 55.2% of patients requiring testing.In similar high risk HIV testing sites, acute screening using "supplemental" HIV p24 antigen or RNA tests can be rationally targeted to testers who report particular HIV risk behaviors. By improving the efficiency of acute HIV testing, such criteria could facilitate expanded acute case identification

Adjusting for sampling variability in sparse data: geostatistical approaches to disease mapping

Abstract Background Disease maps of crude rates from routinely collected health data indexed at a small geographical resolution pose specific statistical problems due to the sparse nature of the data. Spatial smoothers allow areas to borrow strength from neighboring regions to produce a more stable estimate of the areal value. Geostatistical smoothers are able to quantify the uncertainty in smoothed rate estimates without a high computational burden. In this paper, we introduce a uniform model extension of Bayesian Maximum Entropy (UMBME) and compare its performance to that of Poisson kriging in measures of smoothing strength and estimation accuracy as applied to simulated data and the real data example of HIV infection in North Carolina. The aim is to produce more reliable maps of disease rates in small areas to improve identification of spatial trends at the local level. Results In all data environments, Poisson kriging exhibited greater smoothing strength than UMBME. With the simulated data where the true latent rate of infection was known, Poisson kriging resulted in greater estimation accuracy with data that displayed low spatial autocorrelation, while UMBME provided more accurate estimators with data that displayed higher spatial autocorrelation. With the HIV data, UMBME performed slightly better than Poisson kriging in cross-validatory predictive checks, with both models performing better than the observed data model with no smoothing. Conclusions Smoothing methods have different advantages depending upon both internal model assumptions that affect smoothing strength and external data environments, such as spatial correlation of the observed data. Further model comparisons in different data environments are required to provide public health practitioners with guidelines needed in choosing the most appropriate smoothing method for their particular health dataset

Brief but Efficient: Acute HIV Infection and the Sexual Transmission of HIV

Background. We examined whether viral dynamics in the genital tract during the natural history of acute human immunodeficiency virus type 1 (HIV-1) infection could explain efficient heterosexual transmission of HIV. Methods. We measured HIV-1 concentration in blood and semen samples from patients with acute and long-term HIV-1 infection. We explored the effect of changes in viral dynamics in semen on the probability of transmission per coital act, using a probabilistic model published elsewhere. Results. Considered over time from infection, semen HIV-1 concentrations, in men with acute infection, increase and decrease in approximate parallel with changes occurring in blood. Modeling suggests that these acute dynamics alone are sufficient to increase probability of heterosexual transmission by 8-10-fold between peak (day 20 after infection, based on the model) and virologic set points (day 54 and later after infection). Depending on the frequency of coitus, men with average semen HIV-1 loads and without sexually transmitted diseases (STDs) would be expected to infect 7%-24% of susceptible female sex partners during the first 2 months of infection. The predicted infection rate would be much higher when either partner has an STD. Conclusions. Empirical biological data strongly support the hypothesis that sexual transmission by acutely infected individuals has a disproportionate effect on the spread of HIV-1 infection. Acute hyperinfectiousness may, in part, explain the current pandemic in heterosexual individual

Trans-activation, post-transcriptional maturation, and induction of antibodies to HERV-K (HML-2) envelope transmembrane protein in HIV-1 infection

Background Human Endogenous Retroviruses (HERVs) comprise about 8% of the human genome and have lost their ability to replicate or to produce infectious particles after having accumulated mutations over time. We assessed the kinetics of expression of HERV-K (HML-2) Envelope mRNA transcript and surface unit (SU) and transmembrane (TM) subunit proteins during HIV-1 infection. We also mapped the specificity of the humoral response to HERV-K (HML-2) Envelope protein in HIV-1 infected subjects at different stages of disease, and correlated the response with plasma viral load. Results We found that HIV-1 modified HERV-K (HML-2) Env mRNA expression, resulting in the expression of a fully N-glycosylated HERV-K (HML-2) envelope protein on the cell surface. Serological mapping of HERV-K (HML-2) envelope protein linear epitopes revealed two major immunogenic domains, one on SU and another on the ectodomain of TM. The titers of HERV-K (HML-2) TM antibodies were dramatically increased in HIV-1 infected subjects (p \u3c 0.0001). HIV-1 infected adults who control HIV-1 in the absence of therapy (“elite” controllers) had a higher titer response against TM compared to antiretroviral-treated adults (p \u3c 0.0001) and uninfected adults (p \u3c 0.0001). Conclusions These data collectively suggest that HIV-1 infection induces fully glycosylated HERV-K (HML-2) envelope TM protein to which antibodies are induced. These anti-HERV-K (HML-2) TM antibodies are a potential marker of HIV-1 infection, and are at higher titer in elite controllers. HERV-K (HML-2) envelope TM protein may be a new therapeutic target in HIV-1 infection