Antoine Chaillon

Clear Links Between Starting Methamphetamine and Increasing Sexual Risk Behavior: A Cohort Study Among Men Who Have Sex With Men.

Background:It remains unclear if methamphetamine is merely associated with high-risk behavior or if methamphetamine use causes high-risk behavior. Determining this would require a randomized controlled trial, which is clearly not ethical. A possible surrogate would be to investigate individuals before and after starting the use of methamphetamine. Methods:We performed a cohort study to analyze recent self-reported methamphetamine use and sexual risk behavior among 8905 men who have sex with men (MSM) receiving the “Early Test,” a community-based HIV screening program in San Diego, CA, between April 2008 and July 2014 (total 17,272 testing encounters). Sexual risk behavior was evaluated using a previously published risk behavior score [San Diego Early Test (SDET) score] that predicts risk of HIV acquisition. Results:Methamphetamine use during the last 12 months (hereafter, recent-meth) was reported by 754/8905 unique MSM (8.5%). SDET scores were significantly higher in the 754 MSM with recent-meth use compared with the 5922 MSM who reported that they have never used methamphetamine (P < 0.001). Eighty-two repeat testers initiated methamphetamine between testing encounter, with significantly higher SDET scores after starting methamphetamine [median 5 (interquartile range, 2–7) at recent-meth versus median 3 (interquartile range, 0–5) at never-meth; P < 0.001, respectively]. Conclusions:Given the ethical impossibility of conducting a randomized controlled trial, the results presented here provide the strongest evidence yet that initiation of methamphetamine use increases sexual risk behavior among HIV-uninfected MSM. Until more effective prevention or treatment interventions are available for methamphetamine users, HIV-uninfected MSM who use methamphetamine may represent ideal candidates for alternative effective prevention interventions (ie, preexposure prophylaxis).

Incidence and Prevalence of Intrasubtype HIV-1 Dual Infection in At-Risk Men in the United States

BACKGROUND Human immunodeficiency virus type 1 (HIV-1) dual infection (DI) has been associated with decreased CD4 T-cell counts and increased viral loads; however, the frequency of intrasubtype DI is poorly understood. We used ultradeep sequencing (UDS) to estimate the frequency of DI in a primary infection cohort of predominantly men who have sex with men (MSM). METHODS  HIV-1 genomes from longitudinal blood samples of recently infected, therapy-naive participants were interrogated with UDS. DI was confirmed when maximum sequence divergence was excessive and supported by phylogenetic analysis. Coinfection was defined as DI at baseline; superinfection was monoinfection at baseline and DI at a later time point. RESULTS  Of 118 participants, 7 were coinfected and 10 acquired superinfection. Superinfection incidence rate was 4.96 per 100 person-years (95% confidence interval [CI], 2.67-9.22); 6 occurred in the first year and 4 in the second. Overall cumulative prevalence of intrasubtype B DI was 14.4% (95% CI, 8.6%-22.1%). Primary HIV-1 incidence was 4.37 per 100 person-years (95% CI, 3.56-5.36). CONCLUSIONS  Intrasubtype DI was frequent and comparable to primary infection rates among MSM in San Diego; however, superinfection rates declined over time. DI is likely an important component of the HIV epidemic dynamics, and development of stronger immune responses to the initial infection may protect from superinfection.

HIV Transmission Networks in the San Diego–Tijuana Border Region

Background HIV sequence data can be used to reconstruct local transmission networks. Along international borders, like the San Diego–Tijuana region, understanding the dynamics of HIV transmission across reported risks, racial/ethnic groups, and geography can help direct effective prevention efforts on both sides of the border. Methods We gathered sociodemographic, geographic, clinical, and viral sequence data from HIV infected individuals participating in ten studies in the San Diego–Tijuana border region. Phylogenetic and network analysis was performed to infer putative relationships between HIV sequences. Correlates of identified clusters were evaluated and spatiotemporal relationships were explored using Bayesian phylogeographic analysis. Findings After quality filtering, 843 HIV sequences with associated demographic data and 263 background sequences from the region were analyzed, and 138 clusters were inferred (2–23 individuals). Overall, the rate of clustering did not differ by ethnicity, residence, or sex, but bisexuals were less likely to cluster than heterosexuals or men who have sex with men (p = 0.043), and individuals identifying as white (p ≤ 0.01) were more likely to cluster than other races. Clustering individuals were also 3.5 years younger than non-clustering individuals (p < 0.001). Although the sampled San Diego and Tijuana epidemics were phylogenetically compartmentalized, five clusters contained individuals residing on both sides of the border. Interpretation This study sampled ~ 7% of HIV infected individuals in the border region, and although the sampled networks on each side of the border were largely separate, there was evidence of persistent bidirectional cross-border transmissions that linked risk groups, thus highlighting the importance of the border region as a “melting pot” of risk groups. Funding NIH, VA, and Pendleton Foundation.

HIV Infection Rates and Risk Behavior among Young Men undergoing community-based Testing in San Diego

Approximately 80% of new HIV infections in the United States occur in men. Four out of five men diagnosed with HIV infection are men who have sex with men (MSM), with an increasing proportion of young MSM (i.e. ≤24 years of age). We performed a retrospective analysis 11,873 cisgender men participating in a community based HIV screening program in San Diego between 2008 and 2014 to characterize the HIV prevalence and sexual risk behaviors among young men. In young heterosexual men HIV prevalence was lower compared to heterosexual men between 25 and 49 years of age (0.3% vs. 1.4%, p = 0.043). Among young MSM, HIV prevalence was 5.5%, per test positivity rate 3.6%, and HIV incidence 3.4 per 100 person years (95% CI 2.2–5.4). Per test positivity rate (p = 0.008) and incidence (p < 0.001) were significantly higher among young MSM than among MSM above 24-years of age. Young MSM diagnosed with HIV infection reported significantly more serodiscordant condomless anal intercourse, bacterial sexually transmitted infections, and higher rates of methamphetamine and gamma hydroxybutyrate use when compared to young MSM who tested negative. In conclusion, young MSM are particularly vulnerable to HIV infection and may represent ideal candidates for targeted prevention interventions that increase testing uptake and/or decrease the risk of acquiring HIV infection.

HIV Migration Between Blood and Cerebrospinal Fluid or Semen Over Time

Previous studies reported associations between neuropathogenesis and human immunodeficiency virus (HIV) compartmentalization in cerebrospinal fluid (CSF) and between sexual transmission and human immunodeficiency virus type 1 (HIV) compartmentalization in semen. It remains unclear, however, how compartmentalization dynamics change over time. To address this, we used statistical methods and Bayesian phylogenetic approaches to reconstruct temporal dynamics of HIV migration between blood and CSF and between blood and the male genital tract. We investigated 11 HIV-infected individuals with paired semen and blood samples and 4 individuals with paired CSF and blood samples. Aligned partial HIV env sequences were analyzed by (1) phylogenetic reconstruction, using a Bayesian Markov-chain Monte Carlo approach; (2) evaluation of viral compartmentalization, using tree-based and distance-based methods; and (3) analysis of migration events, using a discrete Bayesian asymmetric phylogeographic approach of diffusion with Markov jump counts estimation. Finally, we evaluated potential correlates of viral gene flow across anatomical compartments. We observed bidirectional replenishment of viral compartments and asynchronous peaks of viral migration from and to blood over time, suggesting that disruption of viral compartment is transient and directionally selected. These findings imply that viral subpopulations in anatomical sites are an active part of the whole viral population and that compartmental reservoirs could have implications in future eradication studies.

Dynamics of Viral Evolution and Neutralizing Antibody Response after HIV-1 Superinfection

ABSTRACT Investigating the incidence and prevalence of HIV-1 superinfection is challenging due to the complex dynamics of two infecting strains. The superinfecting strain can replace the initial strain, be transiently expressed, or persist along with the initial strain in distinct or in recombined forms. Various selective pressures influence these alternative scenarios in different HIV-1 coding regions. We hypothesized that the potency of the neutralizing antibody (NAb) response to autologous viruses would modulate viral dynamics in env following superinfection in a limited set of superinfection cases. HIV-1 env pyrosequencing data were generated from blood plasma collected from 7 individuals with evidence of superinfection. Viral variants within each patient were screened for recombination, and viral dynamics were evaluated using nucleotide diversity. NAb responses to autologous viruses were evaluated before and after superinfection. In 4 individuals, the superinfecting strain replaced the original strain. In 2 individuals, both initial and superinfecting strains continued to cocirculate. In the final individual, the surviving lineage was the product of interstrain recombination. NAb responses to autologous viruses that were detected within the first 2 years of HIV-1 infection were weak or absent for 6 of the 7 recently infected individuals at the time of and shortly following superinfection. These 6 individuals had detectable on-going viral replication of distinct superinfecting virus in the env coding region. In the remaining case, there was an early and strong autologous NAb response, which was associated with extensive recombination in env between initial and superinfecting strains. This extensive recombination made superinfection more difficult to identify and may explain why the detection of superinfection has typically been associated with low autologous NAb titers.

Rapid HIV Viral Load Suppression in those Initiating Antiretroviral Therapy at First Visit after HIV Diagnosis

Expert guidelines for antiretroviral therapy (ART) now recommend ART as soon as possible in all HIV infected persons to reduce the risk of disease progression and prevent transmission. The goal of this observational study was to evaluate the impact of very early ART initiation and regimen type on time to viral suppression. We evaluated time to viral suppression among 86 persons with newly-diagnosed HIV infection who initiated ART within 30 days of diagnosis. A total of 36 (42%) had acute, 27 (31%) early, and 23 (27%) had established HIV infection. The median time from an offer of immediate ART to starting ART was 8 days. A total of 56/86 (65%) initiated an integrase inhibitor-based regimen and 30/86 (35%) a protease inhibitor-based regimen. The time to viral suppression was significantly shorter in those receiving an integrase inhibitor- versus a protease inhibitor-based regimen (p = 0.022). Twenty-two (26%) initiated ART at their HIV care intake visit and 79% of these participants achieved viral suppression at week 12, 82% at week 24 and 88% at week 48. ART initiated at the intake visit led to rapid and reliable viral suppression in acute, early and chronic HIV infection, in particular when integrase inhibitor-based regimens were used.

The Breadth and Titer of Maternal HIV-1-Specific Heterologous Neutralizing Antibodies Are Not Associated with a Lower Rate of Mother-to-Child Transmission of HIV-1

ABSTRACT It has been hypothesized that neutralizing antibodies (NAbs) should have broad specificity to be effective in protection against diverse HIV-1 variants. The mother-to-child transmission model of HIV-1 provides the opportunity to examine whether the breadth of maternal NAbs is associated with protection of infants from infection. Samples were obtained at delivery from 57 transmitting mothers (T) matched with 57 nontransmitting mothers (NT) enrolled in the multicenter French perinatal cohort (ANRS EPF CO1) between 1990 and 1996. Sixty-eight (59.6%) and 46 (40.4%) women were infected by B and non-B viruses, respectively. Neutralization assays were carried out with TZM-bl cells, using a panel of 10 primary isolates of 6 clades (A, B, C, F, CRF01_AE, and CRF02_AG), selected for their moderate or low sensitivity to neutralization. Neutralization breadths were not statistically different between T and NT mothers. However, a few statistically significant differences were observed, with higher frequencies or titers of NAbs toward several individual strains for NT mothers when the clade B-infected or non-clade B-infected mothers were analyzed separately. Our study confirms that the breadth of maternal NAbs is not associated with protection of infants from infection.

Early Antiretroviral Therapy Is Associated with Lower HIV DNA Molecular Diversity and Lower Inflammation in Cerebrospinal Fluid but Does Not Prevent the Establishment of Compartmentalized HIV DNA Populations.

Even when antiretroviral therapy (ART) is started early after infection, HIV DNA might persist in the central nervous system (CNS), possibly contributing to inflammation, brain damage and neurocognitive impairment. Paired blood and cerebrospinal fluid (CSF) were collected from 16 HIV-infected individuals on suppressive ART: 9 participants started ART <4 months of the estimated date of infection (EDI) (“early ART”), and 7 participants started ART >14 months after EDI (“late ART”). For each participant, neurocognitive functioning was measured by Global Deficit Score (GDS). HIV DNA levels were measured in peripheral blood mononuclear cells (PBMCs) and CSF cell pellets by droplet digital (dd)PCR. Soluble markers of inflammation (sCD163, IL-6, MCP-1, TNF-α) and neuronal damage (neurofilament light [NFL]) were measured in blood and CSF supernatant by immunoassays. HIV-1 partial C2V3 env deep sequencing data (Roche 454) were obtained for 8 paired PBMC and CSF specimens and used for phylogenetic and compartmentalization analysis. Median exposure to ART at the time of sampling was 2.6 years (IQR: 2.2–3.7) and did not differ between groups. We observed that early ART was significantly associated with lower molecular diversity of HIV DNA in CSF (p<0.05), and lower IL-6 levels in CSF (p = 0.02), but no difference for GDS, NFL, or HIV DNA detectability compared to late ART. Compartmentalization of HIV DNA populations between CSF and blood was detected in 6 out of 8 participants with available paired HIV DNA sequences (2 from early and 4 from late ART group). Phylogenetic analysis confirmed the presence of monophyletic HIV DNA populations within the CSF in 7 participants, and the same population was repeatedly sampled over a 5 months period in one participant with longitudinal sampling. Such compartmentalized provirus in the CNS needs to be considered for the design of future eradication strategies and might contribute to the neuropathogenesis of HIV.

Partner services in adults with acute and early HIV infection

Background: To examine the yield of HIV partner services provided to persons newly diagnosed with acute and early HIV infection (AEH) in San Diego, United States. Design: Observational cohort study. Methods: The study investigated the yield (i.e. number of new HIV and AEH diagnoses, genetically linked partnerships and high-risk uninfected partners) of partner services (confidential contact tracing) for individuals with AEH enrolled in the San Diego Primary Infection Resource Consortium 1996–2014. Results: A total of 107 of 574 persons with AEH (19%; i.e. index cases) provided sufficient information to recruit 119 sex partners. Fifty-seven percent of the 119 recruited partners were HIV infected, and 33% of the 119 were newly HIV diagnosed. Among those newly HIV diagnosed, 36% were diagnosed during AEH. There were no significant demographic or behavioral risk differences between HIV-infected and HIV-uninfected recruited partners. Genetic sequences were available for both index cases and partners in 62 partnerships, of which 61% were genetically linked. Partnerships in which both index case and partner enrolled within 30 days were more likely to yield a new HIV diagnosis (P = 0.01) and to be genetically linked (P < 0.01). Conclusion: Partner services for persons with AEH within 30 days of diagnosis represents an effective tool to find HIV-unaware persons, including those with AEH who are at greatest risk of HIV transmission.