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This observational cross-sectional study of 152 people with HIV (PWH) examined the effects of age and estimated duration of HIV infection (EDI) on depressive and anxiety symptoms. All participants were cisgender men and completed the Profile of Moods State (POMS), a self-report inventory of current (i.e., past week) mood states. Overall, study results confirmed higher levels of anxiety and depression in PWH compared to individuals without HIV. Age group (< 50 or ≥ 50 years) moderated the effect of EDI (< 3 or ≥ 3 years) on mood disturbance. Specifically, younger PWH with early diagnosed infection exhibited the highest levels of depression and anxiety, whereas depression and anxiety were attenuated in older PWH with early infection such that their POMS scores did not significantly differ from the HIV-negative and chronically HIV-infected groups. Despite the small sample size and other important limitations in our study design, our preliminary findings confirm previous observations that older people may have some adaptive ability to better handle the acute psychological stressors associated with recent HIV infection. [ABSTRACT FROM AUTHOR]

Background Evolutionary analyses of well-annotated human immunodeficiency virus (HIV) sequence data can provide insights into viral transmission patterns and associated factors. Here, we explored the transmission dynamics of the HIV-1 subtype B epidemic across the San Diego (US) and Tijuana (Mexico) border region to identify factors that could help guide public health policy. Methods HIV pol sequences were collected from people with HIV in San Diego County and Tijuana between 1996–2018. A multistep phylogenetic approach was used to characterize the dynamics of spread. The contributions of geospatial factors and HIV risk group to the local dynamics were evaluated. Results Phylogeographic analyses of the 2034 sequences revealed an important contribution of local transmission in sustaining the epidemic, as well as a complex viral migration network across the region. Geospatial viral dispersal between San Diego communities occurred predominantly among men who have sex with men, with central San Diego being the main source (34.9%) and recipient (39.5%) of migration events. HIV migration was more frequent from San Diego county towards Tijuana than vice versa. Migrations were best explained by the driving time between locations. Conclusions The US-Mexico border may not be a major barrier to the spread of HIV, which may stimulate coordinated transnational intervention approaches. Whereas a focus on central San Diego has the potential to avert most spread, the substantial viral migration independent of central San Diego shows that county-wide efforts will be more effective. Combined, this work shows that epidemiological information gleaned from pathogen genomes can uncover mechanisms that underlie sustained spread and, in turn, can be a building block of public health decision-making. [ABSTRACT FROM AUTHOR]

HIV transmission is increased during acute and early HIV (AEH). Rapid antiretroviral therapy may shorten the duration of infectivity. We show rapid antiretroviral therapy in AEH is acceptable and effective, with 69.0% of participants starting ART within 7 days of HIV diagnosis disclosure, and 88.1% achieving suppression by 48 weeks. [ABSTRACT FROM AUTHOR]

Rapid start of antiretroviral therapy (ART) is quickly becoming best practice around the world. In the US, programs exist to facilitate rapid ART start, but little is known about the experiences of newly diagnosed individuals receiving these recommendations and services. Twenty participants (19 men who have sex with men and 1 transgender woman) from an early ART start program were interviewed to better understand these experiences. Interviews were analyzed for main themes in three general areas: reasons to start, reasons to delay, and factors influencing early ART adherence. Participants reported starting anywhere from right away (same visit as diagnosis) to within a few weeks (median 10.5 days). Reasons to start right away included fear of what could happen if not treated, personal health, influence of people/resources at the clinic, and study participation. Most had small delays in ART start because of structural (insurance, costs) and intentional delays (getting additional medical consultations). Adherence facilitators included desires to improve CD4/viral load and positive beliefs in benefits of suppression. Participants were largely supportive of rapid ART start and appeared to rely on CD4/viral load as "proof" of need for ART, which may be particularly helpful for asymptomatic, newly diagnosed individuals starting ART. [ABSTRACT FROM AUTHOR]

Background. Treatment of acute human immunodeficiency virus (HIV) infection (AHI) decreases transmission and preserves immune function, but AHI diagnosis remains resource intensive. Risk-based scores predictive for AHI have been described for high-risk groups; however, symptom-based scores could be more generalizable across populations. Methods. Adults who tested either positive for AHI (antibody-negative, HIV nucleic acid test [NAT] positive) or HIV NAT negative with the community-based San Diego Early Test HIV screening program were retrospectively randomized 2:1 into a derivation and validation set. In the former, symptoms significant for AHI in a multivariate logistic regression model were assigned a score value (the odds ratio [OR] rounded to the nearest integer). The score was assessed in the validation set using receiver operating characteristics and areas under the curve (AUC). An optimal cutoff score was found using the Youden index. Results. Of 998 participants (including 261 non-men who have sex with men [MSM]), 113 had AHI (including 4 non-MSM). Compared to HIV-negative cases, AHI cases reported more symptoms (median, 4 vs 0; P < .01). Fever, myalgia, and weight loss were significantly associated with AHI in the multivariate model and corresponded to 11, 8, and 4 score points, respectively. The summed score yielded an AUC of 0.85 (95% confidence interval [CI], .77--.93). A score of ≥11 was 72% sensitive and 96% specific (diagnostic OR, 70.27). Conclusions. A 3-symptom score accurately predicted AHI in a community-based screening program and may inform allocation of resources in settings that do not routinely screen for AHI. [ABSTRACT FROM AUTHOR]

Objectives: To determine cost-effectiveness of three community-based acute HIV infection (AHI) testing algorithms compared to HIV antibody testing alone by focusing on the potential of averting new infections occurring within a one-year time horizon among men who have sex with men (MSM).Methods: Data sources for model parameters included actual cost and prevalence data derived from a community-based AHI screening program in San Diego, and published studies. Main outcome measure was costs per infection averted (IA). The lower end of the cost range of discounted lifetime costs of an HIV infection (i.e. $236,948) was used for defining cost-effectiveness.Results: The most sensitive algorithm for AHI detection, which was based on HIV nucleic acid amplification testing, was estimated to prevent between 5 and 45 transmissions, with simulated costs per infection averted between $965 and $141,256 when compared to HIV antibody testing alone.Conclusion: AHI testing was cost-effective in preventing new HIV infections among at risk MSM in San Diego, and also among other MSM populations with similar HIV prevalence but lower proportions of AHI diagnoses. These results indicate that community-based AHI testing among MSM in the United States can pay for itself over the long run. [ABSTRACT FROM AUTHOR]

Effective population screening of HIV and prevention of HIV transmission are only part of the global fight against AIDS. Community-level effects, for example those aimed at thwarting future transmission, are potential outcomes of treatment and may be important in stemming the epidemic. However, current clinical trial designs are incapable of detecting a reduction in future transmission due to treatment. We took advantage of the fact that HIV is an evolving pathogen whose transmission network can be reconstructed using genetic sequence information to address this shortcoming. Here, we use an HIV transmission network inferred from recently infected men who have sex with men (MSM) in San Diego, California. We developed and tested a network-based statistic for measuring treatment effects using simulated clinical trials on our inferred transmission network. We explored the statistical power of this network-based statistic against conventional efficacy measures and find that when future transmission is reduced, the potential for increased statistical power can be realized. Furthermore, our simulations demonstrate that the network statistic is able to detect community-level effects (e.g., reduction in onward transmission) of HIV treatment in a clinical trial setting. This study demonstrates the potential utility of a network-based statistical metric when investigating HIV treatment options as a method to reduce onward transmission in a clinical trial setting. [ABSTRACT FROM AUTHOR]

Background: Many persons with HIV remain out of care (PWH-OOC). We evaluated InstaCare, a complex intervention integrating the brief behavioral intervention 60 minutes for Health with the rapid restart of antiretroviral therapy (rapid ART)., Setting: Prospective open-label randomized controlled trial among PWH-OOC in San Diego, USA., Methods: PWH-OOC were randomized 1:1 to InstaCare or a time-and-attention control integrating a diet-and-nutrition behavioral intervention also with rapid ART initiation (restart ≤7 days from enrollment). All participants had access to support services (free transport, HIV peer navigation, adherence counseling, and linkage to care) and primary care services (mental health, case management, social work, medication-assisted treatment, and specialist pharmacy). The primary outcomes were viral suppression (<50 copies/mL) and re-engagement with care (≥2 HIV care visits >90 days apart) by 24 weeks. Outcomes were reported on an intention-to-treat basis., Results: Between November 2020 and August 2022, 52 PWH-OOC were enrolled. Baseline substance use in the preceding month (49%), unstable housing (51%), moderate/severe depression (49%), and moderate/severe anxiety (41.7%) were prevalent. Rapid ART was provided for all participants. At week 24, the proportion with HIV viral load <50 copies/mL was 37.3% (19/51) (InstaCare 28.0%, control 46.2%, P = 0.25). Fourteen (27.5%) were engaged with care (InstaCare 7/25 [28.0%], control 7/26 [26.9%], P = 1.00). Most participants (94%) reported low or very low emotional distress associated with rapid ART. Study lost to follow-up by week 24 was high (23/51, 45%)., Conclusions: The InstaCare complex intervention did not improve viral suppression or reengagement with care among PWH-OOC. Investigation of high-intensity, individually adapted interventions is needed among PWH-OOC., Competing Interests: S.J.L. reported grant funding paid to the institution from Gilead Sciences. T.C.S.M. has received travel support for conference attendance from Gilead Sciences. The remaining authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Standard-of-care nucleic acid amplification tests (routine NAATs) for Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) can take several days to result and therefore delay treatment. Rapid point-of-care GC/CT NAAT (rapid NAAT) could reduce the time to treatment and therefore onward transmission. This study evaluated the incremental cost per infectious day averted and overall cost of implementation associated with rapid compared with routine NAAT., Methods: Prospective sexually transmitted infection (STI) treatment data from men who have sex with men and transgender women in San Diego who received rapid NAAT between November 2018 and February 2021 were evaluated. Historical time from testing to treatment for routine NAAT was abstracted from the literature. Costs per test for rapid and routine NAAT were calculated using a micro-costing approach. The incremental cost per infectious day averted comparing rapid to routine NAAT and the costs of rapid GC/CT NAAT implementation in San Diego Public Health STI clinics were calculated., Results: Overall, 2333 individuals underwent rapid NAAT with a median time from sample collection to treatment of 2 days compared with 7 to 14 days for routine NAAT equating to a reduction of 5 to 12 days. The cost of rapid and routine GC/CT NAAT was $57.86 and $18.38 per test, respectively, with a cost-effectiveness of between $2.43 and $5.82 per infectious day averted. The incremental cost of rapid NAAT improved when at least 2000 tests were performed annually., Conclusions: Although rapid GC/CT NAAT is more expensive than routine testing, the reduction of infectious days between testing and treatment may reduce transmission and provide improved STI treatment services to patients., Competing Interests: Conflict of Interest and Sources of Funding: S.J.L. has received funding from Gilead Sciences paid to her institution and donation of medications from Gilead Sciences. E.W., T.C.S.M., N.K.M., and W.T. have no conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Sexually Transmitted Diseases Association.)

Background: Meeting sex partners online is associated with increased risk of acquiring sexually transmitted infections. We examined whether different venues where men who have sex with men (MSM) meet sex partners was associated with prevalent Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection, and whether prevalence increased during (vs before) the COVID-19 pandemic., Methods: We conducted a cross-sectional analysis of data from San Diego's 'Good To Go' sexual health clinic from two enrolment periods: (1) March-September 2019 (pre-COVID-19) and (2) March-September 2021 (during COVID-19). Participants completed self-administered intake assessments. This analysis included males aged ≥18 years self-reporting sex with males within 3 months before enrolment. Participants were categorised as (1) meeting new sex partners in-person only (eg, bars, clubs), (2) meeting new sex partners online (eg, applications, websites) or (3) having sex only with existing partners. We used multivariable logistic regression, adjusting for year, age, race, ethnicity, number of sex partners, pre-exposure prophylaxis use and drug use to examine whether venue or enrolment period were associated with CT/NG infection (either vs none)., Results: Among 2546 participants, mean age was 35.5 (range: 18-79) years, 27.9% were non-white and 37.0% were Hispanic. Overall, CT/NG prevalence was 14.8% and was higher during COVID-19 vs pre-COVID-19 (17.0% vs 13.3%). Participants met sex partners online (56.9%), in-person (16.9%) or only had existing partners (26.2%) in the past 3 months. Compared with having only existing sex partners, meeting partners online was associated with higher CT/NG prevalence (adjusted OR (aOR) 2.32; 95% CI 1.51 to 3.65), while meeting partners in-person was not associated with CT/NG prevalence (aOR 1.59; 95% CI 0.87 to 2.89). Enrolment during COVID-19 was associated with higher CT/NG prevalence compared with pre-COVID-19 (aOR 1.42; 95% CI 1.13 to 1.79)., Conclusions: CT/NG prevalence appeared to increase among MSM during COVID-19, and meeting sex partners online was associated with higher prevalence., Competing Interests: Competing interests: SJL has received funding from Gilead Sciences paid to her institution and donation of medications from Gilead Sciences., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Universal HIV and HCV screening in emergency departments (ED) can reach populations who are less likely to get tested otherwise. The objective of this analysis was to evaluate universal opt-out HIV and HCV screening in two EDs in San Diego. HIV screening for persons aged 13-64 years (excluding persons known to be HIV+ or reporting HIV testing within last 12 months) was implemented using a 4 th generation HIV antigen/antibody assay; HCV screening was offered to persons born between 1945 and 1965. Over a period of 16 months, 12,575 individuals were tested for HIV, resulting in 33 (0.26%) new HIV diagnoses, of whom 30 (90%) were successfully linked to care. Universal screening also identified 74 out-of-care for >12-months HIV+ individuals of whom 50 (68%) were successfully relinked to care. Over a one-month period, HCV antibody tests were conducted in 905 individuals with a seropositivity rate of 9.9% (90/905); 61 seropositives who were newly identified or never treated for HCV had HCV RNA testing, of which 31 (51%) resulted positive (3.4% of all participants, including 18 newly identified RNA positives representing 2% of all participants), and 13/31 individuals (42%) were linked to care. The rate of newly diagnosed HCV infections exceeded the rate of newly diagnosed HIV infections by >7-fold, underlining the importance of HCV screening in EDs.

This study evaluated opt-out inpatient HIV screening delivered by admitting physicians, and compared number of HIV tests and diagnoses to signs and symptoms-directed HIV testing (based on physician orders) in the emergency department (ED). The opt-out inpatient HIV screening program was conducted over a one year period in patients who were admitted to the 386-bed University of California San Diego (UCSD) teaching hospital. Numbers of HIV tests and diagnoses were compared to those observed among ED patients who underwent physician-directed HIV testing during the same time period. Survey data were collected from a convenience sample of patients and providers regarding the opt-out testing program. Among 8488 eligible inpatients, opt-out HIV testing was offered to 3017 (36%) patients, and rapid antibody testing was performed in 1389 (16.4%) inpatients, resulting in 6 (0.4% of all tests) newly identified HIV infections (5/6 were admitted through the ED). Among 27,893 ED patients, rapid antibody testing was performed in 88 (0.3%), with 7 (8.0% of all tests) new HIV infections identified. HIV diagnoses in the ED were more likely to be men who have sex with men (MSM) (p = 0.029) and tended to have AIDS-related opportunistic infections (p = 0.103) when compared to HIV diagnoses among inpatients. While 85% of the 150 physicians who completed the survey were aware of the HIV opt-out screening program, 44% of physicians felt that they did not have adequate time to consent patients for the program, and only 30% agreed that a physician is best-suited to consent patients. In conclusion, the yield of opt-out HIV rapid antibody screening in inpatients was comparable to the national HIV prevalence average. However, uptake of screening was markedly limited in this setting where opt-out screening was delivered by physicians during routine care, with limited time resources being the major barrier.

Women comprised 19% of new HIV diagnoses in the United States in 2014, with significant racial and ethnic disparities in infection rates. This cross-sectional analysis of women enrolled in a cohort study compares demographics, risk behaviour, and sexually transmitted infections (STI) in those undergoing HIV testing in San Diego County. Data from the most recent screening visit of women undergoing voluntary HIV screening April 2008 -July 2014 was used. HIV diagnosis, risk behaviour and self-reported STIs were compared among women aged ≤24, 25-49, and ≥50, as well as between HIV-infected and uninfected women and between Hispanic and non-Hispanic women. Among the 2535 women included, Hispanic women were less likely than other women to report unprotected vaginal intercourse (p = 0.026) or stimulant drug use (p = 0.026), and more likely to report one or fewer partners (p < 0.0001), but also more likely to report sex with an HIV-infected individual (p = 0.027). New HIV infection was significantly more prevalent among Hispanic women (1.6% vs. 0.2%; p < 0.001). Hispanic women were more likely than other women to be diagnosed with HIV despite significantly lower rates of risk behaviour. Culturally specific risk reduction interventions for Hispanic women should focus on awareness of partner risk and appropriate testing., Competing Interests: The authors declare no competing financial interests.

Background: Transmitted drug resistance (TDR) remains an important concern when initiating antiretroviral therapy (ART). Here, we describe the prevalence and phylogenetic relationships of TDR among ART-naive, HIV-infected individuals in San Diego from 1996 to 2013., Methods: Data were analyzed from 496 participants of the San Diego Primary Infection Cohort who underwent genotypic resistance testing before initiating therapy. Mutations associated with drug resistance were identified according to the WHO-2009 surveillance list. Network and phylogenetic analyses of the HIV-1 pol sequences were used to evaluate the relationships of TDR within the context of the entire cohort., Results: The overall prevalence of TDR was 13.5% (67/496), with an increasing trend over the study period (P = 0.005). TDR was predominantly toward nonnucleoside reverse transcriptase inhibitors (NNRTIs) [8.5% (42/496)], also increasing over the study period (P = 0.005). By contrast, TDR to protease inhibitors and nucleos(t)ide reverse transcriptase inhibitors were 4.4% (22/496) and 3.8% (19/496), respectively, and did not vary with time. TDR prevalence did not differ by age, gender, race/ethnicity, or risk factors. Using phylogenetic analysis, we identified 52 transmission clusters, including 8 with at least 2 individuals sharing the same mutation, accounting for 23.8% (16/67) of the individuals with TDR., Conclusions: Between 1996 and 2013, the prevalence of TDR significantly increased among recently infected ART-naive individuals in San Diego. Around one-fourth of TDR occurred within clusters of recently infected individuals. These findings highlight the importance of baseline resistance testing to guide selection of ART and for public health monitoring.

The transgender community represents an understudied population in the literature. The objective of this study was to compare risk behavior, and HIV and sexually transmitted infection (STI) rates between transgender women and transgender men undergoing community-based HIV testing.With this retrospective analysis of a cohort study, we characterize HIV infection rates as well as reported risk behaviors and reported STI in 151 individual transgender women and 30 individual transgender men undergoing community based, voluntary screening for acute and early HIV infection (AEH) in San Diego, California between April 2008 and July 2014.HIV positivity rate was low for both, transgender women and transgender men undergoing AEH screening (2% and 3%, respectively), and the self-reported STI rate for the prior 12 months was 13% for both. Although transgender women appeared to engage in higher rates of risk behavior overall, with 69% engaged in condomless receptive anal intercourse (CRAI) and 11% engaged in sex work, it is important to note that 91% of transgender women reported recent sexual intercourse, 73% had more than 1 sexual partner, 63% reported intercourse with males, 37% intercourse with males and females, and 30% had CRAI.Our results indicate that in some settings rates of HIV infection, as well as rates of reported STIs and sexual risk behavior in transgender men may resemble those found in transgender women. Our findings support the need for comprehensive HIV prevention in both, transgender women and men.

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.

The objectives of this study were to identify risk factors associated with acute and early HIV infection (AEH) among men who have sex with men (MSM) undergoing community HIV testing and to compare demographics in those diagnosed with AEH with those diagnosed at chronic stage of HIV infection.In this retrospective cohort study, we analyzed risk factors associated with AEH among 8925 unique MSM (including 200 with AEH [2.2%] and 219 [2.5%] with newly diagnosed chronic HIV infection) undergoing community-based, confidential AEH screening in San Diego, California.The combination of condomless receptive anal intercourse (CRAI) plus ≥5 male partners, CRAI with an HIV-positive male, CRAI with a person who injects drugs, and prior syphilis diagnosis were significant predictors of AEH in the multivariable Cox regression model. Individuals reporting ≥1 of these 4 risk factors had a hazard ratio of 4.6 for AEH. MSM diagnosed with AEH differed in race (P = 0.005; more reported white race [P = 0.001], less black race [P = 0.030], trend toward less Native American race [P = 0.061]), when compared to those diagnosed with chronic HIV infection, while there was no difference observed regarding age.We established a multivariate model for the predicting risk of AEH infection in a cohort of MSM undergoing community HIV screening, which could be potentially used to discern those in need of further HIV nucleic acid amplification testing for community screening programs that do not test routinely for AEH. In addition, we found that race differed between those diagnosed with AEH and those diagnosed at chronic stage of HIV infection underlining the need for interventions that reduce stigma and promote the uptake of HIV testing for black MSM.

Tenofovir-emtricitabine (TDF-FTC) has demonstrated effectiveness as HIV preexposure prophylaxis (PrEP), but it is not commonly prescribed. Our study was designed to determine the barriers preventing utilization of PrEP among men who have sex with men (MSM), the group at greatest risk for HIV infection in the United States. A population-based sample of MSM presenting for HIV testing at 'Early Test' HIV testing and counseling sites in San Diego, California were offered PrEP and education about potential efficacy. Eligible individuals reported having unprotected sex within the past 12 months and who tested negative for HIV were offered study participation. Despite offering procedures for evaluation and prescription for PrEP to 416 eligible subjects, less than 0.5 % of participants received the drug. Surveys collected from 54 of those who declined study participation revealed multiple barriers to PrEP among MSM including cost, low perceived risk of infection and concerns about taking a daily medication and potential long-term side effects. Efforts should be made to address these barriers, especially lowering the cost of TDF-FTC, education about PrEP side effects and awareness of HIV risks.

Our objective here is to demonstrate the population-level effects of individual-level post-diagnosis behavior change (PDBC) in Southern Californian men who have sex with men (MSM), recently diagnosed with HIV. While PDBC has been empirically documented, the population-level effects of such behavior change are largely unknown. To examine these effects, we develop network models derived from the exponential random graph model family. We parameterize our models using behavioral data from the Southern California Acute Infection and Early Disease Research Program, and biological data from a number of published sources. Our models incorporate vital demographic processes, biology, treatment and behavior. We find that without PDBC, HIV prevalence among MSM would be significantly higher at any reasonable frequency of testing. We also demonstrate that higher levels of HIV risk behavior among HIV-positive men relative to HIV-negative men observed in some cross-sectional studies are consistent with individual-level PDBC.

Objective: To reconstruct the local HIV-1 transmission network from 1996 to 2011 and use network data to evaluate and guide efforts to interrupt transmission., Design: HIV-1 pol sequence data were analyzed to infer the local transmission network., Methods: We analyzed HIV-1 pol sequence data to infer a partial local transmission network among 478 recently HIV-1 infected persons and 170 of their sexual and social contacts in San Diego, California. A transmission network score (TNS) was developed to estimate the risk of HIV transmission from a newly diagnosed individual to a new partner and target prevention interventions., Results: HIV-1 pol sequences from 339 individuals (52.3%) were highly similar to sequences from at least one other participant (i.e., clustered). A high TNS (top 25%) was significantly correlated with baseline risk behaviors (number of unique sexual partners and insertive unprotected anal intercourse (p = 0.014 and p = 0.0455, respectively) and predicted risk of transmission (p<0.0001). Retrospective analysis of antiretroviral therapy (ART) use, and simulations of ART targeted to individuals with the highest TNS, showed significantly reduced network level HIV transmission (p<0.05)., Conclusions: Sequence data from an HIV-1 screening program focused on recently infected persons and their social and sexual contacts enabled the characterization of a highly connected transmission network. The network-based risk score (TNS) was highly correlated with transmission risk behaviors and outcomes, and can be used identify and target effective prevention interventions, like ART, to those at a greater risk for HIV-1 transmission.

Objectives: To further understand the role that chronic viral infections of the male genital tract play on HIV-1 dynamics and replication., Design: Retrospective, observational study including 236 paired semen and blood samples collected from 115 recently HIV-1 infected antiretroviral naive men who have sex with men., Methods: In this study, we evaluated the association of seminal HIV-1 shedding to coinfections with seven herpes viruses, blood plasma HIV-1 RNA levels, CD4 T-cell counts, presence of transmitted drug resistance mutations (DRMs) in HIV-1 pol, participants' age and stage of HIV-infection using multivariate generalized estimating equation methods. Associations between herpes virus shedding, seminal HIV-1 levels, number and immune activation of seminal T-cells was also investigated (Mann-Whitney)., Results: Seminal herpes virus shedding was observed in 75.7% of individuals. Blood HIV-1 RNA levels (P < 0.01) and seminal cytomegalovirus (CMV) and human herpes virus (HHV)-8 levels (P < 0.05) were independent predictors of detectable seminal HIV-1 RNA; higher seminal HIV-1 levels were associated with CMV and Epstein-Barr virus (EBV) seminal shedding, and absence of DRM (P < 0.05). CMV and EBV seminal shedding was associated with higher number of seminal T-lymphocytes, but only presence of seminal CMV DNA was associated with increased immune activation of T-lymphocytes in semen and blood., Conclusion: Despite high median CD4 T-cells numbers, we found a high frequency of herpes viruses seminal shedding in our cohort. Shedding of CMV, EBV and HHV-8 and absence of DRM were associated with increased frequency of HIV-1 shedding and/or higher levels of HIV-1 RNA in semen, which are likely important cofactors for HIV-1 transmission.

The contribution of injection drug use to HIV risk among men who have sex with men (MSM) is understudied. MSM infected with HIV within the prior 12 months completed a questionnaire assessing sociodemographic, sexual, drug use, and social factors. Analyses were performed to identify factors associated with lifetime history of injection drug use. Among 212 participants, the mean age was 33.8 years, 72% were White, 89% had attended college, and 9.4% reported ever injecting drugs. In multivariable logistic regression analysis, ever trading sex and using methamphetamine during sex with at least one of their last three partners were associated with injection drug use. Adjusting for these variables, in separate models, ever perpetrating violence against others (Adjusted Odds Ratio [AOR] = 3.16), having physically abusive sexual partners (AOR = 3.08), or physically abusing sexual partners (AOR = 10.17) were significantly (P < 0.05) associated with injection drug use. These findings suggest that violence is more common among MSM who inject drugs, which should be considered in HIV prevention efforts.

Objectives: Assess behavior change of recently HIV-infected men who have sex with men (MSM)., Methods: From 2002 to 2006, 193 recently HIV-infected MSM in the Southern California Acute Infection and Early Disease Research Program were interviewed every 3 months. Changes in HIV status of partners, recent unprotected anal intercourse (UAI), drug use, use of antiretroviral therapy (ART), detectable viral load, and partnership dynamics over 1 year were used to predict recent UAI in a random effect logistic regression., Results: Over a year significantly fewer partners in the past 3 months were reported (mean 8.81 to 5.84; P < 0.0001). Percentage of recent UAI with HIV-status unknown last partners decreased from enrollment to 9 months (49%-27%) and rebounded at 12 months to 71%. In multivariable models controlling for ART use, recent UAI was significantly associated with: baseline methamphetamine use [adjusted odds ratio (AOR): 7.65, 95% confidence interval (CI): 1.87 to 31.30], methamphetamine use at follow-up (AOR: 14.4, 95% CI: 2.02 to 103.0), HIV-uninfected partner at follow-up (AOR: 0.14, 95% CI: 0.06 to 0.33), and partners with unknown HIV status at follow-up (AOR: 0.33, 95% CI: 0.11 to 0.94). HIV viral load did not influence rate of UAI., Conclusions: Transmission behaviors of these recently HIV-infected MSM decreased and serosorting increased after diagnosis; recent UAI with serostatus unknown or negative partners rebounded after 9 months, identifying critical timepoints for interventions targeting recently HIV-infected individuals. There was no evidence in this cohort that the viral load of these recently infected men guided their decisions about protected or unprotected anal intercourse.

We conducted a case-control study to compare illicit substance and erectile dysfunction medication (EDM) use between recently HIV-infected and uninfected men who have sex with men (MSM). Eighty-six recently (previous 12 months) HIV-infected MSM (cases) and 59 MSM who recently tested HIV-negative (controls) completed computer-assisted self-interviews. There were no statistical differences in demographics or number of sexual partners by HIV status. Cases were more likely than controls to report methamphetamine or nitrite use, but not EDM, gamma hydroxybutyrate, 3,4 methylenedioxymethamphetamine, cocaine, or marijuana use, in the previous 12 months and with their last three sexual partners in multivariate logistic regression models. Use of nitrites and amphetamine may increase HIV risk among MSM.

Background: Current public health efforts often use molecular technologies to identify and contain communicable disease networks, but not for HIV. Here, we investigate how molecular epidemiology can be used to identify highly related HIV networks within a population and how voluntary contact tracing of sexual partners can be used to selectively target these networks., Methods: We evaluated the use of HIV-1 pol sequences obtained from participants of a community-recruited cohort (n = 268) and a primary infection research cohort (n = 369) to define highly related transmission clusters and the use of contact tracing to link other individuals (n = 36) within these clusters. The presence of transmitted drug resistance was interpreted from the pol sequences (Calibrated Population Resistance v3.0)., Results: Phylogenetic clustering was conservatively defined when the genetic distance between any two pol sequences was less than 1%, which identified 34 distinct transmission clusters within the combined community-recruited and primary infection research cohorts containing 160 individuals. Although sequences from the epidemiologically linked partners represented approximately 5% of the total sequences, they clustered with 60% of the sequences that clustered from the combined cohorts (odds ratio 21.7; P < or = 0.01). Major resistance to at least one class of antiretroviral medication was found in 19% of clustering sequences., Conclusion: Phylogenetic methods can be used to identify individuals who are within highly related transmission groups, and contact tracing of epidemiologically linked partners of recently infected individuals can be used to link into previously defined transmission groups. These methods could be used to implement selectively targeted prevention interventions.

Background: In patients infected with human immunodeficiency virus type 1 (HIV-1), HIV-1 DNA persists during highly active antiretroviral treatment, reflecting long-lived cellular reservoirs of HIV-1. Recent studies report an association between HIV-1 DNA levels, disease progression, and treatment outcome. However, HIV-1 DNA exists as distinct molecular forms that are not distinguished by conventional assays., Methods: We analyzed HIV-1 RNA levels in plasma, CD4 cell counts, and levels of integrated and nonintegrated HIV-1 DNA in peripheral blood mononuclear cells (PBMCs) from patients with early or chronic infection before and during antiretroviral treatment. We also studied HIV-1 DNA decay in primary CD4 T cells infected in vitro. HIV-1 DNA was analyzed using an assay that is unaffected by the location of HIV-1 integration sites., Results: HIV-1 RNA levels and total HIV-1 DNA levels decayed rapidly in patients during receipt of suppressive antiretroviral therapy. Ratios of total HIV-1 DNA levels to integrated HIV-1 DNA levels were high before initiation of therapy but diminished during therapy. Levels of linear nonintegrated HIV-1 DNA decayed rapidly in vitro (t (1/2) = 1- 4.8 days)., Conclusion: Total HIV-1 DNA decays rapidly with suppression of virus replication in vivo. Clearance of HIV-1 DNA during the first 6 months of therapy reflects a disproportionate loss of nonintegrated HIV-1 DNA genomes, suggesting that levels of total HIV-1 DNA in PBMCs after prolonged virus suppression largely represent integrated HIV-1 genomes.

Objective: The objective of this study was to assess associations between unprotected anal intercourse (UAI) and substance use before and after HIV diagnosis among recently HIV-infected MSM., Study Design: Two hundred seven MSM completed computer-assisted self-interviews regarding type and timing of sexual activity and substance use with their last 3 partners. Date of HIV diagnosis was extracted from medical records. Generalized estimating equations, including interaction terms, were used to assess associations between substance use and UAI before and after HIV diagnosis., Results: Among partners with whom sexual activity occurred before diagnosis, UAI was associated with methamphetamine use alone (odds ratio = 7.12) and a combination of methamphetamine and other substances (odds ratio = 4.06). However, after HIV diagnosis, UAI was associated with use of substances other than methamphetamine (odds ratio = 3.36), but not methamphetamine alone., Conclusions: Use of illicit substances may be differentially associated with UAI based on knowledge of HIV status and could have implications for prevention of HIV transmission.

Objective: We sought to compare baseline and longitudinal plasma HIV-1 loads between herpes simplex virus type 2 (HSV-2)-seropositive and -seronegative individuals who are enrolled in a primary HIV-1 infection cohort in San Diego, California., Design: The study was a retrospective cohort analysis., Methods: We categorized antiretroviral-naive subjects on the basis of HSV-2 serostatus at baseline using an HSV-2 enzyme immunoassay. Low positive results (1.1-3.5) were confirmed by Western blotting. We compared baseline HIV-1 loads of the 2 groups using a linear model. To detect differences in HIV-1 dynamics, we analyzed longitudinal viral loads using a flexible semiparametric model, controlling for the time to antiretroviral therapy and stratifying by HIV-1 infection stage at entry., Results: We studied 294 adult men. Ninety percent reported sex with men as their main HIV-1 risk factor. The seroprevalence of HSV-2 was 41.5%. The HSV-2-seropositive and -seronegative groups had similar baseline HIV-1 loads during acute infection (5.52 vs. 5.72 log(10) copies/mL; P=.39) and early infection (4.57 vs. 4.67 log(10) copies/mL; P=.5). Longitudinally, the difference in HIV-1 loads between HSV-2-seropositive and -seronegative men remained close to 0 during the first year of infection., Conclusions: HSV-2 serostatus has minimal influence on the dynamics of HIV-1 during acute and early HIV-1 infection.

Objectives: Analyze postdiagnosis behaviors of recently HIV-infected men who have sex with men (MSM)., Methods: Recently HIV-infected MSM were interviewed at 6 weeks (n = 153) and 3 months (n = 113) after diagnosis. Behaviors from baseline to follow-up were compared; multivariate logistic regression identified associations between baseline characteristics and behavior at follow-up., Results: At follow-up, MSM reported a significantly lower mean of partners (7.9 vs. 5.2) and lower means of 1-time (1.9 vs. 0.8), unknown (3.7 vs. 2.6), and acquaintance (1.1 vs. 0.5) partners than at baseline. In multivariate analyses, unprotected anal intercourse (UAI) with the last partner at follow-up was more likely if the last partner at baseline was a main partner (odds ratio [OR] = 2.94, 95% confidence interval [CI]: 1.04 to 8.33) or HIV-positive partner (OR = 3.36, 95% CI: 1.27 to 8.88) but less likely if, at follow-up, the last partner was HIV-negative (OR = 0.28, 95% CI: 0.08 to 1.00) or of unknown HIV status (OR = 0.23, 95% CI: 0.08 to 0.71), the participant had a history of nonconsensual sex (OR = 0.25, 95% CI: 0.09 to 0.72), or the participant had more than 1 partner (OR = 0.28, 95% CI: 0.09 to 0.86). More than 1 partner at follow-up was associated with no main partner at baseline or follow-up (OR = 2.76, 95% CI: 1.12 to 6.78), more partners in the last 12 months (OR = 1.02, 95% CI: 1.01 to 1.04), and UAI with the last partner (OR = 0.36, 95% CI: 0.14 to 0.90)., Conclusions: After diagnosis, some but not all recently HIV-infected MSM reduced risky sexual behavior permitting potential HIV transmission.