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Background The incidence of HIV among persons who inject drugs (PWID) in the USA has been increasing since 2014, signaling the need to identify effective ways to engage PWID in HIV prevention services, namely pre-exposure prophylaxis (PrEP). Yet, the uptake of PrEP in this population is minimal compared to other populations at risk of HIV acquisition. In this work, we sought to explore knowledge, attitudes, and perspectives of PrEP acceptability among PWID. Methods In the context of a pilot study to explore the acceptability of pharmacy-based hepatitis C virus (HCV) treatment, we conducted semi-structured interviews (n = 24) and focus groups (n = 4, 16 participants) with people who were living with HCV and reported active injection drug use (≤ 90 days since last use). Participants were asked open-ended questions about their familiarity with and motivation to use PrEP. As part of a sub-analysis focused on PrEP, qualitative data were analyzed using a Rapid Assessment Process, where three coders used structured templates to summarize qualitative data and iteratively reviewed coded templates to identify themes. Participants also completed short quantitative questionnaires regarding drug use history and attitudes toward health concerns. Results Forty-seven percent of participants expressed having little or no concern regarding HIV acquisition. Targeted analyses focused on HIV prevention identified three themes, which help characterize behavioral determinants of nonadoption. First, knowledge of PrEP was limited among PWID and influenced by infrequent open community discussions around HIV risk. Second, PWID perceived sexual behaviors—but not injection drug use—as a motivator for HIV risk prevention. Finally, PWID identified many individual and environmental barriers that hinder PrEP uptake. Conclusion Among PWID, PrEP is rarely discussed and concerns about the feasibility of using daily PrEP are common. Taken with the prevalent perception that drug use is not a high risk for HIV acquisition, our findings point to opportunities for public health work to target PrEP education to PWID and to leverage other successful interventions for PWID as an opportunity to provide PrEP to this vulnerable population.

Point-of-care (POC) nucleic acid tests (NATs) have potential to diagnose acute HIV infection and monitor persons taking pre-exposure prophylaxis or antiretroviral therapy (ART). POC NATs have not yet been evaluated in the US.From June 2018-March 2019, we conducted a cross-sectional evaluation of the Simple Amplification-Based Assay version II (SAMBA II) POC NAT. People with HIV (PWH) and persons testing for HIV were tested with the SAMBA II qualitative (Qual) whole blood (WB) test. From April-September 2019, the Qual test was used on persons who were ART-naive, and SAMBA II Semi-quantitative (Semi-Q) WB was used with ART-experienced PWH. Both were performed on unprocessed venipuncture (VP) and, when indicated by protocol, fingerstick (FS) WB and plasma. SAMBA results were compared with Abbott RealTime HIV-1 polymerase chain reaction results on plasma. We calculated sensitivity, specificity, and concordance between tests.SAMBA was used in 330 visits among 280 participants: 202 (61.2%) visits from PWH, and 128 (38.8%) from HIV-negative persons. Qual test sensitivity with ART-naive participants was 91.4% [32/35, 95% confidence interval (CI): 77.6% to 97.0%] using VP WB and 100% (27/27, 95% CI: 87.5% to 100%) using FS WB. Specificity was 100% using both specimen types. Concordance between the gold standard and Semi-Q at 1000 copies/mL among PWH on ART was 97.7% (86/88, 95% CI: 92.1% to 99.4%) and 100% (30/30, 95% CI: 88.7% to 100%) using VP and FS WB, respectively.The SAMBA II POC NATs showed high sensitivity, specificity, and concordance with the gold standard assay, indicating its potential use in diagnostics and monitoring. Future work will evaluate POC NAT implementation in the US.

Background We update a previous systematic review to inform new World Health Organization HIV self-testing (HIVST) recommendations. We compared the effects of HIVST to standard HIV testing services to understand which service delivery models are effective for key populations. Methods We did a systematic review of randomised controlled trials (RCTs) which compared HIVST to standard HIV testing in key populations, published from 1 January 2006 to 4 June 2019 in PubMed, Embase, Global Index Medicus, Social Policy and Practice, PsycINFO, Health Management Information Consortium, EBSCO CINAHL Plus, Cochrane Library and Web of Science. We extracted study characteristic and outcome data and conducted risk of bias assessments using the Cochrane ROB tool version 1. Random effects meta-analyses were conducted, and pooled effect estimates were assessed along with other evidence characteristics to determine the overall strength of the evidence using GRADE methodology. Results After screening 5909 titles and abstracts, we identified 10 RCTs which reported on testing outcomes. These included 9679 participants, of whom 5486 were men who have sex with men (MSM), 72 were trans people and 4121 were female sex workers. Service delivery models included facility-based, online/mail and peer distribution. Support components were highly diverse and ranged from helplines to training and supervision. HIVST increased testing uptake by 1.45 times (RR=1.45 95% CI 1.20, 1.75). For MSM and small numbers of trans people, HIVST increased the mean number of HIV tests by 2.56 over follow-up (mean difference = 2.56; 95% CI 1.24, 3.88). There was no difference between HIVST and SoC in regard to positivity among tested overall (RR = 0.91; 95% CI 0.73, 1.15); in sensitivity analysis of positivity among randomised HIVST identified significantly more HIV infections among MSM and trans people (RR = 2.21; 95% CI 1.20, 4.08) and in online/mail distribution systems (RR = 2.21; 95% CI 1.14, 4.32). Yield of positive results in FSW was not significantly different between HIVST and SoC. HIVST reduced linkage to care by 17% compared to SoC overall (RR = 0.83; 95% CI 0.74, 0.92). Impacts on STI testing were mixed; two RCTs showed no decreases in STI testing while one showed significantly lower STI testing in the intervention arm. There were no negative impacts on condom use (RR = 0.95; 95% CI 0.83, 1.08), and social harm was very rare. Conclusions HIVST is safe and increases testing uptake and frequency as well as yield of positive results for MSM and trans people without negative effects on linkage to HIV care, STI testing, condom use or social harm. Testing uptake was increased for FSW, yield of positive results were not and linkage to HIV care was worse. Strategies to improve linkage to care outcomes for both groups are crucial for effective roll-out. Supplementary information The online version contains supplementary material available at 10.1186/s12916-020-01835-z.

Background Real-time, objective measures of adherence to antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) are needed to better assess adherence levels and to expedite clinical response for those with suboptimal adherence. Point-of-care tenofovir (POC-TFV) testing has been proposed as a solution to facilitate real-time antiretroviral adherence monitoring, but little is known about how health care providers, people living with HIV (PLWH) receiving ART, and people receiving PrEP will perceive POC-TFV testing. Methods We conducted an exploratory qualitative study to assess perspectives on the utility and interest in POC-TFV testing from potential end users. We conducted three focus group discussions (FGDs) among 17 PLWH receiving ART and four individuals receiving PrEP, as well as eight in-depth interviews (IDIs) with health care providers in the Seattle area and presented participants with a hypothetical urine-based POC-TFV test. FGDs and IDIs were audio recorded, transcribed, coded, and analyzed to describe emerging themes. Results Overall, study participants demonstrated divergent opinions about the POC-TFV test. Among study participants, PLWH were most ambivalent about POC-TFV testing, first demonstrating reluctance to TFV-level monitoring and shifting positions during the FGDs. However, all PLWH participants were receptive to POC-TFV testing if requested by their provider. PrEP participants were generally supportive of POC-TFV testing for routine adherence monitoring and emphasized potential value in self-administered testing. Providers’ perceptions were equally divided – half suggested POC-TFV testing would be valuable, particularly for people receiving PrEP, while half indicated the test would have little benefit for most individuals receiving ART or PrEP in the U.S. All providers agreed that POC-TFV test results could be beneficial for assessing discrepancies in viral load results and self-reported adherence among PLWH. The study also revealed that a low-cost, non-urine-based POC-TFV test with a long-term limit of detection would be preferred over the hypothetical urine-based test. Conclusions Our findings indicate POC-TFV testing may be beneficial for routine, clinic-based adherence monitoring, particularly for individuals receiving PrEP or for PLWH with persistent viremia or following recent ART initiation. These findings should also be used to formulate a target product profile for a POC-TFV test and to guide further developments in tools for objective antiretroviral adherence monitoring.

Aims To evaluate provider perspectives on the use of a point-of-care nucleic acid test (POC NAT) and preferential opinions for motivational interviewing (MI) or problem-solving counseling (PSC) as an ultra-brief intervention for patients experiencing challenges to antiretroviral therapy (ART) adherence. Methods A qualitative study was conducted among providers at an HIV care clinic in Seattle, Washington. Ten in-depth interviews with HIV care providers were completed, which explored determinants of acceptability, feasibility and preferences for a combined adherence counseling and POC NAT intervention for patients living with HIV. Interviews were analyzed through consensus coding and the Five A’s Framework to inform thematic analysis. Results Providers favored the use of a combined adherence counseling technique and POC NAT for their non-adherent patients living with HIV. Providers believed the intervention was an improvement on current assessment and advising practices. However, concerns about extended wait times for the POC NAT results influenced perceptions about feasibility around clinic flow and incorporation into clinic practice. Providers believed that acceptability of POC NAT implementation would be enhanced by including a subset of patient populations whom tend to be in the clinic for longer periods, and in tandem face greater ART adherence challenges. Conclusion The GAIN Study will be the first project to evaluate the implementation of POC NAT in the U.S. Continued formative work is ongoing and may illustrate how best to address feasibility and concern around the two-hour time to result. The planned GAIN study will incorporate some of the findings found in this qualitative study and pilot this intervention, including a time-in-motion analyses of clinic flow, which may help reduce perceived wide-scale adaptation of POC NAT and ART adherence counselling among PLHW. Future work, including a shorter time to results and/or lower limit detection could make a significant improvement in the provision of HIV care.

We examined adherence, medication-taking practices, and preferences to inform development of a wrist-worn adherence system. Two convenience samples of persons taking antiretroviral therapy and HIV pre-exposure prophylaxis completed a survey. Additional online questions asked about willingness to use a wrist-worn device and reminder and feedback preferences. Among 225 participants, 13% reported adherence < 90% this was associated with younger age and clinic sample. Compared to pill bottle–using participants, mediset users less commonly reported adherence < 90% (aOR = 0.16, p = .02), and blister pack users (aOR = 6.3, p = .02) and pill roll users (aOR = 3.3, p = .04) more commonly reported adherence < 90%. Sixty-two percent of the online participants reporting adherence (< 100%) had some interest in receiving adherence reminders, including 42% with interest in receiving reminders by smartwatch notifications. Although confounders are likely, formative work identified potential users and interest in using a wrist-worn adherence system. Future work will determine its acceptability and efficacy.

Objectives High medication adherence is important for HIV suppression (antiretroviral therapy) and pre-exposure prophylaxis efficacy. We are developing sensor-based technologies to detect pill-taking gestures, trigger reminders, and generate adherence reports. Materials and Methods We collected interview, observation, and questionnaire data from individuals with and at-risk for HIV (N = 17). We assessed their medication-taking practices and physical actions, and feedback on our initial design. Results While participants displayed diverse medication taking practices and physical actions, most (67%) wanted to use the system to receive real-time and summative feedback, and most (69%) wanted to share data with their physicians. Participants preferred reminders via the wrist-worn device or mobile app, and summative feedback via mobile app or email. Discussion Adoption of these systems is promising if designs accommodate diverse behaviors and preferences. Conclusion Our findings may help improve the accuracy and adoption of the system by accounting for user behaviors, physical actions, and preferences.

BACKGROUND We aimed to assess HIV preexposure prophylaxis (PrEP) awareness and prescribing practices among Washington State medical providers from diverse professional disciplines and practice types. METHODS In May 2016, we administered an anonymous online survey to licensed medical practitioners who provide primary, longitudinal, walk-in, emergency, obstetric, gynecologic, sexually transmitted infection, or family planning care. RESULTS Of 735 eligible providers, 64.8% had heard of PrEP. Younger providers and providers with a doctor of medicine degree were more likely to be aware of PrEP compared with older providers (P = 0.0001) and providers of other training backgrounds (advanced registered nurse practitioner, doctor of osteopathic medicine, or physician assistant; P = 0.04). Among providers aware of PrEP, most frequent reported concerns about prescribing were adherence (46.0%) and costs (42.9%). Providers felt very (20.1%) or somewhat (33.8%) comfortable discussing PrEP overall, but very (26.8%) or somewhat (44.7%) uncomfortable discussing cost and insurance issues. The 124 PrEP prescribers reported a median of 2 (range, 1-175; total, 1142) patients prescribed PrEP. Prior authorizations and insurance denials had prevented prescriptions for 28.7% and 12.1% of prescribers, respectively. CONCLUSIONS Interventions to improve PrEP access should include education to inform medical providers about PrEP, with particular attention to provider types less likely to be aware. Continued efforts to eliminate cost and insurance barriers and educate providers regarding financial resources would help improve PrEP access.

Background Peer navigation is a promising strategy to link at-risk minority men who have sex with men (MSM) to HIV prevention services including pre-exposure prophylaxis (PrEP). Methods Thirty-two Black and 63 Latinx HIV-negative MSM living in western Washington completed a survey examining attitudes towards peer navigation and PrEP. Factor analysis derived a score for peer navigator acceptability, and linear regression identified associations with this outcome. Results Forty-eight percent were interested in peer navigation. Being insured, higher sexual stigma, and higher PHQ-9 score were associated with higher acceptability, while higher income and having a regular medical provider were associated with lower acceptability. In multivariable analysis, higher sexual stigma predicted higher acceptability, while higher income predicted lower acceptability. Men preferred that peers be matched on sexual orientation, race, age and culture. Conclusion Peer navigation interventions to reach minority men should address stigma, focus on lower-income men, and try to match peers to clients to the extent possible.

One barrier to human immunodeficiency virus preexposure prophylaxis (PrEP) is lack or perceived lack of health insurance or financial assistance. We performed a medical records review at a safety-net PrEP clinic in Seattle, Washington, and found that barriers to obtaining financial assistance were commonly recorded in association with initiation and persistence on PrEP.

The performance of recently approved point-of-care (POC) HIV tests should be assessed using unprocessed specimens.To evaluate the sensitivity and specificity of four POC HIV tests using whole blood (WB) and two using oral fluid (OF) among persons recruited from health clinics in Seattle, Washington, during September 2015-September 2017.Participants were tested with the POC tests, additional plasma and serum were collected for laboratory testing, and participant- reported use of antiretroviral therapy (ART) or pre-exposure prophylaxis (PrEP) was recorded. Participants testing negative on all tests could reenroll every 90 days. Specimens from persons previously diagnosed with HIV infection as well as from those who were newly diagnosed during the study were included in the sensitivity estimate. Sensitivity and specificity were calculated based on HIV status determined by laboratory testing.Of 1,256 visits, 179 were from persons with HIV infection; 120 of these were taking ART. Among 1,077 visits from participants not diagnosed with HIV, PrEP use was reported at 155 (14.4%) visits. Sensitivity was similar among POC WB tests (95.53%-97.21%; p0.05). Among participants on ART, sensitivity was lower for the same test performed on OF compared to WB (p0.003). Specificity was high for all tests (99.44%- 100.00%); we did not detect specificity differences with PrEP use.These POC tests displayed relatively high sensitivity and specificity using unprocessed specimens, suggesting their effectiveness in identifying HIV infections whenever laboratory-based testing is not feasible. Nonetheless, clients with recent risk should retest to rule out the possibility of a false-negative result.

Summary Tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are used for HIV treatment and prevention. Previously, we found that topical rectal tenofovir gel caused immunological changes in the mucosa. Here, we assess the effect of oral TDF/FTC in three HIV pre-exposure prophylaxis trials, two with gastrointestinal and one with cervicovaginal biopsies. TDF/FTC induces type I/III interferon-related (IFN I/III) genes in the gastrointestinal tract, but not blood, with strong correlations between the two independent rectal biopsy groups (Spearman r = 0.91) and between the rectum and duodenum (r = 0.81). Gene set testing also indicates stimulation of the type I/III pathways in the ectocervix and of cellular proliferation in the duodenum. mRNA sequencing, digital droplet PCR, proteomics, and immunofluorescence confirm IFN I/III pathway stimulation in the gastrointestinal tract. Thus, oral TDF/FTC stimulates an IFN I/III signature throughout the gut, which could increase antiviral efficacy but also cause chronic immune activation in HIV prevention and treatment settings., Graphical Abstract, Highlights Tenofovir (TDF) and emtricitabine (FTC) are used for HIV treatment and prevention TDF/FTC induce a type I/III interferon-associated signature throughout the gut IFN I/III induction is confirmed in independent clinical cohorts and 5 assay types IFN I/III induction may contribute to anti-HIV efficacy and chronic immune activation, Many people take the antiretroviral drugs tenofovir and emtricitabine to prevent and treat HIV infection. Hughes et al. show that these medications induce genes and proteins associated with type I/III interferon pathways in the gut. This effect may contribute to HIV inhibition but could also cause chronic immune activation.

These recommendations and resources can help make HIV pre-exposure prophylaxis an essential part of your work.

Background HIV disproportionately affects cisgender men and transgender people who have sex with men (MSM/TG) and use methamphetamine. Pre-exposure prophylaxis (PrEP) uptake has been slow in this group. It is important to understand perceptions about PrEP and barriers to its use among MSM/TG who use methamphetamine to reduce new HIV infections. Methods: We conducted four focus groups with peer educators of a harm reduction program. We assessed their perspectives of PrEP and barriers across the PrEP continuum among MSM/TG who use methamphetamine. Results: Notably, stigma related to the multiple marginalised identities of MSM/TG who use methamphetamine (e.g. MSM/TG-related stigma, methamphetamine-related stigma) was a barrier at each step. We developed a framework that combined the PrEP continuum and a stigma-based treatment cascade to explore these themes and describe the effects of stigma on PrEP engagement. Methamphetamine-related barriers were also identified. Conclusions: The findings of this study emphasise the importance of incorporating stigma reduction into PrEP delivery for MSM/TG who use methamphetamine.

We evaluated detection of HIV-1 RNA from dried blood spots (DBS) and oral fluid specimens. Between February 2010 and August 2014, HIV-1 was newly diagnosed in eight (2.6%) study participants who had median blood HIV-1 RNA of 61 500 copies/ml (interquartile range 7500-146 000). RNA was detected in seven (87.5%) DBS and three (37.5%) oral fluid swabs but was not detected in either specimen from one participant. DBS may be a reasonable specimen collection method to detect acute infection.

There has been increasing recognition of the importance of diagnosing individuals during the earliest stages of human immunodeficiency virus (HIV) infection. Sera from individuals referred to a primary HIV infection research program were screened using the IgG-sensitive Vironostika HIV-1 Microelisa System, IgG/IgM-sensitive GS HIV-1/HIV-2 Plus O antibody enzyme immunoassay (EIA), or Abbott ARCHITECT HIV antigen (Ag)/antibody (Ab) Combo assay and confirmed by the Bio-Rad Multispot and Western blot. A subset of participants was co-enrolled in a study designed to compare the ability of point-of-care tests to detect early infection. We calculated time within primary infection laboratory stages using actual observed transitions and with an expectation-maximization algorithm. Three hundred and sixty participants contributed data to this analysis. Of 123 persons referred with EIA-negative/RNA-positive test results (Fiebig stage I-II) or for concern for symptoms, 24 (20%) were still in stages I-II, and 99 (80%) were in stages III or later at their screening visit. Participants were estimated to spend a median of 13.5 days in stages I and II, 2.3 days in stage III, and 7.8 days in stage IV. OraQuick performed on oral fluids detected 53% of 17 participants in stage V. The durations of stages we observed are consistent with previous publications. Most persons referred for research no longer had acute infection at their first visit. Programs wishing to identify persons in the very earliest stages of infection need to expedite referrals or develop targeted screening programs.

Background Cisgender men and transgender individuals who have sex with men (MSM/TG) and use methamphetamine are at elevated risk for HIV and have had limited pre-exposure prophylaxis (PrEP) uptake. The aim of this study was to quantify the knowledge and use of PrEP, identify barriers to PrEP use, and develop a targeted educational campaign to promote PrEP among MSM/TG who use methamphetamine. Methods: We conducted three consultations with peer educators of Project Needle and Sex Education Outreach Network (NEON) to develop and disseminate educational materials. We surveyed the peers’ HIV-negative contacts before and after this work to explore knowledge and opinions about PrEP and to assess the effect of our materials. Results: There were 221 respondents at baseline (August 2016) and 100 at follow-up (April–May 2017). At baseline, nearly all participants had ‘heard of PrEP’ (96%) and were insured (97%). However, only 3% had ever used PrEP. Peers suggested educational cards that included a definition of PrEP, adherence tips and that PrEP does not prevent other sexually transmissible infections. Peers distributed approximately 2560 educational cards. At follow-up, approximately half the respondents (53%) had seen the cards, and those who did reported significantly more agreement with the majority of the card messages about PrEP. Significantly more participants reported ever receiving PrEP at follow-up (21%; P

Background and objective The rapid test study was a real-time comparison of point-of-care (POC) HIV tests to determine their abilities to detect early HIV infection. Study design Men and transgender persons reporting sex with men in the prior year were recruited at the Public Health—Seattle & King County STD Clinic, Gay City Health Project, and University of Washington Primary Infection Clinic. Study tests included the OraQuick ADVANCE Rapid HIV-1/2 Antibody Test performed on oral fluids and tests performed on fingerstick whole blood specimens including OraQuick, Uni-Gold Recombigen HIV test, Determine HIV-1/2 Ag/Ab Combo, and INSTI HIV-1 Rapid Antibody Test. Specimens from subjects with negative results were sent for EIA and nucleic acid amplification testing. McNemar's exact tests compared the numbers of HIV-infected subjects detected. Results Between February 2010 and August 2014, there were 3438 study visits. Twenty-four subjects had discordant POC results with at least one reactive and one non-reactive test, including one subject with a reactive Determine p24 antigen. OraQuick performed on oral fluids identified fewer persons compared to all fingerstick tests. OraQuick performed on fingerstick whole blood detected fewer persons compared to the Determine Combo antibody component ( p =.008) and Combo overall ( p =.004), and there was a trend when compared to INSTI ( p =.06). The Determine Combo specificity was 98.99%. Conclusions As reported by others, Determine Combo underperforms compared to laboratory-based testing, but it did detect one acute infection. If these results are validated, the specificity of Determine Combo may limit its usefulness in populations with lower HIV incidence.

Background US guidelines recommend genotyping for persons newly diagnosed with HIV infection to identify transmitted drug resistance mutations associated with decreased susceptibility to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors. To date, testing for integrase strand transfer inhibitor (INSTI) mutations has not been routinely recommended. We aimed to evaluate the prevalence of transmitted INSTI mutations among persons with primary HIV-1 infection in Seattle, WA, USA. Methods Persons with primary HIV-1 infection have enrolled in an observational cohort at the University of Washington Primary Infection Clinic since 1992. We performed a retrospective analysis of plasma specimens collected prospectively from the 82 antiretroviral-naive subjects who were enrolled from 2007–2013, after FDA-approval of the first INSTI. Resistance testing was performed by consensus sequencing. Results Specimens for analysis had been obtained a median of 24 (IQR 18–41, range 8–108) days after the estimated date of HIV-1 infection. All subjects were infected with HIV-1 subtype B except for one subject infected with subtype C. Consensus sequencing identified no subjects with major INSTI mutations (T66I, E92Q, G140S, Y143C/H/R, S147G, Q148H/K/R, N155H). Using exact binomial CIs, the upper bound of the 95% CI was 4.4%. Conclusions Although our sample size was small, this study does not support the need at this time to evaluate integrase mutations as part of routine consensus sequencing among persons newly diagnosed with HIV-1 infection. However, it is likely that the prevalence of transmitted INSTI mutations may increase with the recent commercial introduction of additional INSTIs and presumably greater INSTI use among persons living with HIV-1.

Background Maraviroc (MVC) is a candidate drug for HIV preexposure prophylaxis (PrEP). Objective To assess the safety and tolerability of MVC-containing PrEP over 48 weeks in U.S. women at risk for HIV infection. Design Phase 2 randomized, controlled, double-blinded study of 4 antiretroviral regimens used as PrEP. (ClinicalTrials.gov: NCT01505114). Setting 12 clinical research sites of the HIV Prevention Trials Network and AIDS Clinical Trials Group. Participants HIV-uninfected women reporting condomless vaginal or anal intercourse with at least 1 man with HIV infection or unknown serostatus within 90 days. Intervention MVC only, MVC-emtricitabine (FTC), MVC-tenofovir disoproxil fumarate (TDF), and TDF-FTC (control). Measurements At each visit, clinical and laboratory (including HIV) assessments were done. Primary outcomes were grade 3 and 4 adverse events and time to permanent discontinuation of the study regimen. All randomly assigned participants were analyzed according to their original assignment. Results Among 188 participants, 85% completed follow-up, 11% withdrew early, and 4% were lost to follow-up; 19% discontinued their regimen prematurely. The number discontinuing and the time to discontinuation did not differ among regimens. Grade 3 or 4 adverse events occurred in 5 (MVC), 13 (MVC-FTC), 9 (MVC-TDF), and 8 (TDF-FTC) participants; rates did not differ among regimens. One death (by suicide) occurred in the MVC-TDF group but was judged not to be related to study drugs. Of available plasma samples at week 48 (n = 126), 60% showed detectable drug concentrations. No new HIV infections occurred. Limitations Participants were not necessarily at high risk for HIV infection. The regimen comprised 3 pills taken daily. The study was not powered for efficacy. Conclusion Maraviroc-containing PrEP regimens were safe and well-tolerated compared with TDF-FTC in U.S. women. No new HIV infections occurred, although whether this was due to study drugs or low risk in the population is uncertain. Maraviroc-containing PrEP for women may warrant further study. Primary Funding Source National Institutes of Health.

Background Transmission of human immunodeficiency virus type 1 (HIV-1) drug resistance mutations, particularly that of minority drug-resistant variants, remains poorly understood. Population-based studies suggest that drug-resistant HIV-1 is less transmissible than drug-susceptible viruses. We compared HIV-1 drug-resistant genotypes among partner-pairs in order to assess the likelihood of transmission of drug resistance mutations and investigate the role of minority variants in HIV transmission. Methods and findings From 1992–2010, 340 persons with primary HIV-1 infection and their partners were enrolled into observational research studies at the University of Washington Primary Infection Clinic (UWPIC). Out of 50 partner-pairs enrolled, 36 (72%) transmission relationships were confirmed by phylogenetic distance analysis of HIV-1 envelope (env) sequences, and 31 partner-pairs enrolled after 1995 met criteria for this study. Drug resistance mutations in the region of the HIV-1 polymerase gene (pol) that encodes protease and reverse transcriptase were assessed by 454-pyrosequencing. In 25 partner-pairs where the transmission direction could be determined, 12 (48%) transmitters had 1–4 drug resistance mutations (23 total) detected in their HIV-1 populations at a median frequency of 6.0% (IQR 1.5%–98.7%, range 1.0%–99.6%). Of 10 major mutations detected in five transmitters at a frequency >95%, 100% (95% CI 69.2%–100%) were detected in recipients. All of these transmitters were antiretroviral (ARV)-naïve at the time of specimen collection. Fourteen mutations (eight major mutations and six accessory mutations) were detected in nine transmitters at low frequencies (1.0%–11.8%); four of these transmitters had previously received ARV therapy. Two (14% [95% CI 1.8%–42.8%]) G73S accessory mutations were detected in both transmitter and recipient. This number is not significantly different from the number expected based on the observed frequencies of drug-resistant viruses in transmitting partners. Limitations of this study include the small sample size and uncertainties in determining the timing of virus transmission and mutation history. Conclusions Drug-resistant majority variants appeared to be commonly transmitted by ARV-naïve participants in our analysis and may contribute significantly to transmitted drug resistance on a population level. When present at low frequency, no major mutation was observed to be shared between partner-pairs; identification of accessory mutations shared within a pair could be due to transmission, laboratory artifact, or apolipoprotein B mRNA-editing enzyme, catalytic polypeptides (APOBECs), and warrants further study., In a cross-sectional study, Joanne Stekler and colleagues investigate transmission of HIV drug-resistance mutations between serodiscordant partners., Author summary Why was this study done? Previous studies have shown that virus factors like replication capacity (the ability of a virus to multiply) can impact the likelihood of HIV-1 transmission. Little is known about whether HIV-1 drug-resistance mutations impact the likelihood of HIV transmission. What did the researchers do and find? We identified 31 participants with primary HIV-1 infection and their partners. We found that five transmitting partners, none of whom had taken antiretroviral (ARV) therapy at the time of specimen collection, had 10 drug resistance mutations that made up more than 95% of the transmitter’s viral population; all of these mutations were found in their recipient partners. We identified another 14 mutations at low frequencies (1.0%–11.8%) in nine transmitting partners; two of these low frequency mutations were also detected in two recipient partners. What do these findings mean? Our findings suggest that HIV-1 drug resistance may be spread to and by people who have never taken ARV medications. Although we identified low-frequency mutations that were in both the transmitter and recipient in two partner-pairs, the mutation that we detected is considered an “accessory” mutation that does not have a significant impact on the effectiveness of HIV treatment. We are uncertain if these this mutation was transmitted within the two partner-pairs where it was identified or was a result of cellular restriction factors like APOBECs that acted independently in both members of the partner-pairs. Because of its small size, this study was not able to definitively address whether HIV-1 drug resistance mutations reduce the likelihood of HIV-1 transmission.

In the United States, of the 1.1 million persons infected with human immunodeficiency virus (HIV) and the 2.7 million infected with hepatitis C virus (HCV), approximately 16% and 50%, respectively, are unaware of their infection. Highly effective treatments have turned both diseases into manageable conditions, and in the case of hepatitis C, a disease that can be cured. Early diagnosis is imperative so that infected persons can take measures to stay healthy, get into care, benefit from therapy, and reduce the risk of transmission. In this report, we review current recommendations provided by the Centers for Disease Control and Prevention (CDC) and the United States Preventive Services Task Force on whom to screen for HIV and HCV infections, and recommendations from the CDC, the Association of Public Health Laboratories, and the Clinical and Laboratory Standards Institute on how to test for these infections.

BackgroundAfrican-born individuals in the U.S. are disproportionately affected by HIV yet have low HIV testing rates. We conducted a mixed methods study to assess the uptake and feasibility of a novel strategy for integrating HIV testing into residential health fairs among African-born individuals in Seattle, WA.MethodsFrom April to May 2018, we held six health fairs at three apartment complexes with high numbers of African-born residents. Fairs included free point-of-care screening for glucose, cholesterol, body mass index, blood pressure, and HIV, as well as social services and health education. The health fairs were hosted in apartment complex common areas with HIV testing conducted in private rooms. Health fair participants completed a series of questionnaires to evaluate demographics, access to health services, and HIV testing history. We conducted 18 key informant interviews (KIIs) with health fair participants and community leaders to identify barriers to HIV testing among African-born individuals.ResultsOf the 111 adults who accessed at least one service at a health fair, 92 completed questionnaires. Fifty-five (61%) were female, 48 (52%) were born in Africa, and 55 (63%) had health insurance. Half of African-born participants accepted HIV testing; all tested negative. The most common reasons for declining testing were lack of perceived risk for HIV and knowledge of HIV status. We identified a high prevalence of non-communicable diseases (NCDs) among health fair participants; among those tested, 77% (55/71) were overweight/obese, 39% (31/79) had blood pressure > 140/90 mmHg, and 30% (22/73) had total cholesterol > 200 mg/dL. KIIs identified community stigma and misinformation as major barriers to HIV testing among African-born individuals.ConclusionsResidential health fairs are a feasible method to increase HIV testing among African-born individuals in Seattle. The high prevalence of NCDs highlights the importance of integrating general preventive services within HIV testing programs in this population.

The ARCHITECT HIV Ag/Ab Combo assay has a wide dynamic range for determining the sample-to-cutoff ratio (S/CO) values compared to other diagnostic HIV antibody assays.Determine the performance of an HIV testing algorithm that uses the ARCHITECT combo assay in the clinical setting and explore the utility of the signal-to-cutoff (S/CO) ratio to predict acute HIV-1 infection status.A retrospective analysis of clinical samples from a hospital and referral population screened for HIV-1 infection between May 2011 and March 2013. Repeatedly reactive samples were tested using the Multispot HIV-1/HIV-2 rapid test and depending on that result, confirmatory orthogonal testing used the Western blot (WB) for HIV-1, Immunoblot for HIV-2 and nucleic acid amplification testing (NAAT) for HIV RNA.A total of 21,317 test results were evaluated of which 509 were ARCHITECT repeatedly reactive; of these, 422 were Multispot-reactive only for HIV-1 (413 WB-positive; 9 indeterminate), 4 were Multispot-reactive for both HIV-1 and HIV-2 (one HIV-2 immunoblot-positive with 17 HIV-2 RNA copies/mL) and 83 were Multispot-non-reactive of which 15 were HIV-1 RNA positive and represented acute HIV-1 infection. There was an association among the ARCHITECT S/CO (median; IQR) values for antibody-negative (0.14; 0.11-0.16), acute infection (33; 2.1-76) and established HIV-1 infection (794; 494-1,029) (Kruskal-Wallis, p0.0001).The ARCHITECT combo assay with Multispot confirmation and reserved use of HIV-1 WB, HIV-2 Immunoblot and HIV NAAT for Multispot dual HIV-1/2 infection, and NAAT alone for Multispot-negative specimens, had a suitable test performance for detecting acute and established HIV infection.

Background Point-of-care (POC) rapid HIV tests have sensitivity during the “window period” comparable only to earliest generation EIAs. To date, it is unclear whether any POC test performs significantly better than others. Objective Compare abilities of POC tests to detect early infection in real time. Study design Men who have sex with men (MSM) were recruited into a prospective, cross-sectional study at two HIV testing sites and a research clinic. Procedures compared four POC tests: one performed on oral fluids and three on fingerstick whole blood specimens. Specimens from participants with negative POC results were tested by EIA and pooled nucleic acid amplification testing (NAAT). McNemar's exact tests compared numbers of HIV-infected participants detected. Results Between February 2010 and May 2013, 104 men tested HIV-positive during 2479 visits. Eighty-two participants had concordant reactive POC results, 3 participants had concordant non-reactive POC tests but reactive EIAs, and 8 participants had acute infection. Of 12 participants with discordant POC results, OraQuick ADVANCE Rapid HIV-1/2 Antibody Test performed on oral fluids identified fewer infections than OraQuick performed on fingerstick ( p = .005), Uni-Gold Recombigen HIV test ( p = .01), and determine HIV-1/2 Ag/Ab combo ( p = .005). Conclusions These data confirm that oral fluid POC testing detects fewer infections than other methods and is best reserved for circumstances precluding fingerstick or venipuncture. Regardless of specimen type, POC tests failed to identify many HIV-infected MSM in Seattle. In populations with high HIV incidence, the currently approved POC antibody tests are inadequate unless supplemented with p24 antigen tests or NAAT.

The Centers for Disease Control and Prevention recommends at least annual HIV testing for men who have sex with men (MSM), but motivations for testing are not well understood.We evaluated data from MSM testing for HIV at a community-based program in King County, Washington. Correlates of regular testing were examined using generalized estimating equation regression models.Between February 2004 and June 2011, 7176 MSM attended 12,109 HIV testing visits. When asked reasons for testing, 49% reported that it was time for their regular test, 27% reported unprotected sex, 24% were starting relationships, 21% reported sex with someone new, 21% sought sexually transmitted infection/hepatitis screening, 12% reported sex with an HIV-infected partner, 2% suspected primary HIV infection, and 16% reported other reasons. In multivariable analysis, factors associated with regular testing included having a regular health care provider and the following in the previous year: having only male partners, having 10 or more male partners, inhaled nitrite use, not injecting drugs, and not having unprotected anal intercourse with a partner of unknown/discordant status (P ≤ 0.001 for all). Men reporting regular testing reported shorter intertest intervals than men who did not (median of 233 vs. 322 days, respectively; P0.001).Regular testing, sexual risk, and new partnerships were important drivers of HIV testing among MSM, and regular testing was associated with increased testing frequency. Promoting regular testing may reduce the time that HIV-infected MSM are unaware of their status, particularly among those who have sex with men and women or inject drugs.

Author(s): Gulick, Roy M; Wilkin, Timothy J; Chen, Ying Q; Landovitz, Raphael J; Amico, K Rivet; Young, Alicia M; Richardson, Paul; Marzinke, Mark A; Hendrix, Craig W; Eshleman, Susan H; McGowan, Ian; Cottle, Leslie M; Andrade, Adriana; Marcus, Cheryl; Klingman, Karin L; Chege, Wairimu; Rinehart, Alex R; Rooney, James F; Andrew, Philip; Salata, Robert A; Magnus, Manya; Farley, Jason E; Liu, Albert; Frank, Ian; Ho, Ken; Santana, Jorge; Stekler, Joanne D; McCauley, Marybeth; Mayer, Kenneth H | Abstract: BackgroundMaraviroc (MVC) is a candidate for human immunodeficiency virus (HIV) pre-exposure prophylaxis.MethodsPhase 2 48-week safety/tolerability study was conducted, comparing 4 regimens: MVC alone, MVC plus emtricitabine (FTC), MVC plus tenofovir disoproxil fumarate (TDF), and TDF plus FTC. Eligible participants were HIV-uninfected men and transgender women reporting condomless anal intercourse with ≥1 HIV-infected or unknown-serostatus man within 90 days. At each visit, assessments, laboratory testing, and counseling were done. Analyses were intention to treat.ResultsAmong 406 participants, 84% completed follow-up, 7% stopped early, and 9% were lost to follow-up; 9% discontinued their regimen early. The number discontinuing and the time to discontinuation did not differ among study regimens (P = .60). Rates of grade 3-4 adverse events did not differ among regimens (P = .37). In a randomly selected subset, 77% demonstrated detectable drug concentrations at week 48. Five participants acquired HIV infection (4 MVC alone, 1 MVC + TDF; overall annualized incidence, 1.4% [95% confidence interval, .5%-3.3%], without differences by regimen; P = .32); 2 had undetectable drug concentrations at every visit, 2 had low concentrations at the seroconversion visit, and 1 had variable concentrations.ConclusionsMVC-containing regimens were safe and well tolerated compared with TDF + FTC; this study was not powered for efficacy. Among those acquiring HIV infection, drug concentrations were absent, low, or variable. MVC-containing regimens may warrant further study for pre-exposure prophylaxis.Clinical trials registrationNCT01505114.

Objectives Teach HIV-negative men who have sex with men (MSM) symptoms of acute HIV infection (AHI) and direct them to nucleic acid amplification testing (NAAT) though Public Health—Seattle & King County (PHSKC). Design Cross-sectional surveys, retrospective database analysis and chart review. Methods Beginning in June 2009, the ru2hot? campaign described AHI symptoms and NAAT. Two preintervention and two postintervention surveys assessed campaign visibility, symptom knowledge, and healthcare-seeking behaviour. Regression analyses evaluated secular trends in case-finding. Results 366 MSM completed surveys. In survey 4, 23% of 100 men reported seeing the campaign, and 25% knew ‘ru2hot?’ referred to AHI. From survey 1 to survey 4, the proportion of subjects who knew ≥2 symptoms or that AHI was a ‘flu-like’ illness was unchanged (61% vs 57%, p=0.6). However, in survey 4, 13 (72%) of 18 subjects who saw the campaign named fever as a symptom of AHI compared with 19 (35%) of 55 subjects who had not seen the campaign (p=0.005). From 9/2003 to 12/2010, 622 (2.2%) of 27 661 MSM tested HIV-positive, and 111 (18%) were identified by the Public Health—Seattle & King County NAAT programme. In terms of the impact of the campaign on case-finding, diagnosis of EIA-negative/NAAT-positive and OraQuick-negative/EIA-positive cases increased from six in 2004 to 20 in 2010 (p=0.01), but postcampaign numbers were unchanged. 23 (51%) of 45 cases identified before and 8 (44%) of 18 cases identified after the campaign reported symptoms at initial testing (p=0.6). Conclusions Although a quarter of MSM surveyed saw the campaign and knowledge of fever (the symptom of emphasis) was high, case-finding was unchanged. Increasing campaign visibility could have had greater impact.

Serosorting is the practice of choosing sex partners or selectively using condoms based on a sex partner's perceived HIV status. The extent to which serosorting protects African American (AA) and Hispanic men who have sex with men (MSM) is unknown.We analyzed data collected from MSM sexually transmitted diseases clinic patients in Seattle, WA, 2001-2010. Men were asked about the HIV status of their anal sex partners in the prior year and about their condom use with partners by partner HIV status. We defined serosorters as MSM who had unprotected anal intercourse (UAI) only with partners of the same HIV status, and compared the risk of testing HIV positive among serosorters and men who reported having UAI with partners of opposite or unknown HIV status (ie, nonconcordant UAI). We used generalized estimating equations to evaluate the association of serosorting with testing HIV positive.A total of 6694 MSM without a prior HIV diagnosis were tested during 13,657 visits; 274 men tested HIV positive. Serosorting was associated with a lower risk of testing HIV positive than nonconcordant UAI among white MSM (2.1 vs. 4.5%, odds ratio [OR]: 0.45, 95% confidence interval [CI]: 0.34-0.61), but not AA MSM (6.8 vs. 6.0%, OR: 1.1, 95% CI: 0.57-2.2). Among Hispanics, the risk of testing HIV positive was lower among serosorters than men engaging in nonconcordant UAI, though this was not significant (4.1 vs. 6.0%, OR: 0.67, 95% CI: 0.36-1.2).In at least some AA MSM populations, serosorting does not seem to be protective against HIV infection.

Objective To compare population-based metrics for assessing progress toward the US National HIV/AIDS Strategy (NHAS) goals. Design Analysis of surveillance data from persons living with HIV/AIDS (PLWHA) in King County, Washington, USA, 2005-2009. Methods We examined indicators of the timing of HIV diagnosis [intertest interval, CD4 cell count at diagnosis, and AIDS ≤ 1 year of diagnosis (late diagnosis)]; linkage to initial care (CD4 or viral load report ≤3 months after diagnosis) and sustained care (a laboratory report 3-9 months after linkage); engagement in continuous care in 2009 (at least two laboratory reports ≥3 months apart); and virologic suppression. Results Thirty-two percent of persons had late HIV diagnoses, 31% of whom reported testing HIV negative in the 2 years preceding their HIV diagnoses. Linkage to sustained care, but not linkage to initial care, was significantly associated with subsequent virologic suppression. Among 6070 PLWHA in King County, 65% of those with at least one viral load reported in 2009 and 53% of all PLWHA had virologic suppression. Although only 66% of all PLWHA were engaged in continuous care, 81% were defined as engaged using the denominator proposed in the NHAS (at least one laboratory result reported in 2009 excluding persons establishing care in the second half of the year). Conclusions Proposed metrics for monitoring the HIV care continuum may not accurately measure late diagnoses or linkage to sustained care and are sensitive to assumptions about the size of the population of PLWHA. Monitoring progress toward achievement of NHAS goals will require improvements in HIV surveillance data and refinement of care metrics.

HIV dynamics in seminal plasma during primary HIV infection was evaluated through an observational study of individuals with primary HIV infection at the University of Washington Primary Infection Clinic. Seminal plasma HIV RNA was quantified using a real-time reverse transcription PCR assay. Blood plasma RNA was quantified by bDNA or PCR-based assays. Longitudinal analyses of HIV RNA levels over time used random effects regression analysis. From 1993 to 2005, 110 men collected 327 semen specimens. Initial blood and seminal plasma RNA levels in untreated men were only moderately correlated (Spearman r = 0.38, p = 0.0002). Estimated peak and set point levels were lower in semen than blood by 0.8 (p = 0.001) and 0.7 (p0.001) log(10) copies/ml, respectively. RNA decay rates were similar in the two compartments (p = 0.4). For 2 months after infection, mean HIV RNA levels in seminal plasma remained above a threshold level (3.8 log(10) copies/ml) that has been associated with recovery of infectious virus in vitro. HIV-positive men are likely to be most infectious in the first months following HIV acquisition. However, the modest relationship between HIV RNA levels in blood and seminal plasma suggests that the relative risk of HIV transmission during primary infection may vary from current estimates that are solely based on blood levels. Incorporating seminal plasma HIV levels into future mathematical models may increase the accuracy of these models.

Men who have sex with men (MSM) remain the most severely affected risk group in the US HIV/AIDS epidemic. One-third to two-thirds of HIV transmissions among MSM are estimated to come from primary sex partners. Couples HIV testing and counseling (CHTC), in which two individuals receive pre-test counseling, HIV testing and post-test prevention planning together, has been adapted for male couples in the USA, and is now available in more than 30 cities. Previous studies have demonstrated high levels of willingness to use CHTC among MSM, but to date no studies have explored this among Latino MSM (LMSM). To examine the willingness to use CHTC among and further cultural adaptation needed for LMSM, focus group discussions were held with men who self-identified as Latino, were in a relationship with another man, and resided in Seattle. Willingness to use CHTC was high. Participants reported that CHTC could strengthen and validate their relationships, help mitigate stigma, and provide a forum for support, protection, and information sharing. Barriers to CHTC use included fears of rejection, loneliness, and relationship dissolution, and concerns around deportation and financial burden. The high levels of reported willingness to use CHTC among this sample of LMSM point to the potential for CHTC to be further adapted to provide dyadic HIV testing services for LMSM.

Background Post-treatment control of viraemia after discontinuation of antiretroviral therapy begun during primary HIV-1 infection is considered a potential path toward a sustained remission of infection. Methods Subjects enrolled in an observational primary infection cohort who received at least 11 months of highly active antiretroviral therapy beginning within the first 12 weeks of HIV-1 infection and who subsequently discontinued therapy were evaluated for post-treatment control. Results Within a cohort of 389 subjects with primary HIV-1 infection enrolled over 22 years, only 22 met criteria for evaluation of post-treatment control. Among these subjects, 21 (95%) had loss of viral control (HIV-1 RNA>500 copies/ml) within 18 months after treatment discontinuation, and only 1 (4.5%, 95% CI 0.32, 18.9) controlled viral load to levels Conclusions Our data suggest a low likelihood of post-treatment control even when highly active antiretroviral therapy is started within 12 weeks of HIV-1 infection.

Background Pre-exposure prophylaxis (PrEP) is an effective tool to prevent HIV infection for at-risk individuals, but access requires medical providers to be aware of and comfortable with prescribing PrEP. Project ECHO (Extension for Community Healthcare Outcomes) was started to support hepatitis C virus treatment in rural New Mexico, but has since expanded to train health practitioners to treat other medical conditions in other locations. Methods: In 2012, a Project ECHO telehealth program was launched to mentor community HIV practitioners in our region. In July 2015, quarterly PrEP didactics and monthly PrEP case discussions were incorporated into this program. The result was a pilot PrEP telementoring intervention. An initial nine-question survey assessed baseline community practitioner knowledge and attitudes towards PrEP, and a follow-up 16-item survey 2 years later assessed the effect of Project ECHO on PrEP knowledge, concerns and prescribing practices. Results: Twenty-four and 45 medical providers completed the baseline and follow-up surveys respectively. In follow-up, providers reported that Project ECHO participation helped them stay current on PrEP guidelines, improved knowledge, increased likelihood to prescribe PrEP and addressed most concerns about prescribing PrEP. One exception was continued concerns about cost and insurance access, which were addressed by adjusting the didactic curriculum. Many participants reported that the Project ECHO pilot PrEP telementoring intervention assisted them in disseminating PrEP knowledge to other medical providers in their region. Conclusions: It is feasible to incorporate PrEP training into Project ECHO distance telementoring programs as a tool to educate community practitioners and support PrEP prescribing.

Despite treatment guidelines in place since 2005, non-occupational post-exposure HIV prophylaxis (nPEP) remains an underutilized prevention strategy. We conducted a retrospective chart review of patients presenting to a publicly-funded HIV clinic in Seattle, Washington for nPEP between 2000 and 2010 (N = 360). nPEP prescriptions were provided for 324 (90%) patients; 83% of prescription decisions were appropriate according to Centers for Disease Control and Prevention guidelines, but only 31% (N = 111/360) of patients were considered "high risk." In order to use limited resources most efficiently, public health agencies should target messaging for this high-cost intervention to individuals with high-risk HIV exposures.

We conducted a study comparing the OraQuickADVANCE Rapid HIV-1/2 Antibody Test, Uni-Gold Recombigen HIV Test, Determine HIV 1/2 Ag/Ab Combo, EIA, and pooled nucleic acid amplification testing (NAAT). Men who have sex with men rated tests based on specimen collection method and trust in each test. Among 490 subjects, OraQuick performed on oral fluids ranked highest for specimen collection method but lowest on trust; NAAT scored highest on trust. Among a subset of these subjects, 46% would opt for NAAT if choosing one test. Strategies are needed to increase HIV testing that is accurate and consistent with client preferences.

The authors examined temporal trends and correlates of HIV testing frequency among men who have sex with men (MSM) in King County, Washington.The authors evaluated data from MSM testing for HIV at the Public Health-SeattleKing County (PHSKC) STD Clinic and Gay City Health Project (GCHP) and testing history data from MSM in PHSKC HIV surveillance. The intertest interval (ITI) was defined as the number of days between the last negative HIV test and the current testing visit or first positive test. Correlates of the log(10)-transformed ITI were determined using generalised estimating equations linear regression.Between 2003 and 2010, the median ITI among MSM seeking HIV testing at the STD Clinic and GCHP were 215 (IQR: 124-409) and 257 (IQR: 148-503) days, respectively. In multivariate analyses, younger age, having only male partners and reporting ≥10 male sex partners in the last year were associated with shorter ITIs at both testing sites (p0.05). Among GCHP attendees, having a regular healthcare provider, seeking a test as part of a regular schedule and inhaled nitrite use in the last year were also associated with shorter ITIs (p0.001). Compared with MSM testing HIV negative, MSM newly diagnosed with HIV had longer ITIs at the STD Clinic (median of 278 vs 213 days, p=0.01) and GCHP (median 359 vs 255 days, p=0.02).Although MSM in King County appear to be testing at frequent intervals, further efforts are needed to reduce the time that HIV-infected persons are unaware of their status.

Objective In 2006, the Centers for Disease Control and Prevention (CDC) recommended routine HIV screening in healthcare settings for persons between 13 and 64 years old. In 2010, the Washington Administrative Code (WAC) was changed to align testing rules with these recommendations. We designed this survey to ascertain the current state of HIV testing and barriers to routine screening in King County, Washington. Methods Between March 23 and April 16, 2010, a convenience sample of healthcare providers completed an online survey. Providers answered true-false and multiple choice questions about national recommendations and the WAC, policies in their primary clinical settings, and their personal HIV testing practices. Providers were asked to agree or disagree whether commonly reported barriers limited their implementation of routine HIV screening. Results Although 76% of the 221 respondents knew that the CDC recommended routine HIV screening for persons regardless of their risk, 99 (45%) providers reported that their primary clinical setting had a policy to target testing based on patient risk factors. Forty-four (20%) providers reported that their primary clinical setting had a policy of routine HIV screening, 54 (25%) reported no official policy, and 15 (7%) did not know whether a policy existed. Only 11 (5%) providers offer HIV testing to all patients at initial visits. When asked about barriers to routine screening, 57% of providers agreed that perception that their patient population is low risk limits the number of HIV tests they perform. Only 26 (13%) providers agreed that concern about reimbursement posed a barrier to testing. Conclusions Most providers participating in this survey continue to target HIV testing, despite knowledge of national recommendations. Efforts are still needed to educate providers and policymakers, clarify the recent WAC revisions, and implement structural changes in order to increase HIV testing in Washington State.

HIV-1 transmission and viral evolution in the first year of infection were studied in 11 individuals representing four transmitter-recipient pairs and three independent seroconverters. Nine of these individuals were enrolled during acute infection; all were men who have sex with men (MSM) infected with HIV-1 subtype B. A total of 475 nearly full-length HIV-1 genome sequences were generated, representing on average 10 genomes per specimen at 2 to 12 visits over the first year of infection. Single founding variants with nearly homogeneous viral populations were detected in eight of the nine individuals who were enrolled during acute HIV-1 infection. Restriction to a single founder variant was not due to a lack of diversity in the transmitter as homogeneous populations were found in recipients from transmitters with chronic infection. Mutational patterns indicative of rapid viral population growth dominated during the first 5 weeks of infection and included a slight contraction of viral genetic diversity over the first 20 to 40 days. Subsequently, selection dominated, most markedly in env and nef . Mutants were detected in the first week and became consensus as early as day 21 after the onset of symptoms of primary HIV infection. We found multiple indications of cytotoxic T lymphocyte (CTL) escape mutations while reversions appeared limited. Putative escape mutations were often rapidly replaced with mutually exclusive mutations nearby, indicating the existence of a maturational escape process, possibly in adaptation to viral fitness constraints or to immune responses against new variants. We showed that establishment of HIV-1 infection is likely due to a biological mechanism that restricts transmission rather than to early adaptive evolution during acute infection. Furthermore, the diversity of HIV strains coupled with complex and individual-specific patterns of CTL escape did not reveal shared sequence characteristics of acute infection that could be harnessed for vaccine design.

Objective To evaluate minority variant drug resistance mutations detected by the oligonucleotide ligation assay (OLA) but not consensus sequencing among subjects with primary HIV-1 infection. Design/Methods Observational, longitudinal cohort study. Consensus sequencing and OLA were performed on the first available specimens from 99 subjects enrolled after 1996. Survival analyses, adjusted for HIV-1 RNA levels at the start of antiretroviral (ARV) therapy, evaluated the time to virologic suppression (HIV-1 RNA

We examined antiretroviral therapy (ART) use among 501 previously diagnosed HIV-infected men who have sex with men who sought care at a sexually transmitted disease clinic in King County, WA, during 2004-2008. Overall, 42% of men were not taking ART, 71% of whom had CD4 counts >350 cells per microliter. Of those who reported unprotected anal intercourse with a partner of nonconcordant HIV status in the prior year, 48% were not taking ART (78% with CD4 counts >350 cells/μL). Sexually transmitted disease clinics may be an important venue in which to identify persons who are not taking ART. Treating these persons could help diminish HIV transmission.

Recommendations from the Centers for Disease Control and Prevention (CDC) in 2006 [1] aimed to identify the estimated 21% of HIV-infected persons who remain unaware of their human immunodeficiency virus (HIV) status and who may be responsible for up to 50% of transmissions [2]. The CDC specifically recommended that HIV antibody testing should be expanded from targeted, risk-based testing to universal screening of all adults in health care settings aged 13–64 years. Unfortunately, strategies limited to antibody testing may compete with goals of prevention programs in settings where highly infectious individuals in the antibody-negative “window period” [3] represent a significant proportion of HIV-infected testers, and false-negative test results could lead to critical missed opportunities to interrupt onward HIV transmission. The US Food and Drug Administration–approved HIV tests vary in their ability to detect recent infection. The Public Health–Seattle & King County (PHSKC) HIV testing program has used a first- or second-generation enzyme immunoassay (EIA) [4] performed on serum specimens and a rapid antibody test performed on oral fluid or finger-stick blood specimens. Since September 2003, we have tested serum samples obtained from antibody-negative men who have sex with men (MSM) using pooled HIV nucleic acid amplification testing (NAAT) to identify antibody-negative, NAAT-positive MSM with acute HIV infection in real time (Appendix). This analysis summarizes our experience from the first 5 years of the NAAT program. We will present estimates of the sensitivity of early-generation EIAs and a rapid antibody test in a population with a high prevalence (15%) and incidence (0.8 cases per 100 person-years) of HIV infection (Robert Wood, personal communication). We will also provide data on the ability of a fourth-generation antigen-antibody combination assay to detect HIV in frozen serum specimens obtained from persons with acute infection. These findings will illustrate that a one-size-fits-all, antibody test–focused approach may not be sufficient to detect HIV infection, particularly if rapid tests are used in high-incidence populations, and that a program to diagnose highly-infectious antibody-negative, NAAT-positive persons can be successfully integrated with rapid and anonymous HIV antibody testing.

Background: New Centers for Disease Control recommendations suggest that all persons with newly diagnosed HIV receive partner counseling and referral services (PCRS). Methods: We evaluated the King County, WA, PCRS program using a new set of disposition codes that disaggregate the components of PCRS (notification, testing, and test results), distinguish verified and unverified outcomes, and differentiate outcomes that occur before and after cases receive PCRS. Results: Between 2005 and 2007, 427 (65%) of 659 persons with newly diagnosed HIV received PCRS. The number of cases staff needed to interview to identify 1 new case of HIV varied from 12.2 to 47.4 depending on whether number needed to interview was defined to include both verified and unverified outcomes and whether it excluded partners diagnosed with HIV before cases' receipt of PCRS. Age

Serosorting is the practice of preferentially having sex with partners of concordant HIV status or of selectively using condoms with HIV-discordant partners.We evaluated the epidemiology of serosorting among men who have sex with men (MSM) seen in a sexually transmitted disease clinic, Seattle, WA, 2001-2007, and defined the percentage of visits during which MSM tested HIV positive based on whether they reported nonconcordant unprotected anal intercourse (UAI), UAI only with partners thought to be HIV negative (serosorters), no UAI, or no anal intercourse.Men reported serosorting during 3295 (26%) of 12,449 visits. From 2001 to 2007, the proportion of visits during which men reported serosorting increased (P = 0.02); this change was greater among HIV-infected MSM than among HIV-uninfected MSM. Among men who tested HIV negative in the preceding year, HIV tests were positive in 49 (3.5%) of 1386 who reported nonconcordant UAI, 40 (2.6%) of 1526 serosorters, 28 (1.5%) of 1827 who had only protected anal intercourse, and 0 of 410 who had no anal intercourse (P0.0001); 32% of new HIV infections occurred in serosorters. The prevalence of HIV was higher among serosorters tested during 2004-2007 than among those tested during 2001-2003 (0.85% vs. 3.2%, P = 0.03).Serosorting offers MSM limited protection from HIV.

Because of increasing recognition of HIV1 drug resistance among antiretroviral (ARV)-naive individuals, national guidelines now recommend HIV drug-susceptibility genotyping before the start of HIV treatment (a moderate-strength recommendation based on expert opinion) and consideration of genotyping at the time of HIV diagnosis (an optional-strength recommendation based on expert opinion) [1]. In this issue of the Journal, Smith et al. [2] present data that further support the persistence of ARV drug-resistant HIV in seminal plasma and provide evidence for the horizontal transmission of HIV

Although many individuals who acquire HIV are symptomatic, primary HIV infection (PHI) is infrequently diagnosed, even after the integration of RNA testing into HIV screening programs. Until more individuals with PHI seek evaluation, the public health impact of RNA testing is likely to be small.To describe knowledge of PHI and attitudes toward health care-seeking behavior for symptoms consistent with PHI in men who have sex with men (MSM).Between April 2004 and March 2005, HIV-negative MSM attending the Public Health-Seattle and King County sexually transmitted disease (STD) clinic completed an anonymous, self-administered, written questionnaire.Ninety-six (64%) of 150 subjects namedor =1 symptom associated with PHI. Only 18 (39%) of 46 men who knew PHI could resemble influenza would seek care for flu-like symptoms. Fifteen (65%) of 23 men reporting a week-long febrile illness with rash in the preceding year sought health care, but only 7 (30%) were tested for HIV.Although most subjects identified some symptoms of PHI, relatively few would seek care for such symptoms. MSM seeking attention for febrile illnesses were infrequently tested for HIV. Increased symptom recognition, health care-seeking behavior, and routine HIV RNA testing are needed if PHI screening programs are to have meaningful impact.

Whether there is selection for specific viral Env variants upon HIV-1 transmission is controversial. We examined the V1V2 and V1V4 regions of Env in 10 new and 8 previously described transmission pairs infected with HIV-1 subtype B, including a total of 9 pairs in which the infecting partner had developed substantial viral diversity prior to transmission. We found that during transmission of HIV-1 subtype B, as well as for other subtypes reported in the past, viral populations in recipients undergo substantial genetic bottlenecks, as well as weak evidence for a propensity to replicate viruses with shorter variable loops and fewer potential N-linked glycosylation sites.