Rapid Biphasic Decay of Intact and Defective HIV DNA Reservoir During Acute Treated HIV Disease.

Antiretroviral therapy (ART) is not a cure. Upon ART cessation, virus rapidly rebounds from latently-infected cells ("the HIV reservoir"). The reservoir is largely stabilized at the time of ART initiation and then decays slowly. Here, leveraging >500 longitudinal samples from 67 people with HIV (PWH) treated during acute infection, we developed a novel mathematical model to predict reservoir decay using the intact proviral DNA assay (IPDA) from peripheral CD4+ T cells. Nonlinear generalized additive models adjusted for initial CD4+ T count, pre-ART viral load, and timing of ART initiation demonstrated rapid biphasic decay of intact DNA (week 0-5: t1/2 ~0.71 months; week 5-24: t1/2 ~3.9 months) that extended out to 1 year of ART, with similar trends for defective DNA. Predicted reservoir decay were faster for participants individuals with earlier timing of ART initiation, higher initial CD4+ T cell count, and lower pre-ART viral load. These estimates are ~5-fold faster than prior reservoir decay estimates among chronic-treated PWH. Thus, these data add to our limited understanding of host viral control at the earliest stages of HIV reservoir stabilization, potentially informing future HIV cure efforts aimed at diverse, global population of PWH initiating ART at varying stages of disease.

Prevalence of Undiagnosed Monkeypox Virus Infections during Global Mpox Outbreak, United States, June-September 2022.

Since May 2022, mpox has been identified in 108 countries without endemic disease; most cases have been in gay, bisexual, or other men who have sex with men. To determine number of missed cases, we conducted 2 studies during June-September 2022: a prospective serologic survey detecting orthopoxvirus antibodies among men who have sex with men in San Francisco, California, and a retrospective monkeypox virus PCR testing of swab specimens submitted for other infectious disease testing among all patients across the United States. The serosurvey of 225 participants (median age 34 years) detected 18 (8.0%) who were orthopoxvirus IgG positive and 3 (1.3%) who were also orthopoxvirus IgM positive. The retrospective PCR study of 1,196 patients (median age 30 years; 54.8% male) detected 67 (5.6%) specimens positive for monkeypox virus. There are likely few undiagnosed cases of mpox in regions where sexual healthcare is accessible and patient and clinician awareness about mpox is increased.

COVID-19, HIV, and Syphilis Contact Tracing: What Have We Learned and Where Are We Headed?

ABSTRACT: Contact tracing is a core public health intervention for a range of communicable diseases, in which the primary goal is to interrupt disease transmission and decrease morbidity. In this article, we present lessons learned from COVID-19, HIV, and syphilis in San Francisco to illustrate factors that shape the effectiveness of contact tracing programs and to highlight the value of investing in a robust disease intervention workforce with capacity to pivot rapidly in response to a range of emerging disease trends and outbreak response needs.

Using Geocoding to Identify COVID-19 Outbreaks in Congregate Residential Settings: San Francisco's Outbreak Response in Single-Room Occupancy Hotels.

More than 500 single-room occupancy hotels (SROs), a type of low-cost congregate housing with shared bathrooms and kitchens, are available in San Francisco. SRO residents include essential workers, people with disabilities, and multigenerational immigrant families. In March 2020, with increasing concerns about the potential for rapid transmission of COVID-19 among a population with disproportionate rates of comorbidity, poor access to care, and inability to self-isolate, the San Francisco Department of Public Health formed an SRO outbreak response team to identify and contain COVID-19 clusters in this congregate residential setting. Using address-matching geocoding, the team conducted active surveillance to identify new cases and outbreaks of COVID-19 at SROs. An outbreak was defined as 3 separate households in the SRO with a positive test result for COVID-19. From March 2020 through February 2021, the SRO outbreak response team conducted on-site mass testing of all residents at 52 SROs with outbreaks identified through geocoding. The rate of positive COVID-19 tests was significantly higher at SROs with outbreaks than at SROs without outbreaks (12.7% vs 6.4%; P < .001). From March through May 2020, the rate of COVID-19 cases among SRO residents was higher than among residents of other settings (ie, non-SRO residents), before decreasing and remaining at an equal level to non-SRO residents during later periods of 2020. The annual case fatality rate for SRO residents and non-SRO residents was similar (1.8% vs 1.5%). This approach identified outbreaks in a setting at high risk of COVID-19 and facilitated rapid deployment of resources. The geocoding surveillance approach could be used for other diseases and in any setting for which a list of addresses is available.

Testing for Mycoplasma genitalium and Using Doxycycline as First-Line Therapy at Initial Presentations for Non-Gonococcal Urethritis (NGU) Correlate With Reductions in Persistent NGU.

We found that the odds of return clinic visits for persistent non-gonococcal urethritis (NGU) were significantly lower (odds ratio: .4; 95% confidence interval: .3-.6; P < .0001) after implementing (1) testing for Mycoplasma genitalium during initial evaluations for NGU and (2) switching from azithromycin to doxycycline as first-line NGU treatment.

Public Health Detailing on Sexual Health Care in San Francisco: Learnings From Real-World Implementation.

OBJECTIVES: Public health detailing is an intervention in which a public health professional visits health care providers to educate them about evidence-based approaches to improve health. The San Francisco Department of Public Health conducted a public health detailing program from 2016 to 2018 to improve sexual health care and preexposure prophylaxis services in the city. METHODS: We conducted a mixed-methods study to understand the implementation of detailing and explore examples of changes to clinicians' clinical behaviors. We surveyed 203 clinicians, conducted 60-minute qualitative interviews with 7 clinicians and 4 detailers, and analyzed tracking forms. We used descriptive statistics to assess associations in the surveys. We used qualitative thematic analysis to understand facilitators and barriers to detailing and identify ways to improve the process and identify its potential benefits. RESULTS: In interviews, both clinicians and detailers had a favorable view of detailing as a tool to connect health department expertise to clinicians. Detailers cited challenges such as limited clinic time, provider turnover, and policies that limit their access to clinicians. These challenges may attenuate the real-world benefits of detailing. Clinicians offered examples of how detailing altered their behaviors, such as taking sexual health histories, building knowledge and confidence about sexual health, and using health department services. Matched surveys (n = 21) showed preliminary changes to prescribing preexposure prophylaxis. CONCLUSIONS: Public health detailing is a promising approach to increase clinicians' knowledge and confidence to offer sexual health care services, build buy-in, and support connection to health departments. Detailing programs require sufficient investment and staff support to build lasting and collaborative relationships between clinicians and public health departments and to assess the impact of the intervention.

HIV and Sexually Transmitted Infections Among Persons with Monkeypox - Eight U.S. Jurisdictions, May 17-July 22, 2022.

High prevalences of HIV and other sexually transmitted infections (STIs) have been reported in the current global monkeypox outbreak, which has affected primarily gay, bisexual, and other men who have sex with men (MSM) (1-5). In previous monkeypox outbreaks in Nigeria, concurrent HIV infection was associated with poor monkeypox clinical outcomes (6,7). Monkeypox, HIV, and STI surveillance data from eight U.S. jurisdictions* were matched and analyzed to examine HIV and STI diagnoses among persons with monkeypox and assess differences in monkeypox clinical features according to HIV infection status. Among 1,969 persons with monkeypox during May 17-July 22, 2022, HIV prevalence was 38%, and 41% had received a diagnosis of one or more other reportable STIs in the preceding year. Among persons with monkeypox and diagnosed HIV infection, 94% had received HIV care in the preceding year, and 82% had an HIV viral load of <200 copies/mL, indicating HIV viral suppression. Compared with persons without HIV infection, a higher proportion of persons with HIV infection were hospitalized (8% versus 3%). Persons with HIV infection or STIs are disproportionately represented among persons with monkeypox. It is important that public health officials leverage systems for delivering HIV and STI care and prevention to reduce monkeypox incidence in this population. Consideration should be given to prioritizing persons with HIV infection and STIs for vaccination against monkeypox. HIV and STI screening and other recommended preventive care should be routinely offered to persons evaluated for monkeypox, with linkage to HIV care or HIV preexposure prophylaxis (PrEP) as appropriate.

Texting Lost-to-follow-up PrEP Patients from a San Francisco Sexual Health Clinic.

It is critical to understand what happens when PrEP patients are lost-to-follow-up (LTFU) and, where appropriate, attempt to re-engage them in care with the goal of preventing future human immunodeficiency virus (HIV) acquisition. We evaluated the benefits and limitations of using text-based outreach to re-engage with LTFU PrEP patients and offer re-initiation of PrEP care. Using text-messaging, we surveyed San Francisco City Clinic patients who started PrEP from January 2015 to October 2019 and were LTFU by October 1, 2020. Our goals were to better understand (1) whether our patients remained on PrEP through another provider or source, (2) why patients choose to discontinue PrEP, and (3) whether text-based outreach could successfully re-engage such patients in care. Multiple-choice survey questions were analyzed quantitatively to determine the proportion of respondents selecting each option; free-text responses were analyzed qualitatively using an inductive approach to identify any additional recurring themes. Of 846 eligible survey recipients, 130 responded (overall response rate 15.4%). Forty-two respondents (32.3%) were still on PrEP through another provider while 88 (67.7%) were not. Common reasons for stopping PrEP included: COVID-19-related changes in sex life (32.3% of responses), concerns regarding side effects (17.7%), and the need to take a daily pill (8.3%). Free text responses revealed additional concerns regarding risk compensation. While 32 participants agreed to be contacted by City clinic staff for PrEP counseling, only 6 were reached by phone and none of the six subsequently restarted PrEP. We learned that text messaging is a possible approach to survey certain PrEP program participants to determine who is truly LTFU and off PrEP, and to better understand reasons for PrEP discontinuation. While such information could prove valuable as programs seek to address barriers to PrEP retention, efforts to improve acceptability and increase response rates would be necessary. We were less successful in re-engaging LTFU patients in PrEP care, suggesting that text-messaging may not be the optimal strategy for this purpose.

Selective Whole-Genome Amplification as a Tool to Enrich Specimens with Low Treponema pallidum Genomic DNA Copies for Whole-Genome Sequencing.

Downstream next-generation sequencing (NGS) of the syphilis spirochete Treponema pallidum subspecies pallidum (T. pallidum) is hindered by low bacterial loads and the overwhelming presence of background metagenomic DNA in clinical specimens. In this study, we investigated selective whole-genome amplification (SWGA) utilizing multiple displacement amplification (MDA) in conjunction with custom oligonucleotides with an increased specificity for the T. pallidum genome and the capture and removal of 5'-C-phosphate-G-3' (CpG) methylated host DNA using the NEBNext Microbiome DNA enrichment kit followed by MDA with the REPLI-g single cell kit as enrichment methods to improve the yields of T. pallidum DNA in isolates and lesion specimens from syphilis patients. Sequencing was performed using the Illumina MiSeq v2 500 cycle or NovaSeq 6000 SP platform. These two enrichment methods led to 93 to 98% genome coverage at 5 reads/site in 5 clinical specimens from the United States and rabbit-propagated isolates, containing >14 T. pallidum genomic copies/µL of sample for SWGA and >129 genomic copies/µL for CpG methylation capture with MDA. Variant analysis using sequencing data derived from SWGA-enriched specimens showed that all 5 clinical strains had the A2058G mutation associated with azithromycin resistance. SWGA is a robust method that allows direct whole-genome sequencing (WGS) of specimens containing very low numbers of T. pallidum, which has been challenging until now. IMPORTANCE Syphilis is a sexually transmitted, disseminated acute and chronic infection caused by the bacterial pathogen Treponema pallidum subspecies pallidum. Primary syphilis typically presents as single or multiple mucocutaneous lesions and, if left untreated, can progress through multiple stages with various clinical manifestations. Molecular studies often rely on direct amplification of DNA sequences from clinical specimens; however, this can be impacted by inadequate samples due to disease progression or timing of patients seeking clinical care. While genotyping has provided important data on circulating strains over the past 2 decades, WGS data are needed to better understand strain diversity, perform evolutionary tracing, and monitor antimicrobial resistance markers. The significance of our research is the development of an SWGA DNA enrichment method that expands the range of clinical specimens that can be directly sequenced to include samples with low numbers of T. pallidum.

Contact-Tracing Outcomes Among Household Contacts of Fully Vaccinated Coronavirus Disease 2019 (COVID-19) Patients: San Francisco, California, 29 January-2 July 2021.

BACKGROUND: The extent to which vaccinated persons diagnosed with coronavirus disease 2019 (COVID-19) can transmit to other vaccinated and unvaccinated persons is unclear. METHODS: Using data from the San Francisco Department of Public Health, this report describes outcomes of household contact tracing during 29 January-2 July 2021, where fully vaccinated patients with COVID-19 were the index case in the household. RESULTS: Among 248 fully vaccinated patients with breakthrough infections, 203 (82%) were symptomatic and 105 were identified as the index patient within their household. Among 179 named household contacts, 71 (40%) contacts tested, over half (56%) were fully vaccinated and the secondary attack rate was 28%. Overall transmission from a symptomatic fully vaccinated patient with breakthrough infection to household contacts was suspected in 14 of 105 (13%) of households. Viral genomic sequencing of samples from 44% of fully vaccinated patients showed that 82% of those sequenced were infected by a variant of concern or interest and 77% by a variant carrying mutation(s) associated with resistance to neutralizing antibodies. CONCLUSIONS: Transmission from fully vaccinated symptomatic index patients to vaccinated and unvaccinated household contacts can occur. Indoor face masking and timely testing of all household contacts should be considered when a household member receives a positive test result in order to identify and interrupt transmission chains.

Concurrent COVID-19 and Acute HIV: A Case Report and Diagnostic Review.

A 26-year-old male presented to the emergency department feeling unwell in February of 2021 with symptoms including diaphoresis, loose stools, and loss of taste sensation. Workup not only confirmed a diagnosis of COVID-19 but also revealed discordant HIV test results, with a reactive fourth-generation antigen/antibody test but a negative HIV-1/2 differentiation immunoassay. Subsequent HIV viral load testing obtained two days later ultimately established a diagnosis of acute HIV (AHI). Screening for HIV and other sexually transmitted infections decreased during the COVID-19 pandemic. It is critical that providers (1) continue recommended screening for HIV as an essential service; (2) consider acute HIV in the differential when evaluating patients with acute viral syndromes; (3) recognize that AHI can occur concurrently with other infections, including COVID-19; and (4) understand the differential diagnosis for discordant HIV test results and know when HIV viral load testing is needed to resolve such discordant results.

Lubrication Practices and Receptive Anal Sex: Implications for STI Transmission and Prevention.

INTRODUCTION: Implications of lubricant use in men having sex with men (MSM) are poorly characterized, particularly associations with sexual behavior and rectal sexually transmitted infection (STI) risk. AIM: We sought to clarify covariates associated with lubrication type including differing sexual preferences and rectal STI prevalence. METHODS: Primary English-speaking individuals ≥18 years old visiting San Francisco City Clinic (SFCC) between April and May of 2018 who endorsed lubricant use during receptive anal sex within the last 3 months were studied. Associations between lubrication type used and collected covariates were assessed using Kruskal-Wallis analysis of variance for continuous variables and Chi-squared test for categorical variables. We used logistic regression to examine the association between lubrication type and rectal STI test result. MAIN OUTCOME MEASURES: Rectal STI test positivity. RESULTS: From all enrolled participants, 179 completed the survey and endorsed use of a lubricant during receptive anal sex within the last 3 months. Silicone lubricant users had the most sexual partners in the last 3 months (13 [mean] ± 30 [SD], P= .0003) and were most likely to have a history of gonorrhea. Oil-based lubricant users had the most partners with whom they had receptive anal sex in the last 3 months (7 ± 6, P= .03). Water-based lubricant users most commonly used a condom in their last sexual encounter and had the fewest sexual partners in the last 3 months (4 ± 4, P= .0003). Spit/saliva lubricant use was associated with positive rectal STI result. CONCLUSION: Silicone and oil-based lubricant users were more likely to report condomless receptive anal sex and to have a history of gonorrhea while spit/saliva lubricant use associated with positive rectal STI acquisition. Lee A, Gaither TW, Langston ME, et al. Lubrication Practices and Receptive Anal Sex: Implications for STI Transmission and Prevention. Sex Med 2021;9:100341.

Acute HIV at the Time of Initiation of Pre-exposure or Post-exposure Prophylaxis: Impact on Drug Resistance and Clinical Outcomes.

BACKGROUND: Initiating pre-exposure or post-exposure prophylaxis (PrEP/PEP) in the setting of undiagnosed acute HIV (AHI) could cause antiretroviral resistance. We sought to characterize clinical outcomes and drug resistance mutations among individuals prescribed PrEP/PEP with undiagnosed AHI at a San Francisco sexually transmitted disease clinic. SETTING: In our PrEP/PEP program, patients are tested for HIV using a point-of-care antibody test. If negative, patients are started on prophylaxis and screened for AHI using pooled HIV RNA (5-10 days turn-around). We used 2-drug PEP until 05/2016. METHODS: We identified patients who had as-yet-undiagnosed AHI on the day of PrEP/PEP start between 2011 and 2018, then used our clinical record and surveillance data to describe HIV resistance and clinical outcomes. RESULTS: Of 1758 PrEP and 2242 PEP starts, there were 7 AHI cases among PrEP users (0.40%) and 6 among PEP users (0.30%). Median times for linkage to HIV care, initiation of HIV treatment, and viral suppression were 7, 12, and 43 days. On initiation of HIV care, 3 patients (23%) were found to have an M184 mutation 7-12 days after starting PrEP/PEP. All 3 had genotyping performed on stored serum available from the date of PrEP/PEP start, each of which demonstrated wild-type virus. All 3 patients achieved durable viral suppression. CONCLUSIONS: Although rare (occurring <0.5% of the time), AHI in the setting of PrEP/2-drug PEP can result in an M184 within days. Even with M184, persons with AHI achieve viral suppression when rapidly linked to care and initiated on antiretroviral therapy. Providers should consider AHI screening when starting PrEP/PEP.

Decreased Time From Human Immunodeficiency Virus Diagnosis to Care, Antiretroviral Therapy Initiation, and Virologic Suppression during the Citywide RAPID Initiative in San Francisco.

BACKGROUND: Early virologic suppression (VS) after human immunodeficiency virus (HIV) infection improves individual health outcomes and decreases onward transmission. In San Francisco, immediate antiretroviral therapy (ART) at HIV diagnosis was piloted in 2013-2014 and expanded citywide in 2015 in a rapid start initiative to link all new diagnoses to care within 5 days and start ART at the first care visit. METHODS: HIV providers and linkage navigators were trained on a rapid start protocol with sites caring for vulnerable populations prioritized. Dates of HIV diagnosis, first care visit, ART initiation, and VS were abstracted from the San Francisco Department of Public Health HIV surveillance registry. RESULTS: During 2013-2017, among 1354 new HIV diagnoses in San Francisco, median days from diagnosis to first VS decreased from 145 to 76 (48%; P < .0001) and from first care visit to ART initiation decreased from 28 to 1 (96%; P < .0001). By 2017, 28% of new diagnoses had a rapid start, which was independently associated with Latinx ethnicity (AOR, 1.73; 95% CI, 1.15-2.60) and recent year of diagnosis (2017; AOR, 16.84; 95% CI, 8.03-35.33). Persons with a rapid ART start were more likely to be virologically suppressed within 12 months of diagnosis than those with a non-rapid start (RR, 1.17; 95% CI, 1.10-1.24). CONCLUSIONS: During a multisector initiative to optimize ART initiation, median time from diagnosis to VS decreased by nearly half. Immediate ART at care initiation was achieved across many, but not all, populations, and was associated with improved suppression rates.

Quarterly screening optimizes detection of sexually transmitted infections when prescribing HIV preexposure prophylaxis.

OBJECTIVE: The optimal screening frequency of sexually transmitted infections (STIs) for MSM and transgender women (TGW) on HIV pre-exposure prophylaxis (PrEP) is unclear, with present guidelines recommending screening every 3-6 months. We aimed to determine the number of STIs for which treatment would have been delayed without quarterly screening. DESIGN: The US PrEP Demonstration Project was a prospective, open-label cohort study that evaluated PrEP delivery in STI clinics in San Francisco and Miami, and a community health center in Washington, DC. In all, 557 HIV-uninfected MSM and TGW were offered up to 48 weeks of PrEP and screened quarterly for STIs. METHODS: The proportion of gonorrhea, chlamydia, and syphilis infections for which treatment would have been delayed had screening been conducted every 6 versus every 3 months was determined by taking the number of asymptomatic STIs at weeks 12 and 36 divided by the total number of infections during the study follow-up period for each STI. RESULTS: Among the participants, 50.9% had an STI during follow-up. If screening had been conducted only semiannually or based on symptoms, identification of 34.3% of gonorrhea, 40.0% of chlamydia, and 20.4% of syphilis infections would have been delayed by up to 3 months. The vast majority of participants (89.2%) with asymptomatic STIs reported condomless anal sex and had a mean of 8.1 partners between quarterly visits. CONCLUSIONS: Quarterly STI screening among MSM on PrEP could prevent a substantial number of partners from being exposed to asymptomatic STIs, and decrease transmission.

Phylodynamic Analysis Complements Partner Services by Identifying Acute and Unreported HIV Transmission.

Tailoring public health responses to growing HIV transmission clusters depends on accurately mapping the risk network through which it spreads and identifying acute infections that represent the leading edge of cluster growth. HIV transmission links, especially those involving persons with acute HIV infection (AHI), can be difficult to uncover, or confirm during partner services investigations. We integrated molecular, epidemiologic, serologic and behavioral data to infer and evaluate transmission linkages between participants of a prospective study of AHI conducted in North Carolina, New York City and San Francisco from 2011-2013. Among the 547 participants with newly diagnosed HIV with polymerase sequences, 465 sex partners were reported, of whom only 35 (7.5%) had HIV sequences. Among these 35 contacts, 23 (65.7%) links were genetically supported and 12 (34.3%) were not. Only five links were reported between participants with AHI but none were genetically supported. In contrast, phylodynamic inference identified 102 unreported transmission links, including 12 between persons with AHI. Importantly, all putative transmission links between persons with AHI were found among large clusters with more than five members. Taken together, the presence of putative links between acute participants who did not name each other as contacts that are found only among large clusters underscores the potential for unobserved or undiagnosed intermediaries. Phylodynamics identified many more links than partner services alone and, if routinely and rapidly integrated, can illuminate transmission patterns not readily captured by partner services investigations.