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Background In 2023, Tennessee replaced $6.2 M in US Centers for Disease Control and Prevention (CDC) human immunodeficiency virus (HIV) prevention funding with state funds to redirect support away from men who have sex with men (MSM), transgender women (TGW), and heterosexual Black women (HSBW) and to prioritize instead first responders (FR), pregnant people (PP), and survivors of sex trafficking (SST). Methods We used a simulation model of HIV disease to compare the clinical impact of Current, the present allocation of condoms, preexposure prophylaxis (PrEP), and HIV testing to CDC priority risk groups (MSM/TGW/HSBW); with Reallocation , funding instead increased HIV testing and linkage of Tennessee-determined priority populations (FR/PP/SST). Key model inputs included baseline condom use (45%–49%), PrEP provision (0.1%–8%), HIV testing frequency (every 2.5–4.8 years), and 30-day HIV care linkage (57%–65%). We assumed Reallocation would reduce condom use (−4%), PrEP provision (−26%), and HIV testing (−47%) in MSM/TGW/HSBW, whereas it would increase HIV testing among FR (+47%) and HIV care linkage (to 100%/90%) among PP/SST. Results Reallocation would lead to 166 additional HIV transmissions, 190 additional deaths, and 843 life-years lost over 10 years. HIV testing reductions were most influential in sensitivity analysis; even a 24% reduction would result in 287 more deaths compared to Current. With pessimistic assumptions, we projected 1359 additional HIV transmissions, 712 additional deaths, and 2778 life-years lost over 10 years. Conclusions Redirecting HIV prevention funding in Tennessee would greatly harm CDC priority populations while conferring minimal benefits to new priority populations. [ABSTRACT FROM AUTHOR]

Background Analytical treatment interruption (ATI) is the gold standard in HIV research for assessing the capability of new therapeutic strategies to control viremia without antiretroviral treatment (ART). The viral setpoint is commonly used as endpoint to evaluate their efficacy. However, in line with recommendations from a consensus meeting, to minimize the risk of increased viremia without ART, trials often implement short ATI phases and stringent virological ART restart criteria. This approach can limit the accurate observation of the setpoint. Methods We analyzed viral dynamics in 235 people with HIV from 3 trials, examining virological criteria during ATI phases. Time-related (eg time to rebound, peak, and setpoint) and viral load magnitude–related criteria (peak, setpoint, and time-averaged AUC [nAUC]) were described. Spearman correlations were analyzed to identify (1) surrogate endpoints for setpoint and (2) optimal virological ART restart criteria mitigating the risks of ART interruption and the evaluation of viral control. Results Comparison of virological criteria between trials showed strong dependencies on ATI design. Similar correlations were found across trials, with nAUC the most strongly correlated with the setpoint, with correlations >0.70. A threshold >100 000 copies/mL for 2 consecutive measures is requested as a virological ART restart criterion. Conclusions Our results are in line with recommendations and emphasize the benefits of an ATI phase >12 weeks, with regular monitoring, and a virological ART restart criterion of 10 000 copies/mL to limit the risk for patients while capturing enough information to keep nAUC as an optimal proxy to the setpoint. [ABSTRACT FROM AUTHOR]

Background Women in Africa disproportionately acquire human immunodeficiency virus type 1 (HIV-1). Understanding which women are most likely to acquire HIV-1 can guide focused prevention with preexposure prophylaxis (PrEP). Our objective was to identify women at the highest risk of HIV-1 and estimate PrEP efficiency at different sensitivity levels. Methods Nationally representative data were collected from 2015 through 2019 from 15 population-based household surveys. This analysis included women aged 15–49 who tested HIV-1 seronegative or had recent HIV-1. Least absolute shrinkage and selection operator regression models were fit with 28 variables to predict recent HIV-1. Models were trained on the full population and internally cross-validated. Performance was evaluated using area under the receiver operating characteristic curve (AUC), sensitivity, and number needed to treat (NNT) with PrEP to avert 1 infection. Results Among 209 012 participants, 248 had recent HIV-1 infection, representing 118 million women and 402 000 (95% confidence interval [CI], 309 000–495 000) annual infections. Two variables were retained: living in a subnational area with high HIV-1 viremia and having a sexual partner living outside the home. The full-population AUC was 0.80 (95% CI,.76–.84); cross-validated AUC was 0.79 (95% CI,.75–.84). At 33% sensitivity, 130 000 cases could be averted if 7.9 million women were perfectly adherent to PrEP; NNT would be 61. At 67% sensitivity, 260 000 cases could be averted if 25.1 million women were perfectly adherent; NNT would be 96. Conclusions This risk assessment tool was generalizable, predictive, and parsimonious with trade-offs between reach and efficiency. [ABSTRACT FROM AUTHOR]

Background Oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (F/TDF) has high efficacy against HIV-1 acquisition. Seventy-two prospective studies of daily oral F/TDF PrEP were conducted to evaluate HIV-1 incidence, drug resistance, adherence, and bone and renal safety in diverse settings. Methods HIV-1 incidence was calculated from incident HIV-1 diagnoses after PrEP initiation and within 60 days of discontinuation. Tenofovir concentrations in dried blood spots (DBS), drug resistance, and bone/renal safety indicators were evaluated in a subset of studies. Results Among 17 274 participants, there were 101 cases with new HIV-1 diagnosis (.77 per 100 person-years; 95% confidence interval [CI]:.63–.94). In 78 cases with resistance data, 18 (23%) had M184I or V, 1 (1.3%) had K65R, and 3 (3.8%) had both mutations. In 54 cases with tenofovir concentration data from DBS, 45 (83.3%), 2 (3.7%), 6 (11.1%), and 1 (1.9%) had average adherence of <2, 2−3, 4−6, and ≥7 doses/wk, respectively, and the corresponding incidence was 3.9 (95% CI: 2.9–5.3),.24 (.060–.95),.27 (.12–.60), and.054 (.008–.38) per 100 person-years. Adherence was low in younger participants, Hispanic/Latinx and Black participants, cisgender women, and transgender women. Bone and renal adverse event incidence rates were 0.69 and 11.8 per 100 person-years, respectively, consistent with previous reports. Conclusions Leveraging the largest pooled analysis of global PrEP studies to date, we demonstrate that F/TDF is safe and highly effective, even with less than daily dosing, in diverse clinical settings, geographies, populations, and routes of HIV-1 exposure. [ABSTRACT FROM AUTHOR]

Background One month of daily rifapentine + isoniazid (1HP) is an effective, ultrashort option for tuberculosis prevention in people with human immunodeficiency virus (HIV). However, rifapentine may decrease antiretroviral drug concentrations and increase the risk of virologic failure. AIDS Clinical Trials Group A5372 evaluated the effect of 1HP on the pharmacokinetics of twice-daily dolutegravir. Methods A5372 was a multicenter, pharmacokinetic study in people with HIV (≥18 years) already on dolutegravir-containing antiretroviral therapy with HIV RNA <50 copies/mL. Participants received daily rifapentine/isoniazid (600 mg/300 mg) for 28 days as part of 1HP. Dolutegravir was increased to 50 mg twice daily during 1HP, and intensive pharmacokinetic sampling was performed on day 0 (before 1HP) and on the final day of 1HP treatment. Results Thirty-two participants (41% female; 66% Black/African; median [Q1, Q3] age, 42 [34, 49] years) were included in the pharmacokinetic analysis; 31 had HIV RNA <50 copies/mL at the end of 1HP dosing. One participant had an HIV RNA of 160 copies/mL at day 28, with HIV RNA <50 copies/mL upon repeat testing on day 42. The median (Q1, Q3) dolutegravir trough concentration was 1751 ng/mL (1195, 2542) on day 0 versus 1987 ng/mL (1331, 2278) on day 28 (day 28:day 0 geometric mean ratio, 1.05 [90% confidence interval,.93–1.2]; P =.43). No serious adverse events were reported. Conclusions Dolutegravir trough concentrations with 50 mg twice-daily dosing during 1HP treatment were greater than those with standard-dose dolutegravir once daily without 1HP. These pharmacokinetic, virologic, and safety data provide support for twice-daily dolutegravir use in combination with 1HP for tuberculosis prevention. Clinical Trials Registration NCT04272242. [ABSTRACT FROM AUTHOR]

Background The duration of the protective effect of tuberculosis preventive therapy (TPT) is controversial. Some studies have found that the protective effect of TPT is lost after cessation of therapy among people with human immunodeficiency virus (HIV) in settings with very high tuberculosis incidence, but others have found long-term protection in low-incidence settings. Methods We estimated the incidence rate (IR) of new tuberculosis disease for up to 12 years after randomization to 4 months of rifampin or 9 months of isoniazid, among 991 Brazilian participants in a TPT trial in the state of Rio de Janeiro, with an incidence of 68.6/100 000 population in 2022. The adjusted hazard ratios (aHRs) of independent variables for incident tuberculosis were calculated. Results The overall tuberculosis IR was 1.7 (95% confidence interval [CI], 1.01– 2.7) per 1000 person-years (PY). The tuberculosis IR was higher among those who did not complete TPT than in those who did (2.9 [95% CI, 1.3–5.6] vs 1.1 [.4–2.3] per 1000 PY; IR ratio, 2.7 [1.0–7.2]). The tuberculosis IR was higher within 28 months after randomization (IR, 3.5 [95% CI, 1.6–6.6] vs 1.1 [.5–2.1] per 1000 PY between 28 and 143 months; IR ratio, 3.1 [1.2–8.2]). Treatment noncompletion was the only variable associated with incident tuberculosis (aHR, 3.2 [95% CI, 1.1–9.7]). Conclusions In a mostly HIV-noninfected population, a complete course of TPT conferred long-term protection against tuberculosis. [ABSTRACT FROM AUTHOR]

We used group-based trajectory models to identify 4 distinct trajectory patterns of adherence to preexposure prophylaxis (PrEP) among 20 696 users. Only 44.5% were consistently PrEP adherent, with younger age, being female, or having substance use disorder or depression associated with early discontinuation. Public health efforts are needed to improve PrEP adherence. [ABSTRACT FROM AUTHOR]

Background Drug resistance may be acquired in people starting human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) during undiagnosed infection. Population-based estimates of PrEP-related resistance are lacking. Methods We used New York City surveillance and partner services data to measure the effect of PrEP use (tenofovir disoproxil fumarate/tenofivir alafenamide fumarate with emtricitabine) history on the baseline prevalence of M184I/V mutations in people with HIV diagnosed in 2015–2022. PrEP use was categorized as "recent" (defined as PrEP stopped ≤90 days before diagnosis), "past" (PrEP stopped >90 days before diagnosis), or "no known use." Resistance-associated mutations were determined using the Stanford algorithm. We used log binomial regression to generate the adjusted relative risk (aRR) of M184I/V by PrEP use history in people with or without acute HIV infection (AHI). Results Of 4246 people with newly diagnosed HIV and a genotype obtained within ≤30 days of diagnosis, 560 (13%) had AHI; 136 (3%) reported recent and 124 (35%) past PrEP use; and 98 (2%) harbored M184I/V. In people with AHI, recent PrEP use was associated with a 6 times greater risk of M184I/V than no known use (aRR, 5.86 [95% confidence interval, 2.49–13.77]). Among people without AHI, the risk of M184I/V in recent users was 7 times that in people with no known use (aRR, 7.26 [95% confidence interval, 3.98–13.24]), and in past users, it was 4 times that in those with no known use (4.46 [2.15–9.24]). Conclusions PrEP use was strongly associated with baseline M184I/V in New York City, regardless of AHI status. Ordering a nucleic acid test when indicated after assessment of exposure, antiretroviral history, and AHI symptoms can decrease PrEP initiation in people with undetected infection. [ABSTRACT FROM AUTHOR]

We examined changes in the proportion of people with human immunodeficiency virus (PWH) with virologic suppression (VS) in a multisite US cohort before and since the coronavirus disease 2019 (COVID-19) pandemic. Overall, prior gains in VS slowed during COVID-19, with disproportionate impacts on Black PWH and PWH who inject drugs. [ABSTRACT FROM AUTHOR]

Background Adherence and retention concerns raise questions about the effectiveness and cost-effectiveness of oral HIV pre-exposure prophylaxis (PrEP) in young men who have sex with men (YMSM). Methods Using an adolescent-focused simulation model, we compared annual HIV screening alone with tenofovir disoproxil fumarate/emtricitabine–based oral PrEP with every 3-month HIV screening in YMSM (aged 15–24) at increased risk of HIV. Data derived from published sources included: age-stratified HIV incidence/100 person-years (PY) on- or off-PrEP (0.6–10.1 or 0.4–6.4), PrEP retention at 6 years (28%), transmissions by HIV RNA level (0.0–78.4/100PY) and annual costs of antiretroviral therapy ($32 000–69 000), HIV care ($3100–34 600), and PrEP program/generic drug ($900/360). Outcomes included transmissions (percent of cohort infected), quality-adjusted life-years (QALYs), costs ($), and incremental cost-effectiveness ratios ($/QALY). We explored the sensitivity of findings to variation in HIV incidence and drug prices. Results Compared with annual screening alone, PrEP would increase QALYs (9.58 to 9.67), reduce new infections (37% to 30%), and decrease costs (by $5000) over 10 years. PrEP would remain cost-saving for HIV incidence off-PrEP ≥5.1/100PY or annual PrEP price ≤$1200. Over a lifetime horizon, PrEP would be cost-saving for HIV incidence off-PrEP ≥1.0/100PY, across all retention assumptions examined. PrEP would not be cost-effective at HIV incidence ≤0.1/100PY, regardless of drug price, due to programmatic costs. Conclusions In US YMSM at increased risk of HIV, generic oral PrEP and every-3-month screening would be cost-saving compared with annual screening alone, even with high discontinuation and low adherence, over a range of HIV incidences. [ABSTRACT FROM AUTHOR]

Background The HIV Prevention Trials Network (HPTN) 083/084 trials showed up to 88% increased efficacy of long-acting cabotegravir (CAB-LA) versus continuous oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). However, CAB-LA's high price limits the number of people who can be treated within fixed prevention budgets. Global human immunodeficiency virus (HIV) prevention budgets are highly limited, with TDF/FTC widely available as a low-cost generic. In randomized clinical trials, event-driven TDF/FTC has shown similar preventive efficacy to continuous TDF/FTC. Methods A systematic review of global HIV incidence studies was conducted. Weighted incidence was calculated in each at-risk population. HIV infection rates were evaluated for 5 prevention strategies, with additional HIV testing, education, and service access costs assumed for each ($18 per person per year). Assumed efficacies were 90% (continuous CAB-LA), 60% (continuous TDF/FTC), and 60% (event-driven TDF/FTC). Using weighted incidence and an assumed 100 000 target population, annual HIV infection rates by population were calculated for each prevention strategy. Results Ninety-eight studies in 5 230 189 individuals were included. Incidence per 100 person-years ranged from 0.03 (blood donors) to 3.82 (people who inject drugs). Using the number needed to treat to benefit for each strategy, a mean incidence of 2.6 per 100 person-years in at-risk populations, and a 100 000 target population, current-price continuous CAB-LA cost $949 487 per HIV infection successfully prevented, followed by target-price CAB-LA ($11 453), continuous TDF/FTC ($4231), and event-driven TDF/FTC ($1923). Conclusions High prices of CAB-LA limit numbers treatable within fixed budgets. Low-cost event-driven TDF/FTC consistently prevents the most HIV infections within fixed budgets. [ABSTRACT FROM AUTHOR]

Background Aspirational targets to end AIDS by 2030 include having 95% of people with human immunodeficiency virus (HIV; PWH) diagnosed, 95% treated, and 95% with controlled viral load (VL). Our objective was to describe, using a large French prospective cohort, the median transition times through the cascade of care between 2009 and 2019. Methods We analyzed patients whose first HIV diagnosis was made between 1 January 2009 and 31 December 2019. Using the Kaplan–Meier method, we estimated the time to linkage to care (from HIV diagnosis to first biological assessment), to treatment (date of first antiretroviral therapy [ART] prescription), and to controlled VL (first value <200 copies/mL). Analyses were disaggregated by time periods and patients' characteristics. Censoring date was 31 December 2021. Results Among the 16 864 patients linked to care since 2009, the median [Q1; Q3] time from HIV diagnosis to controlled VL decreased from 254 [127–745] to 73 [48–132] days in 2009–2011 and 2018–2019, respectively. Transition times from linkage to care to first ART decreased from 67 [17; 414] in 2009–2011 to 13 [5; 26] days in 2018–2019, and from ART to controlled VL from 83 [35; 130] in 2009–2011 to 38 [28; 90] days in 2018–2019. Differences were observed depending on patients' characteristics. Conclusions We describe drastic reductions in transition time through the cascade of care, allowing reduction in the transmission period following each new infection. Delayed diagnosis remains the main obstacle to ending AIDS in the next decade. [ABSTRACT FROM AUTHOR]

New tools are needed to support PrEP adherence for individuals at risk for HIV, including those that enable provision of real-time feedback. In a large, completed PrEP trial, adequate urine tenofovir levels measured by a novel immunoassay predicted HIV protection and showed good sensitivity and specificity for detectable plasma tenofovir.

BackgroundIn generalized epidemic settings, strategies are needed to prioritize individuals at higher risk of human immunodeficiency virus (HIV) acquisition for prevention services. We used population-level HIV testing data from rural Kenya and Uganda to construct HIV risk scores and assessed their ability to identify seroconversions.MethodsDuring 2013-2017, >75% of residents in 16 communities in the SEARCH study were tested annually for HIV. In this population, we evaluated 3 strategies for using demographic factors to predict the 1-year risk of HIV seroconversion: membership in ≥1 known "risk group" (eg, having a spouse living with HIV), a "model-based" risk score constructed with logistic regression, and a "machine learning" risk score constructed with the Super Learner algorithm. We hypothesized machine learning would identify high-risk individuals more efficiently (fewer persons targeted for a fixed sensitivity) and with higher sensitivity (for a fixed number targeted) than either other approach.ResultsA total of 75 558 persons contributed 166 723 person-years of follow-up; 519 seroconverted. Machine learning improved efficiency. To achieve a fixed sensitivity of 50%, the risk-group strategy targeted 42% of the population, the model-based strategy targeted 27%, and machine learning targeted 18%. Machine learning also improved sensitivity. With an upper limit of 45% targeted, the risk-group strategy correctly classified 58% of seroconversions, the model-based strategy 68%, and machine learning 78%.ConclusionsMachine learning improved classification of individuals at risk of HIV acquisition compared with a model-based approach or reliance on known risk groups and could inform targeting of prevention strategies in generalized epidemic settings.Clinical trials registrationNCT01864603.

Background People with human immunodeficiency virus (HIV) (PWH) may be at increased risk for severe coronavirus disease 2019 (COVID-19) outcomes. We examined HIV status and COVID-19 severity, and whether tenofovir, used by PWH for HIV treatment and people without HIV (PWoH) for HIV prevention, was associated with protection. Methods Within 6 cohorts of PWH and PWoH in the United States, we compared the 90-day risk of any hospitalization, COVID-19 hospitalization, and mechanical ventilation or death by HIV status and by prior exposure to tenofovir, among those with severe acute respiratory syndrome coronavirus 2 infection between 1 March and 30 November 2020. Adjusted risk ratios (aRRs) were estimated by targeted maximum likelihood estimation, with adjustment for demographics, cohort, smoking, body mass index, Charlson comorbidity index, calendar period of first infection, and CD4 cell counts and HIV RNA levels (in PWH only). Results Among PWH (n = 1785), 15% were hospitalized for COVID-19 and 5% received mechanical ventilation or died, compared with 6% and 2%, respectively, for PWoH (n = 189 351). Outcome prevalence was lower for PWH and PWoH with prior tenofovir use. In adjusted analyses, PWH were at increased risk compared with PWoH for any hospitalization (aRR, 1.31 [95% confidence interval, 1.20–1.44]), COVID-19 hospitalizations (1.29 [1.15–1.45]), and mechanical ventilation or death (1.51 [1.19–1.92]). Prior tenofovir use was associated with reduced hospitalizations among PWH (aRR, 0.85 [95% confidence interval,.73–.99]) and PWoH (0.71 [.62–.81]). Conclusions Before COVID-19 vaccine availability, PWH were at greater risk for severe outcomes than PWoH. Tenofovir was associated with a significant reduction in clinical events for both PWH and PWoH. [ABSTRACT FROM AUTHOR]

Using intraerythrocytic tenofovir-diphosphate data from the emtricitabine/tenofovir disoproxil fumarate arms of HIV Prevention Trials Network (HPTN) 083 (men) and HPTN 084 (women), approximately 99% efficacy was achieved at a lower adherence threshold in HPTN 083 (≥2 doses/week) compared with HPTN 084 (daily), suggesting higher adherence is necessary for women vs men. [ABSTRACT FROM AUTHOR]

Could home human immunodeficiency virus (HIV) self-testing make a major difference in identifying persons with undiagnosed HIV in the United States? We argue that approval of new self-test assays for home use would help but must be combined with extensive investment in community outreach and linkage to care to make an impact. [ABSTRACT FROM AUTHOR]

In this viewpoint, we briefly review the status of antiretroviral therapy (ART), its unmet needs, and the role that broadly neutralizing antibodies (bNAbs) might have in the near future for the treatment of human immunodeficiency virus (HIV). We summarize advances in the development of bNAbs as antiretroviral therapy, the results of main clinical trials of bNAbs for HIV treatment and prevention, and its role in cure trials. The limitations of broadly neutralizing antibodies are the current need for primary resistance testing, the still unclear number of antibodies that must be combined, the lack of penetration in anatomical reservoirs, and the role they might play in cure studies. We compare the advantages and disadvantages of "classical ART" and therapy based on broadly neutralizing antibodies. We conclude that broadly neutralizing antibodies still need considerable improvements before they can be considered an alternative to classical ART. [ABSTRACT FROM AUTHOR]

BackgroundGlobal guidelines recommend preexposure prophylaxis (PrEP) for individuals with substantial human immunodeficiency virus (HIV) risk. Data on PrEP uptake in sub-Saharan Africa outside of clinical trials are limited. We report on "early adopters" of PrEP in the Sustainable East Africa Research in Community Health (SEARCH) study in rural Uganda and Kenya.MethodsAfter community mobilization and PrEP education, population-based HIV testing was conducted. HIV-uninfected adults were offered PrEP based on an empirically derived HIV risk score or self-identified HIV risk (if not identified by score). Using logistic regression, we analyzed predictors of early PrEP adoption (starting PrEP within 30 days vs delayed/no start) among adults identified for PrEP.ResultsOf 21212 HIV-uninfected adults in 5 communities, 4064 were identified for PrEP (2991 by empiric risk score, 1073 by self-identified risk). Seven hundred and thirty nine individuals started PrEP within 30 days (11% of those identified by risk score; 39% of self-identified); 77% on the same day. Among adults identified by risk score, predictors of early adoption included male sex (adjusted odds ratio 1.53; 95% confidence interval, 1.09-2.15), polygamy (1.92; 1.27-2.90), serodiscordant spouse (3.89; 1.18-12.76), self-perceived HIV risk (1.66; 1.28-2.14), and testing at health campaign versus home (5.24; 3.33-8.26). Among individuals who self-identified for PrEP, predictors of early adoption included older age (2.30; 1.29-4.08) and serodiscordance (2.61; 1.01-6.76).ConclusionsImplementation of PrEP incorporating a population-based empiric risk score, self-identified risk, and rapid initiation, is feasible in rural East Africa. Strategies are needed to overcome barriers to PrEP uptake, particularly among women and youth.Clinical trials registrationNCT01864603.

Background Participants with human immunodeficiency virus (HIV) seroconversion in The Ring Study, a phase 3 trial of dapivirine vaginal ring (DVR), or in the open-label extension trial dapivirine ring extended access and monitoring (DREAM) were offered enrollment in an observational cohort study (IPM 007) to assess clinical presentation and response to antiretroviral therapy (ART). Methods Participants' HIV infection was managed at local treatment clinics according to national treatment guidelines. IPM 007 study visits occurred 3 and 6 months after enrollment and every 6 months thereafter. Assessments included plasma HIV-1 RNA, CD4+ T-cell counts, and recording of HIV/AIDS-associated events and antiretroviral use. Post hoc virology analyses were performed for participants identified with virologic failure. Results One hundred fifty-one of 179 eligible participants (84.4%) enrolled into IPM 007; 103 had previously received the DVR in the Ring or DREAM studies, and 48 had received placebo in The Ring Study. HIV-1 RNA and CD4+ T-cell counts after 12 months' follow-up were similar for participants who used the DVR in The Ring Study and DREAM, compared to those who received placebo. Of the 78 participants with a study visit approximately 6 months after ART initiation, 59 (75.6%) had HIV-1 RNA <40 copies/mL (The Ring Study: placebo: 13/23 [56.5%]; DVR: 32/39 [82.1%]; DREAM [DVR]: 14/16 [87.5%]). Post hoc virology analysis indicated that genotypic patterns observed at virologic failure were as expected of a nonnucleoside reverse transcriptase inhibitor (NNRTI)–based regimen. Conclusions Seroconversion during DVR use did not negatively affect clinical presentation or treatment outcome. Mutation patterns at virologic failure were in line with individuals failing an NNRTI-based regimen. Clinical Trials Registration NCT01618058. [ABSTRACT FROM AUTHOR]

Background Antiretroviral therapy (ART) is remarkably effective in preventing perinatal transmission (PT) of HIV-1. We evaluated the PT rate in a population of women with widespread access to ART before conception. Methods The analysis included 14 630 women with HIV-1 who delivered from 2000 to 2017 at centers participating in the nationwide prospective multicenter French Perinatal Cohort (ANRS-EPF). PT was analyzed according to time period, timing of ART initiation, maternal plasma viral load (pVL), and gestational age at birth. No infants were breastfed, and all received neonatal prophylaxis. Results PT decreased between 3 periods, from 1.1% in 2000–2005 (58/5123) to 0.7% in 2006–2010 (30/4600) and to 0.2% in 2011–2017 (10/4907; P <.001). Restriction of the analysis to the 6316/14 630 (43%) women on ART at conception, PT decreased from 0.42% (6/1434) in 2000–2005 to 0.03% (1/3117) in 2011–2017 (P =.007). Among women treated at conception, if maternal pVL was undetectable near delivery, no PT was observed regardless of the ART combination [95%CI 0-0.07] (0/5482). Among women who started ART during pregnancy and with undetectable pVL near delivery, PT was 0.57% [95%CI 0.37-0.83] (26/4596). Among women treated at conception but with a detectable pVL near delivery, PT was 1.08% [95%CI 0.49-2.04] (9/834). We also qualitatively described 10 cases of transmission that occurred during the 2011–2017 period. Conclusions In a setting with free access to ART, monthly pVL assessment, infant ART prophylaxis, and in the absence of breastfeeding, suppressive ART initiated before pregnancy and continued throughout pregnancy can reduce PT of HIV to almost zero. [ABSTRACT FROM AUTHOR]

Background Most human immunodeficiency virus (HIV) seroconversions in people who have initiated preexposure prophylaxis (PrEP) occur in the context of insufficient adherence. We describe participants who seroconverted after being dispensed PrEP in a large PrEP implementation study in Australia. Methods Expanded PrEP Implementation in Communities in New South Wales was an implementation study of daily oral PrEP in individuals aged ≥18 years at high risk for acquiring HIV. HIV seroconversions were defined as a positive HIV test by either antigen, antibody, or detectable HIV viral load after enrollment. Insufficient adherence, measured by dispensing logs or participant self-report, was defined as <4 PrEP doses per week. Results A total of 9596 participants were enrolled and dispensed PrEP between 1 March 2016 and 30 April 2018; 30 were diagnosed with HIV by 31 March 2019. The median (interquartile range [IQR]) age was 31 (25–38) years, all identified as male, 29 (97%) identified as gay or homosexual, and 20 (69%) lived in a postcode with a low concentration of gay male residents. The median (IQR) days from first PrEP dispensing to diagnosis was 409 (347–656). There was no evidence that participants who seroconverted had been sufficiently adherent to PrEP. Nineteen (63%) participants who seroconverted were diagnosed with chlamydia, gonorrhoea, syphilis, or new hepatitis C infection. One participant had resistance to emtricitabine (M184V mutation) at diagnosis. Conclusions Participants who seroconverted were insufficiently adherent to PrEP despite being at high risk for acquiring HIV. Understanding the reasons for poor PrEP adherence in individuals who subsequently acquire HIV is critical to improving PrEP effectiveness. [ABSTRACT FROM AUTHOR]

Background Black and Hispanic/Latino men who have sex with men (MSM) are disproportionately affected by human immunodeficiency virus (HIV). In the Targeted Highly Effective Interventions to Reverse the HIV Epidemic (THRIVE) demonstration project, 7 community collaboratives were developed to provide comprehensive HIV prevention services for these populations. Methods We analyzed National HIV Surveillance System data to determine the number of HIV diagnoses for each year from 2014 to 2019 among Black, Hispanic/Latino, and White MSM in 7 THRIVE-eligible Metropolitan Statistical Areas (MSAs) that were awarded funding and 12 THRIVE-eligible MSAs that were not awarded funding. We used generalized linear Poisson regression models to estimate adjusted estimated annual percentage changes (EAPCs) with 95% confidence intervals for HIV diagnosis rates controlling for HIV prevalence, viral suppression, HIV testing rates, preexposure prophylaxis (PrEP) prescription rates, poverty, education, and insurance status. Results We found larger estimated decreases in HIV diagnosis rates in THRIVE jurisdictions compared with non-THRIVE jurisdictions. The adjusted EAPC among Black MSM was −8.2 (−11.7 to −4.6) in THRIVE MSAs compared with −4.2 (−7.8 to −0.4) in non-THRIVE MSAs. The adjusted EAPC among Hispanic/Latino MSM was −8.6 (−12.2 to −4.8) in THRIVE MSAs compared with −2.6 (−5.1 to −0.1)in non-THRIVE MSAs. The adjusted EAPC among White MSM was −7.6 (−12.0 to −3.1) in THRIVE MSAs compared with 5.9 (1.8-10.1) in non-THRIVE MSAs. Conclusions The THRIVE community collaborative model was associated with a decrease in HIV diagnoses among Black and Hispanic/Latino MSM. To achieve the goals of the US Ending the HIV Epidemic initiative, effective interventions aimed to increase PrEP use need to be focused on Black and Hispanic/Latino MSM. [ABSTRACT FROM AUTHOR]

While we have the tools to achieve this goal, the persistent barriers to healthcare services experienced by too many individuals will need to be addressed to make significant progress and improve the health and quality of life of all people with human immunodeficiency virus (HIV). The necessary structural changes require actions by federal, state, and local policymakers and range from ensuring universal access to healthcare services to optimizing care delivery to ensuring a robust and diverse infectious diseases and HIV workforce. In this article, we outlines 10 key principles for policy reforms that, if advanced, would make ending the HIV epidemic in the United States possible and could have much more far-reaching effects in improving the health of our nation. [ABSTRACT FROM AUTHOR]

Background Timely, accurate adherence data may support oral pre-exposure prophylaxis (PrEP) success and inform prophylaxis choice. We evaluated a Food and Drug Administration (FDA)-approved digital health feedback system (DHFS) with ingestible-sensor-enabled (IS) tenofovir-disoproxil-fumarate plus emtricitabine (Truvada®) in persons starting oral PrEP. Methods Human immunodeficiency virus (HIV)-negative adults were prescribed IS-Truvada® with DHFS for 12 weeks to observe medication taking behavior. Baseline demographics, urine toxicology, and self-report questionnaires were obtained. Positive detection accuracy and adverse events were computed as percentages, with Kaplan Meier Estimate for persistence-of-use. In participants persisting ≥28 days, adherence patterns (taking and timing) were analyzed, and mixed-effects logistic regression modeled characteristics associated with treatment adherence. Results Seventy-one participants were enrolled, mean age 37.6 years (range 18–69), 90.1% male, 77.5% White, 33.8% Hispanic, 95.8% housed, and 74.6% employed. Sixty-three participants (88.7%) persisted ≥28 days, generating 4987 observation days, average 79.2 (29–105). Total confirmed doses were 86.2% (95% confidence interval [CI] 82.5, 89.4), decreasing over time, odds ratio (OR) 0.899 (95% CI.876,.923) per week, P <.001; 79.4% (95% CI 66.7%, 87.3%) of participants had ≥80% adherence. Pattern analysis showed days without confirmed doses clustered (P =.003); regular dose timing was higher among participants with ≥80% confirmed doses (0.828, 95% CI.796 to.859) than among those with <80% (0.542, 95% CI95.405 to.679) P <.001. In multi-predictor models, better adherence was associated with older age, OR 1.060 (95% CI 1.033, 1.091) per year, P <.001; negative vs positive methamphetamine screen, OR 5.051 (95% CI 2.252, 11.494), P <.001. Conclusions DHFS with IS-Truvada® distinguished adherent persons from those potentially at risk of prophylactic failure. Ongoing methamphetamine substance use may impact oral PrEP success. [ABSTRACT FROM AUTHOR]

Long-acting antiretroviral products have the potential to transform human immunodeficiency virus (HIV) prevention and treatment approaches in pediatric populations. Broadly neutralizing antibodies and/or long-acting antiretroviral formulations by injection could dramatically improve provision of HIV prophylaxis and/or early treatment to newborns and infants at risk of HIV infection. Challenges in daily oral antiretroviral administration to toddlers and school age children living with HIV may be relieved by use of long-acting formulations, but the pharmacokinetics and safety of these products in children must be studied before they can enter routine clinical use. Although some initial studies of broadly neutralizing antibodies and injectable long-acting agents in infants and young children are underway, more studies of these and other long-acting products are needed. For many adolescents, compliance with daily medication administration is especially challenging. Long-acting products hold particular promise for adolescents living with HIV as well as those at high risk of HIV acquisition, and adolescents can usually be included in the drug development pipeline simultaneously with adults. Long-acting products have the potential to provide alternatives to lifelong daily oral drug administration across the pediatric age spectrum, leading to more effective prevention and treatment of HIV infection in infants, children, and adolescents. [ABSTRACT FROM AUTHOR]

Development of and increased access to generic oral medications to treat high-burden diseases including human immunodeficiency virus (HIV), tuberculosis, viral hepatitis, and malaria have had a major impact on reducing global morbidity and mortality. However, access and adherence to these life-saving treatments remains limited for some of the most vulnerable and underserved populations, for whom stigma, control, and discretion are critical to decisions around care. Current efforts to develop long-acting formulations to treat and prevent these conditions could overcome many of these barriers. However, generic manufacturing of these innovative products will be required to ensure affordable access to the communities and patients in greatest need. Strategic investments in new infrastructure will be required even before markets and manufacturing costs are clear, to ensure that access to these new products is not delayed, particularly for patients in low- and middle-income countries. Unlike conventional oral medications, long-acting products require greater investment for formulation, packaging, and delivery. The requirement for long-term bioequivalence studies will introduce additional delays in regulatory approval of generic long-acting products, and expedited approval pathways must be developed. Lessons learned from the development of long-acting hormonal contraceptives and long-acting antiretroviral products may provide a way forward. [ABSTRACT FROM AUTHOR]

Long-acting injectable antiretroviral therapy (LA ART) has been found to be non-inferior to daily oral ART in phase 3 clinical trials and is poised to soon enter routine clinical care. This treatment modality has the potential to address many barriers to daily oral ART adherence among people living with human immunodeficiency virus (HIV) and for HIV Pre-Exposure prevention. Data from the Patient Reported Outcomes (PROs) showed high rates of satisfaction, acceptability, tolerability and preference for the LA regimen, compared with the daily oral treatment. Once LA ART is available, access and uptake will be limited because of current knowledge gaps in the use of these agents and multiple challenges many specific to low-income and middle-income countries, where the epidemic is most concentrated and HIV prevention and treatment options are limited. These gaps will lead to multiple systems-level and individual-level barriers to implementation. Anticipating and addressing these gaps and barriers will help fulfill the promise of these agents against the pandemic. [ABSTRACT FROM AUTHOR]

Long-acting injectable antiretroviral therapy (LAI-ART) for the treatment and prevention of human immunodeficiency virus (HIV) holds great potential to shift treatment paradigms by offering an alternative to daily oral medication. However, significant challenges at the drug, patient, and system levels risk impeding the uptake and implementation of LAI-ART. This review aims to describe the known and anticipated barriers to uptake of LAI-ART in high-income countries, as well as the ongoing research addressing some of these barriers to improve the delivery and uptake of LAI-ART products. [ABSTRACT FROM AUTHOR]

The landscape for the development of therapeutics for prevention and treatment of human immunodeficiency virus (HIV)-1 infection has pivoted towards long-acting antiretrovirals (LA-ARVs). LA-ARVs have the potential to transform global implementation of HIV-1 prevention and treatment strategies. The ability to identify potential knowledge gaps early in development, proactively address missing information or data gaps, and strategically leverage all the available information is the key to streamline the development of safe and effective LA-ARV therapeutics. The purpose of this article is to discuss some potential considerations for development of LA-ARVs. Three possible drug development scenarios are briefly discussed and include developing (1) a novel LA-ARV, (2) a novel LA formulation of an approved oral ARV, and (3) an LA pro-drug of an approved oral ARV. For each of these scenarios, we briefly describe what type(s) of information may be helpful and discuss potential opportunities to leverage available information. Additionally, we discuss some unique LA-ARV drug development considerations, including the use of an oral lead-in, and assessing the impact of residual ARV exposures on subsequent regimens and evaluation of LA-ARVs in specific populations. We strongly believe that efficient integration of multidisciplinary knowledge can advance the development, availability, and accessibility of therapeutics not only for HIV-1 prevention and treatment but also for other chronic viral infections. [ABSTRACT FROM AUTHOR]

This prospective study enrolled healthcare workers (HCWs) who were nonresponders following at least 5 doses of aluminum-adjuvanted hepatitis B vaccine who received the 2-dose Heplisav-B (HepB-CpG) (Dynavax Technologies Corporation, Emeryville, CA) series. After 2 doses of HepB-CpG, 43/47 (91%) participants, and with 1 dose, 41/49 (84%) responded. HepB-CpG could be the preferred vaccine in HCW nonresponders. Clinical Trials Registration. Clinicaltrials.gov NCT04456504. [ABSTRACT FROM AUTHOR]

Background The use of preexposure prophylaxis (PrEP) for the prevention of human immunodeficiency virus (HIV) has raised concerns of increased sexual risk behaviors. These behaviors may be associated with increased incidence of sexually acquired hepatitis C virus (HCV) among gay and bisexual men. Methods The Expanded PrEP Implementation in Communities–New South Wales (EPIC-NSW) study was a cohort study of daily coformulated tenofovir disoproxil fumarate and emtricitabine for HIV prevention. We recruited 9596 people at high risk of HIV acquisition from 31 clinics across New South Wales and the Australia Capital Territory in Australia. We report prior exposure to HCV and incidence in this cohort between 2016 and 2019. Results At least 1 HCV test result was available for 8658 (90.2%) participants. These individuals had a median age of 34 years (interquartile range, 28–43), most of whom were male (8530, 98.5%), identified as gay (7944, 91.8%), and were born in Australia (51.8%). Prior exposure to HCV was detected among 81 participants at baseline (0.9%; 95% confidence interval [CI]:.71.2). Twenty of 8577 participants were diagnosed with incident infection (rate 0.2/100 person-years [95% CI:.1–.3/100 person-years]). They were significantly older (median age 41 years vs 34 years, P  = .044), and more likely to report methamphetamine use at baseline (incidence rate ratio, 2.7 [95% CI: 1.00–7.2]) than those without incident infection. Conclusions In this population of PrEP users, HCV prior exposure and incidence were low. With high levels of HCV and HIV testing and treatment, the dual goals of HIV and HCV elimination could be achieved in this population. Clinical Trials Registration: number NCT02870790. [ABSTRACT FROM AUTHOR]

BackgroundYoung men-who-have-sex-with-men (MSM) are disproportionately impacted by human immunodeficiency virus (HIV). Preexposure prophylaxis (PrEP) could reduce HIV acquisition among youth, but suboptimal adherence threatens effectiveness. Optimal metrics of PrEP adherence among adolescents have remain undefined.MethodsThe Adolescent Trials Network 110/113 studies provided daily oral PrEP with tenofovir (TFV) disoproxil fumarate/emtricitabine over 48 weeks to a diverse population of MSM (aged 15-22 years). Self-reported adherence was assessed and PrEP drug concentrations measured from hair and dried blood spot (DBS) samples; 23% of participants received Wisepill electronic monitoring devices. The average number of PrEP doses per week taken was estimated, and concordance between measures assessed.ResultsAmong 243 participants, hair samples were collected at 1186/1238 (96%) person-visits. The concordance of TFV levels in hair and TFV-diphosphate in DBS around thresholds consistent with taking ≥4 and 7 PrEP doses/week was high (76% and 80%). Hair and DBS concentrations correlated poorly with self-report and Wisepill metrics. Through week 12, 40%-60% of participants (by hair and DBS), ≤31% (Wisepill), and >85% (self-report) were estimated to have taken ≥4 PrEP doses/week (a threshold associated with protection among MSM). For all measures except self-report, adherence declined over time, with half of participants taking

Data from several modeling studies demonstrate that large-scale increases in human immunodeficiency virus (HIV) testing across settings with a high burden of HIV may produce the largest incidence reductions to support the US Ending the HIV Epidemic (EHE) initiative's goal of reducing new HIV infections 90% by 2030. Despite US Centers for Disease Control and Prevention's recommendations for routine HIV screening within clinical settings and at least yearly screening for individuals most at risk of acquiring HIV, fewer than half of US adults report ever receiving an HIV test. Furthermore, total domestic funding for HIV prevention has remained unchanged between 2013 and 2019. The authors describe the evidence supporting the value of expanded HIV testing, identify challenges in implementation, and present recommendations to address these barriers through approaches at local and federal levels to reach EHE targets. [ABSTRACT FROM AUTHOR]

In countries with high human immunodeficiency virus (HIV) prevalence, up to 30% of pregnant women are living with HIV, with fetal exposure to both HIV and antiretroviral therapy during pregnancy. In addition, pregnant women without HIV but at high risk of HIV acquisition are increasingly receiving HIV preexposure antiretroviral prophylaxis (PrEP). Investments are being made to establish and follow cohorts of children to evaluate the long-term effects of in utero HIV and antiretroviral exposure. Agreement on a key set of definitions for relevant exposures and outcomes is important both for interpreting individual study results and for comparisons across cohorts. Harmonized definitions of in utero HIV and antiretroviral drug (maternal treatment or PrEP) exposure will also facilitate improved classification of these exposures in future observational studies and clinical trials. The proposed definitions offer a uniform approach to facilitate the consistent description and estimation of effects of HIV and antiretroviral exposures on key child health outcomes. [ABSTRACT FROM AUTHOR]

Background After coronavirus disease 2019 (COVID-19) shelter-in-place (SIP) orders, viral suppression (VS) rates initially decreased within a safety-net human immunodeficiency virus (HIV) clinic in San Francisco, particularly among people living with HIV (PLWH) who are experiencing homelessness. We sought to determine if proactive outreach to provide social services, scaling up of in-person visits, and expansion of housing programs could reverse this decline. Methods We assessed VS 24 months before and 13 months after SIP using mixed-effects logistic regression followed by interrupted time series (ITS) analysis to examine changes in the rate of VS per month. Loss to follow-up (LTFU) was assessed via active clinic tracing. Results Data from 1816 patients were included; the median age was 51 years, 12% were female, and 14% were experiencing unstable housing/homelessness. The adjusted odds of VS increased 1.34 fold following institution of the multicomponent strategies (95% confidence interval [CI], 1.21–1.46). In the ITS analysis, the odds of VS continuously increased 1.05 fold per month over the post-intervention period (95% CI, 1.01–1.08). Among PLWH who previously experienced homelessness and successfully received housing support, the odds of VS were 1.94-fold higher (95% CI, 1.05–3.59). The 1-year LTFU rate was 2.8 per 100 person-years (95% CI, 2.2–3.5). Conclusions The VS rate increased following institution of the multicomponent strategies, with a lower LFTU rate compared with prior years. Maintaining in-person care for underserved patients, with flexible telemedicine options, along with provision of social services and permanent expansion of housing programs, will be needed to support VS among underserved populations during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background Uptake of HIV pre-exposure prophylaxis (PrEP) has been increasing in the United States since its FDA approval in 2012; however, the COVID-19 pandemic may have affected this trend. Our objective was to assess the impact of COVID-19 on PrEP prescriptions in the United States. Methods We analyzed data from a national pharmacy database from January 2017 through March 2021 to fit an interrupted time-series model that predicted PrEP prescriptions and new PrEP users had the pandemic not occurred. Observed PrEP prescriptions and new users were compared with those predicted by the model. Main outcomes were weekly numbers of PrEP prescriptions and new PrEP users based on a previously developed algorithm. The impact of the COVID-19 pandemic was quantified by computing rate ratios and percentage decreases between the observed and predicted counts during 15/3/2020–31/3/2021. Results In the absence of the pandemic, our model predicted that there would have been 1 058 162 PrEP prescriptions during 15/3/2020–31/3/2021. We observed 825 239 PrEP prescriptions, a 22.0% reduction (95% CI: 19.1–24.8%) after the emergency declaration. The model predicted 167 720 new PrEP users during the same period; we observed 125 793 new PrEP users, a 25.0% reduction (95% CI: 20.9–28.9%). The COVID-19 impact was greater among younger persons and those with commercial insurance. The impact of the pandemic varied markedly across states. Conclusions The COVID-19 pandemic disrupted an increasing trend in PrEP prescriptions in the United States, highlighting the need for innovative interventions to maintain access to HIV-prevention services during similar emergencies. [ABSTRACT FROM AUTHOR]

The plan for Ending the HIV (human immunodeficiency virus) Epidemic (EHE) in the United States aims to reduce new infections by 75% by 2025 and by 90% by 2030. For EHE to be successful, it is important to accurately measure changes in numbers of new HIV infections after 5 and 10 years (to determine whether the EHE goals have been achieved) but also over shorter timescales (to monitor progress and intensify prevention efforts if required). In this viewpoint, we aim to demonstrate why the method used to monitor progress toward the EHE goals must be carefully considered. We briefly describe and discuss different methods to estimate numbers of new HIV infections based on longitudinal cohort studies, cross-sectional incidence surveys, and routine surveillance data. We particularly focus on identifying conditions under which unadjusted and adjusted estimates based on routine surveillance data can be used to estimate changes in new HIV infections. [ABSTRACT FROM AUTHOR]

Structural determinants of health drive inequities in the acquisition of human immunodeficiency virus (HIV) and the use of preexposure prophylaxis (PrEP) for HIV prevention among cisgender women in the United States. However, current PrEP clinical guidance and implementation paradigms largely focus on individual behaviors and characteristics, resulting in missed opportunities to improve PrEP access, and the implicit transferring of prevention work from health systems to individuals. In this viewpoint article, we outline ways to apply a structural lens to clinical guidance and PrEP implementation for women and propose areas for future work. [ABSTRACT FROM AUTHOR]

Background We aimed to assess if maternal human immunodeficiency virus (HIV) drug resistance is associated with an increased risk of HIV vertical transmission and to describe the dynamics of drug resistance in HIV-infected infants. Methods This was a case-control study of PROMISE study participants. "Cases" were mother-infant pairs with HIV vertical transmission during pregnancy or breastfeeding and "controls" were mother-infant pairs without transmission matched 1:3 by delivery date and clinical site. Genotypic HIV drug resistance analyses were performed on mothers' and their infants' plasma at or near the time of infant HIV diagnosis. Longitudinal analysis of genotypic resistance was assessed in available specimens from infants, from diagnosis and beyond, including antiretroviral therapy (ART) initiation and last study visits. Results Our analyses included 85 cases and 255 matched controls. Maternal HIV drug resistance, adjusted for plasma HIV RNA load at infant HIV diagnosis, enrollment CD4 count, and antepartum regimens, was not associated with in utero / peripartum HIV transmission. In contrast, both maternal plasma HIV RNA load and HIV drug resistance were independent risk factors associated with vertical transmission during breastfeeding. Furthermore, HIV drug resistance was selected across infected infants during infancy. Conclusions Maternal HIV drug resistance and maternal viral load were independent risk factors for vertical transmission during breastfeeding, suggesting that nevirapine alone may be insufficient infant prophylaxis against drug-resistant variants in maternal breast milk. These findings support efforts to achieve suppression of HIV replication during pregnancy and suggest that breastfeeding infants may benefit from prophylaxis with a greater barrier to drug resistance than nevirapine alone. [ABSTRACT FROM AUTHOR]

BackgroundBlinded clinical trials have reported a modest and transient "start-up syndrome" with initiation of tenofovir-based pre-exposure prophylaxis (PrEP). We evaluate this phenomenon and its effect on adherence in an open-label PrEP study.MethodsIn the iPrEx open-label extension (OLE) study, an 18-month open-label, multi-site PrEP cohort taking daily oral co-formulated tenofovir/emtricitabine, we examined the prevalence and duration of PrEP-associated symptoms and their effect on adherence, assessed by drug levels in dried blood spots tested monthly for the first 3 months.ResultsSymptom reports peaked within the first month, with 39% reporting potentially PrEP-related symptoms compared to 22% at baseline. Symptoms largely resolved to pre-PrEP levels by 3 months.Symptoms varied substantially in frequency by study site (range in 1-month symptoms: 11% to 70%). Nongastrointestinal (GI) symptoms were not associated with adherence (odds ratio [OR] = 1.2, 95% confidence interval [CI], .4-3.7); however, GI-associated symptoms in the first 4 weeks were inversely associated with adherence at 4 weeks (OR = 0.47, 95% CI, .23-.96). Reports of GI symptoms were associated with 7% (95% CI, 4%-11%) of suboptimal adherence in this cohort.ConclusionsPrEP-associated symptoms in the open-label setting occur in a minority of users and largely resolve within 3 months. GI symptoms are associated with a modest reduction in PrEP adherence, but good adherence is possible even in the presence of frequent symptom reports.Clinical trials registrationClinicaltrials.govNCT00458393.

Background Hepatitis C virus (HCV) infection has been reported among gay, bisexual, and other men who have sex with men (GBM) globally including GBM with human immunodeficiency virus (HIV) and HIV-negative GBM, particularly those using HIV preexposure prophylaxis (PrEP). In Australia, HCV direct-acting antiviral treatment (DAA) was government-funded from 2016. Large implementation studies of PrEP also began in 2016. We examined HCV incidence among GBM to assess whether HCV incidence has changed since 2015. Methods Data were drawn from the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance. We included GBM who tested HCV antibody negative at their first test and had ≥1 subsequent test. Generalized linear modeling (Poisson distribution) was used to examine HCV incidence from 2009 to 2019 stratified by HIV status, and among HIV-negative GBM prescribed PrEP from 2016 to 2019. Results Among 6744 GBM with HIV, HCV incidence was 1.03 per 100 person-years (PY). Incidence declined by 78% in 2019 compared to 2015 (incidence rate ratio [IRR], 0.22 [95% confidence interval {CI}:.09–.55]). Among 20 590 HIV-negative GBM, HCV incidence was 0.20/100 PY, with no significant change over time. Among 11 661 HIV-negative GBM prescribed PrEP, HCV incidence was 0.29/100 PY. Compared to 2016, incidence among GBM prescribed PrEP declined by 80% in 2019 (IRR, 0.20 [95% CI:.06–.64]). Conclusions HCV incidence among GBM living with HIV declined following DAA availability. There was no observed change in HCV incidence among HIV-negative GBM overall. Among GBM prescribed PrEP, incidence declined since the early years of PrEP implementation in Australia. Australia is on track to eliminate HCV among GBM before global 2030 targets. [ABSTRACT FROM AUTHOR]

Trichomonas vaginalis is likely the most prevalent nonviral sexually transmitted infection, affecting an estimated 3.7 million women and men in the United States. Health disparities are prominent in the epidemiology of trichomoniasis, as African Americans are >4 times more likely to be infected than persons of other races. Since publication of the 2015 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines, additional data have bolstered the importance of T. vaginalis infection sequelae in women, including increased risk of human immunodeficiency virus (HIV) acquisition, cervical cancer, preterm birth, and other adverse pregnancy outcomes. Less is known about the clinical significance of infection in men. Newly available diagnostic methods, including point-of-care assays and multiple nucleic acid amplification tests, can be performed on a variety of genital specimens in women and men, including urine, allowing more accurate and convenient testing and screening of those at risk for infection. Repeat and persistent infections are common in women; thus, rescreening at 3 months after treatment is recommended. In vitro antibiotic resistance to 5-nitroimidazole in T. vaginalis remains low (4.3%) but should be monitored. High rates of T. vaginalis among sexual partners of infected persons suggest a role for expedited partner treatment. A randomized controlled trial in HIV-uninfected women demonstrated that multidose metronidazole 500 mg twice daily for 7 days reduced the proportion of women with Trichomonas infection at 1 month test of cure compared with women receiving single-dose therapy (2 g). The 2-g single-dose oral metronidazole regimen remains the preferred treatment in men. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the author discusses various topics within the issue, including the long-acting (LA) formulations for treating infectious diseases, the approved LA products like LA-rilpivirine, and the LA Extended-Release Antiretroviral Research Resource Program (LEAP).

Background Human immunodeficiency virus (HIV) and syphilis infection continue at disproportionate rates among minority men who have sex with men (MSM) in the United States. The integration of HIV genetic clustering with partner services can provide important insight into local epidemic trends to guide interventions and control efforts. Methods We evaluated contact networks of index persons defined as minority men and transgender women diagnosed with early syphilis and/or HIV infection between 2018 and 2020 in 2 North Carolina regions. HIV clusters were constructed from pol sequences collected through statewide surveillance. A combined "HIV-risk" network, which included persons with any links (genetic or sexual contact) to HIV-positive persons, was evaluated by component size, demographic factors, and HIV viral suppression. Results In total, 1289 index persons were identified and 55% named 1153 contacts. Most index persons were Black (88%) and young (median age 30 years); 70% had early syphilis and 43% had prevalent HIV infection. Most people with HIV (65%) appeared in an HIV cluster. The combined HIV-risk network (1590 contact network and 1500 cluster members) included 287 distinct components; however, 1586 (51%) were in a single component. Fifty-five percent of network members with HIV had no evidence of viral suppression. Overall, fewer index persons needed to be interviewed to identify 1 HIV-positive member without viral suppression (1.3 vs 4.0 for contact tracing). Conclusions Integration of HIV clusters and viral loads illuminate networks with high HIV prevalence, indicating recent and ongoing transmission. Interventions intensified toward these networks may efficiently reach persons for HIV prevention and care re-engagement. [ABSTRACT FROM AUTHOR]

Background Invasive fungal infections in the United States are chronically underdiagnosed and a lack of coordinated surveillance makes the true burden of disease difficult to determine. The purpose of this analysis was to capture mortality-associated burden of risk conditions and fungal infections. Methods We analyzed data from the National Vital Statistics System from 1999 through 2018 to estimate the mortality attributed to risk conditions and related fungal disease. Results The number of risk conditions associated with fungal disease is steadily rising in the United States, with 1 047 422 diagnoses at time of death in 2018. While fungal disease decreased substantially from 1999 to 2010, primarily due to the control of human immunodeficiency virus (HIV) infection, the number of deaths with fungal diagnosis has increased in the non-HIV cohort, with significant increases in patients with diabetes, cancer, immunosuppressive disorders, or sepsis. Conclusions The landscape of individuals at risk for serious fungal diseases is changing, with a continued decline in HIV-associated incidence but increased diagnoses in patients with cancer, sepsis, immunosuppressive disorders, and influenza. Additionally, there is an overall increase in the number of fungal infections in recent years, indicating a failure to control fungal disease mortality in these new immunocompromised cohorts. Improvement in the prevention and management of fungal diseases is needed to control morbidity and mortality in the rising number of immunocompromised and at-risk patients in the United States. [ABSTRACT FROM AUTHOR]

Background Early combined antiretroviral therapy (cART) limits the total HIV-DNA load in children. However, data on its impact in older children and adolescents remain scarce. This study compares HIV reservoirs in children (5–12 years) and adolescents (13–17 years) who started cART <6 months (early [E-] group) or >2 years (late [L-] group). Methods The ANRS-EP59-CLEAC study prospectively enrolled 76 patients perinatally infected with HIV-1 who reached HIV-RNA <400 copies/mL <24 months after cART initiation, regardless of subsequent viral suppression (E-group: 27 children, 9 adolescents; L-group: 19 children, 21 adolescents). Total and integrated HIV-DNA were quantified in blood and in CD4+ T-cell subsets. A substudy assessed HIV reservoir inducibility after ex vivo peripheral blood mononuclear cell (PBMC) stimulation. Results Total HIV-DNA levels were lower in early- versus late-treated patients (children: 2.14 vs 2.87 log copies/million PBMCs; adolescents: 2.25 vs 2.74 log; P <.0001 for both). Low reservoir was independently associated with treatment precocity, protective HLA, and low cumulative viremia since cART initiation. The 60 participants with undetectable integrated HIV-DNA started cART earlier than other patients (4 vs 54 months; P =.03). In those with sustained virological control, transitional and effector memory CD4+ T cells were less infected in the E-group than in the L-group (P =.03 and.02, respectively). Viral inducibility of reservoir cells after normalization to HIV-DNA levels was similar between groups. Conclusions Early cART results in a smaller blood HIV reservoir until adolescence, but all tested participants had an inducible reservoir. This deserves cautious consideration for HIV remission strategies. [ABSTRACT FROM AUTHOR]