Search

Background Persons with acute HIV infection (AHI) have heightened transmission risk. We evaluated potential transmission reduction using behavioral and biomedical interventions in a randomized controlled pilot study in Malawi. Methods Persons were randomized 1:2:2 to standard counseling (SC), 5-session behavioral intervention (BI), or behavioral intervention plus 12 weeks of antiretrovirals (ARVs; BIA). All were followed for 26–52 weeks and, regardless of arm, referred for treatment according to Malawi-ARV guidelines. Participants were asked to refer partners for testing. Results Among 46 persons (9 SC, 18 BI, 19 BIA), the average age was 28; 61% were male. The median viral load (VL) was 5.9 log copies/mL at enrollment. 67% (10/15) of BIA participants were suppressed (<1000 copies/mL) at week 12 vs 25% BI and 50% SC (P =.07). Although the mean number of reported condomless sexual acts in the past week decreased from baseline across all arms (1.5 vs 0.3 acts), 36% experienced incident sexually transmitted infection by 52 weeks (12% SC, 28% BI, 18% BIA). Forty-one percent (19/46) of participants referred partners (44% SC, 44% BI, 37% BIA); 15 of the partners were HIV-infected. Conclusions Diagnosis of AHI facilitates behavioral and biomedical risk reduction strategies during a high-transmission period that begins years before people are typically identified and started on ARVs. Sexually transmitted infection incidence in this cohort suggests ongoing risk behaviors, reinforcing the importance of early intervention with ARVs to reduce transmission. Early diagnosis coupled with standard AHI counseling and early ARV referral quickly suppresses viremia, may effectively change behavior, and could have tremendous public health benefit in reducing onward transmission. [ABSTRACT FROM AUTHOR]

Background: Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the only bnAb HIV prevention efficacy studies to date, the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting bnAb, VRC01, administered intravenously (IV), demonstrated 75% prevention efficacy against highly neutralization-sensitive viruses but was ineffective against less sensitive viruses. Greater efficacy is required before passively administered bnAbs become a viable option for HIV prevention; furthermore subcutaneous (SC) or intramuscular (IM) administration may be preferred. VRC07-523LS is a next-generation bnAb targeting the CD4-binding site and was engineered for increased neutralization breadth and half-life., Methods: Participants were recruited between 02 February 2018 and 09 October 2018. 124 healthy participants without HIV were randomized to receive five VRC07-523LS administrations via IV (T1: 2.5 mg/kg, T2: 5 mg/kg, T3: 20 mg/kg), SC (T4: 2.5 mg/kg, T5: 5 mg/kg) or IM (T6: 2.5 mg/kg or P6: placebo) routes at four-month intervals. Safety data were collected for 144 weeks following the first administration. VRC07-523LS serum concentrations were measured by ELISA after the first dose through Day 112 in all participants and by binding antibody multiplex assay (BAMA) thereafter in 60 participants (10 per treatment group) through Day 784. Compartmental population pharmacokinetic (PK) analyses were conducted to evaluate the VRC07-523LS serum pharmacokinetics. Neutralization activity was measured in a TZM-bl assay and anti-drug antibodies (ADA) were assayed using a tiered bridging assay testing strategy., Results: Injections were well-tolerated, with mild pain or tenderness reported commonly in the SC and IM groups, and mild to moderate erythema or induration reported commonly in the SC groups. Infusions were generally well-tolerated, with infusion reactions reported in 3 of 20 participants in the 20 mg/kg IV group. Peak geometric mean (GM) concentrations (95% confidence intervals) following the first administration were 29.0 μg/mL (25.2, 33.4), 58.5 μg/mL (49.4, 69.3), and 257.2 μg/mL (127.5, 518.9) in T1-T3 with IV dosing; 10.8 μg/mL (8.8, 13.3) and 22.8 μg/mL (20.1, 25.9) in T4-T5 with SC dosing; and 16.4 μg/mL (14.7, 18.2) in T6 with IM dosing. Trough GM concentrations immediately prior to the second administration were 3.4 μg/mL (2.5, 4.6), 6.5 μg/mL (5.6, 7.5), and 27.2 μg/mL (23.9, 31.0) with IV dosing; 0.97 μg/mL (0.65, 1.4) and 3.1 μg/mL (2.2, 4.3) with SC dosing, and 2.6 μg/mL (2.05, 3.31) with IM dosing. Peak VRC07-523LS serum concentrations increased linearly with the administered dose. At a given dose, peak and trough concentrations, as well as serum neutralization titres, were highest in the IV groups, reflecting the lower bioavailability following SC and IM administration. A single participant was found to have low titre ADA at a lone timepoint. VRC07-523LS has an estimated mean half-life of 42 days (95% CI: 40.5, 43.5), approximately twice as long as VRC01., Conclusions: VRC07-523LS was safe and well-tolerated across a range of doses and routes and is a promising long-acting bnAb for inclusion in HIV-1 prevention regimens.

Background: Up to 69% of adults who acquire HIV in Kenya seek care before seroconversion, providing an important opportunity for early diagnosis and treatment. The Tambua Mapema Plus (TMP) trial tested a combined HIV-1 nucleic acid testing, linkage, treatment, and partner notification intervention for adults aged 18-39 years with symptoms of acute HIV infection presenting to health facilities in coastal Kenya. We estimated the potential impact of TMP on the Kenyan HIV epidemic., Methods: We developed an agent-based network model of HIV-1 transmission using TMP data and Kenyan statistics to estimate potential population-level impact of targeted facility-based testing over 10 years. Three scenarios were modeled: standard care [current use of provider-initiated testing and counseling (PITC)], standard HIV rapid testing scaled to higher coverage obtained in TMP (scaled-up PITC), and the TMP intervention., Results: Standard care resulted in 90.7% of persons living with HIV (PLWH) knowing their status, with 67.5% of those diagnosed on treatment. Scaled-up PITC resulted in 94.4% of PLWH knowing their status and 70.4% of those diagnosed on treatment. The TMP intervention achieved 97.5% of PLWH knowing their status and 80.6% of those diagnosed on treatment. The percentage of infections averted was 1.0% (95% simulation intervals: -19.2% to 19.9%) for scaled-up PITC and 9.4% (95% simulation intervals: -8.1% to 24.5%) for TMP., Conclusion: Our study suggests that leveraging new technologies to identify acute HIV infection among symptomatic outpatients is superior to scaled-up PITC in this population, resulting in >95% knowledge of HIV status, and would reduce new HIV infections in Kenya., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: HIV preexposure prophylaxis (PrEP) using daily oral tenofovir-disoproxil-fumarate/emtricitabine (TDF/FTC) is effective for preventing HIV acquisition, but concerns remain about its potential kidney toxicity. This study examined kidney function in individuals using PrEP in real-world clinical settings., Setting: Demonstration project in 2 sexually transmitted infection clinics and a community health center., Methods: We evaluated kidney function among men who have sex with men and transgender women taking tenofovir-disoproxil-fumarate/emtricitabine PrEP for up to 48 weeks. Serum creatinine and urine dipstick for protein were obtained at 12-week intervals. Kidney function was estimated using creatinine clearance (CrCl) (Cockcroft-Gault) and estimated glomerular filtration rate (eGFR) (CKD-EPI)., Results: From October 2012 to January 2014, we enrolled 557 participants (median age 33). Mean creatinine increased from baseline to week 12 by 0.03 mg/dL (4.6%) (P < 0.0001); mean CrCl decreased by 4.8 mL/min (3.0%) (P < 0.0001). These changes remained stable through week 48 (P = 0.81, P = 0.71 respectively). There were 75/478 (15.7%) participants who developed worsening proteinuria at week 12 compared with baseline (P < 0.0001), and this percent remained stable through week 48 (P = 0.73). Twenty-five participants (5.1%) developed new-onset eGFR <70 mL/min/1.73 m; independent predictors of this outcome were age ≥40 years (OR 3.79, 95% CI: 1.43 to 10.03) and baseline eGFR <90 mL/min/1.73 m (OR 9.59, 3.69-24.94)., Conclusions: In a demonstration setting, daily tenofovir-disoproxil-fumarate/emtricitabine PrEP leads to reduced CrCl and eGFR; however, these eGFR changes are based on very small changes in serum creatinine and seem to be nonprogressive after the first 12 weeks. Future studies are needed to understand the prognostic significance of these small changes.

Background and Objectives: Integrating acute HIV-infection (AHI) testing into clinical settings is critical to prevent transmission, and realize potential treatment-as-prevention benefits. We evaluated acceptability of AHI testing and compared AHI prevalence at sexually transmitted infection (STI) clinics and HIV testing and counseling (HTC) clinics in Lilongwe, Malawi., Methods: We conducted HIV RNA testing for HIV-seronegative patients visiting STI and HTC clinics. AHI was defined as positive RNA and negative/discordant rapid antibody tests. We evaluated demographic, behavioral, and transmission-risk differences between STI and HTC patients and assessed performance of a risk-score for targeted screening., Results: Nearly two-thirds (62.8%, 9280/14,755) of eligible patients consented to AHI testing. We identified 59 persons with AHI (prevalence = 0.64%)-a 0.9% case-identification increase. Prevalence was higher at STI [1.03% (44/4255)] than at HTC clinics [0.3% (15/5025), P < 0.01], accounting for 2.3% of new diagnoses vs 0.3% at HTC clinic. Median viral load (VL) was 758,050 copies per milliliter; 25% (15/59) had VL ≥ 10,000,000 copies per milliliter. Median VL was higher at STI (1,000,000 copies/mL) compared with HTC (153,125 copies/mL, P = 0.2). Among persons with AHI, those tested at STI clinics were more likely to report genital sores compared with those tested at HTC clinics (54.6% vs 6.7%, P < 0.01). The risk score algorithm performed well in identifying persons with AHI at HTC clinics (sensitivity = 73%, specificity = 89%)., Conclusions: The majority of patients consented to AHI testing. AHI prevalence was substantially higher in STI clinics than HTC clinics. Remarkably high VLs and concomitant genital scores demonstrate the potential for transmission. Universal AHI screening at STI clinics, and targeted screening at HTC centers, should be considered.

Background: Preexposure prophylaxis (PrEP) is the first biomedical intervention with proven efficacy to reduce HIV acquisition in men who have sex with men (MSM) and transgender women. Little is known about levels of interest and characteristics of individuals who elect to take PrEP in real-world clinical settings., Methods: The US PrEP Demonstration Project is a prospective open-label cohort study assessing PrEP delivery in municipal sexually transmitted disease clinics in San Francisco and Miami and a community health center in Washington, DC. HIV-uninfected MSM and transgender women seeking sexual health services at participating clinics were assessed for eligibility and offered up to 48 weeks of emtricitabine/tenofovir for PrEP. Predictors of enrollment were assessed using a multivariable Poisson regression model, and characteristics of enrolled participants are described., Results: Of 1069 clients assessed for participation, 921 were potentially eligible and 557 (60.5%) enrolled. In multivariable analyses, participants from Miami (adjusted Relative Risk [aRR]: 1.53; 95% confidence interval [CI]: 1.33 to 1.75) or DC (aRR: 1.33; 95% CI: 1.2 to 1.47), those who were self-referred (aRR: 1.48; 95% CI: 1.32 to 1.66), those with previous PrEP awareness (aRR: 1.56; 95% CI: 1.05 to 2.33), and those reporting >1 episode of anal sex with an HIV-infected partner in the last 12 months (aRR: 1.20; 95% CI: 1.09 to 1.33) were more likely to enroll. Almost all (98%) enrolled participants were MSM, and at baseline, 63.5% reported condomless receptive anal sex in the previous 3 months., Conclusions: Interest in PrEP is high among a diverse population of MSM at risk for HIV infection when offered in sexually transmitted disease and community health clinics.