Urine Tenofovir Levels Measured Using a Novel Immunoassay Predict Human Immunodeficiency Virus Protection

Stalter, Randy M; Spinelli, Matthew A; Glidden, David V.; Rodrigues, Warren; Vincent, Michael S.; Mujugira, Andrew; Marzinke, Mark A.; Hendrix, Craig W.; Gandhi, Monica; Celum, Connie; Baeten, Jared M.; Donnell, Deborah; Coombs, Robert W.; Lingappa, Jairam R.; McElrath, M. Juliana; Fife, Kenneth H.; Were, Edwin; Tumwesigye, Elioda; Ndase, Patrick; Katabira, Elly; Ronald, Allan R.; Bukusi, Elizabeth A.; Cohen, Craig R.; Kiarie, James; Farquhar, Carey; John‐Stewart, Grace; Mugo, Nelly; Ngure, Kenneth; Campbell, James D.; Tappero, Jordan W.; Wangisi, Jonathan

doi:10.1093/cid/ciaa785

Cited by 30 publications

(32 citation statements)

References 12 publications

(14 reference statements)

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“…Early pregnancy (Days 0-91) 0.0022 [18] Late pregnancy (Days 92-280) 0.0030 [18] Early post-partum (First 24 weeks after end of full-term pregnancy = Days 281-449) 0.0042 [18] Late post-partum (Days 450-916) 0.0011 [18,23] Relative frequency of condomless sexual acts when partner with HIV is status-aware (vs. unaware) 0.47 [24] Relative per-act risk of heterosexual HIV transmission in the presence (vs. absence) of suppressive ART 0.04 [26] Relative per-act risk of heterosexual HIV transmission in the presence (vs. absence) of adherent PrEP 0.25 [25] a Used in model. b Key intervention uptake parameter varied in modelling scenarios.…”

Section: Model Structure and Initial Conditionsmentioning

confidence: 99%

“…We modelled male-to-female HIV transmission within partnerships as a function of condomless sexual contact rates and per-contact transmission probabilities [18,22,23], both of which varied over the course of pregnancy and the postpartum period [18] (Table 1). HIV diagnosis among male partners reduced condomless sexual contact rates [24] in the model, and both viral suppression (in males) and PrEP use (by females) reduced per-contact transmission probabilities [25,26]. Relative reductions in transmission probabilities were assumed to be multiplicative when two or more prevention strategies (e.g.…”

Section: Model Structure and Initial Conditionsmentioning

confidence: 99%

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Combination HIV prevention during pregnancy and the post‐partum period in Malawi and Zambia: a mathematical modelling analysis

et al. 2023

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Introduction: Despite widespread success in reducing vertical HIV transmission, most antenatal care (ANC) programmes in eastern and southern Africa have not emphasized primary prevention of maternal HIV acquisition during pregnancy and lactation/breastfeeding. We hypothesized that combination HIV prevention interventions initiated alongside ANC could substantially reduce maternal HIV incidence. Methods: We constructed a multi-state model describing male-to-female HIV transmission in steady heterosexual partnerships during pregnancy and lactation/breastfeeding, with initial conditions based on population distribution estimates for Malawi and Zambia in 2020. We modelled individual and joint increases in three HIV prevention strategies at or soon after ANC initiation: (1) HIV testing of male partners, resulting in HIV diagnosis and less condomless sex among those with previously undiagnosed HIV; (2) initiation (or re-initiation) of suppressive antiretroviral therapy (ART) for male partners with diagnosed but unsuppressed HIV; and (3) adherent pre-exposure prophylaxis (PrEP) for HIV-negative female ANC patients with HIV-diagnosed or unknown-status male partners. We estimated the percentage of within-couple, male-to-female HIV transmissions that could be averted during pregnancy and lactation/breastfeeding with these strategies, relative to base-case conditions in which 45% of undiagnosed male partners become newly HIV diagnosed via testing, 75% of male partners with diagnosed but unsuppressed HIV initiate/re-initiate ART and 0% of female ANC patients start PrEP. Results: Increasing uptake of any single strategy by 20 percentage points above base-case levels averted 10%−11% of maternal HIV acquisitions during pregnancy and lactation/breastfeeding in the model. Joint uptake increases of 20 percentage points in two interventions averted an estimated 19%−23% of transmissions, and with a 20-percentage-point increase in uptake of all three interventions, 29% were averted. Strategies achieving 95% male testing, 90% male ART initiation/reinitiation and 40% female PrEP use reduced incident infections by 45%. Conclusions: Combination HIV prevention strategies provided alongside ANC and sustained through the post-partum period could substantially reduce maternal HIV incidence during pregnancy and lactation/breastfeeding in eastern and southern Africa.

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Section: Model Structure and Initial Conditionsmentioning

confidence: 99%

Section: Model Structure and Initial Conditionsmentioning

confidence: 99%

Combination HIV prevention during pregnancy and the post‐partum period in Malawi and Zambia: a mathematical modelling analysis

et al. 2023

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“…Oral PrEP has been shown to effectively reduce the risk of HIV acquisition in clinical trials in diverse settings and populations [4]. Multiple studies have shown that oral PrEP can reduce the chances of HIV infection to near zero when taken consistently and correctly [5][6][7]. The efficacy of oral PrEP depends on high uptake and adherence, particularly among women, as higher concentrations of ARVs are required in the female genital tract to confer protection.…”

Section: Introductionmentioning

confidence: 99%

Uptake and continuation of HIV pre‐exposure prophylaxis among women of reproductive age in two health facilities in Kisumu County, Kenya

et al. 2023

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Introduction:In 2020, Kenya had 19,000 new HIV infections among women aged 15+ years. Studies have shown sub-optimal oral pre-exposure prophylaxis (PrEP) use among sub-populations of women. We assessed the uptake and continuation of oral PrEP among women 15-49 years in two health facilities in Kisumu County, Kenya. Methods: A retrospective cohort of 262 women aged 15-49 years, initiated into oral PrEP between 12 November 2019 and 31 March 2021, was identified from two health facilities in the urban setting of Kisumu County, Kenya. Data on baseline characteristics and oral PrEP continuation at months 1, 3 and 6 were abstracted from patient records and summarized using descriptive statistics. Missing data in the predictor variables were imputed within the joint modelling multiple imputation framework. Using logistic regression, we evaluated factors associated with the discontinuation of oral PrEP at month 1. Results: Of the 66,054 women screened, 320 (0.5%) were eligible and 262 (82%) were initiated on oral PrEP. Uptake was higher among women 25-29 years as compared to those 15-24 years (77% vs. 33%). Oral PrEP continuation declined significantly with increasing duration of follow-up; 37% at month 1, 21% at month 3 and 12% at month 6 (p<0.05). In the adjusted analysis, women 15-24 years had lower adjusted odds of continuing at month 1 than women ≥25 years (adjusted odds ratio [aOR]: 0.41, 95% CI: 0.21-0.82). There was no association between being sero-discordant and continuation of oral PrEP at month 1 (aOR; 1.21, 95% CI 0.59-2.50). Women from the sub-county hospital were more likely to continue at month 1 of follow-up compared to women enrolled in the county referral hospital (aOR 5.11;. Conclusions:The low eligibility for oral PrEP observed among women 15-49 years in an urban setting with high HIV prevalence calls for a review of the screening process to validate the sensitivity of the screening tool and its proper application. The low uptake and continuation among adolescent girls and young women underscores the need to identify and address specific patient-and facility-level barriers affecting different sub-populations at risk for HIV acquisition.

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“…TFV-DP accumulates in red blood cells (RBCs) and peripheral blood mononuclear cells and has a longer half-life [6] than plasma TFV. Urine TFV concentrations have mainly been evaluated among people without HIV, who are using TDF as part of pre-exposure prophylaxis [7], showing an association with HIV seroconversion [8,9]. However, measurement can require liquid chromatography tandem mass spectrometry (LC-MS/MS), which is not feasible in many settings.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic accuracy of a point-of-care urine tenofovir assay, and associations with HIV viraemia and drug resistance among people receiving dolutegravir and efavirenz-based antiretroviral therapy

Dorward

Lessells

Govender

et al. 2023

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Introduction: Novel point-of-care assays which measure urine tenofovir (TFV) concentrations may have a role in improving adherence monitoring for people living with HIV (PLHIV) receiving antiretroviral therapy (ART). However, further studies of their diagnostic accuracy, and whether results are associated with viraemia and drug resistance, are needed to guide their use, particularly in the context of the global dolutegravir rollout. Methods: We conducted a cross-sectional evaluation among PLHIV receiving first-line ART containing tenofovir disoproxil fumarate (TDF). We calculated the diagnostic accuracy of the Abbott point-of-care assay to detect urine TFV measured by liquid chromatography and mass spectrometry. We evaluated the association between point-of-care urine TFV results and self-reported adherence, viraemia ≥1000 copies/mL, and HIV drug resistance, among people receiving either efavirenz or dolutegravir-based ART. Results: Among 124 participants, 55% were women, median age was 39 (IQR 34-45) years. 74 (59.7%) were receiving efavirenz, and 50 (40.3%) dolutegravir. Sensitivity and specificity to detect urine TFV ≥1500ng/mL were 96.1% (95%CI 90.0-98.8) and 95.2% (75.3-100.0) respectively. Urine TFV results were associated with short (p<0.001) and medium term (p=0.036) self-reported adherence. Overall, 44/124 (35.5%) had viraemia, which was associated with undetectable TFV in those receiving efavirenz (OR 6.01, 1.27-39.0, p=0.014) and dolutegravir (OR 25.7, 4.20-294.8, p<0.001). However, in those with viraemia while receiving efavirenz, 8/27 (29.6%) had undetectable urine TFV, compared to 11/17 (64.7%) of those receiving dolutegravir. Drug resistance was detected in 23/27 (85.2%) of those receiving efavirenz and only 1/16 (6.3%) of those receiving dolutegravir. There was no association between urine TFV results and drug resistance. Conclusions: Among PLHIV receiving ART, a rapid urine TFV assay can be used to accurately monitor urine TFV levels. Undetectable point-of-care urine TFV results were associated with viraemia, particularly among people receiving dolutegravir. Trial registration: Pan-African Clinical Trials Registry: PACTR202001785886049.

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Urine Tenofovir Levels Measured Using a Novel Immunoassay Predict Human Immunodeficiency Virus Protection

Cited by 30 publications

References 12 publications

Combination HIV prevention during pregnancy and the post‐partum period in Malawi and Zambia: a mathematical modelling analysis

Combination HIV prevention during pregnancy and the post‐partum period in Malawi and Zambia: a mathematical modelling analysis

Uptake and continuation of HIV pre‐exposure prophylaxis among women of reproductive age in two health facilities in Kisumu County, Kenya

Diagnostic accuracy of a point-of-care urine tenofovir assay, and associations with HIV viraemia and drug resistance among people receiving dolutegravir and efavirenz-based antiretroviral therapy

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