One of the great challenges in science and engineering today is to develop technologies to improve the health of people in the poorest regions of the world. Here we integrated new procedures for ...manufacturing, fluid handling and signal detection in microfluidics into a single, easy-to-use point-of-care (POC) assay that faithfully replicates all steps of ELISA, at a lower total material cost. We performed this 'mChip' assay in Rwanda on hundreds of locally collected human samples. The chip had excellent performance in the diagnosis of HIV using only 1 μl of unprocessed whole blood and an ability to simultaneously diagnose HIV and syphilis with sensitivities and specificities that rival those of reference benchtop assays. Unlike most current rapid tests, the mChip test does not require user interpretation of the signal. Overall, we demonstrate an integrated strategy for miniaturizing complex laboratory assays using microfluidics and nanoparticles to enable POC diagnostics and early detection of infectious diseases in remote settings.
This work demonstrates that a full laboratory-quality immunoassay can be run on a smartphone accessory. This low-cost dongle replicates all mechanical, optical, and electronic functions of a ...laboratory-based enzyme-linked immunosorbent assay (ELISA) without requiring any stored energy; all necessary power is drawn from a smartphone. Rwandan health care workers used the dongle to test whole blood obtained via fingerprick from 96 patients enrolling into care at prevention of mother-to-child transmission clinics or voluntary counseling and testing centers. The dongle performed a triplexed immunoassay not currently available in a single test format: HIV antibody, treponemal-specific antibody for syphilis, and nontreponemal antibody for active syphilis infection. In a blinded experiment, health care workers obtained diagnostic results in 15 min from our triplex test that rivaled the gold standard of laboratory-based HIV ELISA and rapid plasma reagin (a screening test for syphilis), with sensitivity of 92 to 100% and specificity of 79 to 100%, consistent with needs of current clinical algorithms. Patient preference for the dongle was 97% compared to laboratory-based tests, with most pointing to the convenience of obtaining quick results with a single fingerprick. This work suggests that coupling microfluidics with recent advances in consumer electronics can make certain laboratory-based diagnostics accessible to almost any population with access to smartphones.
HIV/AIDS is a leading cause of disease burden in sub-Saharan Africa. Existing evidence has demonstrated that there is substantial local variation in the prevalence of HIV; however, subnational ...variation has not been investigated at a high spatial resolution across the continent. Here we explore within-country variation at a 5 × 5-km resolution in sub-Saharan Africa by estimating the prevalence of HIV among adults (aged 15-49 years) and the corresponding number of people living with HIV from 2000 to 2017. Our analysis reveals substantial within-country variation in the prevalence of HIV throughout sub-Saharan Africa and local differences in both the direction and rate of change in HIV prevalence between 2000 and 2017, highlighting the degree to which important local differences are masked when examining trends at the country level. These fine-scale estimates of HIV prevalence across space and time provide an important tool for precisely targeting the interventions that are necessary to bringing HIV infections under control in sub-Saharan Africa.
Summary Worldwide, nearly half of all individuals living with HIV are now women, who acquire the virus largely by heterosexual exposure. With an HIV vaccine likely to be years away, topical ...microbicide formulations applied vaginally or rectally are being investigated as another strategy for HIV prevention. A review of preclinical and clinical research on the development of microbicides formulated to prevent vaginal HIV transmission yielded 118 studies: 73 preclinical and 45 clinical. Preclinical research included in-vitro assays and cervical explant models, as well as animal models. Clinical research included phase I and II/IIb safety studies, and phase III efficacy studies. Whereas most phase I and phase II clinical trials have found microbicide compounds to be safe and well tolerated, phase III trials completed to date have not demonstrated efficacy in preventing HIV transmission. Topical microbicides are grouped into five classes of agents, based on where they disrupt the pathway of sexual transmission of HIV. These classes include surfactants/membrane disruptors, vaginal milieu protectors, viral entry inhibitors, reverse transcriptase inhibitors, and a fifth group whose mechanism is unknown. The trajectory of microbicide development has been toward agents that block more specific virus–host cell interactions. Microbicide clinical trials face scientifically and ethically complex issues, such as the choice of placebo gel, the potential for viral resistance, and the inclusion of HIV-infected participants. Assessment of combination agents will most likely advance this field of research.
Age-mixing (age-disparate 5-9 years difference and intergenerational ≥ 10 years difference) partnerships are hypothesized drivers of HIV in adolescent girls and young women (AGYW; 15-24 years). These ...partnerships are often associated with increased gender inequities which undermine women's agency and assertiveness. We assessed whether age-mixing partnerships were associated with HIV in Malawi and if endorsement of inequitable gender norms modifies this relationship.
We analyzed data from the Malawi Population-based HIV Impact Assessment, a nationally representative household survey conducted in 2015-2016. Participants underwent HIV testing and completed questionnaires related to actively endorsed gender norms and sexual risk behavior. We used multivariate logistic regression and multiplicative interaction to assess associations among AGYW who reported the age of their primary sex partner from the last year.
The analysis included 1,958 AGYW (mean age = 19.9 years, SD = 0.1), 459 (23.4%) and 131 (6.7%) of whom reported age-disparate and intergenerational partnerships, respectively. AGYW in age-mixing partnerships accounted for 13% of all AGYW and were older, more likely to reside in urban areas, to be married or cohabitating with a partner, and to have engaged in riskier sexual behavior compared with AGYW in age-concordant partnerships (p < 0.05). HIV prevalence among AGYW in age-disparate and intergenerational partnerships was 6.1% and 11.9%, respectively, compared with 3.2% in age-concordant partnerships (p < 0.001). After adjusting for residence, age, education, employment, wealth quintile, and ever been married or cohabitated as married, AGYW in age-disparate and intergenerational partnerships had 1.9 (95% CI: 1.1-3.5) and 3.4 (95% CI: 1.6-7.2) greater odds of HIV, respectively, compared with AGYW in age-concordant partnerships. Among the 614 (31% of the study group) who endorsed inequitable gender norms, AGYW in age-disparate and intergenerational partnerships had 3.5 (95% CI: 1.1-11.8) and 6.4 (95% CI: 1.5-27.8) greater odds of HIV, respectively, compared with AGYW in age-concordant partnerships.
In this Malawi general population survey, age-mixing partnerships were associated with increased odds of HIV among AGYW. These findings highlight inequitable gender norms as a potential focus for HIV prevention and could inform interventions targeting structural, cultural, and social constraints of this key group.
·HIV incidence of 0.08% among adults, indicates a successful national HIV program·Rwanda has a stable HIV Epidemic at 3% and an aging cohort of people living with HIV·District-level modeling has ...helped identify areas disproportionately affected
The 2018–2019 Rwanda Population–based HIV Impact Assessment (RPHIA) was conducted to measure national HIV incidence and prevalence. District-level estimates were modeled to inform resources allocation.
RPHIA was a nationally representative cross-sectional household survey. Consenting adults were interviewed and tested for HIV using the national diagnostic algorithm followed by laboratory-based confirmation of HIV status and testing for viral load (VL), limiting antigen (LAg) avidity, and presence of antiretrovirals. Incidence was calculated using normalized optical density ≤ 1·5, VL ≥ 1,000 copies/mL, and undetectable antiretrovirals. Survey and programmatic data were used to model district-level HIV incidence and prevalence.
Of 31,028 eligible adults, 98·7% participated in RPHIA and 934 tested HIV positive. HIV prevalence among adults in Rwanda was 3·0% (95% CI:2·7–3·3). National HIV incidence was 0·08% (95% CI:0·02–0·14) and 0·11% (95% CI:0·00–0·26) in the City of Kigali (CoK). Based on district-level modeling, HIV incidence was greatest in the 3 CoK districts (0·11% to 0·15%) and varied across other districts (0·03% to 0·10%).
HIV prevalence among adults in Rwanda is 3.0%; HIV incidence is low at 0.08%. District-level modeling has identified disproportionately affected urban hotspots: areas to focus resources.
A limiting antigen avidity enzyme immunoassay (HIV-1 LAg-Avidity assay) was recently developed for cross-sectional HIV incidence estimation. We evaluated the performance of the LAg-Avidity assay ...alone and in multi-assay algorithms (MAAs) that included other biomarkers.
Performance of testing algorithms was evaluated using 2,282 samples from individuals in the United States collected 1 month to >8 years after HIV seroconversion. The capacity of selected testing algorithms to accurately estimate incidence was evaluated in three longitudinal cohorts. When used in a single-assay format, the LAg-Avidity assay classified some individuals infected >5 years as assay positive and failed to provide reliable incidence estimates in cohorts that included individuals with long-term infections. We evaluated >500,000 testing algorithms, that included the LAg-Avidity assay alone and MAAs with other biomarkers (BED capture immunoassay BED-CEIA, BioRad-Avidity assay, HIV viral load, CD4 cell count), varying the assays and assay cutoffs. We identified an optimized 2-assay MAA that included the LAg-Avidity and BioRad-Avidity assays, and an optimized 4-assay MAA that included those assays, as well as HIV viral load and CD4 cell count. The two optimized MAAs classified all 845 samples from individuals infected >5 years as MAA negative and estimated incidence within a year of sample collection. These two MAAs produced incidence estimates that were consistent with those from longitudinal follow-up of cohorts. A comparison of the laboratory assay costs of the MAAs was also performed, and we found that the costs associated with the optimal two assay MAA were substantially less than with the four assay MAA.
The LAg-Avidity assay did not perform well in a single-assay format, regardless of the assay cutoff. MAAs that include the LAg-Avidity and BioRad-Avidity assays, with or without viral load and CD4 cell count, provide accurate incidence estimates.
Oral and vaginal preparations of tenofovir as pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection have demonstrated variable efficacy in men and women prompting ...assessment of variation in drug concentration as an explanation. Knowledge of tenofovir concentration and its active form, tenofovir diphosphate, at the putative vaginal and rectal site of action and its relationship to concentrations at multiple other anatomic locations may provide key information for both interpreting PrEP study outcomes and planning future PrEP drug development.
MTN-001 was designed to directly compare oral to vaginal steady-state tenofovir pharmacokinetics in blood, vaginal tissue, and vaginal and rectal fluid in a paired cross-over design.
We enrolled 144 HIV-uninfected women at 4 US and 3 African clinical research sites in an open label, 3-period crossover study of three different daily tenofovir regimens, each for 6 weeks (oral 300 mg tenofovir disoproxil fumarate, vaginal 1% tenofovir gel 40 mg, or both). Serum concentrations after vaginal dosing were 56-fold lower than after oral dosing (p<0.001). Vaginal tissue tenofovir diphosphate was quantifiable in ≥90% of women with vaginal dosing and only 19% of women with oral dosing. Vaginal tissue tenofovir diphosphate was ≥130-fold higher with vaginal compared to oral dosing (p<0.001). Rectal fluid tenofovir concentrations in vaginal dosing periods were higher than concentrations measured in the oral only dosing period (p<0.03).
Compared to oral dosing, vaginal dosing achieved much lower serum concentrations and much higher vaginal tissue concentrations. Even allowing for 100-fold concentration differences due to poor adherence or less frequent prescribed dosing, vaginal dosing of tenofovir should provide higher active site concentrations and theoretically greater PrEP efficacy than oral dosing; randomized topical dosing PrEP trials to the contrary indicates that factors beyond tenofovir's antiviral effect substantially influence PrEP efficacy.
ClinicalTrials.gov NCT00592124.
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