HIV incidence estimates are used to monitor HIV-1 infection in the United States. Use of laboratory biomarkers that distinguish recent from longstanding infection to quantify HIV incidence rely on ...having accurate knowledge of the average time that individuals spend in a transient state of recent infection between seroconversion and reaching a specified biomarker cutoff value. This paper describes five estimation procedures from two general statistical approaches, a survival time approach and an approach that fits binomial models of the probability of being classified as recently infected, as a function of time since seroconversion. We compare these procedures for estimating the mean duration of recent infection (MDRI) for two biomarkers used by the U.S. National HIV Surveillance System for determination of HIV incidence, the Aware BED EIA HIV-1 incidence test (BED) and the avidity-based, modified Bio-Rad HIV-1/HIV-2 plus O ELISA (BRAI) assay. Collectively, 953 specimens from 220 HIV-1 subtype B seroconverters, taken from 5 cohorts, were tested with a biomarker assay. Estimates of MDRI using the non-parametric survival approach were 198.4 days (SD 13.0) for BED and 239.6 days (SD 13.9) for BRAI using cutoff values of 0.8 normalized optical density and 30%, respectively. The probability of remaining in the recent state as a function of time since seroconversion, based upon this revised statistical approach, can be applied in the calculation of annual incidence in the United States.
Despite extensive global efforts, sub-Saharan Africa remains disproportionately affected by the HIV epidemic. This generalized epidemic can be seen in Lesotho which in 2014 the HIV prevalence rate of ...those aged 15–49 years was 24.6%, with and incidence of 1.9 new infections per 100-person-year exposures. To better understand the impact of Lesotho’s national HIV response and significant predictors associated with HIV infection, the Lesotho Population-based HIV Impact Assessment was conducted. This survey provided a nationally representative sample of individuals aged 15–59 years old in which participants were tested for HIV and given an individual questionnaire that included socio-demographic and behavioral risk questions. The association of factors between survey questions and HIV incident was assessed using logistic regression. Multivariate logistic regression models for men and women were constructed for each outcome using variables known to be or plausibly associated with recent or chronic infection. Overall annualized incidence among people aged 15–49 was 1.19% (95% CI 0.73–1.65) per year. The overall prevalence of HIV was 25.6% with women having significantly higher prevalence. Multiple variables, including decreased wealth status, lower education levels, marital status, condom use at first sex, and circumcision (men only) were identified as being significantly associated with HIV infection for both men and women. In combination with improving the awareness of HIV status, an increased focus is needed on AGYW and men 35–49 years old to prevent new infections. HIV education and prevention programs should focus heavily on younger age groups prior to and soon after sexual debut to prevent HIV transmission. The findings of the survey showed significant room for improvement in increasing awareness of HIV status and reinforcing the need for continued HIV prevention and treatment efforts in Lesotho to prevent new infections.
Accurate and reliable laboratory methods are needed for estimation of HIV-1 incidence to identify the high-risk populations and target and monitor prevention efforts. We previously described a ...single-well limiting-antigen avidity enzyme immunoassay (LAg-Avidity EIA) to detect recent HIV-1 infection.
We describe here further optimization and characterization of LAg-Avidity EIA, comparing it to the BED assay and a two-well avidity-index (AI) EIA. Specimen sets included longitudinal sera (n = 393), collected from 89 seroconverting individuals from 4 cohorts representing 4 HIV-1 subtypes, and sera from AIDS patients (n = 488) with or without TB co-infections from 3 different cohorts. Ninety seven HIV-1 positive specimens were purchased commercially. The BED assay, LAg-Avidity EIA, AI-EIA and HIV serology were performed, as needed.
Monitoring quality control specimens indicated high reproducibility of the LAg-Avidity EIA with coefficient of variation of <10% in the dynamic range. The LAg-Avidity EIA has an overall mean duration of recency (ω) of 141 days (95% CI 119-160) at normalized optical density (ODn) cutoff of 1.0, with similar ω in different HIV-1 subtypes and populations (132 to 143 days). Antibody avidity kinetics were similar among individuals and subtypes by both the LAg-Avidity EIA and AI-EIA compared to the HIV-IgG levels measured by the BED assay. The false recent rate among individuals with AIDS was 0.2% with the LAg-Avidity EIA, compared to 2.9% with the BED assay. Western blot profiles of specimens with increasing avidity confirm accurate detection of recent HIV-1 infections.
These data demonstrate that the LAg-Avidity EIA is a promising assay with consistent ω in different populations and subtypes. The assay should be very useful for 1) estimating HIV-1 incidence in cross-sectional specimens as part of HIV surveillance, 2) identifying risk factors for recent infections, 3) measuring impact of prevention programs, and 4) studying avidity maturation during vaccine trials.
Malawi spearheaded the development and implementation of Option B+ for prevention of mother-to-child transmission of HIV (PMTCT), providing life-long ART for all HIV-positive pregnant and ...breastfeeding women. We used data from the 2015-2016 Malawi Population-based HIV Impact Assessment (MPHIA) to estimate progress toward 90-90-90 targets (90% of those with HIV know their HIV-positive status; of these, 90% are receiving ART; and of these, 90% have viral load suppression VLS) for HIV-positive women reporting a live birth in the previous 3 years. MPHIA was a nationally representative household survey; consenting eligible women aged 15-64 years were interviewed on pregnancies and outcomes, including HIV status during their most recent pregnancy, PMTCT uptake, and early infant diagnosis (EID) testing. Descriptive analyses were weighted to account for the complex survey design. Viral load (VL) results were categorized by VLS (<1,000 copies/mL) and undetectable VL (target not detected/below the limit of detection). Of the 3,153 women included in our analysis, 371 (10.1%, 95% confidence interval CI: 8.8%-11.3%) tested HIV positive in the survey. Most HIV-positive women (84.2%, 95% CI: 79.9%-88.6%) reported knowing their HIV-positive status; of these, 94.9% (95% CI: 91.7%-98.2%) were receiving ART; and of these, 91.2% (95% CI: 87.4%-95.0%) had VLS. Among the 371 HIV-positive women, 76.0% (95% CI: 70.4%-81.7%) had VLS and 66.5% (95% CI: 59.8%-73.2%) had undetectable VL. Among 262 HIV-exposed children, 50.8% (95% CI: 42.8%-58.8%) received EID testing within 2 months of birth, whereas 17.9% (95% CI: 11.9%-23.8%) did not receive EID testing. Of 190 HIV-exposed children with a reported HIV test result, 2.1% (95% CI: 0.0%-4.6%) had positive results. MPHIA data demonstrate high PMTCT uptake at a population level. However, our results identify some gaps in VLS in postpartum women and EID testing.
We analyzed data from the 2018 Kenya Population-Based HIV Impact Assessment (KENPHIA), a cross-sectional, nationally representative survey, to estimate the burden and prevalence of pediatric HIV ...infection, identify associated factors, and describe the clinical cascade among children aged < 15 years in Kenya. Interviewers collected information from caregivers or guardians on child's demographics, HIV testing, and treatment history. Blood specimens were collected for HIV serology and if HIV-positive, the samples were tested for viral load and antiretrovirals (ARV). For participants <18 months TNA PCR is performed. We computed weighted proportions with 95% confidence intervals (CI), accounting for the complex survey design. We used bivariable and multivariable logistic regression to assess factors associated with HIV prevalence. Separate survey weights were developed for interview responses and for biomarker testing to account for the survey design and non-response. HIV burden was estimated by multiplying HIV prevalence by the national population projection by age for 2018. Of 9072 survey participants (< 15 years), 87% (7865) had blood drawn with valid HIV test results. KENPHIA identified 57 HIV-positive children, translating to an HIV prevalence of 0.7%, (95% CI: 0.4%-1.0%) and an estimated 138,900 (95% CI: 84,000-193,800) of HIV among children in Kenya. Specifically, children who were orphaned had about 2 times higher odds of HIV-infection compared to those not orphaned, adjusted Odds Ratio (aOR) 2.2 (95% CI:1.0-4.8). Additionally, children whose caregivers had no knowledge of their HIV status also had 2 times higher odds of HIV-infection compared to whose caregivers had knowledge of their HIV status, aOR 2.4 (95% CI: 1.1-5.4)". From the unconditional analysis; population level estimates, 78.9% of HIV-positive children had known HIV status (95% CI: 67.1%-90.2%), 73.6% (95% CI: 60.9%-86.2%) were receiving ART, and 49% (95% CI: 32.1%-66.7%) were virally suppressed. However, in the clinical cascade for HIV infected children, 92% (95% CI: 84.4%-100%) were receiving ART, and of these, 67.1% (95% CI: 45.1%-89.2%) were virally suppressed. The KENPHIA survey confirms a substantial HIV burden among children in Kenya, especially among orphans.
Mean duration of recent infection (MDRI) and misclassification of long-term HIV-1 infections, as proportion false recent (PFR), are critical parameters for laboratory-based assays for estimating ...HIV-1 incidence. Recent review of the data by us and others indicated that MDRI of LAg-Avidity EIA estimated previously required recalibration. We present here results of recalibration efforts using >250 seroconversion panels and multiple statistical methods to ensure accuracy and consensus.
A total of 2737 longitudinal specimens collected from 259 seroconverting individuals infected with diverse HIV-1 subtypes were tested with the LAg-Avidity EIA as previously described. Data were analyzed for determination of MDRI at ODn cutoffs of 1.0 to 2.0 using 7 statistical approaches and sub-analyzed by HIV-1 subtypes. In addition, 3740 specimens from individuals with infection >1 year, including 488 from patients with AIDS, were tested for PFR at varying cutoffs.
Using different statistical methods, MDRI values ranged from 88-94 days at cutoff ODn = 1.0 to 177-183 days at ODn = 2.0. The MDRI values were similar by different methods suggesting coherence of different approaches. Testing for misclassification among long-term infections indicated that overall PFRs were 0.6% to 2.5% at increasing cutoffs of 1.0 to 2.0, respectively. Balancing the need for a longer MDRI and smaller PFR (<2.0%) suggests that a cutoff ODn = 1.5, corresponding to an MDRI of 130 days should be used for cross-sectional application. The MDRI varied among subtypes from 109 days (subtype A&D) to 152 days (subtype C).
Based on the new data and revised analysis, we recommend an ODn cutoff = 1.5 to classify recent and long-term infections, corresponding to an MDRI of 130 days (118-142). Determination of revised parameters for estimation of HIV-1 incidence should facilitate application of the LAg-Avidity EIA for worldwide use.
Tests for recent HIV infection (TRI) distinguish recent from long-term HIV infections using markers of antibody maturation. The limiting antigen avidity enzyme immunoassay (LAg EIA) is widely used ...with HIV viral load (VL) in a recent infection testing algorithm (RITA) to improve classification of recent infection status, estimate population-level HIV incidence, and monitor trends in HIV transmission. A novel rapid test for recent HIV infection (RTRI), Asanté™, can determine HIV serostatus and HIV recency within minutes on a lateral flow device through visual assessment of test strip or reader device. We conducted a field-based laboratory evaluation of the RTRI among pregnant adolescent girls and young women (AGYW) attending antenatal clinics (ANC) in Malawi.We enrolled pregnant AGYW aged <25 years testing HIV-positive for the first time at their first ANC visit from 121 ANCs in four high-HIV burden districts. Consenting participants provided blood for recency testing using LAg EIA and RTRI, which were tested in central laboratories. Specimens with LAg EIA normalized optical density values ≤2.0 were classified as probable recent infections. RTRI results were based on: (1) visual assessment: presence of a long-term line (LT) indicating non-recent infection and absence of the line indicating recent infection; or (2) a reader; specimens with LT line intensity units <3.0 were classified as probable recent infections. VL was measured for specimens classified as a probable recent infections by either assay; those with HIV-1 RNA ≥1,000 copies/mL were classified as confirmed recent infections. We evaluated the performance of the RTRI by calculating correlation between RTRI and LAg EIA results, and percent agreement and kappa between RTRI and LAg EIA RITA results.Between November 2017 to June 2018, 380 specimens were available for RTRI evaluation; 376 (98.9%) were confirmed HIV-positive on RTRI. Spearman's rho between RTRI and LAg EIA was 0.72 indicating strong correlation. Percent agreement and kappa between RTRI- and LAg EIA-based RITAs were >90% and >0.65 respectively indicating substantial agreement between the RITAs.This was the first field evaluation of an RTRI in sub-Saharan Africa, which demonstrated good performance of the assay and feasibility of integrating RTRI into routine HIV testing services for real-time surveillance of recent HIV infection.
We analyzed data from the 2018 Kenya Population-Based HIV Impact Assessment (KENPHIA), a cross-sectional, nationally representative survey, to estimate the burden and prevalence of pediatric HIV ...infection, identify associated factors, and describe the clinical cascade among children aged < 15 years in Kenya. Interviewers collected information from caregivers or guardians on child's demographics, HIV testing, and treatment history. Blood specimens were collected for HIV serology and if HIV-positive, the samples were tested for viral load and antiretrovirals (ARV). For participants <18 months TNA PCR is performed. We computed weighted proportions with 95% confidence intervals (CI), accounting for the complex survey design. We used bivariable and multivariable logistic regression to assess factors associated with HIV prevalence. Separate survey weights were developed for interview responses and for biomarker testing to account for the survey design and non-response. HIV burden was estimated by multiplying HIV prevalence by the national population projection by age for 2018. Of 9072 survey participants (< 15 years), 87% (7865) had blood drawn with valid HIV test results. KENPHIA identified 57 HIV-positive children, translating to an HIV prevalence of 0.7%, (95% CI: 0.4%-1.0%) and an estimated 138,900 (95% CI: 84,000-193,800) of HIV among children in Kenya. Specifically, children who were orphaned had about 2 times higher odds of HIV-infection compared to those not orphaned, adjusted Odds Ratio (aOR) 2.2 (95% CI:1.0-4.8). Additionally, children whose caregivers had no knowledge of their HIV status also had 2 times higher odds of HIV-infection compared to whose caregivers had knowledge of their HIV status, aOR 2.4 (95% CI: 1.1-5.4)". From the unconditional analysis; population level estimates, 78.9% of HIV-positive children had known HIV status (95% CI: 67.1%-90.2%), 73.6% (95% CI: 60.9%-86.2%) were receiving ART, and 49% (95% CI: 32.1%-66.7%) were virally suppressed. However, in the clinical cascade for HIV infected children, 92% (95% CI: 84.4%-100%) were receiving ART, and of these, 67.1% (95% CI: 45.1%-89.2%) were virally suppressed. The KENPHIA survey confirms a substantial HIV burden among children in Kenya, especially among orphans.
With the highest HIV incidence and prevalence globally, the government of Eswatini started a substantial scale-up of HIV treatment and prevention services in 2011. Two sequential large ...population-based surveys were conducted before and after service expansion to assess the impact of the national response. Cross-sectional, household-based, nationally representative samples of adults, ages 18 to 49 years, were sampled in 2011 and 2016. We measured HIV prevalence, incidence (recent infection based on limiting antigen ≤1.5 optical density units and HIV RNA ≥1000 copies/mL), viral load suppression (HIV RNA <1000 copies/mL among all seropositive adults) and unsuppressed viremia (HIV RNA ≥1000 copies/mL among all, regardless of HIV status) and assessed for temporal changes by conducting a trend analysis of the log ratio of proportions, using a Z statistic distribution. HIV prevalence remained stable from 2011 to 2016 32% versus 30%, p = 0.10. HIV incidence significantly declined 48% 2.48% versus 1.30%, p = 0.01. Incidence remained higher among women than men 2011: 3.16% versus 1.83%; 2016: 1.76% versus 0.86%, with a smaller but significant relative reduction among women 44%; p = 0.04 than men 53%; p = 0.09. The proportion of seropositive adults with viral load suppression significantly increased from 35% to 71% p < .001. The proportion of the total adult population with unsuppressed viremia decreased from 21% to 9% p < .001. National HIV incidence in Eswatini decreased by nearly half and viral load suppression doubled over a five-year period. Unsuppressed viremia in the total population decreased 58%. These population-based findings demonstrate the national impact of expanded HIV services in a hyperendemic country.
The Malawi Ministry of Health implemented a new surveillance activity in April 2019 to detect recent HIV infections using a rapid test for recent infection (RTRI) to identify areas of ongoing ...transmission and guide response activities.
At 23 health facilities in Blantyre District, healthcare workers (HCWs) were trained to conduct recent infection testing. In September 2019, we conducted a cross-sectional survey at these sites to explore the acceptability and feasibility of integrating this activity into routine HIV testing services (HTS).
Research assistants interviewed HCWs using a semi-structured survey. Descriptive statistics were used to summarize quantitative responses and thematic analysis was used to group open-ended text.
We interviewed 119 HCWs. Eighty-two percent of participants reported the RTRI was easy-to-use. HCWs perceived high client acceptability; 100% reported clients as 'somewhat' or 'very accepting'. Challenges included 68% of HCWs estimating they spend ≥20 min beyond routine HTS per client for this activity and 51% performing at least two additional finger pricks to complete the testing algorithm. HCWs differed in their perceptions of whether results should be returned to clients.
This study assessed HCW experiences using point-of-care RTRIs for HIV recent infection surveillance. Overall, HCWs perceived RTRIs to be acceptable, easy-to-use, and valuable. Though only clients with new HIV diagnoses are tested for recent infection, additional time may be substantial at high-volume health service delivery points. Providing response plans or aggregated recent infection results to HCWs and/or clients may support motivation and sustainability of this novel surveillance activity.
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