Ongoing HIV Transmission and the HIV Care Continuum in North Carolina

<div><p>Objective</p><p>HIV transmission is influenced by status awareness and receipt of care and treatment. We analyzed these attributes of named partners of persons with acute HIV infection (index AHI cases) to characterize the transmission landscape in North Carolina (NC).</p><p>Design</p><p>Secondary analysis of programmatic data.</p><p>Methods</p><p>We used data from the NC Screening and Tracing of Active Transmission Program (2002–2013) to determine HIV status (uninfected, AHI, or chronic HIV infection [CHI]), diagnosis status (new or previously-diagnosed), and care and treatment status (not in care, in care and not on treatment, in care and on treatment) of index AHI cases' named partners. We developed an algorithm identifying the most likely transmission source among known HIV-infected partners to estimate the proportion of transmissions arising from contact with persons at different HIV continuum stages. We conducted a complementary analysis among a subset of index AHI cases and partners with phylogenetically-linked viruses.</p><p>Results</p><p>Overall, 358 index AHI cases named 932 partners, of which 218 were found to be HIV-infected (162 (74.3%) previously-diagnosed, 11 (5.0%) new AHI, 45 (20.6%) new CHI). Most transmission events appeared attributable to previously-diagnosed partners (77.4%, 95% confidence interval 69.4–85.3%). Among these previously-diagnosed partners, 23.2% (14.0–32.3%) were reported as in care and on treatment near the index AHI case diagnosis date. In the subset study of 33 phylogenetically-linked cases and partners, 60.6% of partners were previously diagnosed (43.9–77.3%).</p><p>Conclusions</p><p>A substantial proportion of HIV transmission in this setting appears attributable to contact with previously-diagnosed partners, reinforcing the need for improved engagement in care after diagnosis.</p></div

HIV care continuum stages for HIV-infected partners.

<p>The diagnosis status and the care and treatment status (if available) are presented for 1) all HIV-infected partners named by the index AHI cohort and identified by the STAT program, 2) the most likely transmission source among identified HIV-infected partners presented by the pattern of HIV-infected, uninfected, and status-unknown partners reported to the STAT program (unconfirmed linkage) and 3) phlyogenetically-linked partners identified via the CHAVI-001 study (confirmed linkage). For the data originating from the STAT program, repeated random sampling was used to estimate diagnosis, care, and treatment status of the most likely transmission source when >1 potential transmitting partner was named.</p

HIV Status of sexual and needle-sharing partners reported by index AHI cases.

<p>(A) HIV status of partners of index AHI cases identified via the STAT program between November 2002 and June 2013. (B) HIV status of partners reported by index AHI cases enrolled in CHAVI-001 between May 2006 and June 2011.</p

Demographics of Index AHI and Named Partners.

<p>*The North Carolina Screening and Tracing of Active Transmission Program. The STAT cases are inclusive of CHAVI-001 cases.</p><p>** Center for HIV/AIDS Vaccine Immunology 001 Study: Acute HIV Infection Prospective Cohort Study.</p><p>^{^} 932 partners were named by Index AHI cases during the STAT investigation. Index AHI cases refused to provide detailed demographic information for the STAT Program for a total of 276 partners, leaving 656 with detailed demographic information.</p><p>^@ One partner identified in CHAVI-001 was missing gender.</p><p>^# Missing Race not included in table.</p><p>Demographics of Index AHI and Named Partners.</p

Timeline of AHI: estimated HIV exposure, symptom onset, presentation to care, AHI diagnosis and enrollment in subjects with a narrow window of exposure based on self-report.

<p>A narrow window of exposure is defined as all patients with high or medium exposure date confidence (<i>n</i> = 6), plus patients with a one-time exposure in the 8 weeks prior to diagnosis with a partner of unknown status (<i>n</i> = 4).</p

Viral loads and plasma levels of IFNα, IL-15, IL-18 and IL-1βin sample time courses from three subjects acutely infected with HIV.

<p>A is a US plasma donor, whose sample time course is plotted in days and is aligned relative to the time (designated day 0) when the plasma viral load first reached 100 copies/ml (i.e. the start of the viral expansion phase). B and C are CHAVI 001 subjects, whose sample time courses are plotted in weeks, and are aligned relative to the time of study enrollment (week 0). Subject B started ART just after study enrollment, as indicated by the black arrow. Viral load data is plotted as open squares joined by dotted lines, and is expressed as log₁₀ RNA copies/ml. Data for each cytokine is plotted as filled symbols joined by solid lines, and is expressed as pg/ml.</p

Comparison of the estimated the date of infection based on Bayesian Evolutionary Analysis by Sampling Trees (BEAST) versus acute retroviral symptom onset.

a<p>Symptom onset minus 14 days.</p>b<p>Sample date minus BEAST estimated days post-infection.</p>c<p>BEAST estimated days post-infection from time of sampling.</p>d<p>Sample date minus symptom estimated infection date.</p

Demographic and clinical characteristics of participants with acute HIV infection and seronegative controls.

a<p>No participants endorsed injection drug use.</p>b<p>MSM  =  Men who have sex with men.</p>c<p>STI  =  sexually transmitted infection</p>d<p>Syphilis (n = 2), gonorrhea (n = 1), Chlamydia trachomatis (n = 1), non-gonococcal urethritis (n = 1) and genital ulcer disease (n = 1). One female subject was diagnosed with concurrent bacterial vaginosus, pelvic inflammatory disease, trichomoniasis and genital ulcer disease.</p>e<p>Viral Loads >750,000 copies/ml were included in the calculation of the medians as equal to 750,000 copies/ml unless sample was diluted and retested, in which case the true value was used.</p>f<p>Other diagnosis sites included student health and drug treatment program</p

Comparative analysis of plasma levels of 10 selected analytes at enrollment and week 16–24 in AHI subjects commencing ART, AHI subjects choosing not to start ART and HIV-seronegative controls.

<p>Plasma levels of 22 cytokines and chemokines were measured in sample time courses from a total of 23 AHI subjects and 21 HIV seronegative controls (Neg). Data for ten analytes (IL-1β, IL-2, IL-7, IFNγ, GM-CSF, MIG, MIP-1β, IP-10, IL-18 and IL-15, each expressed as pg/ml plasma) is shown at A) the enrollment time point (prior to commencement of therapy), when samples were available from 10 CHAVI 001 AHI subjects who chose to commence ART after the enrollment time point (AHI - T) and 12 AHI subjects who chose to remain untreated (AHI - UT) and B) week 16 or 24, when samples were available from 11 CHAVI 001 AHI subjects who chose to commence ART after the enrollment time point (AHI - T) and 7 AHI subjects who chose to remain untreated (AHI - UT). In both A and B, data are also shown from 21 HIV-seronegative subjects (sampled at the enrollment time point), except for IL-18 where n = 14 and IL-15 where n = 10. Each symbol represents data for an individual subject, and horizontal lines represent the median analyte level in the subject groups. Bars at the top of each graph show statistically significant differences between groups (p<0.01; Kruskal-Wallis non-parametric test).</p