Search

Understanding of repeat human immunodeficiency virus (HIV) testing (RHT) is limited and the impact of rural residence as a potential barrier to RHT is unknown. Rural populations are of particular interest in the Southeastern United States because of their disproportionate HIV burden.We used HIV surveillance data from publicly funded HIV testing sites in North Carolina to assess repeat testing by transmission risk group and residential rurality in a retrospective cohort study. Linear binomial regression models were used to estimate adjusted, 1-year cumulative incidences and cumulative incidence differences comparing RHT within transmission risk populations by level of rurality.In our total study population of 600,613 persons, 19,275 (3.2%) and 9567 (1.6%) self-identified as men who have sex with men (MSM) and persons who inject drugs (PWID), respectively. A small minority, 13,723 (2.3%) resided in rural ZIP codes. Men who have sex with men were most likely to repeat test (unadjusted, 1-year cumulative incidence after an initial negative test, 16.4%) compared with PWID (13.2%) and persons who did not identify as either MSM or PWID (13.6%). The greatest effect of rurality was within PWID; the adjusted, 1-year cumulative incidence of RHT was 6.4 (95% confidence interval, 1.4-11.4) percentage points higher among metropolitan versus rural PWID.One-year cumulative incidence of RHT was low among all clients of publicly funded HIV testing sites in North Carolina, including MSM and PWID for whom annual testing is recommended. Our findings suggest a need for public health efforts to increase access to and support for RHT, particularly among rural PWID.

Background Understanding of repeat human immunodeficiency virus (HIV) testing (RHT) is limited and the impact of rural residence as a potential barrier to RHT is unknown. Rural populations are of particular interest in the Southeastern United States because of their disproportionate HIV burden. Methods We used HIV surveillance data from publicly funded HIV testing sites in North Carolina to assess repeat testing by transmission risk group and residential rurality in a retrospective cohort study. Linear binomial regression models were used to estimate adjusted, 1-year cumulative incidences and cumulative incidence differences comparing RHT within transmission risk populations by level of rurality. Results In our total study population of 600,613 persons, 19,275 (3.2%) and 9567 (1.6%) self-identified as men who have sex with men (MSM) and persons who inject drugs (PWID), respectively. A small minority, 13,723 (2.3%) resided in rural ZIP codes. Men who have sex with men were most likely to repeat test (unadjusted, 1-year cumulative incidence after an initial negative test, 16.4%) compared with PWID (13.2%) and persons who did not identify as either MSM or PWID (13.6%). The greatest effect of rurality was within PWID; the adjusted, 1-year cumulative incidence of RHT was 6.4 (95% confidence interval, 1.4-11.4) percentage points higher among metropolitan versus rural PWID. Conclusions One-year cumulative incidence of RHT was low among all clients of publicly funded HIV testing sites in North Carolina, including MSM and PWID for whom annual testing is recommended. Our findings suggest a need for public health efforts to increase access to and support for RHT, particularly among rural PWID.

Long-term HIV care and treatment engagement is required for maximal clinical and prevention benefits, but longitudinal care patterns are poorly understood. We used the last 10 years' worth of HIV surveillance data from North Carolina to describe longitudinal HIV care trajectories from diagnosis.We conducted a retrospective, population-based cohort study of all persons newly diagnosed with HIV in North Carolina between March 31, 2006 and March 31, 2015 (N = 16,207). We defined HIV care attendance in each 3-month and 6-month interval after diagnosis as the presence of viral load and/or CD4 records (care visit proxies) in the interval. We used group-based trajectory modeling to identify common care trajectories and baseline predictors thereof.A predicted 26% of newly HIV-diagnosed persons showed consistently high care attendance over time; ∼16% exhibited steadily declining attendance; ∼26% showed consistently low attendance; ∼17% had initially weak attendance with an increase starting ∼1.5 year later; and ∼15% showed initially weak attendance with an increase starting ∼3 years later. Older age at diagnosis was protective against all suboptimal trajectories (with the "consistently high" pattern as referent), and being a man who has sex with men was protective against 3 of the 4 suboptimal patterns.As measured by surveillance-based laboratory proxies, most newly HIV-diagnosed persons exhibited suboptimal care trajectories, but there was wide variation in the particular pathways followed. The insights provided by this analytical approach can help to inform the design of epidemic models and tailored interventions, with the ultimate goal of improving HIV care engagement and transmission prevention.

Long-term HIV care and treatment engagement is required for maximal clinical and prevention benefits, but longitudinal care patterns are poorly understood. We used the last ten years’ worth of HIV surveillance data from North Carolina (NC) to describe longitudinal HIV care trajectories from diagnosis.

Early HIV diagnosis enables prompt treatment initiation, thereby contributing to decreased morbidity, mortality, and transmission. We aimed to describe the association between distance from residence to testing sites and HIV disease stage at diagnosis. Using HIV surveillance data, we identified all new HIV diagnoses made at publicly-funded testing sites in central North Carolina during 2005-2013. Early-stage HIV was defined as acute HIV (antibody-negative test with a positive HIV RNA) or recent HIV (normalized optical density

The HIV care continuum is a critical framework for situational awareness of the HIV epidemic; yet challenges to accurate enumeration of continuum components hamper continuum estimation in practice. We describe local surveillance-based estimation of the HIV continuum in the United States, reviewing common practices as recommended by the Centers for Disease Control and Prevention. Furthermore, we review some challenges and biases likely to threaten existing continuum estimates. Current estimates rely heavily on the use of CD4 cell count and HIV viral load laboratory results reported to surveillance programs as a proxy for receipt of HIV-related outpatient care. As such, continuum estimates are susceptible to bias because of incomplete laboratory reporting and imperfect sensitivity and specificity of laboratory tests as a proxy for routine HIV care. Migration of HIV-infected persons between jurisdictions also threatens the validity of continuum estimates. Data triangulation may improve but not fully alleviate biases.

OBJECTIVE: To review the evidence for antiretroviral 'treatment as prevention' for HIV transmission among MSM. METHODS: We reviewed studies that assess the biological plausibility that virally suppressive antiretroviral therapy (ART) reduces HIV infectiousness via anal intercourse and the epidemiologic evidence of whether ART has played a role in attenuating HIV incidence among MSM. RESULTS: Although ART treatment among MSM is likely to provide some preventive benefit, it is unknown whether it will reduce HIV infectiousness via anal intercourse to the same extent as via penile-vaginal intercourse. Additional research is needed on the pharmacokinetic properties of specific antiretroviral agents in the gastrointestinal tract. Estimates of risk behaviors and the incidence of HIV among MSM before and after the introduction and expansion of ART suggest that the population-level protective benefits of ART may be attenuated by a number of factors, most notably, continuing or increasing frequency of condomless anal intercourse and incidence of other sexually transmitted infections (STIs). Additional studies are needed on the impact of ART on HIV sexual risk behaviors and transmission among MSM outside of developed countries in North America, western Europe, and Australia. CONCLUSION: The benefits of treatment as prevention for MSM are highly plausible, but not certain. In the face of these unknowns, treatment guidelines for earlier ART initiation should be considered within a combination prevention strategy that includes earlier diagnosis, expanded STI treatment, and structural and behavioral interventions.

Hepatitis B e antigen (HBeAg)–negative chronic hepatitis B infection has a presentation and clinical course that is divergent from that of HBeAg‐positive infection. The former usually presents with lower viral levels but faster progression to liver disease. We sought to better understand the balance between replication and the immune response against hepatitis B virus (HBV).Viral kinetics in 50 HBeAg‐negative patients under various treatment protocols with interferon α and/or nucleoside or nucleotide analogs was analyzed. HBV DNA level was measured frequently and the data fitted to a viral dynamic model. A meta‐analysis of all published studies of viral kinetics in HBeAg‐positive and HBeAg‐negative infection was also conducted.We found that the clearance of both HBV virions and infected cells was significantly faster in HBeAg‐negative infection than in HBeAg‐positive infection. In HBeAg‐negative infection, there was also a negative correlation between baseline HBV DNA levels and infected cell half‐life, suggesting that the higher the viral load the faster the turnover of infected cells.These results reveal the dual role played by the immune response in maintaining lower viral levels and inducing faster turnover of infected cells, the latter of which may be responsible for the more aggressive nature of HBeAg‐negative infection.

Acute HIV infection (AHI), the earliest period after HIV acquisition, is only a few weeks in duration. In this brief period, the concentration of HIV in blood and genital secretions is extremely high, increasing the probability of HIV transmission. Although a substantial role of AHI in the sexual transmission of HIV is biologically plausible, the significance of AHI in the epidemiological spread of HIV remains uncertain.

Although remarkable progress has been made in the diagnosis, treatment, and prevention of HIV, a cure is unavailable and many of the most promising prevention interventions have failed. At this critical juncture in the epidemic, there is a necessity for improved understanding of the fundamental drivers of the epidemic, as well as an urgent need for innovative interventions against HIV. This dissertation focuses on two of these fundamental drivers - the heterosexual infectivity of HIV-1 and the details of sexual partnership patterns - as well as the power of interventions initiated during the highly infectious period of early HIV infection (EHI). We conducted a systematic review and meta-analysis of the heterosexual infectivity of HIV-1, defined as the per-contact probability of HIV-1 transmission in a single heterosexual contact between an infected and a susceptible individual. Infectivity estimates were extremely heterogeneous, ranging from zero transmissions after more than 100 penile-vaginal contacts in some sero-discordant couples to one transmission for every 3.1 episodes of heterosexual anal intercourse. Several co-factors were associated with increased infectivity. Infectivity differences (95% confidence intervals), expressed as number of transmissions per 1000 contacts, were 8 (0-16) comparing uncircumcised to circumcised male susceptibles, 6 (3-9) comparing susceptible individuals with and without GUD, 2 (1-3) comparing late-stage to mid-stage index cases, and 3 (0-5) comparing early-stage to mid-stage index cases. We also analyzed recent sexual partnership patterns in a sexually transmitted infections (STI) clinic in Lilongwe, Malawi. We found that multiple sexual partnerships were uncommon (14%), and partnerships were long on average (mean=858 days). Among those reporting multiple recent partners, patterns ranged from long-term concurrency (mean overlap=246 days) to narrowly spaced consecutive partnerships (mean gap=21 days), presenting a substantial risk for efficient HIV transmission. Finally, we conducted a mathematical modeling study to determine the contribution of EHI to epidemic spread in Lilongwe, Malawi. Our analyses suggest that 38.4% (95% CI: 18.6%-57.5%) of ongoing HIV transmissions in Lilongwe can be attributed to EHI index cases, and that interventions targeting the entire duration of infection will be needed to have a significant, lasting effect on the epidemic.

Individuals with acute (preseroconversion) HIV infection (AHI) are important in the spread of HIV. The identification of AHI requires the detection of viral proteins or nucleic acids with techniques that are often unaffordable for routine use. To facilitate the efficient use of these tests, we sought to develop a risk score algorithm for identifying likely AHI cases and targeting the tests towards those individuals.