The Relationship Between the Human Immunodeficiency Virus-1 Transmission Network and the HIV Care Continuum in Los Angeles County

Abstract

Background: Public health action combating human immunodeficiency virus (HIV) includes facilitating navigation through the HIV continuum of care: timely diagnosis followed by linkage to care and initiation of antiretroviral therapy to suppress viral replication. Molecular epidemiology can identify rapidly growing HIV genetic transmission clusters. How progression through the care continuum relates to transmission clusters has not been previously characterized.

Methods: We performed a retrospective study on HIV surveillance data from 5226 adult cases in Los Angeles County diagnosed from 2010 through 2014. Genetic transmission clusters were constructed using HIV-TRACE. Cox proportional hazard models were used to estimate the impact of transmission cluster growth on the time intervals between care continuum events. Gamma frailty models incorporated the effect of heterogeneity associated with genetic transmission clusters.

Results: In contrast to our expectations, there were no differences in time to the care continuum events among individuals in clusters with different growth dynamics. However, upon achieving viral suppression, individuals in high growth clusters were slower to experience viral rebound (hazard ratio 0.83, P = .011) compared with individuals in low growth clusters. Heterogeneity associated with cluster membership in the timing to each event in the care continuum was highly significant (P < .001), with and without adjustment for transmission risk and demographics.

Conclusions: Individuals within the same transmission cluster have more similar trajectories through the HIV care continuum than those across transmission clusters. These findings suggest molecular epidemiology can assist public health officials in identifying clusters of individuals who may benefit from assistance in navigating the HIV care continuum.

Keywords: Cox proportional hazard; HIV; care continuum; cluster; gamma frailty; molecular epidemiology; transmission network.

Figure 1.

Flow diagram of the human immunodefiency virus care continuum based on cluster growth at diagnosis. Values indiciate adjusted hazard ratios, with low cluster growth at diagnosis serving as the reference category. Arrows show path between care continuum events (i.e., diagnosis to care). Thick arrows denote significantly increased rate of progression between care continuum events; thin arrows denote significantly slower rate of progression between care continuum events. Asterisks indicate significance at P < .05 in the Cox proportional hazards model.

Figure 2.

Kaplan-Meier survival estimates and adjusted HRs of time from diagnosis to viral suppression by linked to care in 2 months. Median months from diagnosis to suppression is 5 (IQR 3–11), 6 (IQR 4–14), and 6 (IQR 4–12) if linked to care in 2 months for low, medium and high growing clusters, respectively. Median months from diagnosis to suppression is 19 (IQR 9–36), 16 (IQR 8–28), and 15 (IQR 8–29) if linked to care >2 months after diagnosis for low, medium and high growing clusters, respectively. There was no significant difference in hazards for cases linked to care within 2 months. For cases linked to care in >2 months after diagnosis, medium and high growing clusters reached suppression 26–29% faster (P < .01) compared with low growing clusters, after adjusting for age at diagnosis, race/ethnicity, poverty level at ZIP code diagnosis, transmission risk category, birth sex, and CD4⁺ at diagnosis. Abbreviations: HIV, human immunodeficiency virus; HR, hazard ratio; IQR, interquartile range.