Impact along the HIV pre-exposure prophylaxis "cascade of prevention" in western Kenya: a mathematical modelling study.

INTRODUCTION: Over one hundred implementation studies of HIV pre-exposure prophylaxis (PrEP) are completed, underway or planned. We synthesized evidence from these studies to inform mathematical modelling of the prevention cascade for oral and long-acting PrEP in the setting of western Kenya, one of the world's most heavily HIV-affected regions. METHODS: We incorporated steps of the PrEP prevention cascade - uptake, adherence, retention and re-engagement after discontinuation - into EMOD-HIV, an open-source transmission model calibrated to the demography and HIV epidemic patterns of western Kenya. Early PrEP implementation research from East Africa was used to parameterize prevention cascades for oral PrEP as currently implemented, delivery innovations for oral PrEP, and future long-acting PrEP. We compared infections averted by PrEP at the population level for different cascade assumptions and sub-populations on PrEP. Analyses were conducted over the 2020 to 2040 time horizon, with additional sensitivity analyses for the time horizon of analysis and the time when long-acting PrEP becomes available. RESULTS: The maximum impact of oral PrEP diminished by over 98% across all prevention cascades, with the exception of long-acting PrEP under optimistic assumptions about uptake and re-engagement after discontinuation. Long-acting PrEP had the highest population-level impact, even after accounting for possible delays in product availability, primarily because its effectiveness does not depend on drug adherence. Retention was the most significant cascade step reducing the potential impact of long-acting PrEP. These results were robust to assumptions about the sub-populations receiving PrEP, but were highly influenced by assumptions about re-initiation of PrEP after discontinuation, about which evidence was sparse. CONCLUSIONS: Implementation challenges along the prevention cascade compound to diminish the population-level impact of oral PrEP. Long-acting PrEP is expected to be less impacted by user uptake and adherence, but it is instead dependent on product availability in the short term and retention in the long term. To maximize the impact of long-acting PrEP, ensuring timely product approval and rollout is critical. Research is needed on strategies to improve retention and patterns of PrEP re-initiation.

The influence of mobility among high-risk populations on HIV transmission in Western Kenya.

Western Kenya suffers a highly endemic and also very heterogeneous epidemic of human immunodeficiency virus (HIV). Although female sex workers (FSW) and their male clients are known to be at high risk for HIV, HIV prevalence across regions in Western Kenya is not strongly correlated with the fraction of women engaged in commercial sex. An agent-based network model of HIV transmission, geographically stratified at the county level, was fit to the HIV epidemic, scale-up of interventions, and populations of FSW in Western Kenya under two assumptions about the potential mobility of FSW clients. In the first, all clients were assumed to be resident in the same geographies as their interactions with FSW. In the second, some clients were considered non-resident and engaged only in interactions with FSW, but not in longer-term non-FSW partnerships in these geographies. Under both assumptions, the model successfully reconciled disparate geographic patterns of FSW and HIV prevalence. Transmission patterns in the model suggest a greater role for FSW in local transmission when clients were resident to the counties, with 30.0% of local HIV transmissions attributable to current and former FSW and clients, compared to 21.9% when mobility of clients was included. Nonetheless, the overall epidemic drivers remained similar, with risky behavior in the general population dominating transmission in high-prevalence counties. Our modeling suggests that co-location of high-risk populations and generalized epidemics can further amplify the spread of HIV, but that large numbers of formal FSW and clients are not required to observe or mechanistically explain high HIV prevalence in the general population.

People living with HIV travel farther to access healthcare: a population-based geographic analysis from rural Uganda.

INTRODUCTION: The availability of specialized HIV services is limited in rural areas of sub-Saharan Africa where the need is the greatest. Where HIV services are available, people living with HIV (PLHIV) must overcome large geographic, economic and social barriers to access healthcare. The objective of this study was to understand the unique barriers PLHIV face when accessing healthcare compared with those not living with HIV in a rural area of sub-Saharan Africa with limited availability of healthcare infrastructure. METHODS: We conducted a population-based cross-sectional study of 447 heads of household on Bugala Island, Uganda. Multiple linear regression models were used to compare travel time, cost and distance to access healthcare, and log binomial models were used to test for associations between HIV status and access to nearby health services. RESULTS: PLHIV travelled an additional 1.9 km (95% CI (0.6, 3.2 km), p=0.004) to access healthcare compared with those not living with HIV, and they were 56% less likely to access healthcare at the nearest health facility to their residence, so long as that facility lacked antiretroviral therapy (ART) services (aRR=0.44, 95% CI (0.24 to 0.83), p=0.011). We found no evidence that PLHIV travelled further for care if the nearest facility supplies ART services (aRR=0.95, 95% CI (0.86 to 1.05), p=0.328). Among those who reported uptake of care at one of two facilities on the island that provides ART (81% of PLHIV and 68% of HIV-negative individuals), PLHIV tended to seek care at a higher tiered facility that provides ART, even when this facility was not their closest facility (30% of PLHIV travelled further than the closest ART facility compared with 16% of HIV-negative individuals), and travelled an additional 2.2 km (p=0.001) to access that facility, relative to HIV-negative individuals (aRR=1.91, 95% CI (1.00 to 3.65), p=0.05). Among PLHIV, residential distance was associated with access to facilities providing ART (RR=0.78, 95% CI (0.61 to 0.99), p=0.044, comparing residential distances of 3-5 km to 0-2 km; RR=0.71, 95% CI (0.58 to 0.87), p=0.001, comparing residential distances of 6-10 km to 0-2 km). CONCLUSIONS: PLHIV travel longer distances for care, a phenomenon that may be driven by both the limited availability of specialized HIV services and preference for higher tiered facilities.

Modeling the combined influence of host dispersal and waterborne fate and transport on pathogen spread in complex landscapes.

Environmental models, often applied to questions on the fate and transport of chemical hazards, have recently become important in tracing certain environmental pathogens to their upstream sources of contamination. These tools, such as first order decay models applied to contaminants in surface waters, offer promise for quantifying the fate and transport of pathogens with multiple environmental stages and/or multiple hosts, in addition to those pathogens whose environmental stages are entirely waterborne. Here we consider the fate and transport capabilities of the human schistosome Schistosoma japonicum, which exhibits two waterborne stages and is carried by an amphibious intermediate snail host. We present experimentally-derived dispersal estimates for the intermediate snail host and fate and transport estimates for the passive downstream diffusion of cercariae, the waterborne, human-infective parasite stage. Using a one dimensional advective transport model exhibiting first-order decay, we simulate the added spatial reach and relative increase in cercarial concentrations that dispersing snail hosts contribute to downstream sites. Simulation results suggest that snail dispersal can substantially increase the concentrations of cercariae reaching downstream locations, relative to no snail dispersal, effectively putting otherwise isolated downstream sites at increased risk of exposure to cercariae from upstream sources. The models developed here can be applied to other infectious diseases with multiple life-stages and hosts, and have important implications for targeted ecological control of disease spread.