2025 Theses Doctoral

Identifying and Addressing Gaps in the HIV Treatment Cascade in Lesotho: Assessing Risk Heterogeneity, Reaching Those Left Behind, and Evaluating the Feasibility of Achieving Epidemic Control

Ganesan, Kavitha

Background:
Despite significant progress in their national HIV response, including treatment scale-up by reaching UNAIDS 90-90-90 treatment targets in 2020, Lesotho continues to face a disproportionate burden of disease, having the second highest HIV incidence and prevalence globally. While the number of new infections annually have declined substantially since 2010, the downward trend appears to have plateaued since 2022, putting into question Lesotho’s ability to achieve epidemic control (less than 1 new infection per 1,000 population annually) by 2030 and end AIDS as a public health threat. This may largely be due to the 10% who have yet to reach the 90-90-90 targets. People with HIV (PWH) left behind that do not access HIV primary prevention, testing, and treatment services have disproportionately higher risk of transmission and acquisition, driving new infections and sustaining the epidemic, preventing epidemic control. This dissertation informs the path forward by identifying who is left behind in Lesotho’s HIV response, why they are left behind, and how they impact national incidence projections.

Methods:
This dissertation integrated three aims to assess how risk heterogeneity of PWH left behind can impact Lesotho’s incidence trajectory. Aim 1 included a scoping review of peer-reviewed and grey literature conducted in accordance with the 2021 Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The review contextualized gaps in the UNAIDS treatment cascade in Southern Africa from 2014-2024 and identified existing HIV modeling studies in comparable settings that evaluated the impact of those left behind on national incidence projections. Findings from the scoping review informed the mathematical modeling framework used in Aim 3. Aim 2 included a multilevel modeling analysis using the nationally representative Lesotho Population-based HIV Impact Assessment (LePHIA) from 2016-2017 to assess sociodemographic, behavioral, clinical, and social heterogeneity of those missed in each component of the treatment cascade. This aim also examined the association between individual- and community-level factors and being left behind. Aim 3 used the Goals risk structured model (RSM) to incorporate risk heterogeneity of those left behind the treatment cascade and predict HIV incidence in Lesotho from 2021-2035. Various treatment and prevention scale-up scenarios stratified by risk group, were modeled to assess their potential impact on HIV incidence over time.

Results:
The scoping review yielded 95 eligible studies assessing gaps in the UNAIDS treatment cascade and five predictive modeling studies assessing risk heterogeneity on population-level HIV incidence. There was evidence of sociodemographic, behavioral, and social heterogeneity in who was left behind in the treatment cascade, with key and priority populations (men who have sex with men, female sex workers, people who inject drugs, men, adolescent girls and young women, mobile and migrant populations, and clients of sex workers) experiencing the most pronounced gaps. There was limited literature on community-level and societal drivers of being missed in the cascade. Modeling studies included in the review only incorporated heterosexual risk-groups in their incidence projections.
Aim 2 found that HIV-seropositive subgroups with the highest testing and treatment gaps per LePHIA 2016-2017, were adolescent girls and young women (AGYW), men, migrant workers, and those engaged in transactional sex. Condom nonuse, multiple sexual partners, regressive gender-based beliefs, and HIV-related stigma were significant barriers to testing and treatment, while community condom nonuse negatively influenced individual antiretroviral therapy (ART) uptake.

Aim 3 found that while Lesotho met the 90-90-90 treatment targets by 2020, maintaining this level of achievement without prioritizing high-risk groups often left behind the cascade did not result in epidemic control by 2030, with an estimated 3.0 new infections per 1,000 population in 2030. Scaling-up treatment to achieve the 95-95-95 UNAIDS targets by 2025 without focusing on high-risk groups, also did not result in epidemic control by 2030, reducing incidence to an estimated 1.7 new infections per 1,000 in 2030. However, epidemic control was feasible in 2033 only with combined targeted treatment and primary prevention scale-up across all risk groups, resulting in an annual incidence of 1.0 new infection per 1,000 population.

Conclusion:
This dissertation underscores the need to use current available data to seek further precision in Lesotho’s HIV response, advocating for targeted interventions tailored to the needs of key and priority populations. While achieving the current UNAIDS treatment targets is critical, it was not enough to achieve epidemic control by 2030 in Lesotho per modeling estimations. These efforts must be supplemented with expanded treatment and prevention programs targeting those left behind. This can be done by creating enabling environments that address HIV-related stigma, discrimination, and inequities to enhance access and uptake into HIV services. Additionally, by integrating risk heterogeneity into national incidence models, this dissertation provides actionable insights to optimize Lesotho’s national HIV response. It contributes valuable research on the heterogeneity of populations at highest risk of acquisition and transmission and their unmet needs, supporting equity of prevention and treatment in leaving no one behind, which is critical to ending AIDS.