The intervention at the heart of the study, called Game Changer for HIV Prevention (GC-HIV), is an eight-session group program designed to turn people living with HIV into prevention advocates within their own social networks. Participants attended weekly two-hour sessions in groups of eight to ten, facilitated by trained Ugandan peer facilitators who were themselves living with HIV. Sessions covered self-compassion and peer support to overcome internalized stigma, decision-making around HIV disclosure, the facts and myths of HIV transmission and treatment, and—critically—the practical skills of starting and sustaining conversations about HIV prevention with the people around them.

The theoretical foundation draws on social diffusion theory and principles of social influence, which hold that behavior change can be initiated by a few individuals and spread through communities via shifting social norms. Because peer advocacy hinges on interpersonal, bidirectional exchange rather than one-way mass messaging, people living with HIV are uniquely positioned as messengers: their close, trusted relationships and personal lived experience with HIV lend their words a credibility that no broadcast campaign can match. In a setting like Uganda, where HIV prevalence has remained above 5 percent for more than two decades and virtually every family is touched by the epidemic, the researchers describe people living with HIV as potential “game changers” for prevention.

The trial enrolled 210 people living with HIV at the Infectious Diseases Institute in Kampala between January 2022 and February 2023, randomizing them in equal numbers to the intervention or a usual-care control group. Each participant, referred to as an “index participant,” was asked to name up to 20 people with whom they interact most frequently—their social network “alters.” At baseline and at 6-, 12-, and 18-month follow-ups, participants reported whether they had talked with each alter in the past three months about five HIV protective behaviors: condom use, HIV testing, and pre-exposure prophylaxis (PrEP) for alters not living with HIV, and engagement in HIV care and antiretroviral therapy (ART) use for alters living with HIV. All assessments were administered in Luganda or English using Network Canvas social network software, and measures had been validated through standard translation and back-translation procedures.

The results were striking. Controlling for baseline advocacy and demographic characteristics, participants in the intervention arm targeted a significantly greater percentage of their network members with every one of the five forms of advocacy over the follow-up period. Advocacy for condom use reached 32.4 percent of alters in the intervention group versus 20.7 percent in the control group; advocacy for HIV testing reached 40.1 percent versus 26.5 percent; PrEP advocacy reached 20.3 percent versus 7.7 percent; HIV care advocacy reached 51.7 percent versus 43.1 percent; and ART advocacy reached 62.3 percent versus 51.3 percent. A previous report from the same trial had shown that network members who received testing and condom advocacy were themselves more likely to report recent HIV testing and consistent condom use, giving the advocacy measures real behavioral relevance.

But the central question of the new analysis was mechanistic: through what pathways did the training produce these effects? The researchers hypothesized four candidate mediators, each targeted directly by the intervention content—internalized HIV stigma, HIV disclosure, HIV knowledge, and self-efficacy for conducting advocacy. Internalized stigma was measured with the eight-item Internalized AIDS-Related Stigma Scale, which captures feelings such as guilt and the sense that something is wrong with oneself because of HIV status. HIV knowledge was assessed with 13 true-false statements covering medication goals, drug resistance, adherence, prevention including the concept that an undetectable viral load makes transmission very difficult, and myths such as the belief that HIV can be acquired through witchcraft. Disclosure was measured as the percentage of alters to whom a participant had revealed their HIV status, and self-efficacy as confidence in starting a conversation about HIV on a 0-to-10 scale.

Using path analysis with SAS software, the team modeled each mediator separately, specifying how study arm affected both the mediator at month 6 and the advocacy outcome across 18 months of follow-up, while adjusting for baseline values and participant characteristics. The analysis of 208 participants who completed the month-6 assessment showed that the intervention significantly improved all four candidate mediators by month 6: internalized stigma fell, while disclosure, knowledge, and self-efficacy all rose.

Yet only two of the four constructs actually carried the intervention’s effect. Reduced internalized stigma was associated with increased advocacy for all five protective behaviors, and it fully mediated the intervention effect on HIV care advocacy—the indirect effect was significant while the direct effect was not. For the other four behaviors, stigma reduction partially mediated the effect, meaning both the stigma pathway and an unexplained direct pathway remained significant. Increased HIV knowledge likewise fully mediated the effect on HIV care advocacy and partially mediated effects on HIV testing and PrEP advocacy, though it played no mediating role for condom or ART advocacy. When both mediators were modeled jointly, the results held: the intervention effect on HIV care advocacy was fully explained, while testing and PrEP advocacy remained only partially mediated.

In contrast, HIV disclosure and advocacy self-efficacy, despite both being significantly improved by the intervention and both being associated with some forms of increased advocacy, did not statistically mediate any of the intervention effects. The authors suggest that disclosure may be less a mechanism than a form of advocacy itself—an initial stage in a cascade that begins with sharing one’s status and leads to subsequent encouragement of protective behaviors. They also note that the single-item self-efficacy measure may have been too crude, and that more distal measurements of change in disclosure and confidence might reveal mediating roles that month-6 assessments could not detect.

The findings carry immediate practical weight. Roughly a third to one half of people living with HIV in Uganda report experiencing HIV-related discrimination, from job loss to social ridicule and relationship abandonment, and about a quarter of people living with HIV do not know their status. Consistent condom use ranges from 10 to 40 percent depending on the population, and PrEP access remains poor. The authors argue that helping people cope with stigma and master basic HIV facts—dispelling common misconceptions—may deserve proportionally greater resources in future iterations of advocacy training. They also suggest exploring whether enrolling participants with higher baseline internalized stigma could yield even greater gains, while cautioning that heavily stigmatized individuals may be less likely to join or fully engage in group programs.

The study contributes empirical support to theories of social diffusion and social influence by demonstrating the psychological mechanisms through which peer networks can propagate behavior change. It also acknowledges limitations: advocacy relied on participant self-report rather than verified observations, the measure captured only whether a discussion occurred rather than its duration or quality, and participants—recruited from a center of excellence and required to have been in HIV care for at least a year—may be more motivated than the broader population of people living with HIV. Still, given the recent drastic reduction in United States government funding for HIV care and prevention in the region, the appeal of an intervention that mobilizes existing social networks with modest resources is hard to overstate. In a high-prevalence setting where nearly everyone is already connected to someone living with HIV, equipping those individuals with reduced shame and solid knowledge appears to be the key that turns personal experience into community-wide prevention.

The backdrop is an epidemic that has become intensely concentrated. Nationwide, HIV prevalence among people aged 13 and older sits below 0.5 percent, but that average conceals staggering disparities. Among trans feminine women — transgender women along the trans feminine spectrum — estimated HIV prevalence ranges from 22 to 28 percent, the greatest burden of any population group. Among cisgender men who have sex with men, estimated prevalence is roughly 15 percent. PrEP medications, including daily oral regimens and newer long-acting injectables, are highly effective at blocking sexual transmission of the virus — but only if people start them, keep taking them, and remain engaged in monitoring, the three stages of the so-called PrEP Care Continuum where most attrition occurs. For people living with substance use disorder, every one of those steps is markedly harder. Clinical research has shown that stimulant use in particular undermines PrEP adherence among men who have sex with men, and substance use disorder is one of the most consistent barriers to progression along the entire continuum.

The economics of inaction are stark. Estimates cited in the study put the average lifetime cost of HIV-related medical care in the United States at about $368,000 per person — a figure that climbs to between $441,600 and $588,800 for people living with both HIV and a comorbid substance use disorder. The non-medical toll is heavier still. Substance use disorder is associated with reduced quality of life, elevated risk of overdose death, heavy reliance on high-cost emergency and inpatient care, participation in street economies, and incarceration; one economic analysis of opioid use disorder cited by the authors suggests these downstream consequences can add roughly $2 million per person over a lifetime. Against those figures, a combined prevention-and-treatment package costing four figures per client per year begins to look less like an expense and more like an investment. That logic animated the parent trial, funded by the National Institute on Drug Abuse, and frames the new analysis: before adopting a program, planners need to know precisely what it consumes.

A.S.K.-PrEP — short for Assistance Services Knowledge-PrEP — is built around a stepped-care philosophy. In the parent trial, HIV-negative sexual and gender minority adults aged 18 and older with a substance use disorder, all living in Los Angeles County, were randomly assigned in a 3:1 ratio to either the intervention or standard of care. Standard of care was deliberately minimal: an educational session about PrEP, an informational pamphlet, and a list of local clinics that prescribe it. The intervention arm instead received three months of client-centered PrEP navigation — five one-on-one sessions with a trained navigator — supplemented by weekly supportive text messages tailored to the experiences of sexual and gender minorities. Navigators tackled not only access to PrEP but the social determinants of health that sabotage it, from housing and food insecurity to transportation. At the three-month mark, participants were assessed on PrEP initiation, adherence, and use of their self-identified target substance. Those who had not responded — who had not started or adhered to PrEP, or kept using — were stepped up and re-randomized, this time 1:1, to contingency management alone or to contingency management plus three additional months of navigation and texting. The design, registered as clinical trial NCT05934877, generated three distinct intervention strategies whose costs could be compared head to head.

Contingency management, the escalation step, is among the most robustly evidence-backed behavioral treatments for stimulant use disorder, a condition for which no approved medication exists. The protocol is operationally simple but behaviorally sophisticated. Over 12 weeks, participants met with a behavioral technician three times per week to provide urine samples. Each sample testing negative for the participant’s target substance earned voucher points, starting at $2.50 and rising by $0.50 with every subsequent negative sample — an escalating schedule rooted in a core principle of behavioral science: reinforcement gains power as it grows. Three consecutive negative samples triggered an additional weekly bonus voucher worth $7.50, available throughout the 12 weeks. Vouchers, each valued at $1.00, could be redeemed at any time for goods and services that reinforce a prosocial, healthy lifestyle — clothing, groceries, a bicycle, help paying bills — but never for cigarettes, alcohol, or firearms. A positive sample dropped the participant back to the initial voucher value; three consecutive clean samples afterward restored their place in the escalation schedule, a design feature that keeps a single lapse from destroying hard-won momentum.

Quantifying the cost of all this required microcosting, the granular, bottom-up accounting method regarded as the gold standard in health economics. Rather than dividing a lump-sum budget by patient counts, the team applied activity-based costing: researchers visited the community-based organization delivering the program and conducted semi-structured interviews with everyone involved in daily operations, including the PrEP navigators, the clinical director, the clinical manager, and behavioral technicians cross-trained as phlebotomists. A follow-up virtual interview verified the initial findings and captured any changes in workflow. Every resource was then assigned a nationally representative price, expressed in 2024 dollars, to make the estimates portable to other regions. The researchers deliberately excluded PrEP medications themselves, since drug costs fall outside the intervention being evaluated. Resources were sorted into three categories — fixed start-up, time-dependent, and variable — and mapped onto two phases: a 12-month implementation phase from planning through steady state, and an open-ended sustainment phase aligned with the three-to-five-year budget cycles typical of health agencies. Crucially, the team estimated how many clients the program could actually serve with its resources — about eight per month — rather than the artificially constrained throughput of a research trial, so the figures describe a program a clinic could realistically operate.

The resulting ledger is unusually granular. Start-up costs of $25,958 were dominated by outreach — two behavioral technicians spending roughly 16 hours per month for a year distributing flyers and contacting partner organizations — plus one-time equipment purchases such as desk and cellular phones, tablets, a computer, and online marketing, and initial trainings covering HIV testing, counseling, and bloodborne pathogens. PrEP navigators completed about 80 hours of training in non-clinical support skills such as recovery planning and coping strategies, an eight-hour motivational interviewing course led by a clinical manager, and an eight-hour introduction to PrEP covering available medications and local access points. Time-dependent costs of $68,442 per year covered rent for a modest 130-square-foot office in Hollywood — deliberately positioned within the health service district carrying the county’s highest HIV incidence — along with monthly fees for the automated text-messaging platform, laboratory supplies for bloodwork and urine screening, phones, regular supervision meetings for navigators, biannual phlebotomy retraining, and annual HIV certification. Variable costs, which scale with each client served, averaged roughly $31,333 per year across strategies: $31,716 for A.S.K.-PrEP alone, $31,994 for A.S.K.-PrEP plus contingency management, and $30,271 for contingency management alone. A typical journey involves a 15-minute intake under standard of care, an initial one-hour navigation session with 30-minute follow-ups, a 10-minute introduction to contingency management, 15-minute visits three times weekly, and an average contingency management payout of $75 per participant. Staff also logged another 10 to 16 hours each month on scheduling, screening, and follow-up contacts. The first year of operation totals $125,325; each subsequent sustainment year runs about $99,366 — roughly $1,035 per client served.

Those numbers matter because the cost literature on HIV prevention is startlingly thin. As the authors note, a recent systematic review of the costs and cost-effectiveness of biomedical, non-surgical HIV prevention interventions found that most published studies were model-based economic evaluations; only nine collected primary data, and real-world delivery mechanisms were rarely examined. Against that sparse backdrop, this is, to the team’s knowledge, the first microcosting analysis of a client-centered PrEP navigation intervention designed specifically for sexual and gender minorities living with substance use disorder. One instructive benchmark comes from South Africa, where a demonstration project among female sex workers estimated PrEP delivery costs at roughly $168 per person-year after inflation — a figure the Los Angeles program’s per-client costs approach, while adding addiction treatment that most PrEP programs lack. Perhaps most consequential for practitioners is the counterintuitive pattern in per-participant costs: full navigation alone costs $104 per participant, navigation plus contingency management $73, and contingency management alone just $16, compared with $55 for standard of care. Because stepped-up clients have already completed intake and locator forms earlier in the program, later stages consume fewer resources — the stepped-care architecture is itself a cost-saving device.

To translate the findings into action, the team released a budget impact tool through CHERISH — the Center for Health Economics of Treatment Interventions for Substance Use Disorder, HCV, and HIV — freely accessible at CHERISHresearch.org, letting any prospective adopter plug in local wages, rents, and client volumes to see what the program would cost in their own setting. The authors caution that the analysis reflects a single urban site on the West Coast of the United States, shaped by Los Angeles wages and rents and by the local contours of the HIV and substance use syndemic, so other regions may face different figures. Even so, the broader implication is difficult to escape: uncertainty about cost, more often than cost itself, is what kills promising interventions before they spread. By showing that a program integrating HIV prevention with addiction treatment can be launched for about $26,000 and sustained for under $100,000 a year — with incremental per-participant costs measured in tens of dollars — the study converts a vague worry into a solvable budgeting problem. For the communities bearing the heaviest burden of the American HIV epidemic, that clarity may prove as consequential as the science behind the program itself.