What is the most effective comprehensive strategy for HIV prevention in low‑ and middle‑income countries?

HIV Prevention in Low- and Middle-Income Countries

The most effective comprehensive strategy for HIV prevention in LMICs combines biomedical interventions—specifically daily oral emtricitabine/tenofovir (FTC/TDF) for pre-exposure prophylaxis in high-risk populations and early antiretroviral therapy for all HIV-infected individuals—with behavioral counseling that provides self-management skills and condoms, delivered through structural interventions that address barriers like extended clinic hours, patient navigation, and integration with social services. 1, 2, 3

Core Prevention Components

Biomedical Interventions

Pre-Exposure Prophylaxis (PrEP) is the cornerstone of biomedical prevention for uninfected high-risk individuals:

• Daily oral FTC/TDF reduces HIV acquisition by approximately 90% when adherence is optimal, with detection of tenofovir in peripheral blood mononuclear cells associated with 99% risk reduction (95% CI: 96% to >99%) 1
• PrEP has proven efficacy in men who have sex with men (MSM), serodiscordant heterosexual couples, heterosexual adults, and people who inject drugs 1, 3
• Critical caveat: Medication adherence is the key determinant of PrEP efficacy—trials showing TDF detection in less than 30% of participants demonstrated no efficacy 1
• Rule out acute HIV infection before initiating PrEP to prevent drug resistance development 1

Treatment as Prevention through universal ART:

• Immediate ART initiation for all HIV-infected individuals regardless of CD4 count prevents disease progression, improves clinical outcomes, and limits transmission 3
• WHO guidelines now recommend initiating ART at CD4 counts <500 cells/mm³, representing an aspirational public health approach that prioritizes prevention benefits 1
• Integrase strand transfer inhibitor (InSTI)-based regimens plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) are recommended as first-line therapy 3

Behavioral Interventions

HIV prevention must integrate behavioral counseling with biomedical approaches—not either/or but combination intervention 1:

• Brief behavioral counseling reduces sexual risk behaviors, increases condom use, and reduces subsequent STIs including HIV 1
• The Explore Study demonstrated 39% reduction in HIV incidence over 12-18 months and 18% reduction over 48 months with multi-session counseling among MSM 1
• Single-session counseling interventions are effective, though longer duration sessions produce greater effects 1
• Face-to-face counseling outperforms media-delivered messages 1

Effective counseling content should include 1:

• Self-management skills training and condom provision
• Fostering self-belief and self-worth
• Distinguishing fact from myth about HIV transmission
• Evaluating options and consequences of risk behaviors
• Formulating commitment to change with specific planning skills
• Negotiating safer behaviors and setting limits
• Establishing pleasurable alternatives to high-risk sexual activity

Important note: Trial participants receiving regular risk assessment and counseling did not exhibit increased risk behaviors, dispelling concerns about risk compensation with PrEP availability 1

Structural Interventions: The Critical Differentiator for LMICs

Structural interventions addressing environmental, social, and economic barriers produce more positive and sustainable outcomes than individual-level approaches alone 2:

Healthcare Access Modifications

• Extended clinic hours directly address joblessness and inability to afford time off work, which are commonly cited barriers to care 2
• Walk-in or "open access" clinic models combined with low-threshold care show dramatic improvements in viral suppression among patients with complex needs 2
• Extended clinic access should be implemented alongside print reminders and brief verbal messages from all clinic staff 2

Patient Support Systems

• Patient navigation interventions increase retention in care, particularly for underserved populations including persons of color 2
• Community and peer outreach programs improve engagement and retention 2
• Case management services addressing food insecurity, housing, and transportation needs improve ART adherence, retention, and clinical outcomes 2
• Integration with social services and housing programs improves HIV-1 RNA levels in homeless populations 2

Monitoring and Optimization

• Systematic monitoring of time from diagnosis to care linkage, retention in care, and viral suppression rates is essential to identify ongoing barriers 2
• Real-time surveillance-based messaging through health information exchanges increases engagement rates for patients no longer in care 2
• Economic consideration: Investments in retention and linkage are more economically efficient than those devoted solely to increasing HIV screening 2

LMIC-Specific Implementation Considerations

Resource Constraints and Adaptations

The WHO guidelines have evolved toward aspirational recommendations that balance evidence with public health impact 1:

• Many newer antiretroviral classes (integrase inhibitors, entry inhibitors) remain inaccessible in LMICs due to high prices 1
• Generic manufacturing and compulsory licensing have brought some first-line medications within reach 1
• Viral load monitoring is preferred but if unavailable, CD4 count and clinical monitoring should be used 1

Common Pitfalls in LMIC Settings

Violence and environmental instability can undermine all intervention components—El Salvador's national HIV strategy was significantly impacted by increased violence during implementation 4

Resistance to decentralization and budget constraints negatively affect intervention delivery 4

Adherence challenges are magnified in resource-limited settings:

• Two PrEP trials failed to show efficacy when TDF was detected in less than 30% of female participants 1
• Structural barriers (food insecurity, housing instability, transportation) directly impact medication adherence 2

Capacity building of grassroots organizations is essential but often insufficient—human resource capacity limitations and conflicts between national HIV strategies and organizational missions can diminish intervention effectiveness 4

Integration Strategy

The evidence strongly supports combination prevention that is not additive but synergistic 5, 6:

• Biomedical approaches require behavioral risk reduction and adherence as essential components 5
• Structural interventions create the enabling environment for both biomedical and behavioral strategies to succeed 2, 7
• Conditional economic incentives can improve HIV testing rates, voluntary male circumcision, and other prevention outcomes in certain LMIC settings in the short term 8

Critical implementation principle: Interventions must clearly articulate a theory of change and measure intermediate variables between the intervention and HIV outcomes to understand mechanisms and optimize effectiveness 7

Retention in Care: The Ultimate Outcome Driver

Retention in care is directly linked to mortality reduction, with consistent retention associated with 2:

• Shorter time to viral suppression
• Lower cumulative viral load burden
• Improved immune function
• Decreased mortality

This underscores why structural interventions addressing retention barriers are not optional add-ons but essential components of effective HIV prevention in LMICs 2.