Background:  Partially efficacious HIV prevention interventions offer the best strategy to control HIV through synergistic combination and targeting. Wide-spread HIV testing is necessary for roll-out of combination prevention and facilitates access to HIV prevention interventions:  expedited referral to ART for HIV⁺ persons, counseling for behavior change, promotion of and referral for male circumcision, and evolving strategies such as topical or oral PrEP for high-risk HIV^– persons. Home-based HIV testing and counseling (HBCT) is a way to rapidly achieve population-level knowledge of HIV serostatus.

Methods:  We used a risk-sex stratified mathematical model to investigate the impact of HBCT-Plus as combination prevention, comprised of HBCT—behavior change counseling, initiation of ART for HIV⁺ persons meeting the current WHO CD4 ≤350 guideline, and male circumcision—on population-level HIV incidence. Our model was calibrated with data for KwaZulu-Natal, South Africa. Effects of HBCT and other components of the combination intervention package were based on empirical data from Africa:  90% knowledge of HIV serostatus through HBCT in year 1 with 25% behavior change following HBCT; 70% uptake of male circumcision with 60% efficacy; and ART with 92% reduction in HIV transmission and a drop out rate of ~14% per person-years (p-yrs) on ART. We modeled expanding ART to all HIV⁺ persons in an HBCT-Enhanced Arm.

Results:  With 90% testing coverage in HBCT-Plus, the model indicates HIV incidence could be reduced by ≈50%, from 2.0%/person-year to 1.0%/person-year, within 4 years. Behavior changes following HBCT mediate short-term reduction in HIV incidence and male circumcision and ART mediate long-term reductions. Longer-term impacts are supported by a reduction in infectiousness (due to timely initiation of ART as a result of earlier knowledge of serostatus through HBCT) and susceptibility (due to male circumcision) as well as associated “herd immunity” effects. The HBCT-Enhanced scenario is estimated to reduce incidence by 63% in 4 years.

Conclusions:  A combination of evidence-based HIV preventive interventions, if delivered with high coverage through HBCT, could reduce population-level HIV incidence in South Africa by >50% within 4 years. Slow-acting components affecting infectiousness and susceptibility will provide combination packages with greater impact on HIV incidence in the long term.