Introduction The Malawi Ministry of Health (MoH) has been in collaboration with Médecins sans Frontières (MSF) to increase access to quality HIV care through decentralization of antiretroviral therapy (ART) diagnosis and treatment from hospital to clinics in Nsanje District since 2011. A population-based household survey was implemented to provide information on HIV prevalence and cascade of care to inform and prioritize community-based HIV interventions in the district. Methods A cross-sectional survey was conducted between September 2016 and January 2017. Using two-stage cluster sampling, eligible adult individuals aged ≥15 years living in the selected households were asked to participate. Participants were interviewed and tested for HIV at home. Those tested HIV-positive had their HIV-RNA viral load (VL) measured, regardless of their ART status. All participants tested HIV-positive at the time of the survey were advised to report their HIV test result to the health facility of their choice that MSF was supported in the district. HIV-RNA VL results were made available in this health facility. Results Among 5,315 eligible individuals, 91.1% were included in the survey and accepted an HIV test. The overall prevalence was 12.1% (95% Confidence Interval (CI): 11.2–13.0) and was higher in women than in men: 14.0% versus 9.5%, P<0.001. Overall HIV-positive status awareness was 80.0% (95%CI: 76.4–83.1) and was associated with sex (P<0.05). Linkage to care was 78.0% (95%CI: 74.3–81.2) and participants in care 76.2% (95%CI: 72.4–79.5). ART coverage among participants aware of their HIV-positive status was 95.3% (95%CI: 92.9–96.9) and was not associated with sex (P = 0.55). Viral load suppression among participants on ART was 89.9% (95%CI: 86.6–92.4) and was not statistically different by sex (p = 0.40). Conclusions Despite encouraging results in HIV testing coverage, cascade of care, and UNAIDS targets in Nsanje District, some gap remains in the first 90, specifically among men and young adults. Enhanced community engagement and new strategies of testing, such as index testing, could be implemented to identify those who are still undiagnosed, particularly men and young adults.

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