BACKGROUND: Lymphatic filariasis (LF) and human immunodeficiency virus (HIV) are major public health problems. Individuals may be co-infected, raising the possibility of important interactions between these two pathogens with consequences for LF elimination through annual mass drug administration (MDA). METHODOLOGY AND PRINCIPAL FINDINGS: We analysed circulating filarial antigenaemia (CFA) by HIV infection status among adults in two sites in northern Malawi, a region endemic for both LF and HIV. Stored blood samples and data from two geographically separate studies were used: one a recruitment phase of a clinical trial of anti-filarial agent dosing regimens, and the other a whole population annual HIV sero-survey. In study one, 1,851 consecutive adult volunteers were screened for HIV and LF infection. CFA prevalence was 25.4% (43/169) in HIV-positive and 23.6% (351/1487) in HIV-negative participants (p=0.57). Geometric mean CFA concentrations were 859 and 1660 antigen units per ml of blood (Ag/ml) respectively, geometric mean ratio (GMR) 0.85, 95%CI 0.49-1.50. In 7,863 adults in study two, CFA prevalence was 20.9% (86/411) in HIV-positive and 24.0% (1789/7452) in HIV-negative participants (p=0.15). Geometric mean CFA concentrations were 630 and 839 Ag/ml respectively (GMR 0.75, 95%CI 0.60-0.94). In the HIV-positive group, antiretroviral therapy (ART) use was associated with a lower CFA prevalence, 12.7% (18/142) vs. 25.3% (67/265), (OR 0.43, 95%CI 0.24-0.76). Prevalence of CFA decreased with duration of ART use, 15.2% 0-1 year (n=59), 13.6% >1-2 years (n=44), 10.0% >2-3 years (n=30) and 0% >3-4 years treatment (n=9), p<0.01 χ2 for linear trend. CONCLUSIONS/SIGNIFICANCE: In this large cross-sectional study of two distinct LF-exposed populations, there is no evidence that HIV infection has an impact on LF epidemiology that will interfere with LF control measures. A significant association of ART use with lower CFA prevalence merits further investigation to understand this apparent beneficial impact of ART.