Intestinal helminth infection activates and dysregulates the immune system and impacts the host's capacity to respond to illness. Such neglected tropical infections exact the greatest burden on resource-limited settings and there appears to be considerable overlapping epidemiology with HIV-1 and other high-burden infections and illnesses in such settings. Recent limited yet controlled RCT evidence suggests a potentially beneficial therapeutic effect when persons co-infected with soil-transmitted worms and HIV-1, are treated with albendazole. The positive impact on CD4+ counts and plasma RNA levels appears to delay HIV-1 progression. The evidence-base has been conflicting and the unequivocal evidence needed to support large-scale de-worming remains lacking. The recent RCT by Walson and colleagues provides the first real tantalizing evidence of a beneficial impact of worm treatment and adds to a prior Cochrane review that was inconclusive. Further controlled, longer duration and larger trial arm designs that are minimally biased and comparable, are needed to provide the conclusive evidence needed yet the case for de-worming in delaying high-burden illnesses such as HIV-1 has been made much stronger.