South Africa currently has the highest number of cases of HIV in the world. HIV antiretrovirals (ARVs) are publicly available across the country to address this crisis. However, a consequence of widely available ARVs has been the diversion of these drugs for recreational usage in a drug cocktail commonly known as “nyaope” or “whoonga,” which poses a significant public health concern. To better understand nyaope, we conducted a systematic review investigating the risks and consequences associated with its usage. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searches were conducted in eight different databases and screened thereafter. Articles were eligible for inclusion if they included analysis of least one nyaope user and considered either demographics, risk factors, or consequences of usage. Data extracted included study characteristics and limitations, as well as demographic factors, risk factors for usage in the general population, and consequences. Quality assessments were performed using the Joanna Briggs Institute’s tools. Searches produced a total of 228 articles and, after screening, a total of 19 articles were eligible for inclusion. There was a pooled total of 807 nyaope users, all in South Africa. Major risk factors for usage were being male, unemployed, not completing secondary education, pressure from peer groups, having HIV, prior use of cannabis, and to a lesser extent, usage of other substances such as alcohol and tobacco. While young adults tend to be at high-risk, evidence indicates that adolescents are also at-risk. Consequences of usage include high rates of infection, cortical atrophy, depression, and addiction. Addiction was shown to lead to individuals stealing from friends and family to pay for the drugs. HIV-positive nyaope users were more likely to partake in risk behaviours and tended to have high viral loads. Nyaope’s rise has been linked to many health and social issues. Considering that this may also disrupt HIV control efforts in South Africa, there is an urgent need to address the rise of nyaope.
