The potential risks of long term exposure to low concentrations of antiretrovirals in treated and untreated water sources in Gauteng, South Africa

Abstract

Access to safe and affordable drinking water and sanitation is highlighted in the Sustainable Development Goal Target 6.1 while Target 6.3 addresses the release of hazardous chemicals into water sources. Pharmaceuticals and personal care products in treated drinking water have been receiving growing attention from environmental and health organizations worldwide because they are more frequently being detected in water sources. The fact that pharmaceuticals are manufactured with the intention to cause biological effects continue raising concerns about the impact of unintentional exposure to pharmaceuticals on human health. Despite the relatively fast growing numbers of studies on the prevalence and potential risk associated with pharmaceuticals in potable water, few studies that have addressed the potential human health risks associated with ingestion of low doses antiretrovirals (ARVs) through drinking water. The aim of the study was to assess the potential risks posed by long-term exposure to trace levels of ARVs in treated and untreated water sources in South Africa (SA), more specifically the Gauteng Province. A review of national and international literature was conducted to determine the extent and risks posed by ARV contamination in water sources globally. From the review it was evident that there is paucity of data on pharmaceuticals in water sources worldwide, including Africa. Where such data was available, pharmaceuticals targeted and detected in each investigation were country-dependent and linked to the most commonly used drugs or antivirals in the region, e.g. oseltamivir in Japan, with only a few reviews reporting on the presence and fate of ARVs in environmental samples. From a review of global human immunodeficiency virus (HIV) epidemic it was evident that SA uses more ARVs per capita compared to any other country fighting the HIV/acquired immunodeficiency syndrome (AIDS) epidemic with 71% (5 million) of adults living with HIV on combination antiretroviral therapy (cART). From 2003 to 2019 the drugs used in the first-line regimen for adults were the most used for the management of HIV with tenofovir disoproxil fumarate, lamivudine (3TC), emtricitabine and efavirenz (EFV) used more widely from 2010-2019. A newly approved ARV, dolutegravir, was included in the first-line regimen from 2020. A systematic review, conducted to establish which ARVs have been detected in water sources in SA, revealed that all ARVs that have been used historically in the first-line (stavudine, 3TC, EFV, nevirapine) and in second-line (didanosine, ritonavir boosted lopinavir, zidovudine [AZT]) regimens have been detected in one or more water sources, including treated drinking water, surface water and wastewater influent and effluent. To establish whether the low concentrations of ARVs in drinking water posed a possible health risk to individual ingesting polluted drinking water, a risk assessment was conducted. The method comprised of five general steps: a) selection of ARVs to be assessed; b) derivation of acceptable daily intake; c) derivation of predicted no effect concentrations; d) Exposure assessment - determination of environmental concentrations; and e) risk calculation. The risk quotient values needed for the risk assessment were sourced from studies that utilised acceptable daily intake values derived from dose-response model studies. The present study showed that from the current levels of AZT, 3TC and abacavir (ABC) detected in drinking water sources in SA, the possible human health risk was insignificant, although harmful to aquatic species. The predicted no effect concentrations were not available for the other ARVs present in the water sources in SA. Overall, this study showed that selected ARVs, namely EFV, in water were harmful to aquatic species, while the current levels of AZT, 3TC and ABC detected in drinking water sources in SA posed an insignificant human health risk. The study has therefore provided new data on the potential human health risk posed by exposure to low levels of ARVs in treated water sources in SA.