/ 10 July 2025

Antiretroviral drugs in South Africa’s rivers raise environmental concerns

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A new study has found that lopinavir and efavirenz are the top pollutants in water bodies, many associated with waste water treatment plants

Significant concentrations of antiretroviral drugs (ARVs) have been detected in South Africa’s water sources, particularly downstream of wastewater treatment plants, new research has found.

The drugs most frequently detected were lopinavir and efavirenz, with concentrations at some sites far exceeding global norms. This is attributed to South Africa’s HIV treatment programme, the most extensive of its kind in the world.

The research, by North-West University’s unit for environmental sciences and management and its Africa unit for transdisciplinary health research, included professors Suranie Horn, Rialet Pieters, Henk Bouwman and Petra Bester

The study found that aquatic ecosystems and wastewater management systems were affected. Freshwater snails exposed to ARVs exhibited altered embryonic development, while bacteriophages — viruses critical to controlling bacteria in wastewater treatment — were significantly affected. Such disruptions could lead to bacterial blooms and reduced water quality, the authors said.

“The consumption of any type of exogenous drug by any organism in sufficient quantities may intervene with the regulation of metabolic systems and bring about adverse effects,” said the study, warning that the presence of antiretrovirals in water “can be considered a hidden or latent risk”.

The potential risks for human health were also red-flagged.

“Humans are also exposed to these compounds via drinking water, and at concentrations exceeding calculated hazard quotients,” the authors said. “Although not found in this study, humans and other organisms may potentially ingest antiretrovirals and their breakdown products via aquatic organisms such as fish.”

Concentrations of ARVs in some water sources exceeded acceptable thresholds, posing potential long-term health risks to humans. Current wastewater treatment processes are inadequate for removing these bioactive compounds, underlining the need for technological advancements.

Nearly all antiretrovirals were found in natural systems and some in drinking water, although none were found in the fish tissue samples, nor were antiretroviral metabolites found. 

South Africa has the greatest consumption of antiretroviral drugs per capita, with prescribed amounts of up to several tonnes a year.

The antiviral drugs being consumed and excreted through various pathways, including domestic and sewage wastes, into the natural environment pose an “ever-increasing risk of pharmaceutical pollution”, the study said. It is thus necessary to investigate water quality upstream and downstream from wastewater treatment plants.

Many of the biological, economic and social concerns of these highly bioactive compounds are unknown while endeavours to mount an effective solution are “fragmented and vastly under-resourced”. 

The research noted that certain antiretroviral compounds can be excreted largely unchanged after consumption, including acyclovir didanosine and tenofovir, whereas other compounds undergo extensive bio-transformation before elimination from the body. 

“Up to 90% of orally consumed pharmaceutical drugs reach wastewater in one form or another,” the report said.

“Research also suggests that compounds such as emtricitabine, ganciclovir and lamivudine are metabolised only to a small extent in the human body (10% to 30%), whereas abacavir and zidovudine are primarily metabolised to their glucuronide-adducts.”

To quantify ARV levels in waterways, the researchers used state-of-the-art analytical methods, including liquid chromatography/mass spectrometry. Their work also involved biological assays to gauge the toxicological effects of ARVs on non-target organisms and hazard assessments to evaluate risks to human health.

The compounds detected included ARVs (nevirapine, ritonavir, lopinavir, efavirenz, zidovudine) and the antifungal fluconazole. Although most pharmaceuticals are not persistent in nature, they are constantly introduced into the water sources, the researchers said. ARVs have not yet been classified to be hazardous to the environment or vertebrates that are indirectly exposed. 

Of the 72 sites sampled, 69 sites had never been investigated. Water was sampled upstream and downstream of wastewater treatment plants — specifically Sunderland Ridge, Vlakplaats, Waterval, Olifantsfontein River, Welgedacht, Zeekoegat, Flip Human and Baragwanath — in northern and southern Gauteng. 

Sampling sites included the Jukskei, Hennops, Klip, and Crocodile rivers. The Mooi River, which is close to Khutsong in North West and downstream of Wonderfonteinspruit in Gauteng, was also sampled. 

The most frequently detected compound was fluconazole (28 detections from 72 samples), with concentrations ranging from 0.06 to 1.8 μg/L (micrograms per litre). Nevirapine and efavirenz were the second-most detected compounds, both with 22 out of 72 samples. 

On average, lopinavir and efavirenz had the highest concentrations of the compounds analysed. Didanosine and zidovudine were the least detected compounds — two and six out of 72.

The research found the ARVs and the antifungal fluconazole that is used with ARVs are in water bodies and drinking water sources across Gauteng and in the Mooi River in the North West. 

These compounds are “pseudopersistent in the environment”, and it is unknown what effects these might have on the biota that are exposed to these compounds. “These may also accumulate in the tissues of organisms exposed.” 

Humans can be exposed to these compounds if they consume organisms from these water sources. “It is possible that these could cause detrimental effects, especially when other pharmaceuticals and their metabolites (resulting in a mixture effect) would also likely be present.”

The researchers calculated the hazard quotient (HQ) for each ARV detected in the

sampling sites and found that “certain ARVs from different rivers, over five months of sampling, pose an unacceptable level of risk”. 

“The HQs calculated for the ARVs and fluconazole ranged from 0 to 216 with lopinavir having the highest HQ and also exceeding the HQ risk level of 1 in almost all of the samples.” 

Fluconazole was the only compound that did not have a HQ greater than 1 in any of the samples. “The majority of the sites located in the Hennops, Jukskei, Klip and Crocodile rivers, except for the drinking water sites, had a hazard index indicating cumulative risk, greater than 1 indicating that the mixtures pose a significant risk for consumer’s health and that monitoring is needed.”

The results showed that surface water sources from urbanised and industrial areas were contaminated with high concentrations of ARVs and fluconazole compared to other countries worldwide. “In this study, an unacceptable risk to human health was identified when a hazard assessment was applied by using the minimum therapeutic dose approach.”

Humankind’s “relentless attempt” to provide therapeutic benefits from chemicals is coupled to the inevitable discharge of pharmaceuticals into the natural and social environment, the authors said. 

Several key recommendations include developing regulatory guidelines for ARV concentrations in water, improving wastewater treatment technologies, and conducting further research to understand the long-term ecological and human health impacts of these pharmaceuticals. 

The researchers also advocate for a multidisciplinary approach to address the intersections of public health and environmental sustainability.

“It is difficult to recognise the perils ahead, and even more difficult to provide an effective response,” they said. “If tipping points or thresholds are reached, it can lead to abrupt changes in the services provided by ecological systems, which, aside from triggering undesirable shifts in the natural balance, can have adverse social and economic consequences.”