The Reactive was published in 2014 by Random House Struik. Following three Cape Town friends as they get high and sell antiretroviral drugs on the black market, the novel was positively received, praised for the beauty of its language despite its "harrowing" subject matter. In a review for Aerodrome, Eckard Smuts wrote: "From time to time a novel comes along that is so strange, yet so utterly fresh and compelling, that it feels tuned into a reality with which you are not yet familiar." In 2016, the novel was published in the United States by Two Dollar Radio, and to promote it, Ntshanga went on a North American tour, beginning at the Brooklyn Book Festival in New York City and concluding at City Lights Bookstore in San Francisco. Reviewing the US edition for Slate, Marian Ryan described the novel as what would happen "if Judd Apatow directed Jesus' Son and set it in Cape Town...The Reactive often teems with a beauty that seems to carry on in front of its glue-huffing wasters despite themselves." The book was translated into Italian and German, and in 2018, it was awarded a Betty Trask Award, becoming the first South African publication to receive the accolade.
