Third-line ART Has Potential to Improve Care for People Living with HIV in Lower-to-Middle Income Countries

There is limited information about which HIV drugs can be best used to treat people living with HIV who have multi-drug resistance. To address this gap, A5288 was conducted in 2013-2015 among 545 participants whose secondary treatment with a boosted PI-based regimen was ineffective in suppressing their HIV. The study was conducted at 19 urban sites in 10 low-to-middle income countries. This analysis assessed the use and efficacy of raltegravir, darunavir, and/or etravirine beyond the 48 weeks of the original A5288 among 257 participants who experienced treatment failure from multi-drug resistance (including resistance to lopinavir/ritonavir, which was the most common PI used in this setting during that time period).

The study found that the third-line regimens including raltegravir, darunavir, and/or etravirine were able to suppress HIV to a lower limit of detection for more than three years. Apart from good efficacy, this regimen was also well tolerated. These drugs are beneficial in delaying HIV progression and can prevent onward HIV transmission of multi-class drug resistance for a long period of time. The findings from this study provide evidence that these HIV drugs can be used among diverse populations of people living with HIV with multidrug resistance in lower-to-middle income countries and have the potential to improve care for people living with HIV.

Editor’s note: One of the important roles for studies like this is demonstrating that newer antiretrovirals can be used in diverse geographic settings, adding data to help countries and the World Health Organization (WHO) update treatment guidelines in a timely manner. A5288 is a part of the WHO Consolidated Guidelines for HIV prevention, testing, treatment, service delivery, and monitoring (

Avihingsanon, A.; Hughes, M.D.; Salata, R.; Godfrey, C.; McCarthy, C.; Mugyenyi, P.; Hogg, E.; Gross, R.; Cardoso, S.W.; Bukuru; A.; Makanga, M.; Badal‐aesen, S.; Mave, V.;  Ndege, B.W.; Fontain, S.N.; Samaneka, W.; Secours, R.; Van Schalkwyk, M.; Mngqibisa, R.; Mohapi, L.; Valencia, J.; Sugandhavesa, P.; Montalban, E.; Munyanga, C.;  Chagomerana, M.; Santos, B.R.; Kumarasamy, N.; Kanyama, C.; Schooley, R.T.; Mellors, J.W.; Wallis, C.L.; Collier, A.C.; Grinsztejn, B. and for the A5288 Study team. Third‐line antiretroviral therapy, including raltegravir (RAL), darunavir (DRV/r) and/or etravirine (ETR), is well tolerated and achieves durable virologic suppression over 144 weeks in resource‐limited settings: ACTG A5288 strategy trial. J Int AIDS Soc. 2022 Jun; 25(6): e25905.