FDA Programs to Register HIV Drugs for Use in Resource-Constrained Settings

An evaluation of the FDA program to review antiretroviral drugs for use in low-resource settings, conducted by the PEPFAR, showed that the FDA’s efforts have made many HIV drugs available for use globally.

An evaluation of the United States Food and Drug Administration’s (FDA) program to review antiretroviral drugs for use in low-resources settings, conducted by the US President’s Emergency Plan for AIDS Relief (PEPFAR), showed that the FDA’s efforts have made many HIV drugs available for use globally. The results of the evaluation published in JAMA Network Open also showed that more pediatric-specific therapies are needed and suggested that the quality of applications needs to improve.

A cross-sectional study of all PEPFAR applications submitted from December 1, 2004 through May 31, 2018 was conducted to assess program achievements and mechanisms to increase effectiveness. The numbers and types of applications were reviewed, along with the time it took for applications to gain approval or tentative approval. Also reviewed was how often the FDA issued a complete response letter identifying deficiencies precluding application approval or tentative approval and their reasons, along with the association between complete response letters and time to registration.

The study evaluated 260 applications for 327 antiretroviral therapies reviewed by the FDA, of which 216 applications for 272 drugs were authorized for use and 184 applications for 231 drugs remain in active status. The 216 approved applications included 56 for pediatric-specific formulations or strengths.

The median time to registration for the 216 authorized applications was 10.0 (interquartile range [IQR] 7.0-17.5) months. Ninety-five applications received >1 complete response letters, resulting in 172 in total. Most applications received only 1 complete response letter while others received up to 6. When reviewing all letters, 264 deficiency reasons were identified, with the most common being associated with the manufacturing processes (n=155), followed by product labeling and failing facility inspections (n=62 and 54, respectively). Complete response letters were associated with increased time to registration. Applications without complete response letters vs those with at least 1 had median times to registration of 9.0 (IQR, 5.5-12.0) months and 22.0 (IQR, 14.0-38.0) months, respectively (P <.001).

Investigators reported several study limitations, including not analyzing whether the FDA-registered HIV drugs included in the analysis are clinically needed. As a proxy, researchers conducted an analysis to determine what fraction of the drugs supported the World Health Organization’s first-line HIV treatment guidelines. They also did not determine whether the FDA-registered products are being actively manufactured or procured and they only reviewed high-level reasons for FDA rejection of applications. An in-depth review of rejections was beyond the scope of this investigation, but would be useful in improving the application quality. Finally, as the review focused solely on the PEPFAR program the findings are not generalizable to other FDA reviewed drugs.

Related Articles

The PEPFAR program now supports treatment for more than 14 million patients with HIV and the FDA supports global HIV efforts by quickly reviewing and registering new, safer, and more effective antiretroviral therapies. According to investigators, the FDA and pharmaceutical companies need to find ways to improve the quality of applications so as to prevent avoidable deficiencies in manufacturing processes and labeling. Furthermore, an international effort is needed to develop better and easier to use pediatric-specific HIV therapies.


Chahal HS, Koukounas K, Capella P, et al. An evaluation of US Food and Drug Administration’s program to register HIV drugs for use in resource-constrained settings. JAMA Netw Open. 2019;2:e1915787.