Antiretroviral drugs have evolved significantly over time, with new drugs continuously being developed. The analysis below provides some insights into the development timeline, the focus on drug classes, and the use of drugs in combination formulations.

Evolution of Drug Classes

The following timeline summarizes the development of major drug classes over time:

1.  1980s-1990s: Early development of Nucleoside Reverse Transcriptase Inhibitors (NRTIs), the earliest class to be approved, such as Zidovudine (Retrovir) in 1987, followed by Abacavir (Ziagen) and Lamivudine (Epivir) in 1998 and 1995 respectively.

2.  1990s-2000s: Focus on the development of Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) and Protease Inhibitors (PIs).

3.  Mid-2000s - Present: Intensive development of Integrase Strand Transfer Inhibitors (INSTIs) and a new wave of different drug classes such as Fusion Inhibitors, CCR5 Antagonists, and others.

It is important to note that the development of different drug classes has been primarily based on overcoming the limitations of previous drugs, as well as improving the effectiveness and reducing the side effects.

generic name	drug class	brand name	approval date	combinations
abacavir	NRTIs	Ziagen	1998/12/17	Epzicom, Triumeq, Triumeq PD, Trizivir
emtricitabine	NRTIs	Emtriva	2003/07/02	Biktarvy, Symtuza, Atripla, Genvoya, Stribild, Odefsey, Complera, Descovy, Truvada
lamivudine	NRTIs	Epivir	1995/11/17	Epzicom, Triumeq, Triumeq PD, Trizivir, Dovato, Delstrigo, Symfi, Symi Lo, Cimduo, Combivir
tenofovir disoproxil fumarate	NRTIs	Viread	2001/10/26	Delstrigo, Atripla, Stribild, Complera, Truvada, Cimduo
tenofovir alafenamide fumarate	NRTIs			Biktarvy, Symtuza, Symfi, Symi Lo, Genvoya, Odefsey, Descovy
zidovudine	NRTIs	Retrovir	1987/03/19	Trizivir, Combivir
doravirine	NNRTIs	Pifeltro	2018/08/30	Delstrigo
efavirenz	NNRTIs	Sustiva	1998/09/17	Atripla, Symfi, Symi Lo
etravirine	NNRTIs	Intelence	2008/01/18
nevirapine	NNRTIs	Viramune	2011/03/25
extended-release nevirapine	NNRTIs	Viramune XR	2011/05/20
rilpivirine	NNRTIs			Cabenuva, Juluca, Odefsey, Complera
atazanavir	PIs	Reyataz	2003/06/20	Evotaz
darunavir	PIs	Prezista	2006/06/23	Symtuza
fosamprenavir	PIs	Lexiva	2003/10/20
ritonavir	PIs	Norvir	1996/03/01	Kaletra
tipranavir	PIs	Aptivus	2005/06/22
opinavir	PIs			Kaletra
enfuvirtide	Fusion Inhibtors, g41	Fuzeon	2003/03/13
maraviroc	CCR5 Antagonists	Selzentry	2007/08/06
cabotegravir	INSTIs	Vocabria	2021/01/22	Cabenuva
dolutegravir	INSTIs	Trivicay	2013/08/12	Triumeq, Triumeq PD, Dovato, Juluca
dolutegravir sodium	INSTIs	Trivicay PD	2020/06/12
raltegravir	INSTIs	Isentress	2007/10/12
raltegravir potassium	INSTIs	Isentress HD	2017/05/26
elvitegravir	INSTIs			Genvoya, Stribild
bictegravir	INSTIs			Biktarvy
fostemsavir	Fusion Inhibtors, gp120	Rukobia	2020/07/02
ibalizumab	Post-attachment inhibitors, CD4	Trogarzo	2018/03/06
lenacapavir	Capsid inhibitors	Sunlenca	2022/12/22
cobicistat	PK enhancers	Tybost	2014/09/24	Evotaz, Symtuza, Genvoya

Use in Combination Formulations

NRTIs lead the charge in terms of combination formulations. Nearly every NRTI listed, such as Emtricitabine (Emtriva), Lamivudine (Epivir), and Tenofovir disoproxil fumarate (Viread), are used in multiple combination therapies.

INSTIs are also increasingly used in combination formulations, notably Dolutegravir (Trivicay) and Cabotegravir (Vocabria).

Drug Class Distribution in Combination Formulations.png

Mostly Used Drugs in Combinations

Among all the drugs, Emtricitabine and Lamivudine are the two drug most frequently found in different combinations, suggesting a high versatility and effectiveness when it comes to treating HIV infection.

Antiretroviral Drug in Combination Formulations.png

In conclusion, these insights suggest that while the focus has shifted from NRTIs towards more novel classes like INSTIs and capsid inhibitor, drugs from these early classes like NRTIs still play a key role, particularly in combination treatments. This probably indicates the efficacy of the drug in synergy with others and its continued relevance in the fight against HIV, despite the development of newer drug classes. However, this tendency for combinations also indicates the complexity of HIV treatment, underlining the need for a personalized and integrated treatment approach.

References