**4.3. Congeners of HAART**

The currently available anti-retroviral drugs specifically inhibit a select few steps of HIV replication such as HIV entry and fusion, reverse transcription, protease action and integration. Apart from their beneficiary action, the anti-retroviral drugs possess significant adverse reactions which form the principal reason behind poor compliance and drug withdrawal. With the advent of pharamacological techniques, congeners of anti-retroviral drugs are being developed with the aim of minimizing the side effects.

The congeners are molecules of any particular drug class which are engineered to overcome the pitfalls faced by the existing members of the same drug class. They possess minor structural modifications that confer one or more favourable properties such as increased biovailability, increased target site binding affinity or longer half life. By virtue of these properties, the congeners can be effectively administered at reduced dose and interval and hence possess a low adverse effect profile. The congeners are subject to clinical trials and would probably fail or get pass the trial stages to get approved by the United Staes Food and Drug Administration (FDA) and relevant international bodies. Table-1 summarizes the FDA approved antiretroviral dugs for use in the USA and their congeners in the pipeline (updated to October 2014) [18-21].



**Table 1.** Anti-retroviral drugs approved by the FDA and their congeners under consideration

#### **4.4. Reducing the pill burden**

**4.3. Congeners of HAART**

2014) [18-21].

**inhibited**

receptor

membrane

**Stage of HIV replication**

Attachment to CCR5 co-

Fusion of envelope with cell

Reverse transcription Nucleoside / Nucleotide

Reverse Transcriptase Inhibitors (NRTIs)

Non-Nucleoside Reverse Transcriptase Inhibitors

(NNRTIs)

developed with the aim of minimizing the side effects.

214 Trends in Basic and Therapeutic Options in HIV Infection - Towards a Functional Cure

The currently available anti-retroviral drugs specifically inhibit a select few steps of HIV replication such as HIV entry and fusion, reverse transcription, protease action and integration. Apart from their beneficiary action, the anti-retroviral drugs possess significant adverse reactions which form the principal reason behind poor compliance and drug withdrawal. With the advent of pharamacological techniques, congeners of anti-retroviral drugs are being

The congeners are molecules of any particular drug class which are engineered to overcome the pitfalls faced by the existing members of the same drug class. They possess minor structural modifications that confer one or more favourable properties such as increased biovailability, increased target site binding affinity or longer half life. By virtue of these properties, the congeners can be effectively administered at reduced dose and interval and hence possess a low adverse effect profile. The congeners are subject to clinical trials and would probably fail or get pass the trial stages to get approved by the United Staes Food and Drug Administration (FDA) and relevant international bodies. Table-1 summarizes the FDA approved antiretroviral dugs for use in the USA and their congeners in the pipeline (updated to October

**Anti-retroviral drug class FDA approved agents Congeners**

Entry inhibitors Maraviroc Cenicriviroc

Fusion inhibitors Enfuvirtide Albuvirtide

Zidovudine Lamivudine Stavudine Didanosine Emtricitabine Abacavir

Tenofovir disoproxil

fumarate

Nevirapine Efavirenz Delaviridine Etravirine Rilpivirine

Vicriviroc Adaptavir INCB-9471 PRO-140

tenofovir Amdoxovir Racivir Festinavir Elvucitabine Dexelvucitabine

Doravirine

Tenofovir alafenamide Hexadecycloxy propyl One of the practical difficulties faced by the multi-drug HAART regimen is the pill burden. It is glaringly obvious and even scientifically proven that, therapeutic regimens with lesser number of pills have a better patient adherence [22]. In this context, pills with a fixed dose combination of more than one anti-retroviral agent are being developed and few have also been approved by the FDA. Table-2 summarizes the list of combinations approved by the FDA as of October 2014 [18].


**Table 2.** Fixed dose combinations of anti-retroviral drugs approved by the FDA

Designing a single drug molecule containing the active moieties of two different anti-retroviral compounds is yet another strategy to reduce the pill burden. These molecules termed 'port‐ manteau inhibitors' can exert their anti-retroviral action at two different steps of HIV replica‐ tion and could thereby reduce an extra pill. Caffeoyl-anilide compounds are evaluated for their dual action in inhibiting HIV integrase and blocking the CCR5 receptor mediated entry [23].
