IMPORTANT PHARMACOLOGICAL CONSIDERATIONS OF ANTIRETROVIRAL (ARV) DRUGS & OPPORTUNISTIC INFECTIONS (OIs) DRUGS

Substantial advances have been made in antiretroviral (ARV) therapy since the introduction of first agent, zidovudine in 1987. Since then there are many ARV agents available in market. Research on viral dynamics, such as viral load and resistance, has made clear that combination therapy with most efficient and potent agents reduce viral replication as well as emergence of resistance. Thus administration of highly active ARV therapy (HAART) includes 3 – 4 ARV agents from different

 pharmacological classes have become the standard of care. Combination must be chosen with care and tailored to individual, considering susceptibility, tolerability, and convenience of each individual.

Aims:

• To discuss important pharmacological aspects of those ARV drugs that are recommended by NACO for treatment of HIV/AIDS
• To discuss important pharmacological aspects of drugs used in commonly occurring opportunistic infections (OI)

Objectives By the end of session – Pharmacists will be able to understand and assimilate most important pharmacological features of ARV and OI drugs. Pharmacist will be able to apply knowledge in monitoring adverse drug reaction (ADR), drug – drug interaction and therapeutic response.

There are four classes of ARV agents –

(A)       Nucleoside / Nucleotide Reverse Transcriptase Inhibitors (NRTIS) viz.,

             zidovudine, tenofovir, lamivudine, stavudine, emtricitabine, abacaviir,

            didanosine.

(B)       Non-nucleoside Reverse Transcription Inhibitors (NNRTIS) viz., Efavirenz,  

            Nevirapine.

(C)       Protease inhibitors viz., Indinavir, Lopinavir, Ritonavir, Saquinavir.

(D)       Fusion inhibitors viz., enfuvirtide

Several newer ARV agents have been developed and are in pipeline. Though quite a few ARV drugs available in India, in the present context pharmacology of drugs included in National AIDS Programme as “first line” and “second line” drugs will be discussed.

Nucleoside / Nucleotide Reverse Transcription Inhibitors (NRTIS)

LAMIVUDINE (3TC)

It is a synthetic nucleoside analogue that inhibits HIV and HBV reverse transcription via viral DNA chain termination.

Pharmacokinetics

Its oral bioavailability is almost 80%. Food does not interfere with absorption. The majority of lamivudine is excreted as such in urine. The dose should be reduced in renal insufficiency or low body weight. It has synergistic effect (beneficial effect) with zidovudine. Lamivudine should not be used alone.

Cotrimoxazole may decrease plasma clearance of lamivudine and increase its plasma concentration leading to toxicity. Women should stop breast feeding if lamivudine is prescribed.

Dose:   Adult 150mg twice a day.

            Children 14-21 kg 75 mg twice a daily

            Children 22-29 kg 75 mg in the morning & 150 mg in evening.

STAVUDINE (D4T)

It is a thymidine analog acts like lamivudine.

Pharmacokinetics

It gets completely absorbed after oral administration, oral bioavailability is 86%. Food does not interfere with absorption. It is excreted in urine, therefore, dose needs to be adjusted in renal insufficiency or low body weight.

Major dose limiting toxicity is dose related peripheral sensory neuropathy which may or may not be reversible. Administration of stavudine should be avoided with other drugs those cause neuropathy. Concurrent administration with agents causing lactic acidosis and pancreatitis should be avoided .

Zidovudine reduces phosphorylation of stavudine resulting into decrease in action of stavudine. Both should not be given together.

Dose: Adult 30mg twice a day, Children over 3 months under 30 kg 1mg/kg twice a day, Over 30 kg 30mg twice daily.

ZIDOVUDINE (AZT)

It is deoxythymidine analog, acts in similar manner as lamivudine and stops virus replication.

Pharmacokinetics

Zidovudine was first ARV drug that was approved and used. It is well absorbed after oral ingestion and gets metabolized in liver and excreted by kidneys. Both in liver and renal insufficiency dose need to be adjusted.

Besides treatment of HIV, it is also used in prevention of maternal to fetal transmission of HIV. It is also available in injectible form used during labor.

Method for IV Administration

Dissolve required dose in dextrose 5% in water to final strength as 4mg/ml. infuse drug over one hour at a constant rate. Avoid rapid infusion or bolus injection. Do not add to blood product or protein solution. Protect undiluted vials from light.

Paracetamol may inhibit metabolism of zidovudine in liver resulting into increased levels. The increased level of zidovudine may also be seen with fluconazole, valporic acid, phenytoin and lamivudine by decreasing clearance. In such circumstances patient may develop toxicity .

Myclosuppression is most common ADR.

Dose: Adult 300mg twice a day.

          Child 3 months - 12 years 360-480/m²/day not to exceed 200mg/day.

Non-nucleoside Reverse Transcription Inhibitors (NNRTIS)

EFAVIRENZ

It is a non-nucleoside reverse transcriptase inhibitor that inhibits transcription of HIV-1 RNA to DNA a critical step in the viral replication and stops viral replication.

Pharmacokinetics

It is moderately absorbed from G.I.T, therefore, its bioavailability is 45% after oral administration. Bioavailability increases after high fat meal. It is advised to take it on an empty stomach. It is metabolized in liver by hepatic microsomal enzyme (CYP₃A₄ & CYP₂B₆). Most part is excreted as metabolite and some unchanged in feces.

Efavirenz is both enzyme inducer and enzyme inhibitor, can induce its own metabolism and metabolism of other drugs. It has a very long plasma half-life (40 – 55 hours), therefore, given once-a-day.

The principal adverse effect involves central nervous system.

Efavirenz has been shown to cause fetal abnormalities, therefore, should not be given to pregnant women especially in first trimester. It should be given with caution in patients with hepatic failure.

Dose: Adult & Child over 40 kg 600mg once daily

          Child over 10 -14 kg 200 mg once daily

          Child over 15 -19 kg 250 mg once daily

          Child over 20 -24 kg 300 mg once daily

          Child over 25 -32 kg 350 mg once daily

          Child over 33 -39 kg 400 mg once daily

NEVIRAPINE

A non-nucleoside reverse transcriptase inhibitor that binds directly to reverse transcriptase and block RNA dependant and DNA dependant, DNA polymerase activity and viral replication.

Pharmacokinetics

It has good oral bioavailablity (90%) and food intake does not interfere with absorption. The drug is highly lipophilic and reaches brain. It is metabolized in liver by hepatic microsomal enzyme (CYP₃A) and excreted in urine. It is moderate hepatic enzyme inducer, may increase metabolism of other drugs and drug inducer of CYP₃A may affect metabolism of nevirapine.

Therapeutic Use

In addition to its use as a component of a combination therapy, it is used to prevent mother to child transmission at the onset of labor, and then to neonate 2mg/kg within 3 days of delivery.

Skin rashes are commonly seen in patients.

Monitor liver function and renal function before starting therapy and at regular intervals.

Dose: Adult 200mg once a day for two weeks.

                     200mg twice a day.

Drugs discussed above are first line ARV drugs available at ART centers. In certain cases when there is treatment failure to first line drugs, second line ARV drugs have been recommended by NACO. Amongst them three drugs are available at specialized centers, one of them is NtRTIS (Tenfovir) and two are protease inhibitors (ritonavir & lopinavir). Following are important pharmacological features of these drugs:

TENOFOVIR DISOPROXIL FUMARATE

It is a nucleotide reverse transcriptase inhibitor. It is a prodrug and undergoes sequential phophorylation to yield active tenofovir diphosphate. It is competitive antagonist of HIV reverse transcriptase resulting into DNA chain termination and viral replication.

Pharmacokinetics

It is water soluble product and oral absorption from G.I.T is poor, therefore, has low bioavailability. However, after high fat meal, absorption increases to 39%. It is excreted as such in urine; therefore, dose adjustment is required in renal insufficiency. It has a long plasma half-life (17 hours) and administered once-a-day.

Tenofovir may compete with other drugs that are actively secreted by kidneys viz., acyclovir, gancyclovir, and, therefore, there may increase in blood levels of these drugs leading to toxicity.

The combination of tenofovir with didanosine is associated with decreased virological efficacy and increased toxicity, therefore, their combination should be avoided.

Dose: Adult 300mg once a day.

Protease Inhibitors

RITONAVIR

An HIV protease inhibitor with activity against HIV – 1 and HIV – 2 protease. Ritonavir binds to protease active site and inhibits activity of enzyme, preventing cleavage of viral poly-proteins and resulting in formation of immature, non-infectious viral particles.

Pharmacokinetics

It has high oral bioavailability (75%) which increases when drug is administered with food. It gets metabolized to active metabolite in liver by enzyme CYP₃A. The most important feature of ritonavir is that it is a potent inhibitor of CYP₃A₄ enzyme. It may inhibit metabolism of theophyline leading to its toxicity. However, inhibiting property of CYP₃A₄ has been exploited to raise trough concentration and prolonging half-life of more potent and less toxic protease inhibitors. Thus lower than therapeutic doses of ritonavir are commonly given in combination with agents such as lopinavir to reduce risk of resistance by increasing time of drug exposure. Moreover, prolonged half-life allows for less frequent dosing of other PI agents thus enhancing adherence. High incidence of common adverse effects viz., gastrointestinal, paresthesia, altered taste, hypertriglycidemia require slow dose escalation over 4 – 5 days.

LOPINAVIR / RITONAVIR (200mg + 50mg)

It is a licensed combination. Lopinavir has good oral bioavailability which is enhanced with food intake. It is extensively metabolized by CYP₃A enzyme.

In the combination, ritonavir is acting as a pharmacokinetic enhancer than an antiretroviral agent. The combination is generally well tolerated. Potential drug-drug interactions are extensive. Increased dosage of combination is recommended when co-administered with efavirenz or nevirapine, which induce lopinavir metabolism.

Dose: Adult and Adolescent 2 Cap. twice a day

Drugs Available for opportunistic infection (OI) in ART Centers

Drugs can be categorized as:

a)      Antibacterial.

b)      Antifungal.

c)      Antiviral.

d)     Antiprotozoal.

Antibacterial

Cotrimoxazole, ciprofloxacin, levofloxacin, amoxicillin + clavulanic acid, azithromycin, clindamycin

COTRIMOXAZOLE

It is a combination of trimethoprim – sulfamethoxazole in ratio of 1:5. Two strengths are available; 80mg + 400mg and 160mg + 800mg.

Action

Sulfamethoxazole inhibits formation of dihydrofolic acid from PABA; trimethprim inhibits dihydrofolate reductase formation. Both decrease bacterial folic acid synthesis and exert bactericidal effect (Kills bacteria).

Sulfonamides inhibit both gram-positive and gram-negative bacteria. However, many strains of formerly susceptible species are now resistant. The Cotrimoxazole is the drug of choice for infection such as pneumocystis jiroveci pneumonia, toxoplasmosis, nocardasis and occasionally other bacterial infections.

Pharmacokinetics

Cotrimoxazole is well absorbed orally and widely distributed in body tissues and fluids including CSF, Trimethprim is more lipophillic and has large volume of distribution. Trimethoprim gets concentrated in prostrate and in vaginal fluid, therefore, it has more bacterialcidal activity in both these organs.

Therapeutic Uses

Besides its use in UTI, prostitis infections caused by sensitive organisms, it is a very useful agent in treatment of P.jiroveci pneumonia in immuno-compromised patient such as AIDS patient.

Cotrimoxazole is available for intravenous use in patients suffering from moderate to severe pneumocystis pneumonia.

Patients with AIDS and pneumocystis pneumonia have a particularly high frequency of untoward reactions to combination especially fever, rashes, leucopenia, diarrhea, elevation of hepatic enzyme hyperkalemia and hyponatremia.

It is recommended for the treatment of GIT, respiratory infections and lymphadnopathy caused by OI.

Cotrimoxazole Prophylaxis Therapy (CPT) – It is routinely given for the prevention of OI in HIV infected patients. CPT reduces Morbidity and mortality of HIV infected patients and HIV infected patient with tuberculosis.

Dose: Adult 14 years and above ≥ 30Kg 960 mg of combined (800mg Sulfamethoxazole +160mg Trimethoprim) once daily.

CIPROFLOXACIN

It is a fluoroquinolones.

Action

It inhibits bacterial DNA synthesis mainly by blocking DNA gyrase (bactericidal). It is more effective against gram-negative bacterial than gram-positive bacteria.

Pharmacokinetics

It is rapidly absorbed orally but food delays absorption. Bioavailability is 60 – 80%. It has high tissue penetration and higher levels are achieved. However, CSF levels are low, administered both by oral and I/V route. It is excreted by kidneys.

I/V Administration

Dissolve drug in dextrose 5% water or normal saline to a final concentration of 1 – 2 mg/ml before use. Infuse slowly over one hour. Discontinue other I/V solution during ciprofloxacin administration. Use cautiously in patients with CNS disorders. Ask patients to take drug two hours before or after taking antacid. Drug should be taken empty stomach.

Therapeutic Uses

It is prescribed in patients suffering from OI infections of GIT and respiratory tract.

In Children it is given only in restricted condition.

Dose: Adult- 250-750 mg by oral route.

LEVOFLOXACIN

It is also a fluoroquinolone, acts like ciprofloxacin. It is levoisomer of ofloxacin having improved activity against strept.pneumonia and some other gram-positive and gram-negative bacteria. Anaerobes are moderately susceptible.

Pharmacokinetics

Very well absorbed after oral administration and bioavailability is 100%. Oral and I/V doses are similar, it gets concentrated in lungs. It is mainly excreted unchanged and a single daily dose is sufficient. Dose adjustment is required in renal insufficiency. For I/V administration, reconstitute drug in D₅W or normal saline 5mg/ml and inject slowly over a period of 60 minutes. It should be used with caution in patients having history of seizures.

It is mainly prescribed for pneumonia and other respiratory tract infections caused by OI.

Dose : Adult- 500mg once a day orally.

AZITHROMICIN

It belongs to maccrolide group of antibiotics. Chemically it is derived from erythromycin. It is less active against gram-positive organism than erythromycin but more active against H.influenzae, highly active against Chlamydia. High activity is exerted against respiratory pathogens.

Pharmacokinetics

It has remarkable pharmacokinetic properties. It is rapidly and well absorbed after oral administration. Tissue penetration is excellent. It gets distributed in all tissues except CSF. Tissue concentration exceeds serum concentration (10 to 100 folds). This unique property permits once daily dosing and shortening of duration of treatment in many diseases.

It should be administered one hour before or two hours after meal.

It has a very few drug-drug interactions.

It is recommended for pneumonia and chlamydial infections.

Dose: Adult -   L. pneumonia 500mg Once a day orally. Chlamydial  infection one single dose.

CLINDAMYCIN

It is lincosamide antibiotic. It has similar mechanism of action and antibacterial spectrum as erythromycin. It has high activity against variety of anaerobes. It is effective against penicillinase producing straph.aures.

Pharmacokinetics

Oral absorption is very good. It penetrates in most skeletal and soft issues, but does not reach CSF. It is metabolized in liver.

It is good alternative to Cotrimoxazole in combination with primaquin in P.jiroveci pneumonia in AIDS patients. Due to adverse effects, this is a reserve drug. It is prescribed for pneumonia caused by pneumocystis jiroveci when patient does not respond to other drugs.

Dose: 150-300mg four times a day orally.

AMOXICILLIN + CLAVULANIC ACID  (AUGMENTIN)

Amoxicillin is a congener of ampicillin and has activity against gram-positive bacteria as well as gram-negative bacteria. However, due to wide spread use, organisms have developed resistance. The organisms develop resistance by producing enzyme β-lactamases, which in turn destroy amoxicillin.

Clavulanic acid is a β-lactamase inhibitor, therefore, by inhibiting the enzymes, destruction of amoxicillin is prevented and the sensitivity of organisms returns. Clavulanic acid by itself has a very poor antibacterial activity. It is available in fixed dose combination.

Pharmacokinetics

Amoxicillin has better pharmacokinetic profile, viz., oral absorption is better; food does not interfere with absorption. Even adverse effects are less. Incidences of diarrhea are less. It is prescribed for respiratory infection by sensitive bacteria.

Dose:  Amoxicillin 250 mg + 125 Clavulanic acid

            Adult 1-2 tab. 8 hourly.

            Children under 40 kg 25mg /kg/day of Amoxicillin.

Cefotaxime-

It is third generation cephalosporin effective against aerobic gram-negative and some gram-positive bacteria. It is used in CNS infections such as meningitis and respiratory infections (pneumonia).

Pharmacokinetics:

It is only given either intramuscularly or intravenously. Its metabolite also has antibacterial activity

Dose:

Adults- 1-2 gm i.m/i.v. 6 hourly

Children- 50-100 mg/kg/day i.m/i.v

Sulfadiazine

It is a sulfa drug having antibacterial activity. Since many organisms have developed resistance, it is replaced by other effective antibiotics. However, it is still useful in toxoplasmosis in immunodeficient patients such as in AIDS, suffering from encephalitis.

Pharmacokinetics:

It is well and completely absorbed from G.I.T., highly protein bound. CSF concentration achieved is almost equal to plasma. It is excreted in urine.

Dose:

Adults- 0.5-1 gm 4 times a day orally.:

Clarithromycin

It is a macrolide antibiotic having antimicrobial spectrum similar to erythromycin. In addition, it is also effective against mycobacterium avium complex (MAC) and other atypical mycobacterium.

Pharmacokinetics:

It is rapidly absorbed orally. Food delays absorption. It gets distributed in all tissues in the body. It is used in upper and lower respiratory tract infections (atypical pneumonia).

It is a first line drug in combination regimen for MAC infection in AIDS patients.

Dose:

Adult -250-500mg every 12 hours orally.

Children≥6months -7.5mg /Kg every 12 hours orally.

FLUCONAZOLE

It is an antifungal agent having broad spectrum antifungal activity (fungicidal). It inhibits fungal cytochrome P₄₅₀ and weakens fungal cell wall. it is indicated in Cryptococcus meningitis, systemic and mucosal candidasis in both normal and immuno-compromised patients.

Pharmacokinetics

Oral bioavailability is very good, absorption not affected by food intake, and excreted unchanged in urine. Dose reduction is needed in renal insufficiency. The safety profile is good, well tolerated.

It is prescribed in opportunistic fungal infections of GIT, respiratory tract and CNS.

Serious hepatitoxicty can occur, therefore, liver function test should be monitored. Risk of ADR more in HIV infected patients.

Dose: A single 150 mg oral dose for vaginal candidisis, for oral 2 weeks treatment is required.

Itraconazole

It is also an antifungal agent with broader spectrum of antifungal activity (more than fluconazole). It is fungistatic but effective in immunocompromised patients.

Pharmacokinetics:

Oral absorption variable, enhanced by food, gets accumulated in vaginal mucosa, skin and nails. It inhibits hepatic microsomal enzymes and interacts with quite a few drugs.

Dose:

For vaginal candidiasis- 200 mg O.D orally for 3 days.

Dose is different in other conditions.

Amphotericin B (AMB)

It is an antifungal agent, effective against wide variety of fungi. It is fungicidal at high concentration and static at low concentration.

Pharmacokinetics:

It is not absorbed when given orally. For systemic infections, it has to be given by parenteral route. However, for intestinal candidiasis, it can be given by oral roué for local actions. It gets widely distributed in the body but CSF penetration is low. Most of AMB gets metabolized in liver.

Dose:

It is available as 50 mg dry powder/vial.

Adult dose- Dissolve it in 500 ml of dextrose after initial reconstitution with 10 ml water. Adults are administered 0.3 mg/kg i.v. over a period of 4-8 hours.

Neonates and children- 250mcg/kg daily.

ACYCLOVIR

It is an antiviral agent, interferes with DNA synthesis and inhibits viral multiplication. It is active only against herpes group of viruses.

Pharmacokinetics

Oral absorption is poor (20%). Tissue penetration is high. It is excreted unchanged in urine. It has a very short half-life

It is used in genital herpes, herpes keratitis, mucocutaneus herpes, and herpes zoster in immuno-deficient individuals. It may interact with ARV drugs (zidovudine). It should be used with caution in patients with neurological problems, renal insufficiency.

It is prescribed in dermatological infection caused by herpes virus both in normal and immuno-deficient patients.

Dose: Adult 200mg 4 times a day.

Ganciclovir

It is also an antiviral drug. It is an analogue of acyclovir. It is active against all herpes viruses. It is more active than acyclovir against cytomegalovirus (CMV). It is highly effective against CMV in immunocompromised patients. Mechanism of action is similar to acyclovir.

Pharmacokinetics:

It is administered orally as well as intravenously. It gets accumulated in CMV infected cells. Oral administration is used for prophylaxis of CMV infections.

Dose:

Adult- 5mg/kg every 12 hours i.v.

METRONIDAZOLE

It is a directly acting trichomonacidal and ambicidal that works at both intestinal and extra intestinal sites. It is thought to enter the cell of microorganisms that contain nitroreductose. Unstable compounds are then formed that bind to NA and inhibit synthesis, causing cell death.

Pharmacokinetics

Metronidazole is almost completely absorbed from small intestines. Little unabsorbed drug reaches the colon. It is widely distributed in the body attaining therapeutic concentration in vaginal secretion, semen, saliva and CSF. It is metabolized in liver and excreted in urine. It is effective against trichommas vaginitis, entmoeba histolytica and giradia lamblia. It is very efficacious against anaerobic bacterial infection.

Metronidazole is contraindicated in patients with neurological disease, in first trimester of pregnancy, and blood dyscrasis.

In AIDS patients, it is recommended for treatment of gastrointestinal infection due to entamoeba histolytica. Tablet 400 mg PO three times a day for seven days and for giardiasis tablet 200mg orally three times a day for 10 days.

Nitazoxanide

It is a synthetic antiprotozoal agent primarily used for the treatment of diarrhea caused by Giardia lambia and cryptosporidium parvum in HIV infected patients both in adults and children.

Pharmacokinetics:

After oral intake, it is converted into active metabolite. When taken with food, plasma concentration increases by 2 fold. It is excreted in the urine.

Dose:

1-3 years- 100 mg 12 hourly.

4-11 years- 200 mg 12 hourly

≥ 12 years- 500 mg 12 hourly

Essentially the drug should be taken with food.

ALBENDAZOLE

It has broad spectrum oral antihelmintic having action against ascariasis, hookworms and entrobiasis. It has an advantage of single dose treatment and is very well tolerated.

It causes in some cases gastrointestinal adverse effects. No pre drug administration, preparation or post drug fasting / purging is required.

It is recommended in strongyloides stercoralis infection in AIDS patients, both fior treatment and maintenance therapy.

For treatment, the dose is tablet 400mg twice a day for five days and for suppression therapy, the dose is tablet 400mg PO once a month.

Tuberculosis and HIV/AIDS

Tuberculosis is the most common cause of death in people with HIV. HIV infected person have less immunity and have less ability to kill bacteria. All patients with pulmonary or extrapulmonary tuberculosis should be referred to DOTS centre and they are given treatment according to the RNTCP programme in India. The regimens used for the treatment of pulmonary and extrapulmonary tuberculosis are same in both HIV-positive and negative individuals.

Revised National Tuberculosis Control Programme (RNTCP)

Treatment regimens followed vary according to the type of patient (whether the patient is a new case of TB or one who has been treated for TB previously), severity of illness and response to treatment.

Category I- Regimen used: 2(EHRZ)₃ 4(HR)₃

This regimen is recommended in patients with new sputum smear positive TB, seriously ill smear negative TB, seriously ill extrapulmonary TB, and all new TB patients who voluntarily disclose their HIV status.

Category II- Regimen used: 2(SEHRZ)₃/1(EHRZ)/5(EHR)₃

This regimen is recommended in patients with previously treated smear- positive TB (including relapse, failure and treatment after default).

Category III- Regimen used: 2(HRZ)₃/4(HR)₃

This regimen is recommended in patients with new smear- negative TB, extrapulmonary TB and those who are not seriously ill.

In all categories, treatment is given in 2 phases.

·         The first or intensive phase consists of treatment lasting for 2-3 months. In the intensive phase, 3-5 anti-TB drugs are administered depending on the category of treatment prescribed and all the thrice weekly doses are given under direct observation.

·         This is followed by the Continuation Phase, which lasts for 4-5 months. In the continuation phase, the number of anti-TB drugs administered is reduced to 2 or 3 drugs depending on the regimen prescribed and only the first dose of the week is given under direct supervision and the remaining 2 doses in the week are self-administered.

·         E (Ethambutol), H (Isoniazid), R (Rifampicin), Z (Pyrazinamide) and S (Streptomycin).

·         The numbers before the bracket indicate the number of months for which the drugs are to be administered.

·         The number”3” given as a subscript after the bracket indicates that the drugs are administered thrice weekly.

·         Category I and Category III regimens are given for 6 months, while the Category II regimen is for 8 months.

Key Learning Points Antiretroviral drugs are given in combination to avoid resistance. 3 – 4 drugs are combined from different classes. Five drugs (lamivudine, stavudine, zidovudine, efavirenz, nevirapine) are used in different combinations as first-line drugs. Zidovudine and stavudine should not be given together. The absorption of zidovudine, lamivudine, stavudine and nevirapine is not interfered by food intake. Oral absorption of efavirenz and tenofovir increases with high fat meal intake. Efavirenz and nevirapine are likely to cause more drug-drug interactions; therefore, one has to be vigilant for interactions and ADRs. Second-line drugs are protease inhibitors and they have tendency to cause complex drug-drug interactions resulting in lack of efficacy or ADRs. One has to be over cautious. Drugs used for OI are otherwise also used in normal individuals. However, their doses and patient’s response may be different from AIDS patients.