• UNIT 5: ANTIVIRAL DRUGS

              Key Unit Competence:

    Utilize antiretroviral medications to limit HIV/AIDS transmission 

    Introductory activity 5.0

                      

    Observe the images (A, B, C) above and describe briefly what they indicate for 

    you.

    5.1. Introduction to antiretroviral drugs

            Learning Activity 5.1

           During your clinical practice ,you receive a client in consultation. In data collection, 

    the client reports that he is taking antiretroviral drug.

    1) What is an antiretroviral drug?

    2) What is a protease inhibitor?

    Guidance: Use internet and library textboks. 

    CONTENT SUMMARY

    Antiviral: An agent that kills a virus or that suppresses its ability to replicate and, 
    hence, inhibits its capability to multiply and reproduce.
    For example, amantadine (Symmetrel) is a synthetic antiviral. It acts by inhibiting the 
    multiplication of the influenzaA virus. It was used to lessen the severity of the disease, 
    particularly in individuals at high-risk such as those who are immunosuppressed or 
    in a nursing home. 
    The antivirals that have been developed are generally less effective than one 
    would like. Viruses can replicate rapidly and, in many cases sloppily, giving rise to 
    mutations that make them resistant to drugs. And for fast-moving viral infections 
    like flu or a cold, a drug must be very powerful to make a difference before the 
    disease runs its natural course.
    Antivirals and Antiretrovirals are a class of medication specifically used to treat 
    viral and retroviral infections caused by viruses like HIV, herpes viruses, hepatitis 
    B and C. Antivirals are a class of drugs which are used to treat viral infections. 
    The antiviral drugs target diverse group of viruses such as herpes, hepatitis, and 
    influenza viruses. Whereas antiretroviral drugs are the drugs that are used to fight 
    retrovirus infections which mainly include HIV. Different classes of antiretroviral 
    drugs act on different stages of the HIV life cycle.
    Retrovirus is a group of viruses that belong to the family Retroviridae and that 
    characteristically carry their genetic blueprint in the form of ribonucleic acid (RNA). 
    Retroviruses are named for an enzyme known as reverse transcriptase, which was 
    discovered independently in 1971 by American virologists Howard Temin and David 
    Baltimore. Reverse transcriptase transcribes RNA into deoxyribonucleic 
    acid (DNA), a process that constitutes a reversal of the usual direction of 
    cellular transcription (DNA into RNA). The action of reverse transcriptase makes it 
    possible for genetic material from a retrovirus to become permanently incorporated 
    into the DNA genome of an infected cell; the enzyme is widely used in the biological 
    sciences to synthesize genes.
    Integrase inhibitor: a drug that inhibits the activity of the virus-specific enzyme 
    integrase, an encoded enzyme needed for viral replication; blocking this enzyme 
    prevents the formation of the HIV-1 provirus.
    Interferon: tissue hormone that is released in response to viral invasion; blocks 
    viral replication nonnucleoside reverse transcriptase inhibitors: drugs that bind to 
    sites on the reverse transcriptase within the cell cytoplasm, preventing RNA- and 
    DNA-dependent DNA polymerase activities needed to carry out viral DNA synthesis; 
    prevents the transfer of information that allows the virus to replicate and survive.
    Nucleoside reverse transcriptase inhibitors: drugs that prevent the growth of the 
    viral DNA chain, preventing it from inserting into the host DNA, so viral replication 

    cannot occur.

    Protease inhibitors: drugs that block the activity of the enzyme protease in HIV; 

    protease is essential for the maturation of infectious virus, and its absence leads to 

    the formation of an immature and noninfective HIV particle.

    CCR5 coreceptor antagonist: a drug that blocks the receptor site on the T cell 

    membrane that the HIV virus needs to interact with in order to enter the cell.

    Fusion inhibitor: a drug that prevents the fusion of the HIV-1 virus with the human 

    cellular membrane, preventing it from entering the cell. 

    Self-assessment 5.1

    1) which of the following is a definition of antiviral drugs?
    a) Antivirals are a class of drugs which are used to treat viral infections
    b) Antivirals are a class of drugs which are used to treat viral and bacterial 
    infections
    c) Antivirals are a class of drugs which are used to treat retroviral infections
    d) Antivirals are a class of drugs which are used to treat viral and retroviral 
    infections
    2) You receive a client with signs and symptoms of helps simplex. Among 
    the two following groups of drugs, which one will you choose as effective 
    to the disease?
    a) Antiretroviral drugs
    b) Antiviral drugs
    3) With an example of the virus infections. Differentiate antiviral and retroviral 

    drugs.

    5.2. Classification of antiretroviral drugs

             Learning Activity 5.2

    You are an asociate nurse carrying out the clinical placement. You receive a 
    patient at the health facility who has been diagnosed with HIV/AIDS. What does 
    an associate nurse will tell the patient?
    1) Which classes of antiretroviral drugs can be used in HIV/AIDS 
         management?

    2) What are the five basic goals of ART?

    CONTENT SUMMARY

    In this lesson we discuss on classification of antiretroviral drugs. HIV infection has 
    been transformed from a near-certain death sentence to a manageable chronic 
    disease. Because of viruses are contained inside human cells while they are in 
    the body, researchers have difficulty developing effective drugs that destroy a virus 
    without harming the human host. Since the introduction of ART, the incidence of 
    new opportunistic infections has declined dramatically. For example, the incidences 
    of cytomegalovirus retinitis and disseminated mycobacterial infection have fallen 
    by as much as 75% to 80%. In many patients with low CD4 T-cell counts, ART 
    has caused CD4 counts to rise, restoring some immunocompetence and permitting 
    withdrawal of prophylactic drugs. 

    Patients with HIV infection should receive ART regardless of the CD4 count or 
    phase of HIV disease. Treatment has five basic goals: Maximal and long-lasting 
    suppression of viral load, restoration and preservation of immune function, improved 
    quality of life, reduction of HIV-related morbidity and mortality and prevention of 
    HIV transmission. Most patients take several antiretroviral drugs typically two 
    nucleoside reverse transcriptase inhibitors (NRTIs) combined with either a PI or 
    non-nucleoside reverse transcriptase inhibitors (NNRTIs).
     

    These highly effective regimens can reduce plasma HIV to undetectable levels, 
    causing CD4 T-cell counts to return toward normal, thereby restoring some immune 
    function. However, despite these advances, treatment cannot cure HIV. The HIV 
    mutates over time, presenting a slightly different configuration with each new 
    generation. Treatment of AIDS and ARC has been difficult for two reasons: (1) 
    the length of time the virus can remain dormant within the T cells (i.e., months to 
    years), and (2) the adverse effects of many potent drugs, which may include further 
    depression of the immune system. A combination of several different antiviral drugs 
    is used to attack the virus at various points in its life cycle to achieve maximum 
    effectiveness with the least amount of toxicity.

    Antiretroviral drugs are classified into six classes of antiretroviral drugs. Four 
    classes: nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non                                                                                      nucleoside reverse transcriptase inhibitors (NNRTIs), integrase strand transfer 
    inhibitors (INSTIs), and protease inhibitors (PIs) inhibit HIV enzymes. 
    The other two classes: HIV fusion inhibitors and CCR5 antagonists, work outside 
    CD4 cells to block HIV entry. 

    NRTIs suppress HIV replication in two ways: (1) they become incorporated into 
    the growing strand of viral DNA (through the actions of reverse transcriptase) and 
    thereby prevent further strand growth, and (2) they compete with natural nucleoside 
    triphosphates for binding to the active center of reverse transcriptase and thereby 
    competitively inhibit the enzyme. To interact with reverse transcriptase, NRTIs must 

    first undergo intracellular conversion to their active (triphosphate) forms.

    The NNRTIs differ from the NRTIs in structure and mechanism of action. As 
    their name suggests, the NNRTIs have no structural relationship with naturally 
    occurring nucleosides. Also unlike NRTIs, the NNRTIs are active only against HIV1. In practice, they are usually combined with an NRTI. The NNRTIs bind to the 
    active center of reverse transcriptase enzyme. At this location, the NNRTI causes 
    stereochemical changes (i.e., changes in the spatial arrangement of atoms forming 
    the structure of molecules). This hampers the ability of nucleosides to bind, which 
    inhibits DNA replication and promotes premature termination of the growing DNA 
    strand.
    NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIs)
    The NRTIs were the first drugs used against HIV infection. As their name suggests, 
    the NRTIs are chemical relatives of naturally occurring nucleosides or nucleotides, 
    the building blocks of DNA. At this time, seven NRTIs are available: Abacavir, 
    didanosine, emtricitabine, lamivudine, stavudine, tenofovir, and zidovudine. The 
    NRTIs are effective against both HIV-1 and HIV-2; however, their activity is greater 
    for HIV-1. The NRTIs are ineffective as monotherapy because resistance develops 
    rapidly. First-line antiretroviral regimens include two NRTIs and one other drug. The 
    availability of combination antiretroviral products has simplified treatment. 
    Mechanism of Action 
    All NRTIs are prodrugs that inhibit HIV replication by suppressing synthesis 
    of viral DNA. To do this, they must first undergo intracellular conversion to their 
    active (phosphate) form. In their active form, they act as substrates for reverse 
    transcriptase. However, after they become incorporated into the growing DNA 
    strand, they prevent reverse transcriptase from adding more bases. As a result, all 
    further growth of the DNA strand is blocked. In addition to causing premature strand 
    termination, the activated NRTI competes with natural nucleoside triphosphates for 
    binding to the active site of reverse transcriptase. 
    Adverse Effects 
    The NRTIs share a core of adverse effects associated with mitochondrial toxicity. 
    Recall that mitochondria are cellular organelles that take in nutrients and convert 
    them into ATP for energy. NRTIs can disrupt synthesis of mitochondrial DNA and 
    can thereby impair mitochondrial function. 
    The main adverse effects of NRTIs are: Lactic acidosis, hepatic steatosis. Other 
    adverse effects include: pancreatitis and myopathies, which are likely tied to lactic 
    acidosis. Adverse effects of individual NRTIs are discussed separately. 
    Drug Interactions 
    NRTIs have fewer drug interactions than most antiretroviral drugs, in part because 
    most are not metabolized by the P450 enzymes. Interactions of individual drugs are 

    discussed separately.

    Table 5.1.1: NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIs)

                               

                            

           NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

    The NNRTIs differ from the NRTIs in structure and mechanism of action. As their 
    name suggests, the NNRTIs have no structural relationship with naturally occurring 
    nucleosides. Also unlike NRTIs, the NNRTIs are active only against HIV-1. In 
    practice, they are usually combined with an NRTI. At this time, five NNRTIs are 
    available: efavirenz (Sustiva), nevirapine (Viramune), Delavirdine (Rescriptor), 

    etravirine (Intelence), and rilpivirine (Edurant). 

    Mechanism of Action
    In contrast to the NRTIs, the NNRTIs bind to the active center of reverse transcriptase 
    enzyme. At this location, the NNRTI causes stereochemical changes (i.e., changes 
    in the spatial arrangement of atoms forming the structure of molecules). This 
    hampers the ability of nucleosides to bind, which inhibits DNA replication and 
    promotes premature termination of the growing DNA strand. 
    Adverse Effects 
    Unlike NRTIs, there are no adverse effects shared by all NNRTIs. However, two of 
    the NNRTIs, efavirenz and rilpivirine, can both cause CNS effects. 
    Drug Interactions 
    The NNRTIs have multiple drug interactions with commonly used drugs across 
    many drug classes. These vary according to the individual NNRTI in question.

    Table 5.1.2: NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

                              

         PROTEASE INHIBITORS 

    PIs are active against both HIV-1 and HIV-2. They are among the most effective 
    antiretroviral drugs available. When used in combination with NRTIs, they can 
    reduce viral load to a level that is undetectable with current assays.
    As with other antiretroviral drugs, HIV resistance can be a significant problem. 
    Mutant strains of HIV that are resistant to one PI are likely to be cross-resistant 
    to other PIs. In contrast, since PIs do not share the same mechanism as other 
    antiretroviral drugs, cross-resistance between PIs and these drugs does not occur. 
    To reduce the risk for resistance, PIs should never be used alone; rather, they 
    should always be combined with at least one reverse transcriptase inhibitor, and 
    preferably two. 
    Nine PIs are available: atazanavir, darunavir, fosamprenavir, indinavir, lopinavir 
    (with ritonavir), nelfinavir, ritonavir, saquinavir, and tipranavir.
    Mechanism of Action 
    Maturation is necessary for HIV to infect CD4 cells; immature forms are noninfectious. 
    Protease inhibitors prevent HIV maturation by blocking the HIV enzyme protease. It 
    may help to look at the process of HIV maturation. 
    When the various enzymes and structural proteins of HIV are synthesized, they 
    are not produced as separate entities; rather, they are strung together in large 
    polyproteins. Protease catalyzes the cleavage of bonds in the polyproteins, thereby 
    freeing the individual enzymes and structural proteins. Once these components 
    have been freed, HIV uses them to complete its maturation. Protease inhibitors 
    bind to the active site of HIV protease and prevent the enzyme from cleaving HIV 
    polyproteins. As a result, the structural proteins and enzymes of HIV are unable to 
    function, and hence the virus remains immature and non-infectious.
    Adverse Effects 
    There are several adverse effects that all protease inhibitors have in common. 
    These include hyperglycemia and the development of diabetes, lipodystrophy 
    (fat redistribution), elevation of serum transaminases, and decreased cardiac 
    conduction velocity. They can also increase bleeding in patients with hemophilia. 
    Drug Interactions 
    All PIs are metabolized by cytochrome P450 enzymes, and all PIs can inhibit 
    selected cytochrome P450 enzymes. Typically, they will also induce other enzymes. 
    As a result, PIs can interact with drugs that inhibit or induce P450 enzymes and 
    with drugs that are substrates for P450 enzymes. Not all interactions are harmful, of 
    course. By inhibiting selected P450 enzymes one PI can increase the level of another 

    PI and can thus intensify therapeutic effects. One PI—ritonavir [Norvir]—is routinely     

    combined with other PIs with the specific purpose of increasing the therapeutic 
    effects of the other PI. In this technique, known as ritonavir boosting, the dose of 
    ritonavir is low: 100 to 400 mg/day. This dosage is too low to contribute significant 
    antiviral effects, but still high enough to inhibit P450 metabolism. Unfortunately, 
    most interactions with PIs are not beneficial. We will highlight interactions commonly 

    experienced by patients with HIV in our discussion of individual PIs.

    Table 5.1.3: PROTEASE INHIBITORS

                       

                        

            INTEGRASE STRAND TRANSFER INHIBITORS 

    HIV integrase strand transfer inhibitors (INSTIs), or simply integrase inhibitors, 

    target HIV by terminating the integration of HIV into DNA. Integrase is one of three 

    viral enzymes needed for HIV replication. As its name implies, integrase inserts 

    HIV genetic material into the DNA of CD4 cells. By inhibiting integrase, these drugs 

    prevent insertion of HIV DNA and thereby stop HIV replication. They are effective 

    against both HIV-1 and HIV-2. 

    We currently have three approved INSTIs: raltegravir, dolutegravir, and elvitegravir. 

    All are indicated for combined use with other antiretroviral agents to treat adults 

    infected with HIV-1. 


    Actions and Use 

    Raltegravir [Isentress] was the first HIV integrase strand transfer inhibitor to be 

    developed. Raltegravir stops HIV replication by preventing insertion of HIV DNA. 

    Raltegravir is active against HIV strains resistant to some of the other drugs. 

    Raltegravir was originally approved only for treatmentexperienced patients but is 

    now approved for treatment-naïve patients as well. In current guidelines, raltegravir 

    (in combination with tenofovir plus either emtricitabine or lamivudine) is considered 

    a first-choice drug for HIV treatment. In clinical trials, raltegravir demonstrated 

    increased viral suppression when compared to protease inhibitors and the NNRTI 

    efavirenz. Unfortunately, HIV resistance was also more likely to develop. 

    Adverse Effects 

    Raltegravir is generally well tolerated by most. The most common adverse effect 

    is an elevation in liver enzymes that occurs in about 10% of those taking the 

    drug. Approximately 4% to 5% will have elevations in serum amylase and lipase. 

    Symptomatic adverse effects occur infrequently. In fact, the most common adverse 

    effects, insomnia and headache, occur in only 2% to 4% of those taking this drug. 

    In clinical trials, a few patients experienced myopathy and rhabdomyolysis, but 

    a causal relationship has not been established. Rarely, patients have developed 

    severe hypersensitivity reactions. Skin reactions include Stevens-Johnson 

    syndrome and toxic epidermal necrolysis, which can be fatal. Organ dysfunction, 

    including liver failure, may also develop. 

    Patients who develop signs of a hypersensitivity reaction (e.g., severe rash, or rash 

    associated with blisters, fever, malaise, fatigue, oral lesions, facial edema, hepatitis, 

    angioedema, muscle or joint aches) should discontinue raltegravir immediately. 

    Contraindications 

    There are no contraindications to taking raltegravir. Those with pre-existing hepatic 

    impairment may be at risk for worsening of this condition. Caution should be 

    maintained when taken by patients with a history of rhabdomyolysis or by those 

    taking other drugs that have this adverse effect. 

    Drug Interactions 

    Because raltegravir is metabolized by glucuronidation, it does not have as many 

    drug interactions as those with roles in P450 enzyme systems. Atazanavir and other 

    inhibitors of UGT can increase levels of raltegravir. Conversely, inducers of UGT 

    (e.g., efavirenz, fosamprenavir, rifabutin, tipranavir) can lower raltegravir levels. 

    HIV FUSION INHIBITORS 

    Unlike most other drugs for HIV, which inhibit essential viral enzymes (i.e., reverse 

    transcriptase, integrase, protease), HIV fusion inhibitors block entry of HIV into 

    CD4 T cells. Earlier in the chapter, we discussed the replication cycle of HIV. Recall 

    that in step 2, the lipid bilayer envelope of HIV fuses with the lipid bilayer of the host 

    cell membrane. HIV fusion inhibitors block this fusion process. 

    Enfuvirtide 

    Enfuvirtide [Fuzeon], widely known as T-20, is the first and only HIV fusion inhibitor 

    currently approved by the FDA. Unfortunately, although enfuvirtide is effective, 

    it is also inconvenient (treatment requires twice-daily subQ injections) and very 

    expensive (treatment costs about $52,000 a year). Furthermore, injection-site 

    reactions occur in nearly all patients. 

    Mechanism of Action 

    Enfuvirtide prevents the HIV envelope from fusing with the cell membrane of CD4 

    cells, and thereby blocks viral entry and replication. Fusion inhibition results from 

    binding of enfuvirtide to gp41, a subunit of the glycoproteins embedded in the 

    HIV envelope (see Fig. 94.1). As a result of enfuvirtide binding, the glycoprotein 

    becomes rigid, and hence cannot undergo the configurational change needed to 

    permit fusion of HIV with the cell membrane. 

    Resistance 

    Resistance to enfuvirtide has developed in cultured cells and in patients. The cause 

    is a structural change in gp41. In clinical trials, reductions in drug susceptibility have 

    ranged from 4- to 422-fold. Fortunately, the HIV mutations that confer resistance to 

    enfuvirtide do not confer cross-resistance to NRTIs, NNRTIs, PIs, INSTIs, or CCR5 

    antagonists. Conversely, resistance to NRTIs, NNRTIs, PIs, INSTIs, or CCR5 

    antagonists does not confer cross-resistance to enfuvirtide. The rate at which 

    resistance develops depends on the efficacy of the drugs used concurrently. When 

    the patient’s other antiretroviral drugs are still effective, resistance to enfuvirtide 

    develops relatively slowly. However, when there is significant resistance to the 

    other drugs, resistance to enfuvirtide develops rapidly.

    Therapeutic use

    Use Enfuvirtide is reserved for treating HIV-1 infection that has become resistant 

    to other antiretroviral agents. Specifically, the drug is indicated for HIV-1 infection 

    in patients who are treatment experienced and have evidence of HIV replication 

    despite ongoing ART. To delay emergence of resistance, enfuvirtide should always 

    be combined with other antiretroviral drugs.

    Adverse Effects 

    They include injection-site reactions, pneumonia, and hypersensitivity 

    reactions.

    Drug Interactions 

    Enfuvirtide appears devoid of significant drug interactions. There are no interactions 

    with other antiretroviral drugs that would require a dosage adjustment for either 

    enfuvirtide or the other agent. 

    Table 5.1.4: INTEGRASE INHIBITORS 

                  

                   CCR5 ANTAGONISTS 

    CCR5 antagonists, like the fusion inhibitors, block entry of HIV into CD4 T cells. 
    However, the mechanism by which they accomplish this is different. 
    Maraviroc 
    Maraviroc [Selzentry, Celsentri ] is the first, and currently only, representative of 
    the CCR5 antagonists. Maraviroc isn’t usually used for initial treatment of HIV. It 
    appears most effective in treating patients with drug-resistant HIV. 
    Mechanism of Action 
    CCR5 is a co-receptor that some strains of HIV must bind with to enter CD4 cells. 
    Maraviroc binds with CCR5 and thereby blocks viral entry. HIV strains that require 
    CCR5 for entry are referred to as being CCR5 tropic. Between 50% and 60% 
    of patients are infected with this type of HIV. Maraviroc and enfuvirtide (a fusion 
    inhibitor) are the only antiretroviral drugs that block HIV entry.
    Therapeutic Use 
    Maraviroc is indicated for combined use with other antiretroviral agents to treat 
    patients age 16 years and older who are infected with CCR5-tropic HIV-1 strains. 
    The drug was originally approved only for treatment-experienced patients but is 
    now approved for treatment-naïve patients as well. Before maraviroc is used, a test 
    must be performed to confirm that the infecting HIV strain is CCR5 tropic. 
    Adverse Effects 
    The most common side effects are cough, dizziness, pyrexia, rash, abdominal 
    pain, musculoskeletal symptoms, and upper respiratory tract infections. Intensity is 
    generally mild to moderate. Liver injury has been seen in some patients and may be 
    preceded by signs of an allergic reaction (e.g., eosinophilia, pruritic rash, elevated 
    immunoglobulin E). 
    Patients should be informed about signs of an evolving reaction (itchy rash, jaundice, 
    vomiting, and/or abdominal pain) and instructed to stop maraviroc and seek medical 
    attention. During clinical trials, a few patients experienced cardiovascular events, 
    including myocardial ischemia and MI. Maraviroc should be used with caution in 
    patients with cardiovascular risk factors. 
    Drug Interactions 
    Because maraviroc is metabolized by CYP3A4, drugs that inhibit or induce this 
    enzyme will affect maraviroc levels. Levels will be raised by strong CYP3A4 
    inhibitors, including protease inhibitors (except tipranavir/ritonavir) and delavirdine. 
    Conversely, maraviroc levels will be lowered by strong CYP3A4 inducers, including 
    etravirine and efavirenz. As always, it is important to check for interactions via a 

    comprehensive database before administering drugs such as this one.

    Table 5.1.5: FUSIOIN INHIBITORS

                   

                     

                           Self-assessment 5.2

    1) Why is combination therapy necessary in HIV treatment?
    2) Which of the following antiretroviral drugs is classified in the protease 
    inhibitors?
    a) Enfuvirtide
    b) Raltegravir
    c) Atazanavir
    d) Nevirapine

    3) What is the mechanism of action of enfuvirtide?      

    5.3. Antiretroviral treatment in adolescents and adults

            Learning Activity 5.3

     A 33-year-old newly diagnosed HIV patient was advised to start antiretroviral 
    treatment at ART sevice where you are appointed as an associate nurse. During 
    pre-treatment counselling, you focus on the number of combined medications 
    to use.
    1) What is the number of medications combinations is required to use in 
    HIV/AIDS management?
    2) What should the nurse include in the teaching as the ideal time to initiate 

    ARVs after HIV diagnosis?

    CONTENT SUMMARY

    People with HIV should take medicine to treat HIV as soon as possible. HIV 
    medicine reduces the amount of HIV in the body (viral load) to a very low level, 
    which keeps the immune system working and prevents illness. It can even make 
    the viral load so low that a test can’t detect it. This is called an undetectable viral 
    load. Getting and keeping an undetectable viral load* is the best thing people with 
    HIV can do to stay healthy.

    Initiating Antiretroviral Therapy: ART regimens typically contain at least three 
    drugs. Regimens that contain only two drugs are not generally recommended, 
    and monotherapy should always be avoided, except possibly during pregnancy. 
    Additionally, all ART regimens contain drugs from at least two different classes. 
    By using drugs from different classes, we can attack HIV in two different ways 
    (e.g., inhibition of reverse transcriptase and inhibition of protease) and can thereby 
    enhance antiviral effects. 

    Criteria for Eligibility to ART in Adults and adolescent: Antiretroviral therapy 
    (ART) is recommended for all persons with HIV to reduce morbidity and mortality 
    and to prevent the transmission of HIV to others. The Panel on Antiretroviral 
    Guidelines for Adults and Adolescents recommends initiating ART immediately (or 
    as soon as possible) after HIV diagnosis in order to increase the uptake of ART and 
    linkage to care, decrease the time to viral suppression for individual patients, and 
    improve the rate of virologic suppression among persons with HIV.

    In addition to enhancing antiviral effects, the use of multiple drugs reduces the risk 
    for resistance. Resistance reduction occurs because the probability that HIV will 
    undergo a mutation that confers simultaneous resistance to three or four drugs is 
    much smaller than the probability of undergoing a mutation that confers resistance 
    to just one drug. 

    Below are key considerations in clinical management of adolescents and adults 
    living with HIV:
    • Clinical and laboratory evaluations are the cornerstones of care and treatment 
       of HIV positive adolescents and adults. 
    • Renal creatinine clearance is mandatory for adolescents and adults since 
       they initiate with TDF based regimen. 
    • Viral load monitoring should be conducted at 6 months and at 12 months 
       after ART initiation, and annually thereafter. DTG-based regimen remains the 
       preferred first-line option. 
    • TDF/3TC/EFV600mg is the alternative first-line regimen for adults and 
       adolescents who cannot take TLD 
    • DTG-based regimen is the preferred 2nd line option for patients failing                                                                                                              a non DTG 1st line regimen. 
    • For patients failing DTG-based regimen, specialist consultation and 
       genotyping should be considered. 
    • PLHIV with advanced HIV disease should be offered a package of interventions 
    including screening, treatment and/or prophylaxis for major OIs, rapid ART 
    initiation and intensified adherence support.
    • TB screening should be done at enrolment and at each clinical visit 
    • Cotrimoxazole should be given to patients with advanced diseases.
    Clinical evaluation
    • Present and past medical history
    • Comprehensive physical examination 
    • WHO staging 
    • Drug history 
    • Sexual history 
    • Nutrition status assessment 
    • OI screening (e.g. TB) 
    • NCDs screening mainly (Refer annex V).
    • Cardiovascular disease: blood pressure, cardiomyopathies 
    • Malignancies: cervical cancer, breast cancer 
    • Metabolic diseases: diabetes, hyperlipidemia, hypocholesteremia 
    • Mental health illness
    Laboratory evaluation Baseline: 
    • CD4 cell count, 
    • Cryptococcus antigen (if CD4 count < 200 cells/mm3) 
    • Renal function (creatinine and calculation of creatinine clearance)
    • Hepatitis B surface antigen (Ag HBs)
    • Hepatitis C antibody (HCV Ab) 
    • LFTs
    • GeneXpert if TB screening is positive 
    • Additional investigations as clinically indicate

    ART Regimen in adolescents and Adult
                    
     First line ART regimen options
    There are two options recommended in first line regimen
    DTG-based
    NNRTI-based 
                 
     Dosage and administration of first-line regimen

    Dosage and administration of first-line regimen

                  

    Prescription of ART first line regimen
    1) TDF/3TC/DTG (300/300/50 mg) (OD)
    2) ABC/3TC (600/300 mg) + DTG (50 mg) (OD)
    3) TDF/3TC/EFV (300/300/400mg) 
    4) ABC/3TC (600/300mg) + EFV 600mg

    Notes:
    • Encourage taking EFV based regimens in the evening before 8:00 pm to 
    minimize dizziness 
    • Patients with EFV associated side effects should be advised to take it either 
    1-2 hours before or after meals to minimize side effects
    Management of treatment failure among adolescents and adults
    The monitoring of ART response and identification of treatment failure are the same 
    as for children 
    • For early management of treatment failure as well as second line treatment 
    failure refer to the treatment failure algorithm in children section.

    Recommended regimens for second-line ART

    Recommended regimens for 2nd line ART in adults after failure of specific first line 

    regimens.

                  

    If TDF is contraindicated, replace with ABC
    In case of hepatitis B co-infection, maintain TDF: TDF+AZT/3TC+ATC/r or LPV/r
    Recommended regimens for third-line
    • DTG 50mg BID + Darunavir/ritonavir + Optimized NRTI or Etravirine can be 
      used based on genotyping results
    • The 3rd line regimen must only be given upon expert consultation and usually 
       with the assistance of genotyping results.

    • Before prescribing third-line therapy, the patient must undergo extensive 

    additional adherence counselling and should have a treatment partner 
    involved in adherence assistance. Adherence counselling is critical to the 
    success of this regimen. 
    • NRTI backbone may be necessary based on genotyping test or in case of 
    Hepatitis B co-infection
    Monitoring of adolescents and adults on ART
    Clinical evaluation and laboratory tests play a key role in assessing adolescents 
    and adults before ART initiation, and then monitoring their treatment response as 
    well as possible toxicity of antiretrovirals. Note that once started, ART is a treatment 
    for life but should be changed in the following cases:
    • Drug toxicity 
    • Drug-drug interactions
    • Co-infection
    • Treatment failure confirmed by viral load
    Notes: 
    • The follow up of CD4 count should be done whenever clinically indicated. 
    • For STIs management, refer to national guidelines for STIs and hepatitis.
    1) TREATMENT FAILURE
    Treatment failure is arguably the most compelling reason for changing the regimen. 
    Failure is indicated if: 
    • Plasma HIV RNA remains above 200 copies/mL after 24 weeks 
    • Plasma HIV RNA remains above 50 copies/mL after 48 weeks 
    • Plasma HIV RNA rebounds after falling to an undetectable level 
    • CD4 T-cell counts continue to drop despite antiretroviral treatment 
    • Clinical disease progresses despite antiretroviral treatment
    2) DRUG TOXICITY
    If a patient experiences toxicity typical of a particular drug in the regimen, that drug 
    should be withdrawn and replaced with a drug that is (1) from the same class and 
    (2) of equal efficacy. For example, if a patient taking zidovudine were to develop 
    anemia and neutropenia, zidovudine should be discontinued and replaced with 
    another NRTI (e.g., stavudine). Note that when toxicity is the reason for altering the 
    regimen, changing just one drug is proper, whereas when resistance or suboptimal 
    treatment is the reason, at least two of the drugs should be changed.
    3) Promoting Patient Adherence 
    To achieve treatment goals and delay emergence of resistance, strict adherence 
    to the prescribed regimen is critical. Unfortunately, several factors: duration of  

    treatment, complex medication regimens, multiple adverse drug effects, drug-drug 

    interactions, and drug-food interactions make adherence to ART challenging for 
    patients. 
    The factors that predict poor adherence (e.g., poor clinician-patient relationship, 
    active use of alcohol or street drugs, depression and other mental illnesses), as well 
    as factors that predict good adherence (e.g., availability of emotional and practical 
    support, ability to fit dosing into the daily routine, appreciation that poor adherence 

    will cause treatment failure).

    Self-assessment 5.3

    1) What is the preferred 1st line regimen for adolescents and adults?
    2) What is the alternative first-line regimen for adults and adolescents who 
    cannot take TLD?
    3) What can be done if a patient experiences toxicity typical of a particular 

    drug in the regimen?

    5.4. Antiretroviral treatment in Children

            Learning Activity 5.4

    You are an associate nurse and you receive a mother bringing her 2-year-old baby 
    who was born with HIV. She wants the baby to be started on antiretroviral drugs, 
    and there is a student in the clinical placement who doubts on the antiretroviral 
    drugs to administer to the baby.
    1) Which regimen should the baby start with?
    2) The symptoms of HIV infection generally start later compared to the time 
    it takes for adults to develop symptoms. TRUE or FALSE
    3) The preferred 1st line ART option for children of 30kgs and above is 

    ABC/3TC+LPV/r. TRUE or FALSE

    CONTENT SUMMARY 

    In young children, the course of HIV infection is accelerated. Whereas adults 
    generally remain symptom free for a decade or more, many children develop 
    symptoms by their first birthday. Death often ensues by age 5 even with ART. Why 
    do young children succumb so quickly? 
    Primarily because their immune systems are immature, and hence less able to fend 
    off the virus. Because immune function is limited, levels of HIV RNA climb higher in 
    toddlers than in adults, and then decline at a much slower rate. 

    In very young patients, diagnosis and monitoring of HIV infection employs different 

    methods than those used in adolescents and adults. In particular, for infants under 
    18 months of age, diagnosis should be based on viral load assays, not on antibody 
    tests. For children under 5 years of age, monitoring of immune status should be 
    based on the percentage of CD4 cells, not on absolute CD4 counts. 

    Like older patients, young patients should be treated with a combination of 
    antiretroviral drugs, with the goals of (1) reducing plasma viral HIV to an undetectable 
    level and (2) stabilizing or improving immune status. 
    Clinical and laboratory evaluations are the cornerstones of care and treatment of 
    HIV positive children of ≤10 years old. DTG is used for children with weight ≥ 20kgs. 
    The preferred 1st line option for children less than 20kg is ABC/3TC+LPV/r. The 
    preferred 1st line option for children of ≥ 20kg ABC/3TC+DTG. The preferred 1st 
    line option for children of 30kgs and above without renal failure is TDF/3TC/DTG. 
    For children on LPV/r, the preferred formulation is pellet (40mg/10mg, oral pellet) 
    due to its storage and palatability reasons. 

    For children with more than 15kg, ATV/r can be used to replace LPV/r. For children 
    on ABC/3TC, 120/60mg is the preferred strength. ABC is contra-indicated for 
    children less than 3 months. If HIV is confirmed before 3 months, the recommended 
    1st line ART regimen is AZT+3TC+LPV/r. Switch to AZT-based regimen in case 
    of intolerance to ABC. LPV/r is contra-indicated for new-born less than 15 days. 
    If switching from AZT-based regimen, consider VL (viral load) suppression. If 
    treatment failure, consider second line regimen. 

    TB screening is mandatory for all children at enrolment and at each clinical visit. 
    TPT (Tuberculosis preventive therapy) should be integrated in HIV management. 
    IPT (Isoniazid preventive therapy: Isoniazid 10mg/Kg) is used for 6 Months to all 
    HIV children of ≤5 years old without active TB but with a history of TB contact.                                                                                            Anti TB should be initiated immediately and ART within 2 to 8 weeks. The treatment 
    failure (TF) is defined by the virological failure (plasma viral load >1000 copies/ml) 
    based on two consecutive viral load measurements after 3 months with intensive 
    adherence support. The management of 1st line TF is done after identifying its 
    probable cause and then act as shown by figure 7. The recognition of 2nd line TF 
    is similar to the 1st line TF and the shift to 3rd line is guided by genotyping and 
    expert consultation. The monitoring of children on ART encompasses clinical and 
    laboratory monitoring in order to assess treatment response and potential drug 

    toxicity.

    ART Regimen for children younger than 10 years of age 

    Table 5.4.1 First line options for ART regimen in children:

                  

                   Table 5.1.2: Initiation of ART in children

                     

                       Table 5.1.3:Children who are already on ART

                        Second-line ART in Children

                         

                             Self-assessment 5.4

    1) When the HIV positive children should be screened for TB infection?
    2) Which ART regimen should a 9-year-old child be started with?
    3) Which of the following options is true with regard to treatment of patients 
    with HIV and TB coinfection?
    a) ART should be initiated immediately and anti-TB within 2 to 8 weeks
    b) Anti-TB should be initiated immediately and ART within 2 to 8 weeks
    c) ART should be initiated immediately and anti-TB within 6 weeks

    d) Anti-TB should be initiated immediately and ART within 12 weeks

            5.5. ARV Treatment in Pregnant Women

                    Learning Activity 5.5

     A woman of 25 years of age was diagnosed for HIV positive during antenatal 
    care at the health center. According to WHO/CDC, it is recommended that all 
    HIV positive women should take ARTs.
    Read the pharmacology book and respond the following questions
    1) When a pregnant woman newly diagnosed HIV positive should start the 
         treatment?

    2) What is the ART regimen for an HIV positive pregnant woman?

         CONTENT SUMMARY

    In general, the management of HIV infection in pregnant women should follow the 
    same guidelines for managing HIV infection in nonpregnant adults. Accordingly, 
    current guidelines recommend ART for all pregnant HIV-infected women. ART is 
    needed not only for maternal health, but also to reduce the risk for perinatal HIV 
    transmission. 
    Drug selection is challenging in that information on pharmacokinetics and safety 
    during pregnancy is limited.

    When treating HIV infection in pregnant women, the goal is to balance the benefits 
    of treatment, reducing viral load, thereby promoting the health of the mother and 
    decreasing the risk for vertical HIV transmission (i.e., transmission to the foetus) 
    against the risks of drug-induced fetal harm (e.g., teratogenesis, lactic acidosis, 
    death). As a rule, the benefits of treatment outweigh the risks.
     

    The primary determinants of therapy are the clinical, virologic, and immunologic 
    status of the mother; pregnancy is a secondary consideration. Nonetheless, 
    pregnancy should not be ignored. 
    Routine HIV testing for all pregnant women attending ANC for first time during 
    current pregnancy together with their male partners (unless already known HIV 
    positive status). It is preferable that these services are offered during the first 
    trimester of pregnancy but they should be ongoing until delivery.

    Every HIV-positive woman will be provided with specific counselling on family 
    planning and get an access to a family planning method of her choice.
    HIV positive pregnant and breastfeeding women should be offered index testing, 

    partner notification and family testing services.

    Every pregnant woman whose HIV status is unknown during ANC should be tested 
    for HIV at the time of delivery.
    Every pregnant woman who tested HIV negative during ANC should be retested at 
    the time of delivery. Thereafter, retesting during postnatal period will be based on 
    HIV risk assessment outcomes.
    Women tested HIV positive during ANC or at the time of labor, should start anti                                                                                  retroviral therapy immediately. In case of delay, ART initiation should not go beyond 
    7days.
    Every pregnant or breastfeeding woman newly tested positive for HIV should start 
    with ART regimen Tenofovir + Lamivudine + Dolutegravir.

    Every pregnant or breastfeeding woman newly tested HIV-positive and on ART, 
    should receive the first viral load test three months after ART initiation and then 
    after every six months until the end of PMTCT follow up.

    All infants born to a known HIV positive mother should receive ART prophylaxis 
    with zidovudine and Nevirapine immediately. If not done immediately, it should be 
    in first 72 hours post-partum or as soon as possible during the first six weeks of life.

    All HIV exposed or infected children should have regular growth monitoring to enable 
    early detection of growth retardation and undertake appropriate management.

    Pre exposure prophylaxis is offered in the context of PMTCT to HIV negative 
    pregnant and/or breastfeeding women in the following circumstances:
    • Women in discordant relationship whose partners are either not on ART or 
       are on ART but not virally suppressed
    • Women practicing sex work

    The regimen recommended for PrEP is a once daily TRUVADA or Tenofovir and 
    Lamivudine for the entire pregnancy and breastfeeding period.
    The use of ART for HIV positive pregnant women will depend on whether she was 
    already on ART or not. The following situations are possible during pregnancy:

    c) If the HIV-Positive pregnant woman is already initiated on ART, 
    consider the following aspects:

    • Adherence to the current ART regimen
    • Viral load suppression as per the most recent viral load test results
    • Consider viral load result as ‘recent’ if it was performed less than six months 
    prior to the first ANC visit.
    • It is mandatory to repeat the viral load test for all pregnant women not tested 
    at the first ANC, before the third term of pregnancy (preferably at 6 months of 
    pregnancy)
    • If the woman is virally suppressed, she will be kept on her current ART 

    regimen

    • If the woman is not virally suppressed (>200 copies/ml), she will be switched 
        to a Dolutegravir based regimen plus two NRTIs.
    • The switch to Dolutegravir- based regimen will be conducted concurrently with 
    the adherence counselling for patients with documented poor adherence.
    d) If a woman is newly diagnosed HIV positive during pregnancy:
    • The woman is immediately enrolled in care and initiated on ART
    • The preferred ART regimen is Tenofovir + Lamivudine + Dolutegravir 
    (TDF+3TC+DTG)
    • Any woman with impaired renal function or any contraindication to TDF will 
       receive ABC + 3TC+DTG
    NOTE: Doses are the same as in non-pregnant adults’ HIV treatment. 

    Monitoring of renal function is important.

    NOTE: Doses are the same as in non-pregnant adults’ HIV treatment. 

    Monitoring of renal function is important.

            Self-assessment 5.5

    1) Any pregnant woman whose HIV status is unknown during ANC doesn’t 
    need to be tested for HIV at the time of delivery. TRUE or FALSE
    2) Given their fragile status, the pregnant women with HIV positive status 
    should benefit from lower doses of ARTs compared to the non-pregnant 
    adults. TRUE or FALSE
    3) Which of the following treatment regimens is used as ART initiation among 
    pregnant women in Rwanda?
    a) Abacavir + Lamivudine + Dolutegravir.
    b) Tenofovir + Lamivudine + Dolutegravir.
    c) Efavirenz + Lamivudine + Dolutegravir.

    d) Nevirapine + Lamivudine + Dolutegravir.

    5.6. Prophylaxis in new-borns with Perinatal HIV Exposure 

    or HIV Infection

         Learning Activity 5.6

    Visit library and read pharmacology books /use internet and respond to following 
    question:
    When should the newborn exposed perinatally to HIV start taking newborn ARV 

    regimens?

    CONTENT SUMMARY

    A child is considered as ‘exposed to HIV’, if he/she is born to an HIV positive mother. 
    The initiation of infant prophylaxis depends on the time the mother was diagnosed 
    HIV positive. Children born to HIV negative mothers in discordant couple will not 
    receive any prophylaxis as long as their mothers remain HIV negative.

    Infant born to a known HIV-positive mother: 
    All children born to a known HIV positive mother (before or during labour) will receive 
    zidovudine and Nevirapine (AZT+ NVP) as soon as possible within 72 hours after 
    birth up to six weeks of life. The baby will also start cotrimoxazole prophylaxis at 
    the age of 6 weeks until the final confirmation of HIV negative status at the age of 
    24 months.

    Infant born to a mother diagnosed for HIV after delivery
    If the mother is identified to be HIV-positive at the time of breastfeeding, she should 
    be put on ART. The child will start a combined AZT and NVP as soon as possible 
    for six weeks. At the end of 6 weeks ART prophylaxis; the child will also start 
    cotrimoxazole prophylaxis until the final confirmation of HIV negative status at 24 
    months of life.

    All Breastfed infants who are at high risk of acquiring HIV, including those first 
    identified as exposed to HIV during the postpartum period, should continue infant 
    prophylaxis for an additional 6 weeks (total of 12 weeks of infant prophylaxis) using 
    NVP and AZT.
    High-risk infants are defined as:
    Infant born to women with established HIV infection who have received less than 
    four weeks of ART at the time of delivery; or born to women with established HIV 
    infection with viral load >1000 copies/mL in the four weeks before delivery, if viral 
    load measurement available; OR identified for the first time during the postpartum 

    period, with or without a negative HIV test prenatally.

          Self-assessment 5.6

    1) During clinical practice in maternity ward, you receive a woman with 
    baby at the second day of home delivery. You take blood sample for HIV 
    testing. After 3 hours you receive a laboratory technician’ s call informing 
    you that the mother is HIV positive. Explain the management of mother 

    and her baby to prevent mother to child transmission.

    5.7. HIV Prevention among Discordant Couples

             Learning Activity 5.7  

    1) A couple consults the healthcare facility where you are carrying out the 
    clinical placement, and they report they are discordant. The senior nurse 
    tasks you to explain to the couple the overall interventions package for 
    that discordant couple. What is that package?

    2) What are the objectives of these interventions?

    CONTENT SUMMARY

    Evidence-based interventions package for HIV sero-discordant couples can 
    be provided through facility based and/or community interventions. Although 
    these interventions are delivered in a package, providers must ensure that they 
    contextualize the specific, particular needs of the couple since different couples 
    may have different needs.
    The objectives of these interventions are:
    • To protect the negative partners from acquiring HIV infection
    • To provide care and treatment to HIV positive partners, allowing them access 
       to early treatment that improves clinical outcomes
    • To protect future children from HIV infections
    • To offer the appropriate HIV prevention package for children and other family 
       members of the HIV positive individuals
    • To support the prevention of unwanted pregnancies in discordant couples
    The overall intervention package for discordant couples consists of the 
     following:
    • Risk reduction counselling and condom provision
    • Initiation of pre-exposure prophylaxis for those whose HIV positive partner is 
    not yet on ARV or are not virally suppressed
    • Family planning counselling and service provision
    • Repeat HIV testing for the uninfected partner every 12 months
    • Care and treatment for the HIV-positive partner
    • STI screening and treatment
    In case of a pregnant HIV-negative partner:
    • The HIV testing shall be done every three months
    • A pre-exposure prophylaxis should be offered in case of non-viral suppression 
       for the positive partner.
    • At labor a single dose of TDF+3TC+DTG will be offered for all women who 

       are not taking the pre-exposure prophylaxis.

    The health care provider should encourage the discordant couple to follow up in 
    the same health facility and synchronize with pharmacy refills and appointment 
    schedule. Ongoing psychosocial support and counselling shall be offered to the 

    discordant couple.

            Self-assessment 5.7

    1) The health care provider should encourage the discordant couple to 
    follow up in the same health facility and synchronize with pharmacy refills 
    and appointment schedule. TRUE or FALSE
    2) Pregnant HIV-negative partner in discordant couples should receive a 

    single dose of TDF+3TC+DTG at labor if they are not taking the pre exposure prophylaxis.                                                                           TRUE or FALSE

    5.8. ART for Post-Exposure Prophylaxis (PEP)

            Learning Activity 5.8

    3) While he was giving IM injection to a known HIV positive patient, an 

    associate nurse injured himself with a needle after injecting the drug. The 

    senior nurse sends him to the ART service for post exposure prophylaxis. 

    Which drugs may preferably be administered to this patient?

    4) An HIV serology test should be performed for the exposed caregiver as 

    soon as possible (ideally within 72 hours). TRUE or FALSE

    CONTENT SUMMARY

    Every person who has experienced exposure to blood/body fluids, victim of sexual 
    assault, or accidental sexual exposure 
    (i.e., condomless, sex with a known HIV positive person; condom breakage)                                                                                                  must have access to an early evaluation of the risk of HIV infection and antiretroviral                                                                     prophylaxis if indicated. It is therefore necessary to have PEP services.
    Evidence shows that initiating ART prophylaxis 
    soon after exposure to HIV reduces the risk of HIV infection by about 80%. 
    Postexposure prophylaxis (PEP) is short-term ART to reduce the likelihood of 
    acquiring HIV infection after potential exposure.

    Post-exposure prophylaxis should be provided immediately or preferably within 
    72 hours of exposure. An HIV serology test should be performed on the exposed 
    individual as soon as possible (ideally within 48 hours).
    Case of Accidental Exposure to Blood (AEB) or Other Biological Fluids
    In case of accidental exposure to blood, always clean the exposed area immediately. 

    In case of exposure through needle stick or skin injury, clean the wound immediately

     with clean water and soap. In case of splash on the mucous membranes (particularly 
    the conjunctiva), rinse at least for 5 minutes with copious amounts of water or 
    preferably physiological saline or any available saline and do not apply disinfectant 
    on the mucous membranes. One of the health care providers from the health facility 

    must evaluate the actual risk for a given patient. 

    This evaluation includes:

    • The severity of the exposure, which is directly linked to the depth of the wound 
    and the type of needle that was responsible for the injury (venipuncture 
    needle, needle for injection, non sharp instrument). 
    • For external contact of secretions with the skin or mucosa (splash), the risk is 
    higher with blood than with any other body secretions (amniotic fluid, serous 
    fluid). The person assumed to be the source should be assessed on his 
    or her HIV status, clinical and immunological status and history of ART. If 
    the HIV status is not known, it is important to establish it with his/her free 
    consent. If the HIV status of the source person cannot be obtained within 
    4 hours, prophylaxis for the exposed person should be started immediately 
    after a negative HIV test. If eventually the person assumed to be the source is 
    proven to be HIV-negative, then ARV prophylactic treatment may be stopped

    Case of Sexual Assault or Rape
    In case of rape, the provider must first follow the HIV counselling and testing.PEP 
    should be offered to the sexual assault victim once the clinician has assessed all 
    the factors involved in the likelihood of HIV transmission (suspicion of HIV positivity 
    in the assailant, probability of HIV transmission). PEP might help the victim gain 
    a sense of control and decrease their anxiety about acquiring HIV. Consider HIV 
    post-exposure prophylaxis for survivors of sexual assault presenting within 72 
    hours of the assault. In addition to HIV post-exposure prophylaxis, women should 
    be offered emergency contraception to prevent unintended pregnancy immediately 
    or preferably within 72 hours after sexual exposure.

    ART Prophylaxis in PEP
    The current recommended duration of post-exposure prophylaxis for HIV infection 
    is 28 days. Treatment should start as early as possible, within the first 4 hours 
    following the exposure, without waiting for results of HIV serology of the source 
    person. A limit of 72 hours is reasonable in seeking maximum efficacy, however the 
    sooner the better.
    The recommended post-exposure prophylaxis drugs are based on the current 
    second and first line regimen:

    1.TDF+ 3TC / FTC +ATV/r
    2. AZT + 3TC/ FTC + ATV/r(If noTDFor a contraindication)
    NB: The recommended ART Prophylaxis is the same in rape/sexual assault and 

    exposure to biological fluids.

    Self-assessment 5.8

    1) When HIV post-exposure prophylaxis for survivors of sexual assault is 
    taken into consideration?
    2) What are the actual risks the health care providers from the health facility 

    must evaluate in case of exposure through needle stick or skin injury?

    5.9. End unit assessment

            End of unit assessment

     I. Complete the empty spaces with the appropriate terms.

    a) Antiretroviral drugs
    b) Antiviral
    c) Retrovirus
    1) ………………………An agent that kills a virus or that suppresses its ability 
    to replicate and, hence, inhibits its capability to multiply and reproduce.
    2) ………………………is a group of viruses that belong to the family 
    Retroviridae and that characteristically carry their genetic blueprint in the 
    form of ribonucleic acid (RNA). 
    3) ………………………….. are the drugs that are used to fight retrovirus 
    infections which mainly include HIV. Different classes of antiretroviral 
    drugs act on different stages of the HIV life cycle.
    II. Respond by true or false 
    1) Abacavir (Ziagen), lamivudine (Epivir) and stavudine (Zerit XR), tenofovir 
    (Viread). 
    2) Efavirenz (Sustiva), nevirapine (Viramune) are drugs in the class of 
    protease inhibitors 
    3) Abacavir (Ziagen) lamivudine (Epivir), stavudine (Zerit XR), tenofovir 
    (Viread), and zidovudine (Retrovir) drugs in the class of Nonnucleoside 
    reverse transcriptase inhibitors . 
    4) Atazanavir, indinavir and lopinavirare drugs in protease inhibitors.
    5) Like older patients, HIV positive young patients should be treated with a 
    combination of antiretroviral drugs. 
    6) Antiretroviral therapy (ART) is recommended for all persons with HIV to 

    cure the patient by killing the virus.

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    Rosenthal, L. D., Rosenjack Burchum, J., & Associate Professor, C. (2019). Lehne’s 
    Pharmacotherapeutics for Advanced Practice Nurses and Physician Assistants 2 
    EDITION.
    Snyder, J. S., Collins, S. R., Savoca, D., & Lilley, L. L. S. edition. (2014). Study 
    guide for Pharmacology and the nursing process, seventh edition, Linda Lane 
    Lilley, Shelly Rainforth Collins, Julie S. Snyder. Elsevier/Mosby.
    Willihnganz, M. J., Gurevitz, S. L., Clayton, B. D., & Pharm, B. S. (2020). Clayton’s 
    Basic Pharmacology for Nurses 18 EDITION.
    Demler, T. L., & Rhoads, J. (2018). Pharmacotherapeutics for advanced nursing 
    practice.

    Chen, S. C. A., & Sorrell, T. C. (2007). Antifungal agents. Medical Journal of 
    Australia, 187(7), 404–409. https://doi.org/10.5694/j.1326-5377.2007.tb01313.x
    David, E. G., Ehrin, J. A., & April, W. A. (2017). Principles of pharmacology: the 
    pathophysiologic basis of drug therapy (4th ed.). Philadelphia : Wolters Kluwer 
    Health. Lippincott Williams & Wilkins.

    Karch, A. M. (2013). Focus on Nursing Pharmacology (6th ed., Vol. 1). Wolters 

    Kluwer/ Lippincott Williams and Wilkins. www.ketabpezeshki.com
    Nett, J. E., & Andes, D. R. (2015). Antifungal Agents: Spectrum of Activity, 
    Pharmacology, and Clinical Indications. Infectious Disease Clinics of North America, 
    1–33. https://doi.org/10.1016/j.idc.2015.10.012
     Demler, T. L., & Rhoads, J. (2018). Pharmacotherapeutics for advanced nursing 
    practice.
    Lilley, L. L., & Collins, S. R. (2020). Pharmacology and the Nursing Process NINTH 
    EDITION.
    Chen, S. C. A., & Sorrell, T. C. (2007). Antifungal agents. Medical Journal of 
    Australia, 187(7), 404–409. https://doi.org/10.5694/j.1326-5377.2007.tb01313.x
    David, E. G., Ehrin, J. A., & April, W. A. (2017). Principles of pharmacology: the 
    pathophysiologic basis of drug therapy (4th ed.). Philadelphia : Wolters Kluwer 
    Health. Lippincott Williams & Wilkins.

    Karch, A. M. (2013). Focus on Nursing Pharmacology (6th ed., Vol. 1). Wolters 
    Kluwer/ Lippincott Williams and Wilkins. www.ketabpezeshki.com
    Nett, J. E., & Andes, D. R. (2015). Antifungal Agents: Spectrum of Activity, 
    Pharmacology, and Clinical Indications. Infectious Disease Clinics of North America, 
    1–33. https://doi.org/10.1016/j.idc.2015.10.012

    Chen, S. C. A., & Sorrell, T. C. (2007). Antifungal agents. Medical Journal of 
    Australia, 187(7), 404–409. https://doi.org/10.5694/j.1326-5377.2007.tb01313.x
    David, E. G., Ehrin, J. A., & April, W. A. (2017). Principles of pharmacology: the 
    pathophysiologic basis of drug therapy (4th ed.). Philadelphia : Wolters Kluwer 
    Health. Lippincott Williams & Wilkins.

    Karch, A. M. (2013). Focus on Nursing Pharmacology (6th ed., Vol. 1). Wolters 
    Kluwer/ Lippincott Williams and Wilkins. www.ketabpezeshki.com
    Nett, J. E., & Andes, D. R. (2015). Antifungal Agents: Spectrum of Activity, 
    Pharmacology, and Clinical Indications. Infectious Disease Clinics of North America, 

    1–33. https://doi.org/10.1016/j.idc.2015.10.012

    Electronic links:

    https://www.cdc.gov/malaria/travelers/drugs.html

    https://www.cdc.gov/malaria/travelers/drugs.html

    https://www.ncbi.nlm.nih.gov/books/NBK8263/

    https://patient.info/medicine/metronidazole-for-infection-flagyl

    https://patient.info/medicine/quinine-for-malaria

    https://medlineplus.gov/druginfo/meds/a609024.html

    https://www.ncbi.nlm.nih.gov/books/NBK8263/

    • HIV Drugs and the HIV Lifecycle | The Well Project

    https://www.medicinenet.com/antiviral/definition.htm

    https://www.britannica.com/science/retrovirus

    https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/initiation ;                                                                           antiretroviral-therapy?view=full

    https://clinicalinfo.hiv.gov/en/guidelines/pediatric-arv/when-initiate-therapy ;                                                                                     antiretroviral-naive-children

    https://clinicalinfo.hiv.gov/en/guidelines/perinatal/antiretroviral-management ;                                                                                    newborns-perinatal-hiv-exposure-or-hiv-infection

    https://courses.lumenlearning.com/microbiology/chapter/introduction-to ;                                                                                                     antimicrobial-drugs/

    https://courses.lumenlearning.com/microbiology/chapter/drug-resistance/

    https://www.rxlist.com/mefoxin-drug.htm#description, https://www.rxlist.com/

    mefoxin-drug.htm#indicationshttps://www.webmd.com/drugs/2/drug-18352/

    cefoxitin-intravenous/details/list-contraindications

    https://www.webmd.com/drugs/2/drug-3779-8011/cefuroxime-axetil-oral/

    cefuroxime-oral/details/list-contraindications

    https://www.drugs.com/dosage/cefadroxil.html

    https://www.rxlist.com/duricef-side-effects-drug-center.htm

    https://www.sciencedirect.com/topics/medicine-and-dentistry/ ;                                                                                                                          cephalosporin derivative

    https://www.rxlist.com/cefazolin-drug.htm#description

    https://medlineplus.gov/druginfo/meds/a682731.html

    https://www.drugs.com/dosage/cefazolin.html

    https://www.medicines.org.uk/emc/product/7072/smpc#gref

    https://www.rxlist.com/cipro-drug.htm#description

    https://reference.medscape.com/drug/cipro-xr-ciprofloxacin-342530

    https://www.rxlist.com/levaquin-drug.htm

    https://reference.medscape.com/drug/levaquin-levofloxacin-systemic ;                                                                                                        levofloxacin-342532

    https://www.ncbi.nlm.nih.gov/books/NBK8263/

    UNIT 4 : ANTIFUNGAL DRUGS