Nursing Pharmacology:  Antiviral Drugs

• Antiviral Drugs

  • Anti-viral drugs with activity against HIV (Human Immunodeficiency Virus)

    • Viral Transmission²

      • Blood Transfusion

        • The risk of acquiring HIV following transfusion of 1 unit of infected blood has been estimated at 90%.⁹ 

          • Concentrated blood products derived from multiple units of pooled blood also have been responsible for HIV transmission.⁹  

            • These blood products accounted for an early high prevalence of HIV infection among those individuals with hemophilia who received coagulation factor replacement concentrated from many units of blood.

          • In March 1985 screening of all donated blood was initiated and subsequent to routine heat/solvent detergent treatment of clotting factor concentrates resulted in a dramatic decline in new transfusion-associated HIV infections.⁹  

          • Appropriate HIV inactivation in clotting factor concentrates have been detailed.

          • The risk of HIV infection occurring as a result of receiving one unit of blood which tested negative for HIV-1 antibodies is about one in 500,000 or less.⁹ 

            • In the U.S. the estimated HIV infection risk for transfused screen blood is about 1 in 1.5 million units.²

      • Mother to Fetus Transmision:²

        • An infected mother may transmit HIV virus to the fetus during pregnancy, delivery, or through breast-feeding.² 

          • In some developing countries this transmission mode is especially important as the ratio of infected women to infected men is about 1:1.²

            • Fetal transmission may occur early (first or second pregnancy trimester), although is most likely during the perinatal period.

            • Prophylactic antiviral drug therapy to the mother during pregnancy, labor, delivery and to the fetus following birth is an effective approach to this transmission mode.

              • Absent antiviral treatment, however, mother to infant/fetus HIV transmission likelihood is about 20% in industrialized countries and about 30% in developing nations.

                • The most likely single factor accounting for relatively higher HIV-1 transmission rates is higher maternal levels of plasma viremia.

                  • A number of other factors have been implicated.² 

          • In the contemporary circumstance in which HIV-positive pregnant women receive combination antiviral drugs, along with cesarean section delivery, the likelihood of mother-to-child transmission is likely less than 1% and is an unusual clinical occurrence in the US and other developed countries.²

        • Short duration treatment with zidovudine (AZT) by itself or in combination with lamivudine (3TC) even late in the pregnancy and then to the infant for a week or less dramatically reduces infant transmission, compared to placebo.

          • Similarly, short-duration antiretroviral agent such as single-dose nevirapine (Viramune) may also be effective and especially important in low-to mid-income nations due to low drug cost and given that perinatal care may not be available, with pregnant women perhaps seen by the health care provider for the first time around delivery.

            • The availability of "effective combination antiretroviral therapy" or cART in developing nations has had a important, beneficial effect, not only for the woman but also blocking HIV maternal-fetal transmission and protecting against later transmission by breast-feeding.²

        • "HIV Among Pregnant Women, Infants, and Children"¹⁰

          "Fast Facts" "All pregnant women should be screened for HIV as early as possible during each pregnancy. "Women with HIV who take antiretroviral medication during pregnancy as recommended can reduce the risk of transmitting HIV to their babies to less than 1%. "HIV disproportionately affects black/African American children in the United States

          "HIV transmission from mother to child during pregnancy, labor and delivery, or breastfeeding is known as perinatal transmission and is the most common route of HIV infection in children. "When HIV is diagnosed before or during pregnancy, perinatal transmission can be reduced to less than 1% if appropriate medical treatment is given, the virus becomes undetectable, and breastfeeding is avoided. "Since the mid-1990s, HIV testing and preventive interventions have resulted in more than a 90% decline in the number of children perinatally infected with HIV in the United States."

          "The Numbers" "In 2010, an estimated 217 children younger than the age of 13 years were diagnosed with HIV in the 46 states with long-term, confidential name-based HIV infection reporting since at least 2007; 162 (75%)1 of those children were perinatally infected. "At the end of 2009, an estimated 10,834 persons who were diagnosed with HIV when they were younger than 13 years were living in the 46 states with long-term, confidential name-based HIV reporting. Of the total, 9,522 (88%) of these persons acquired HIV perinatally. Of these diagnoses of perinatal HIV infection, 63% were in blacks/African Americans, 22% were in Hispanics/Latinos,2 and 13% were in whites. These numbers include persons of all ages who were infected with HIV as children. "The number of women with HIV giving birth in the United States increased approximately 30%, from 6,000–7,000 in 2000 to 8,700 in 2006. "Despite the increase in the number of women with HIV giving birth, the estimated number of perinatal HIV infections per year in all 50 states and 5 US dependent areas continues to decline. "Among perinatally infected children born during 2007 through 2009, black/African American children had the highest HIV rate per 100,000 live births each year, although the rate decreased from 15.2 in 2007 to 9.9 in 2009. The rates for Hispanic/Latino and white children remained stable during this time. "From the beginning of the epidemic through 2009, an estimated 5,626 people who were diagnosed with AIDS when they were younger than 13 years died in the 50 states and the District of Columbia. Of the total, 4,986 (89%) of them were infected perinatally."

          "Prevention Challenges" "The reduction in perinatal HIV infections in the United States represents an important achievement in public health. However, perinatal transmission of HIV continues to occur—and infant infections can be associated with interruptions of care at any stage of pregnancy for HIV-infected women and their infants. "The following challenges can be categorized as missed opportunities in preventing perinatal HIV transmission: "Enhanced primary HIV prevention strategies for women and girls continue to be needed and evaluated to prevent new infections in these populations, which will in turn, prevent perinatal HIV infections. "Few HIV medical care providers routinely provide preconception care or family planning services to their patients with HIV, which may result in unintended pregnancies. "Other missed opportunities for perinatal HIV prevention include lack of the following: appropriate prenatal care, prenatal HIV testing (see bullet below), prenatal antiretroviral medication, Cesarean delivery for women with a viral load greater than 1,000 copies/mL, and education on avoidance of breastfeeding. Among the mothers of HIV-infected infants reported to CDC from 2003–2007, only 62% had at least one prenatal visit, 27% were diagnosed with HIV after delivery, and only 29% received some antiretroviral medication during pregnancy. "HIV testing. Because approximately 18% of all people with HIV do not know their HIV status, many women who are infected with HIV may not know they are infected. The Centers for Disease Control and Prevention (CDC) recommends routine, opt-out3 HIV testing for all persons aged 13–64 years in health care settings, including women during every pregnancy. If women are tested and diagnosed with HIV infection before or early in their pregnancy, they can be given medication to improve their own health and reduce the risk of transmitting HIV to their infant. "Other factors also pose prevention challenges, including Substance abuse, mental illness, and HIV-related stigma present barriers to prenatal care in women living with HIV. Increasing accessibility to prenatal care services is crucial to sustain and maximize the decline in perinatal HIV infections. "Socioeconomic issues associated with poverty, including limited access to high-quality health care, housing, and HIV prevention education, may directly or indirectly increase the risk factors for HIV infection. "Lack of awareness that pre-chewing of food for infants is a transmission risk. Of the more than 140,000 HIV-serodiscordant heterosexual couples (one partner is HIV-infected and the other is not) in the United States, about half of them want additional children; and many of these couples have limited access to safe conception methods and services." CDC:  Centers for Disease Control and Prevention:  HIV Among Pregnant Women, Infants, and Children, reviewed January 10, 2014

References

Flexner C Antiretroviral Agents and Treatment of HIV Infection, Chapter 59  in Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12th edition (Brunton LL Chabner BA Knollmann BC, eds; Brunton LL, ed; Blumenthal DK  Murri N Hilal-Dandan R, assoc eds, Knollmann BC, consulting ed, on-line edition) The McGraw-Hill Companies, 2011. Fauci AS Lane HC Chapter 189, Human Immunodeficiency Virus Disease:  AIDS and Related Disorders, in Harrison's Online   (Dan L. Longo, Anthony S. Fauci, Dennis L. Kasper, Stephen L. Hauser, J. Larry Jameson, Joseph Loscalzo, Eds.),  Harrison's Principles of Internal Medicine, 18th edition, The McGraw-Hill Companies, Inc. 2012. Longo DL Fauci AS  188, The Human Retroviruses, in Harrison's Online   (Dan L. Longo, Anthony S. Fauci, Dennis L. Kasper, Stephen L. Hauser, J. Larry Jameson, Joseph Loscalzo, Eds.),  Harrison's Principles of Internal Medicine, 18th edition, The McGraw-Hill Companies, Inc. 2012. Safrin S Antiviral Agents, Chapter 49 in Basic & Clinical Pharmacology, 12 e (Katzung BG Masters SB Trevor AJ) The McGraw-Hill Companies, 2012 (on-line edition). Cochrane A Retroviruses Chapter 28 in Fundaments of Molecular Virology, 2e, Acheson NH, ed., John Wiley & Sons pp 342-353 2011. Cochrane A Human Immunodeficiency Virus Chapter 29  in Fundaments of Molecular Virology, 2e, Acheson NH, ed., John Wiley & Sons pp 354-364 2011. Ryan KJ, Ray C. Chapter 18. Retroviruses: Human T-Lymphotropic Virus, Human Immunodeficiency Virus, and Acquired Immunodeficiency Syndrome. In: Ryan KJ, Ray C. eds. Sherris Medical Microbiology (Part editor, Ahmad N Ray CG Drew WL), 5e. New York, NY: McGraw-Hill; 2010. Carter JB Saunders VA Virology:  Principles and Applications Chapter 18, Figure 18.13 John Wiley & Sons Ltd, 2013. Reid EG Chapter 83. Hematologic Manifestations of Acquired Immunodeficiency Syndrome in Williams Hematology 8e (Lichtman MA Kipps TJ Seligsohn U Kaushansky K Prchal JT, eds) The McGraw-Hill Companies, Inc, 2010. CDC:  Centers for Disease Control and Prevention:  HIV Among Pregnant Women, Infants, and Children, reviewed January 10,2014.  http://www.cdc.gov/hiv/risk/gender/pregnantwomen/facts/index.html

 

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