Human Immunodeficiency Virus, Herpes Simplex and Zoster, Lyme Disease, MRSA Infection, and Sexually Transmitted Diseases
HUMAN IMMUNODEFICIENCY VIRUS
Human Immunodeficiency Virus (HIV) Specifics
HIV is an infection caused by the human immunodeficiency virus that was formerly called the human T-lymphotropic virus-III (HTLV-III). HIV-1 and HIV-2 are the two species of HIV that infect humans. HIV-1 is the more aggressive of the two and it accounts for the majority of the infections worldwide. HIV-2 is less aggressive and is limited to western Africa.
The reverse transcriptase enzyme in the virus helps with the transfer of viral RNA into the DNA of the host cell. The virus attacks the CD4 T cells causing them to become infected. The infected cells are destroyed in one of three ways: direct viral killing, death by apoptosis, and death through the cytotoxic effects mediated by CD8 lymphocytes.
The T4 lymphocytes are like the “pilots” of immunity that also govern the quality and quantity of the B lymphocytes. Defective cell-mediated and lymphokine-mediated humoral immunity consequently occurs. Impaired immunity accounts for the increased incidence of opportunistic infections when the patient becomes symptomatic.
In addition to the CD4 cells, the virus affects the monocytes, macrophages, neural cells, or glial cells and crosses the blood-brain barrier. The virus has been isolated from almost all bodily fluids as free viral particles or embedded in previously specified cell. Isolation is most pronounced from the blood and the seminal fluid.
Gradual decline in immunity over time ultimately leads to the patient developing the acquired immunodeficiency syndrome (AIDS). The patient is said to have AIDS when the CD4 count is <200 cells/mm3. With the implementation of HIV/AIDS treatment, the CD4 count can improve and rise >200 cells/mm3. However, the patient will retain the diagnosis of AIDS even if the CD4 improves. It is important to remember that throughout the asymptomatic phase the CD4 count is on a steady decline.
Modes of HIV Transmission
HIV transmission can occur via the following:
Epidemiology of HIV
Epidemiology of HIV in the Developed Nations
Initially in the developed world, men having sex with men (MSM) was the leading cause of HIV transmission. With increased awareness of risk practices and prevention strategies, those numbers declined in the 1990s, but the numbers are now increasing again. Current transmission types are as follows, MSM > heterosexual contact > injection drug use (showing small improvement).
Recently, there has been an increased rate of transmission of the virus in the heterosexual population because of unprotected sex and among people of color because of IV drug use (IVDU). However, injection drug use numbers have shown some improvement. Vertical transmission from mother to child is now rare in the developed world because of initiation of treatment during pregnancy and the implementation of elective caesarian section around the thirty-eighth week of pregnancy.
Epidemiology of HIV in the Developing Nations
About 33 million adults and children total are living with HIV, and 2.5 million children <15 years old are living with HIV. There are 2.6 million new infections in adults and children, and the incidence of infection in children <15 years old is 370,000. There are about 1.8 million AIDS-related deaths each year in adults and children, and last year the deaths among children <15 years old were 260,000, which is less than the number of new infections. Most people with HIV are in sub-Saharan Africa (22.5 million people) with the Middle East and northern Africa comprising a distant second (4.1 million people). In the developing nations, the highest rate of transmission has been encountered among the heterosexual population because of unprotected sex and IVDU. Mother-to-child vertical transmission is another leading cause for the increased numbers of infected cases.
There is a dire need to provide antiretroviral therapy (ART) in the developing nations along with improved prevention strategies to decrease the numbers. Prevention can be achieved by educating the population about HIV infection and the modes by which the virus is transmitted.
HIV Natural History
The following sections detail the ways in which the viral infection can progress, once exposure occurs.
Acute Retroviral Infection
An acute retroviral infection progresses in one of two ways:
The Asymptomatic Patient
This patient has CD4 >250 cells/mm3 and a viral load up to 50–100 K/mL. The patient can stay asymptomatic for ten years, or even longer, while the CD4 count gradually declines over time. No treatment is recommended in the presence of established disease if the patient is asymptomatic.
The Symptomatic Patient
This patient presents with AIDS-defining conditions (ADC): weight loss, oral candidiasis, opportunistic infections, tumors, and so on. The opportunistic infections that occur must be diagnosed and treated appropriately.
The Early Symptomatic Stage
The CD4 count is >200 cells/mm3 and the usual range at this stage is 250–300 cells/mm3. MTB, candida infections, cryptococcus infection, histoplasmosis, and recurrent bacterial infections occur.
The Late Symptomatic Stage
Pneumocystis carinii pneumonia (PCP), now called Pneumocystis jiroveci, and chronic cryptosporidia diarrhea occur when the CD4 count is <200 cells/mm3. Toxoplasmosis, cytomegalovirus (CMV), and mycobacterium avium complex (MAC) infections can occur when the CD4 is <100 cells/mm3.
AIDS-Defining Conditions (ADC) in the Symptomatic Stage
The following are ADC conditions that can occur in the symptomatic stage:
- Recurrent bacterial infections.
- Candida infection affecting the esophagus, trachea, and bronchi.
- Disseminated coccidiomycosis, histoplasmosis.
- Extrapulmonary cryptococcosis.
- Chronic cryptosporidiosis.
- Cytomegalovirus (CMV).
- More advanced cases present with persistent mucocutaneous herpes simplex infection (HSV), HIV encephalopathy, Kaposi’s sarcoma, primary lymphoma of the brain, non-Hodgkin’s B-cell lymphoma, MAC, extrapulmonary TB (dissem TB), Pneumocystis jiroveci pneumonia, progressive multifocal leukoencephalopathy, recurrent salmonella infection, and toxoplasmosis of the brain.
- Cytomegalovirus (CMV) can affect the eyes, the brain, and the adrenal glands.
- Papilloma virus that causes warty cauliflower type of lesions on the gums.
- Mycobacterium avium complex (MAC) and mycobacterium kansasii (MK) occur only in the immune-compromised patients and not in healthy, immune-competent patients.
- Kaposi’s sarcoma begins as a pink, pinhead-sized lesion that gradually enlarges and changes in color from pink to purple to black. Kaposi’s sarcoma is usually multifocal and involves the trunk, the upper extremities, and the head and neck region.
HIV and AIDS Criteria Summary
The patient is said to have HIV when there is evidence that confirms presence of HIV. There is ongoing viral replication and progressive immune system decline.
The patient is said to have AIDS when there is HIV infection and ADCs or the patient has CD4 <200 cells/mm3. There is ongoing viral replication and progressive immune system decline.
General Overview of HIV/AIDS in the United States
HIV is now one of the top-ten causes of death in the United States. However, people are now living longer with HIV due to effective antiretroviral therapy, and the death rate is decreasing. Numbers of new infections remain low but stable. Transmission-risk groups vary every year, but greater numbers of males than females are infected overall. The numbers of HIV cases among blacks and Hispanics have increased; the numbers among whites have declined. The numbers among Asians has stayed low throughout. Overall, the numbers by race show African Americans outnumbering Caucasians, Hispanics, Asians, and Native Americans.
Transmission by intravenous drug use (IVDU) has increased, and unprotected heterosexual contacts recorded the steepest rise. The numbers had decreased for men having sex with men (MSM) and MSM IV drug users, but these numbers are now increasing again.
HIV tests detect the presence of the human immunodeficiency (HIV) antibodies, antigens, or RNA in the serum or saliva. There are three sets of tests associated with HIV/AIDS:
The average window period (the time from infection until antibodies develop) with the antibody tests is about 22 days. Occasionally, a patient may have a delay in forming antibodies and do so in about three to six months. There are two sets of diagnostic tests that help with the diagnosis of infection:
The Non-Rapid Diagnostic Tests
It takes about seven to ten days to obtain the results. The two non-rapid diagnostic tests are:
The ELISA Test
The ELISA test is said to be reactive when it detects antibodies to HIV-1. Once positive, the blood is tested again to reconfirm that the ELISA test is indeed positive. Results from the ELISA test are reported as a number; the test is 99% sensitive.
The Western Blot Test
The Western Blot test is a more specific test that is 99.5% sensitive. The Western Blot test determines the size of the antigens binding to the antibodies in the test kit. Blood showing a positive ELISA is subjected to the Western Blot test. Thus, the Western Blot test is confirmatory testing for HIV infection. A positive Western Blot test confirms that the patient is infected with HIV.
It is estimated that one-third of those infected with HIV do not know their status. HIV testing requires written informed consent and the CDC recommends “opt-out” testing on the grounds that early treatment is effective. Therefore, early identification is especially encouraged. Furthermore, people with suppressed viral loads are at a lower risk of transmitting to someone, so this recommendation is not only good for the patient, it is also an excellent public health measure.
In opt-out testing it is assumed that every primary-care patient will get tested, unless they specifically request not to be tested, but no written consent is required. For any patient being seen for a general physical, the physician will test for HIV, unless there is an objection by a patient. This testing is not based on a person’s risk factors. Consequently, this eliminates the necessity for informed consent. This measure will identify HIV-positive individuals in populations that may not otherwise undergo testing.
The First FDA-Approved OTC HIV Test Kit
The OraQuick in-home HIV test, manufactured by OraSure Technologies, is the first over-the-counter (OTC), self-administered FDA-approved HIV test kit to detect the presence of antibodies to HIV-1 and HIV-2. The patient collects an intraoral sample by swabbing the upper and lower gums and then places the sample into a developer vial. The patient obtains test results within 20–40 minutes. A positive test does not mean that an individual is definitely infected with HIV. A positive result indicates only that additional testing in a medical setting is necessary to confirm the result. A negative test result does not mean that an individual has definitely not been infected with HIV, especially when exposure may have occurred within the past three months. The OraQuick in-home HIV test has 92% test sensitivity and 99.98% test specificity. A version of this test for use by trained technicians in clinical settings was approved in 2004.
The Rapid Diagnostic Tests
These tests provide results immediately or within 20 minutes. The two rapid diagnostic tests are:
The OraQuick Rapid HIV-1 Antibody Test
This test detects antibodies and is approved for use with a finger-stick or anticoagulated whole blood or serum or oral fluid specimens. Results are obtained within 20 minutes from the testing. The test is 99.6% sensitive and 100% specific. The specificity of the OraQuick assay is higher than the Reveal Rapid assay.
The Reveal Rapid HIV-1 Antibody Test
This test requires the use of a serum or plasma specimen that is added to the test cartridge. The result is read immediately after the solution is absorbed. If a serum sample is used, the Reveal Rapid assay is 99.8% sensitive and 99.1% specific. If a plasma sample is used, the test is 98.6% specific.
There are two tests:
The Role of Quantitative Virology and Antiretroviral Therapy
CD4 counts and HIV/RNA assays are of greatest clinical significance for efficient monitoring of the HIV infection. The CD4 count provides an estimate of the patient’s immune system status. CD4 counts also are used to determine a patient’s response to therapy. The CD4 count should be repeated every three to six months, and the normal CD4 count fluctuates between 900–1,200 cells/mm3.
Correlation of CD4 Count and Lymphocyte Percentage Reported on Laboratory Tests
Lymphocyte percentage reported on laboratory tests can be correlated to the appropriate CD4 count to get a better understanding of the patient’s immunity status.
Lymphocyte Percentage to CD4 Count Conversion
- 29% lymphocytes = CD4 count >500 cells/mm3
- 14–28% lymphocytes = CD4 200–500 cells/mm3
- <14% lymphocytes = CD4 count <200 cells/mm3
HIV RNA or Viral Load
HIV RNA/viral load assays permit the detection of minute quantities of HIV RNA in the blood and tissues of the patient, in all stages of the disease. It is a strong predictor of disease progression. A threefold change with successive tests is said to be significant. If HIV RNA levels are repeatedly <10,000 copies/mL, therapy may be deferred. HIV RNA levels <50 copies/mL indicate an “undetectable viral load.”
Serial HIV RNA assays must be repeated every three to four months. Longevity is increased if viral loads are kept constantly at negligible levels.
ORGAN ASSESSMENT TESTS WITH MEDICATION INTAKE
The following tests are required when the patient is on HIV/AIDS medications to detect adverse side effects with the medications:
Table 47.1 provides a summary of HIV/AIDS medications
|Drug Class||Drug Name||Side Effects|
|Nucleoside reverse transcriptase inhibitors (NRTIs):
Tenofovir + Emtricitabine are primary therapy NRTIs.
Abacavir + Lamivudine are alternate therapy NRTIs.
|Tenofovir (Viread)||Causes renal insufficiency|
|Emtricitabine (Emtriva)||Causes hyperpigmentation|
|Abacavir (Ziagen)||Needs HLA*B5701 screening prior to administration to avoid hypersensitivity|
|Lamivudine (Epivir)||Minimal toxicity, severe acute exacerbation of hepatitis may occur with HBV-coinfection upon discontinuation|
|Stavudine (Zerit)||Causes peripheral neuropathy|
|Didanosine (Videx)||Causes peripheral neuropathy, lactic acidosis|
|Zalcitabine (Hivid)||Causes peripheral neuropathy and stomatitis|
|Zidovudine (Retrovir)||Drug discontinued|
|Nonnucleoside reverse transcriptase inhibitors (NNRTIs):
Efavirenz is primary therapy NNRTI
Nevirapine or Rilpivirine are alternate therapy NNRTIs
|Efavirenz (Sustiva)||Rash, hyperlipidemia|
|Nevirapine (Viramune, Viramune XR)||Rash, hepatitis|
|Protease inhibitors (PIs):
Primary therapy PIs are Ritonavir “boosted” Atazanavir or Ritonavir “boosted” Darunavir.
Alternate therapy PI: Ritonavir “boosted” Lopinavir
|Atazanavir (Reyataz): always combined with Ritonavir as “booster” drug||Prolonged PR interval, hyperglycemia, skin rash, hyperlipidemia|
|Darunavir (Prezista): always combined with Ritonavir as “booster” drug||Hyperlipidemia, hyperglycemia|
|Lopinavir/ritonavir (Kaletra): always combined with Ritonavir as “booster” drug||Hyperlipidemia, hyperglycemia|
|Indinavir (Crixivan)||Hyperlipidemia, hyperglycemia|
|Fosamprenavir (Lexiva)||Hyperlipidemia, hyperglycemia|
|Nelfinavir (Viracept)||Hyperlipidemia, hyperglycemia|
|Ritonavir (Norvir)||Hyperlipidemia, hyperglycemia, and oral parasthesias|
|Saquinavir (Invirase)||Hyperlipidemia, hyperglycemia, and QT interval prolongation|
|Tipranavir (Aptivus)||Hyperlipidemia, hyperglycemia, hepatotoxicity, and rash|
|Integrase inhibitor (II):
II, Raltegravir is part of primary therapy
|Raltegravir (Isentress)||CK elevations, myopathy, or rhabdomyolysis|
|Chemokine receptor antagonist (CCR5 antagonist)|
|Maraviroc (Selzentry)||CYP3A4 inducer and inhibitor effect
Constipation, dizziness, infection
|Fusion inhibitor (FI)|
|Enfuvirtide (Fuzeon), subcutaneous injection||Injection-site reactions|
|Epzicom − Abacavir + lamivudine|
|Trizivir − Abacavir + lamivudine + zidovudine|
|Truvada – Tenofovir + emtricitabine|
|Atripla − Tenofovir + emtricitabine + efavirenz|
|Complera – Tenofovir + emtricitabine + rilpivirine|
|Combivir − Zidovudine + lamivudine|
Highly Active Antiretroviral Therapy (HAART)
HAART has been able to suppress the virus such that HIV is now considered a chronic disease. Once started, HAART has to be continued for life, so the question is when to start the treatment. The physician and the patient have to weigh the short- and long-term risks or toxicities associated with HAART. The biggest benefit has been a 50% reduction in mortality. The drawbacks have been lipodystrophy and metabolic abnormalities, thus increasing the risks for cardiovascular disease.
Not all HIV-associated disease states are reduced with HAART. Suppression of HIV does not mean that there is an associated decline in the replication of hepatitis C virus. In fact, it some cases it may worsen the hepatitis C co-infection. Incidence of Kaposi’s sarcoma is decreasing, but the incidence of immunoblastic lymphoma, Hodgkin’s lymphoma, invasive cervical cancer, and Burkitt’s lymphoma are not.
HAART-Associated Lipodystrophy Syndrome and Metabolic Abnormalities
The resultant lipodystrophy syndrome is associated with abnormal fat accumulation causing central, intra-abdominal obesity and fat buildup around the back of the neck, which is known as a “buffalo hump.” Subcutaneous fat atrophy between the skin and the muscles occurs, mostly affecting the face, arms, and legs. HAART is also associated with lipid metabolism changes demonstrating a low HDL and high triglycerides. Glucose metabolism changes showing insulin resistance and glucose intolerance is another side effect of HAART.
Cumulative Side Effects of HIV/AIDS Medications
The side effects associated with HIV/AIDS medications must be assessed and appropriately treated, when possible, by the dentist prior to the start of dentistry. The side effects that can occur are heart disease, liver disease (demonstrating elevated ALT levels and hepatic necrosis), xerostomia, change in prevalence and incidence of oral lesions, Stevens-Johnson syndrome, lactic acidosis, pancreatitis, nephrotoxicity, marrow suppression, gastrointestinal intolerance, peripheral neuropathy, rash, CNS toxicity, insulin resistance, hyperlipidemia, fat atrophy, and fat accumulation.
PROPHYLAXIS AND TREATMENT OF OPPORTUNISTIC INFECTIONS
PCP occurs within one year in 60% of patients with HIV with CD4 <200 cells/mm3. Thus, prophylaxis against PCP is a must as a preventative therapy.
Primary and Secondary Opportunistic Infections Prophylaxis
Primary prophylaxis is provided when there is no evidence of the disease against which the prophylaxis is being given. PCP prophylaxis is an example of primary prophylaxis. PCP prophylaxis is inexpensive and effective. Trimethoprim-sulfamethoxazole (Bactrim) is the recommended regimen for PCP prophylaxis. Bactrim also protects the patient from toxoplasmosis, salmonellosis, or any staphylococcal infection. Bactrim does not protect the patient against shigella, pneumococcal or pneumococcal strep, klepsiella, or pseudomonas.
All adults and adolescents are given prophylaxis when any one of these states occurs, regardless of whether they are taking HAART:
- The patient has CD4 <200 cells/mm3.
- There is a history of oral candidiasis.
- The CD4 cells account for <14% of the lymphocyte count.
- There is a history of AIDS but without CD4 <200/mm3.
Secondary prophylaxis is provided after the disease against which the prophylaxis is being given has occurred. The patient gets treated for the disease first, and the prophylaxis is given after recovery to prevent any future attacks with the disease. Prophylaxis against CMV is secondary prophylaxis. It is expensive and its effectiveness is questionable.
- Antiretroviral therapy (ART) guidelines are constantly updated on an ongoing basis by The US Department of Health and Human Services, in conjunction with the panels on International AIDS Society (IAS) and the World Health Organization (WHO).
- With the advent of highly active antiretroviral therapy (HAART), HIV-1 infection is now managed as a chronic disease, especially in patients who are being treated and who continue to maintain significant viral suppression. HAART therapy has nearly halved the mortality rate in patients with AIDS. Treatment should be based on at least two consistent determinations of CD4 and viral load because they fluctuate.
- Current guidelines state that treatment must begin when a patient has a history of an AIDS-defining illness (symptomatic disease) or when the patient is asymptomatic but has a CD4 count <350 cells/mm3. Treatment must definitely begin with CD4 <200 cells/mm3. Treatment is also strongly recommended for asymptomatic patients with CD4 counts from 350–500 cells/mm3 and moderately recommended or optional for patients with CD4 counts above 500 cells/mm3, when associated with viral load >100,000 copies, or in the presence of CD4 decline >100 cells/year.
- Pregnant women with HIV infection should get therapy regardless of CD4 count, in order to prevent transmission of infection from mother to child. HAART therapy is started at the end of the first trimester.
- Antiretroviral therapy preserves renal function and prolongs survival regardless of CD4 count in patients with HIV-associated nephropathy, so HAART therapy is started regardless of CD4 count in patients with underlying kidney disease. Treatment is also started in the presence of cardiovascular risk factors or in the presence of active hepatitis B or C infection.
- The International Antiviral Society–USA panel (IAS-USA) for antiretroviral therapy (ART) issued recommendations at the XIX International AIDS Conference, and these provide the direction in which HIV/AIDS care will proceed in the future.
2012 Recommendations of the IAS-USA for ART
- New data show that antiretroviral therapy (ART) has dramatically reduced the numbers of opportunistic diseases and deaths in people infected with HIV; ART therapy results in viral suppression, thus decreasing human immunodeficiency virus (HIV) transmission, and when used consistently by HIV-uninfected persons ART may provide protection against HIV infection. Studies have shown that ART therapy was 96% effective in reducing HIV transmission from infected individuals to their non-infected partners. Thus, offering ART therapy to at-risk individuals or to their partners, especially in the absence of a vaccine, can benefit the population at large.
- All adults who are HIV-positive should get ART therapy as soon as possible, regardless of the CD4 cell count, and the earlier the better. There is no CD4 cell count threshold at which starting therapy is contraindicated.
- The aim of therapy is to trigger maximum, lifelong, and continuous suppression of HIV replication and to ultimately improve health.
- Initial therapy for HLA-B*5701-negative patients with baseline plasma HIV-1 RNA <100,000copies/mL consists of a combination of two nucleoside reverse transcriptase inhibitors (NRTIs) and a nonnucleoside reverse transcriptase inhibitor (NNRTI), a ritonavir-boosted protease inhibitor (PI/r), an integrase strand transfer inhibitor (InSTI), or, very occasionally, a chemokine receptor 5 (CCR5) antagonist. Regimens in fixed-dose combinations (FDCs) are used once daily, thus improving medication adherence. Initial Therapy Drugs: two nucleoside reverse transcriptase inhibitors (NRTIs), tenofovir/emtricitabine or abacavir/lamivudine + nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz + ritonavir-boosted protease inhibitor (PI), atazanavir/darunavir, or integrase strand transfer inhibitor (InSTI), raltegravir (see Table 47.1).
- Alternatives in each class are selected if these drugs cannot be used.
- CD4 cell count and HIV-1 RNA level should be monitored throughout therapy. Suppression of plasma HIV-1 RNA to less than 50 copies/mL by 24 weeks needs to occur with effective therapy, regardless of prior treatment.
- Current third-generation HIV-1 RNA assays show a lower limit of quantification of 40 or 20 copies/mL and can report qualitative RNA detection below these cutoffs. In addition, many patients receiving stable suppressive treatment show residual viremia of 1–10 copies/mL by research-based assays.
- Plasma HIV-1 RNA levels should be monitored at least every three months after beginning or modifying treatment, to confirm suppression of viremia <50 copies/mL.
- Once viral load is suppressed for one year and CD4 cell count is stable at 350 cells/mm3 or greater, HIV-1 RNA and CD4 cell count can be monitored at intervals of up to six months in patients who are good about adhering to therapy.
- ART has a role in postexposure prophylaxis.
- Preexposure prophylaxis (PrEP): The FDA recently approved tenofovir disoproxil fumarate/emtricitabine (Truvada) for use as preexposure prophylaxis for HIV-seronegative gay men, in order to protect them from contracting the infection through sexual activity. Patients prescribed tenofovir disoproxil fumarate/ emtricitabine for preexposure prophylaxis (PrEP) are required to take the drug daily, in addition to practicing safe sex and getting tested regularly for HIV.
- When to initiate ART: ART is recommended regardless of CD4