Within weeks of infection, many people will develop the varied symptoms of primary or acute infection, which typically has been described as a mononucleosis- or influenza-like illness but can range from minimal fever, aches, and pains to very severe symptoms. The most common symptoms of primary HIV infection are
Jump up ^ Nachega, JB; Marconi, VC; van Zyl, GU; Gardner, EM; Preiser, W; Hong, SY; Mills, EJ; Gross, R (April 2011). “HIV treatment adherence, drug resistance, virologic failure: evolving concepts”. Infectious disorders drug targets. 11 (2): 167–74. doi:10.2174/187152611795589663. PMID 21406048.
Each year about 5 million people contract AIDS worldwide, and 3 million die of it. Some 40-50 million are estimated to be living with the disease. The gender incidence is approximately equal. The highest prevalence is in some African countries, where as many as 25% of the adult population may test HIV positive; about 70% of the world’s infected population lives in sub-Saharan Africa. The first cases of AIDS were reported in the U.S. in June 1981. During the succeeding 2 decades an estimated 1.4 million people in this country were infected with HIV and 816,149 cases of AIDS and 467,910 deaths were reported to the U.S. Centers for Disease Control and Prevention (CDC). The numbers of new AIDS cases and deaths declined substantially after introduction of combination antiretroviral therapy in the late 1990s. The annual number of new cases of AIDS in the U.S. has remained stable at about 40,000, with 16,000 deaths since 1998. The number of people infected with HIV continues to increase, and of an estimated 1 million, one fourth are unaware that they are infected. In the U.S., AIDS is the leading cause of death among men 25-44 years old, and the fourth leading cause of death among women in the same age group. The development of effective antiretroviral agents (for example, reverse transcriptase inhibitors and protease inhibitors) and of quantitative plasma HIV RNA assays that can monitor progression of disease and response to treatment has shifted the goal of management in AIDS from prophylaxis and treatment of opportunistic infections to achievement of remission through suppressive therapy. Immune compromise is monitored by serial CD4 counts, viral replication by plasma HIV RNA assay (that is, plasma viral load, PVL). Indications for starting antiretroviral are the appearance of symptoms of opportunistic infection, decline of the CD4 count below 350/mm3, or viral load exceeding 30,000 copies/mL. The CD4 count is considered a more sensitive predictor of disease progression than viral load. Empiric treatment may be begun early (within 6 months after conversion to HIV-positive status) in an effort to preserve immune function and mobilize the patient’s own defenses against the virus. But current guidelines advise deferring treatment as long as possible so as to limit induction of drug resistance. Protease inhibitors have been shown to be highly effective antiretroviral agents and standard treatment regimens combining 2 reverse transcriptase inhibitors with 1 protease inhibitor (“triple therapy”) have clearly demonstrated superiority over monotherapy. These drugs are expensive. Regimens are often complex, with varying requirements for fasting and timing of doses, and adverse effects and drug interactions are common. Protease inhibitors have been associated with elevation of cholesterol and triglycerides, insulin resistance, and disfiguring lipodystrophy. In one large study, more than one half of HIV-infected adults under treatment were found to be infected with strains of virus resistant to one or more antiretroviral drugs, and strains of HIV that are resistant to all available protease inhibitors have appeared. The rationale for current AIDS regimens is an effort to eradicate HIV infection by inhibiting spread of virus to new cells until all infected cells have died. However, actual cure seldom if ever occurs. A small number of resting CD4 memory cells in treated patients with undetectable plasma HIV RNA levels harbor HIV proviral DNA capable of replication, and these cells may survive for months or years. Macrophages and CNS neurons may serve as an anatomic sanctuary for HIV into which antretroviral drugs cannot penetrate in adequate concentration. When antiretroviral therapy is initiated early, CD4 helper cell counts rise, CD4 cell activity is preserved, and HIV RNA levels may remain undetectable for long periods. But in about 50% of patients with advanced disease, even multidrug regimens fail to suppress plasma viral RNA to undetectable levels. Many treatment failures result from poor compliance with multidrug regimens. Failure of one therapeutic regimen often precludes success with others because of the high degree of cross-resistance among antiretroviral drugs. After failure of an initial regimen, genotypic testing can be used to identify mutations in the HIV genome that confer resistance to one or more classes of HIV drugs. Many patients remain vulnerable to opportunistic infections despite restoration of CD4 counts to normal, probably because some subpopulations of T cells have been annihilated and cannot be recovered even after HIV has been suppressed. Moreover, even HIV-infected patients with undetectable viral loads must still be considered infectious. In a small set of those infected with HIV, impairment of immunity progresses to AIDS slowly or not at all. CD8 T-cells from such nonprogressors have been found to produce proteins called α-defensins. Evolving standards of treatment in HIV disease include aggressive prophylaxis in pregnancy and after accidental needle stick and sexual assault. Administration of antiretroviral agents to HIV-positive mothers before birth and during labor and delivery, and to newborns for the first 6 weeks of life, markedly decrease the risk of vertical transmission of HIV infection. The risk of HIV infection after occupational parenteral exposure to blood from an HIV-infected patient is approximately 0.3%. Postexposure prophylaxis with antiretroviral agents continued for 28 days have been shown to reduce the risk by 80%. The selection of agents depends on the source patient’s therapeutic history. Efforts to develop a vaccine against HIV have been hampered by the unique properties of the virus and the long incubation period of AIDS. Early in the 21st century, public health authorities sought to make HIV testing a routine part of medical care, to facilitate diagnosis outside formal clinical settings, to prevent new infections by educating people and their sexual partners, and to decrease perinatal HIV transmission through routine HIV testing of pregnant women and of infants whose mothers were not screened.
The crisis is most acute in Southern states, which hold 37 percent of the country’s population and as of 2014 accounted for 54 percent of all new H.I.V. diagnoses. The South is also home to 21 of the 25 metropolitan areas with the highest H.I.V. prevalence among gay and bisexual men. Jackson, the capital of Mississippi, the country’s poorest state, is best known for blues, barbecue and “The Help.” It also has the nation’s highest rate — 40 percent — of gay and bisexual men living with H.I.V., followed by Columbia, S.C.; El Paso; Augusta, Ga.; and Baton Rouge, La. In Jackson, a small city of just over 170,000, half a dozen black gay or bisexual men receive the shock of a diagnosis every month, and more than 3,600 people, the majority of them black men, live with the virus.
Humoral: Antibodies to HIV are usually measurable within a few weeks after primary infection; however, antibodies cannot fully control HIV infection because mutated forms of HIV that are not controlled by the patient’s current anti-HIV antibodies are generated.
Infection with the human immunodeficiency virus (HIV) is the cause of acquired immune deficiency syndrome (AIDS). This worldwide epidemic is now spreading at an alarming rate, especially through heterosexual contact in less-developed countries. HIV is an enveloped retrovirus that replicates in cells of the immune system. Viral entry requires the presence of CD4 and a particular chemokine receptor, and the viral cycle is dependent on transcription factors found in activated T cells. Infection with HIV causes a loss of CD4 T cells and an acute viremia that rapidly subsides as cytotoxic T-cell responses develop, but HIV infection is not eliminated by this immune response. HIV establishes a state of persistent infection in which the virus is continually replicating in newly infected cells. The current treatment consists of combinations of viral protease inhibitors together with nucleoside analogues and causes a rapid decrease in virus levels and a slower increase in CD4 T-cell counts. The main effect of HIV infection is the destruction of CD4 T cells, which occurs through the direct cytopathic effects of HIV infection and through killing by CD8 cytotoxic T cells. As the CD4 T-cell counts wane, the body becomes progressively more susceptible to opportunistic infection with intracellular microbes. Eventually, most HIV-infected individuals develop AIDS and die; however a small minority (3–7%), remain healthy for many years, with no apparent ill effects of infection. We hope to be able to learn from these individuals how infection with HIV can be controlled. The existence of such people and other people who have been naturally immunized against infection gives hope that it will be possible to develop effective vaccines against HIV.
Two distinct species of HIV (HIV-1 and HIV-2) have been identified, and each is composed of multiple subtypes, or clades. All clades of HIV-1 tend to cause similar disease, but the global distribution of the clades differs. This may have implications on any future vaccine, as the B clade, which is predominant in the developed world (where the large pharmaceutical companies are located), is rarely found in the developing countries that are more severely affected by the disease.
The United States struggled to cope with AIDS from the early 1980s until the late 1990s, when new drug therapies started to extend the length and quality of life for many people with AIDS. Since the beginning, AIDS and its resulting epidemic in the United States have raised a great number of legal issues, which are made all the more difficult by the nature of the disease. AIDS is a unique killer, but some of its aspects are not: epidemics have been seen before; other sexually transmitted diseases have been fatal. AIDS is different because it was discovered in—and in the United States still predominantly afflicts—unpopular social groups: gay men and drug users. This fact has had a strong impact on the shaping of AIDS law. Law is often shaped by politics, and AIDS is a highly politicized disease. The challenge in facing an epidemic that endangers everyone is complicated by the stigma attached to the people most likely to be killed by it.
Zoufaly A, an der Heiden M, Kollan C, et al. Clinical outcome of HIV-infected patients with discordant virological and immunological response to antiretroviral therapy. J Infect Dis. 2011 Feb 1. 203(3):364-71. [Medline]. [Full Text].
Treatment cannot (with rare exceptions) eliminate the virus from the body, although the HIV level often decreases so much that it cannot be detected in blood or other fluids or tissues. An undetectable level is the goal of treatment. If treatment is stopped, the HIV level increases, and the CD4 count begins to fall.
Definition (CSP) one or more indicator diseases, depending on laboratory evidence of HIV infection (CDC); late phase of HIV infection characterized by marked suppression of immune function resulting in opportunistic infections, neoplasms, and other systemic symptoms (NIAID).
Jump up ^ Cunningham AL, Donaghy H, Harman AN, Kim M, Turville SG (2010). “Manipulation of dendritic cell function by viruses”. Current Opinion in Microbiology. 13 (4): 524–529. doi:10.1016/j.mib.2010.06.002. PMID 20598938.
The history of the human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) dates back to 1981, when gay men with symptoms and signs of a disease that now are considered typical of AIDS were first described in Los Angeles and New York. The men had an unusual type of lung infection (pneumonia) called Pneumocystis carinii (now known as Pneumocystis jiroveci) pneumonia (PCP) and rare skin tumors called Kaposi’s sarcomas. The patients were noted to have a severe reduction in a type of cell in the blood (CD4 cells) that is an important part of the immune system. These cells, often referred to as T cells, help the body fight infections. Shortly thereafter, this disease was recognized throughout the United States, Western Europe, and Africa. In 1983, researchers in the United States and France described the virus that causes AIDS, now known as HIV, belonging to the group of viruses called retroviruses. While HIV infection is required to develop AIDS, the actual definition of AIDS is the development of a low CD4 cell count (<200 cells/mm3) or any one of a long list of complications of HIV infection ranging from a variety of so-called "opportunistic infections," cancers, neurologic symptoms, and wasting syndromes. There are at least 25 medications approved to treat HIV. They work to prevent HIV from reproducing and destroying CD4 cells, which help your immune system fight infection. This also helps reduce the risk of transmitting the virus. "It's no longer a death sentence," Boswell said of HIV. "It's a very different time now. Most people just diagnosed with HIV will live an almost normal life span if they get an early diagnosis, appropriate care and stay on their medications." Nicholas John Bennett, MBBCh, PhD, MA(Cantab), FAAP Assistant Professor of Pediatrics, Co-Director of Antimicrobial Stewardship, Medical Director, Division of Pediatric Infectious Diseases and Immunology, Connecticut Children's Medical Center WHO recommends lifelong ART for all people living with HIV, regardless of their CD4 count clinical stage of disease, and this includes women who pregnant or breastfeeding. In 2016, 76% of the estimated 1.4 million pregnant women living with HIV globally received ARV treatments to prevent transmission to their children. A growing number of countries are achieving very low rates of MTCT and some (Armenia, Belarus, Cuba and Thailand) have been formally validated for elimination of MTCT of HIV as a public health problem. Several countries with a high burden of HIV infection are also progressing along the path to elimination. Risk of HIV infection is increased when semen or vaginal fluids contain a large amount of HIV and/or when there are tears or sores, even small ones, in the skin or membranes lining the genitals, mouth, or rectum. Thus, transmission is much more likely during the following: *PEP is optional and should be based on an individualized decision by the exposed person and the treating clinician. If PEP is offered and taken and the source is later determined to be HIV-negative, PEP should be stopped. The typical course of an infection with HIV is illustrated in Fig. 11.21. However, it has become increasingly clear that the course of the disease can vary widely. Thus, although most people infected with HIV go on to develop AIDS and ultimately to die of opportunistic infection or cancer, this is not true of all individuals. A small percentage of people seroconvert, making antibodies against many HIV proteins, but do not seem to have progressive disease, in that their CD4 T-cell counts and other measures of immune competence are maintained. These long-term nonprogressors have unusually low levels of circulating virus and are being studied intensively to determine how they are able to control their HIV infection. A second group consists of seronegative people who have been highly exposed to HIV yet remain disease-free and virus-negative. Some of these people have specific cytotoxic lymphocytes and TH1 lymphocytes directed against infected cells, which confirms that they have been exposed to HIV or possibly noninfectious HIV antigens. It is not clear whether this immune response accounts for clearing the infection, but it is a focus of considerable interest for the development and design of vaccines, which we will discuss later. There is a small group of people who are resistant to HIV infection because they carry mutations in a cell-surface receptor that is used as a co-receptor for viral entry, as we will see below. Poropatich K, Sullivan DJ Jr. Human immunodeficiency virus type 1 long-term non-progressors: the viral, genetic and immunological basis for disease non-progression. J Gen Virol. 2011 Feb. 92:247-68. [Medline]. In developing nations, co-infection with HIV and tuberculosis is very common. The immunosuppressed state induced by HIV infection contributes not only to a higher rate of tuberculosis reactivation but also to an increased disease severity, as with many other opportunistic infections. For the next two months, Sturdevant and Dot kept a close eye on the young man, scolding, nagging and pleading with him to stay in treatment and to tell his family the truth so he would have someone to support him. On a Friday in March 2016, Sturdevant arranged to visit him and take medication to his house. But when he arrived, there was no answer. “I banged on the door, and then constantly called him all weekend,” Sturdevant said. “On Monday, they told me he had passed away.” Production of the clotting factor concentrates, mainly to treat patients with haemophilia A and haemophilia B (Christmas disease), involves the pooling of very many donations and a single donation could contaminate a batch of concentrate used to treat many patients. There have been no recorded transmissions of HIV by this route in the UK since the introduction of heat inactivation of concentrates and donor screening in 1985. About 97 percent of people develop detectable HIV antibodies within 21 to 84 days after infection. Some may take longer. A nucleic acid test can detect the virus in the blood as early as seven to 28 days after infection. This test is expensive and rarely given unless you’re at particularly high risk or already have symptoms of HIV. HIV is an enveloped retrovirus whose structure is shown in Fig. 11.22. Each virus particle, or virion, contains two copies of an RNA genome, which are transcribed into DNA in the infected cell and integrated into the host cell chromosome. The RNA transcripts produced from the integrated viral DNA serve both as mRNA to direct the synthesis of the viral proteins and later as the RNA genomes of new viral particles, which escape from the cell by budding from the plasma membrane, each in a membrane envelope. HIV belongs to a group of retroviruses called the lentiviruses, from the Latin lentus, meaning slow, because of the gradual course of the diseases that they cause. These viruses persist and continue to replicate for many years before causing overt signs of disease. Most healthy people have a CD4 count of 500 to 1,000 cells per microliter of blood. Typically, the number of CD4+ lymphocytes is reduced during the first few months of infection. After about 3 to 6 months, the CD4 count stabilizes, but without treatment, it usually continues to decline at rates that vary from slow to rapid. ^ Jump up to: a b c d e f Coutsoudis, A; Kwaan, L; Thomson, M (October 2010). "Prevention of vertical transmission of HIV-1 in resource-limited settings". Expert review of anti-infective therapy. 8 (10): 1163–75. doi:10.1586/eri.10.94. PMID 20954881. Early diagnosis of HIV infection is important because it makes early treatment possible. Early treatment enables infected people to live longer, be healthier, and be less likely to transmit HIV to other people. Burgard M, Jasseron C, Matheron S, et al. Mother-to-child transmission of HIV-2 infection from 1986 to 2007 in the ANRS French Perinatal Cohort EPF-CO1. Clin Infect Dis. 2010 Oct 1. 51(7):833-43. [Medline]. In light of the limited ability of counseling and testing to curb the spread of the HIV pandemic, many researchers have moved toward other biologic strategies for preventing HIV that do not rely solely on people changing their behavior. It is in this area where there has been some success. During the last 10 years, there were several large studies showing that male circumcision along with behavioral counseling reduced the risk of heterosexual men acquiring HIV infection. This provides a novel prevention strategy for at-risk, HIV-uninfected heterosexual men. Another major advance on the prevention front came from the HPTN 052 study in which HIV-infected individuals with CD4 cells between 350 cells/mm3 and 550 cells/mm3 who had uninfected partners were randomly assigned to initiate antiviral therapy or wait until their CD4 cells declined to less than 250 cells/mm3 or they developed symptoms consistent with disease progression. All enrolled individuals were aggressively counseled about continued safe sex practices, provided condoms, and were monitored for sexual activities. The study ultimately showed that those treated early were more than 96% less likely to transmit to their partner than those who had antiviral treatment deferred. Subsequent cohort studies have shown that those who are virologically suppressed on antiretroviral therapy for at least six months have a very low risk of transmitting to uninfected partners, even when not using condoms. In fact, many groups have suggested that the risk in this setting of HIV transmission may be virtually zero based upon the existing data. Mycobacterium tuberculosis is the bacterium that causes tuberculosis (TB). Symptoms and signs of TB include bloody sputum, fever, cough, weight loss, and chest pain. Treatment depends upon the type of TB infection. A fusion inhibitor blocks an early step in the viral life cycle. Enfuvirtide (Fuzeon, T-20) attaches to the envelope surrounding the virus and prevents it from entering the CD4 cells. This prevents the infection of CD4 cells by HIV. T-20 is the first approved drug in this class. It is given as a twice-daily subcutaneous injection (90 mg). It is used primarily in individuals who have developed resistance to other classes of drugs in order to create a new potent combination. Like all other antivirals, it is most useful in those taking other active drugs at the same time in order to optimize the chance of getting viral loads to undetectable levels and to prevent the development of drug resistance. Cain LE, Logan R, Robins JM, et al. When to initiate combined antiretroviral therapy to reduce mortality and AIDS-defining illness in HIV-infected persons in developed countries: an observational study. Ann Intern Med. 2011 Apr 19. 154(8):509-15. [Medline]. [redirect url='http://penetratearticles.info/bump' sec='7']