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ACQUIRED INFORMATION DEFICIENCY SICKNESS (a.i.d.s)

AIDS has killed more than 25 million people since 1981. That's half as many deaths as in World War II. And it's not over. 1.1 million Americans are among the 33 million people now living with HIV, the virus that causes AIDS. In this entry, we have included a pictorial history of some landmarks of AIDS in the world and a synopsis of AIDS and its Management for those interested in the modern epidemic. Despite its highly technical in nature, we have tried to avoid the heavy stuff medical jargons. Happy reading. Please share it with your mate(s) and friends.

HIV At A Glance

* The human immunodeficiency virus (HIV) is a type of virus called a retrovirus, which infects humans when it comes in contact with tissues such as those that line the vagina, anal area, mouth, or eyes, or through a break in the skin.
* HIV infection is generally a slowly progressive disease in which the virus is present throughout the body at all stages of the disease.

* Three stages of HIV infection have been described.

1. The initial stage of infection (primary infection), which occurs within weeks of acquiring the virus, and often is characterized by a "flu-" or "infectious mononucleosis-"like illness that generally resolves within weeks.

2. The stage of chronic asymptomatic infection (meaning a long duration of infection without symptoms) which lasts an average of 8 to10 years.

3. The stage of symptomatic infection, in which the body's immune (or defense) system has been suppressed and complications have developed. This stage is called the acquired immunodeficiency syndrome (AIDS). The symptoms are caused by the complications of AIDS, which include one or more unusual infections or cancers, severe loss of weight, and intellectual deterioration (called dementia).

* When HIV grows (that is, by reproducing itself), it acquires the ability to change (mutate) its own structure. This mutation enables the virus to become resistant to previously effective drug therapy.

* The goals of drug therapy are to prevent damage to the immune system by the HIV virus and to halt or delay the progress of the infection to symptomatic disease.

* Therapy for HIV includes combinations of drugs that decrease the growth of the virus to such an extent that the treatment prevents or markedly delays the development of viral resistance to the drugs.

* The best combination of drugs for HIV has not yet been defined, but one of the most important factors is that the combination be well tolerated so that it can be followed consistently without missing doses.


AIDS Timeline

Between 1884 and 1924, somewhere near modern-day Kinshasa in West Central Africa, a hunter kills a chimpanzee. Some of the animal's blood enters the hunter's body, possibly through an open wound. The blood carries a virus harmless to the chimp, but lethal to humans: HIV. The virus spreads as colonial cities sprout up, but deaths are blamed on other causes.

1981: First Cases Recognize

In June, the CDC (Centre For Disease Control in USA) publishes a report from Los Angeles of five young homosexual men with fatal or life-threatening PCP pneumonia. Almost never seen in people with intact immune systems, PCP turns out to be one of the major "opportunistic infections" that kill people with AIDS. On the Fourth of July, the CDC reports that an unusual skin cancer -- Kaposi's sarcoma or KS -- is killing young, previously healthy men in New York City and California.


1982

* The CDC calls the new disease acquired immune deficiency syndrome or AIDS. AIDS is seen in people with hemophilia, convincing scientists that the disease is spread by an infectious agent in contaminated blood.
* Gay men form the first AIDS advocacy organizations.

1983

* The CDC warns that AIDS may spread by heterosexual sex and by mother-to-child transmission.
* The U.S. Public Health Service asks "members of groups at increased risk for AIDS" to stop donating blood.
* Heterosexual spread of AIDS in Africa is confirmed.
* Public apprehension grows. False rumors of "household spread" abound. In New York, landlords are reported to evict AIDS patients.

A baby with AIDS, abandoned after her mother's death from the disease.



1983 Drs. Montagnier and Barre-Sinoussi discovered the AIDS virus.


Pasteur Institute researchers Luc Montagnier and Francoise Barre-Sinoussi isolate a virus from the swollen lymph gland of an AIDS patient. They called it lymphadenopathy-associated virus or LAV.

Independently, UCSF researcher Jay Levy isolates ARV -- AIDS-related virus. Not until 1986 does everybody agree to call the virus HIV: human immunodeficiency virus.

1984

National Cancer Institute (NCI) researcher Robert Gallo reports isolation of an AIDS virus he calls HTLV-III. Later, it turns out to be LAV from a sample sent by the Montagnier lab.

1985

* Rock Hudson dies of AIDS.

1985 The Burke family: The father, mother, and son have HIV.


AIDS patient and advocate Ryan White, 15, wins battle to attend school

1986

* Surgeon General Everett Koop urges parents to have a "frank and open conversation" about AIDS with their children and teens.
* For the first time, President Reagan publicly utters the word "AIDS."


1987


* President Reagan makes his first speech on AIDS.
* The U.S. forbids immigration by people with HIV, a policy later signed into law by President Clinton.
* Liberace dies of AIDS.

1989

* Scientists find that even before AIDS symptoms develop, HIV replicates wildly in the blood. The goal of treatment shifts to keeping HIV at low levels.
* Robert Mapplethorpe dies of AIDS.

Esteban De Jesus, a boxer, dying of AIDS

1991-1992


* Magic Johnson announces he is HIV positive.
* Queen singer Freddy Mercury dies of AIDS.
* AIDS becomes the leading cause of death in U.S. men aged 25-44.
* FDA (Food And Drug Administration) licenses the first rapid HIV test.


1996-1997

A treatment breakthrough: The AIDS drug cocktail -- highly active anti-retroviral therapy or HAART -- can cut HIV viral load to undetectable levels. Hope surges when AIDS researcher David Ho suggests treatment could eliminate HIV from the body. He's wrong -- it's later found that HIV hides in dormant cells -- but U.S. AIDS deaths decline by more than 40%.

Dr Ho

1998-2000

Awareness grows that HAART has serious side effects. Treatment failures underscore the need for newer, more powerful AIDS drugs. In the ensuing years, the FDA approves new classes of drugs that make HIV treatment safer, easier, and more effective. But the drugs still do not cure.



2001-2002
* UN Secretary General Kofi Annan proposes the Global Fund for AIDS to extend AIDS treatment -- still totally unavailable to the vast majority of people living with AIDS. Only 1% of the 4.1 million sub-Saharan Africans with HIV receive anti-HIV drugs.
* AIDS becomes the leading cause of death worldwide for people aged 15 to 59.


2003-2005

* There is an HIV outbreak in the California porn industry.


* President Bush announces the $15 billion President's Emergency Plan for AIDS Relief. The prevention portion of the plan is criticized for over-emphasis on abstinence. But the plan provides much-needed AIDS-treatment funds to 15 nations.



2006-2007

* HIV treatment is shown to extend life by 24 years, at a cost of $618,900.
* Merck's AIDS vaccine fails in clinical trials -- the latest in a long line of vaccine failures. However, new candidate vaccines continue to move through the development pipeline.
* UNAIDS recommends adult circumcision after it's found to halve AIDS transmission from women to men in regions of high prevalence.


2008

* The CDC says improved surveillance shows AIDS in America is worse than we'd thought: 1.1 million infected, up 11% from 2003.
* New HIV infection rates soar among men who have sex with men.
HIV infections go way up in young gay men, especially young African Americans


2008

* Luc Montagnier and Francoise Barre-Sinoussi awarded Nobel Prize in medicine for discovery of HIV.
* Of the 33 million people now living with HIV, 3 million are getting treatment. That's less than a third of those who need immediate treatment. Yet for the first time, global AIDS deaths decline.

A Synopsis Of AIDS and its Management


Adapted From Work Of Medical Author : Eric S. Daar, MD

1.When was HIV discovered and how is it diagnosed?


2. How is HIV spread (transmitted)?


3.
What happens after an exposure to the blood or genital secretions of an HIV- infected person?

4.
What laboratory tests are used to monitor HIV-infected people?

5
. What are the key principles in managing HIV infection?.

6. Factors to consider before starting antiviral therapy.

7.
When to start antiviral therapy

8.
Initial therapy for HIV

9.
What about treatment for HIV during pregnancy?

10.
What about treating people exposed to the blood or genital secretions of an HIV-infected person?

11.
What can be done for people who have severe immunosuppression?

12.
What is in the future for HIV-infected individuals and for those at risk to contract HIV?





1.When was HIV discovered and how is it diagnosed?

In 1981, homosexual men with symptoms of a disease that now are considered typical of the acquired immunodeficiency syndrome (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 sarcoma. The patients were noted to have a severe reduction of a type of cell in the blood that is an important part of the immune system, called CD4 cells. 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 the human immunodeficiency virus (HIV) and belonging to the group of viruses called retroviruses. In 1985, a blood test became available that measures antibodies to HIV that are the body's immune response to the HIV. This blood test remains the best method for diagnosing HIV infection. Recently, tests have become available to look for these same antibodies in the saliva and urine, and some can provide results within 20 minutes of testing.

2.How is HIV spread (transmitted)?


HIV is present in the blood and genital secretions of virtually all individuals infected with HIV, regardless of whether or not they have symptoms. The spread of HIV can occur when these secretions come in contact with tissues such as those lining the vagina, anal area, mouth, or eyes (the mucus membranes), or with a break in the skin, such as from a cut or puncture by a needle. The most common ways in which HIV is spreading throughout the world include sexual contact, sharing needles, and by transmission from infected mothers to their newborns during pregnancy, labor (the delivery process), or breast-feeding. (See the section below on treatment during pregnancy for a discussion on reducing the risk of transmission to the newborn.)

Sexual transmission of HIV has been described from men to men, men to women, women to men, and women to women through vaginal, anal, and oral sex. The best way to avoid sexual transmission is abstinence from sex until it is certain that both partners in a monogamous relationship are not HIV-infected. Because the HIV antibody test can take up to 6 months to turn positive, both partners would need to test negative 6 months after their last potential exposure to HIV. If abstinence is out of the question, the next best method is the use of latex barriers. This involves placing a condom on the penis as soon as an erection is achieved in order to avoid exposure to pre-ejaculatory and ejaculatory fluids that contain infectious HIV. For oral sex, condoms should be used for fellatio (oral contact with the penis) and latex barriers (dental dams) for cunnilingus (oral contact with the vaginal area). A dental dam is any piece of latex that prevents vaginal secretions from coming in direct contact with the mouth. Although such dams occasionally can be purchased, they are most often created by cutting a square piece of latex from a condom.

The spread of HIV by exposure to infected blood usually results from sharing needles, as in those used for illicit drugs. HIV also can be spread by sharing needles for anabolic steroids to increase muscle, tattooing, and body piercing. To prevent the spread of HIV, as well as other diseases including hepatitis, needles should never be shared. At the beginning of the HIV epidemic, many individuals acquired HIV infection from blood transfusions or blood products, such as those used for hemophiliacs. Currently, however, because blood is tested for antibodies to HIV before transfusion, the risk of acquiring HIV from a blood transfusion in the United States is extremely small and is considered insignificant.

There is little evidence that HIV can be transferred by casual exposure, as might occur in a household setting. For example, unless there are open sores or blood in the mouth, kissing is generally considered not to be a risk factor for transmitting HIV. This is because saliva, in contrast to genital secretions, has been shown to contain very little HIV. Still, theoretical risks are associated with the sharing of toothbrushes and shaving razors because they can cause bleeding, and blood contains large amounts of HIV. Consequently, these items should not be shared with infected persons. Similarly, without sexual exposure or direct contact with blood, there is little if any risk of HIV contagion in the workplace or classroom.

3.What happens after an exposure to the blood or genital secretions of an HIV- infected person?


The risk of HIV transmission occurring after any potential exposure to bodily fluids is poorly defined. The highest risk sexual activity, however, is thought to be anal intercourse without a condom. In this case, the risk of infection may be as high as 3% to 5% for each exposure. The risk is probably less for vaginal intercourse without a condom and even less for oral sex without a latex barrier. Despite the fact that no single sexual exposure carries a high risk of contagion, HIV infection can occur after even one sexual event. Thus, people must always be diligent in protecting themselves from potential infection.

Within 2 to 6 weeks of an exposure, the majority of infected persons will have a positive HIV antibody test, with virtually all being positive by 6 months. The test used most commonly for diagnosing infection with HIV is referred to as an ELISA. If the ELISA finds the HIV antibody, the presence of the antibody is confirmed by a test called a Western blot. During this period of time shortly after infection, more than 50% of those infected will experience a "flu-like" or "infectious mono-like" illness for up to several weeks. This illness is considered the stage of primary HIV infection. The most common symptoms of primary HIV infection are:

* fever
* aching muscles and joints
* sore throat, and;
* swollen glands (lymph nodes) in the neck.

It is not known, however, why only some HIV-infected persons develop these symptoms. It also is unknown whether or not having the symptoms is related in any way to the future course of HIV disease. Regardless, infected persons will become symptom-free (asymptomatic) after this phase of primary infection. During the asymptomatic phase, infected individuals will know whether or not they are infected only if a test for HIV is done. Therefore, anyone who might possibly have been exposed to HIV should seek testing even if they are not experiencing symptoms. HIV testing can be performed by a physician or at a testing center.

During the asymptomatic stage of infection, literally billions of HIV particles (copies) are produced every day and circulate in the blood. This production of virus is associated with a decline (at an inconsistent rate) in the number of CD4 cells in the blood over the ensuing years. Although the precise mechanism by which HIV infection results in CD4 cell decline is not known, it probably results from a direct effect of the virus on the cell as well as the body's attempt to clear these infected cells from the system. In addition to virus in the blood, there is also virus throughout the body, especially in the lymph nodes, brain, and genital secretions. The time from HIV infection to the development of AIDS varies. Some people develop symptoms, signaling the complications of HIV that define AIDS, within 1 year of infection. Others, however, remain completely asymptomatic after as many as 20 years. The average time for progression from initial infection to AIDS is 8 to10 years. The reason why different people experience clinical progression of HIV at different rates remains an area of active research.

4.What laboratory tests are used to monitor HIV-infected people?


Two blood tests are routinely used to monitor HIV-infected people. One of these tests, which counts the number of CD4 cells, assesses the status of the immune system. The other test, which determines the so-called viral load, directly measures the amount of virus.

In individuals not infected with HIV, the CD4 count in the blood is normally above 500 cells per cubic milliliter (mm3) of blood. HIV-infected people generally do not become at risk for complications until their CD4 cells are fewer than 200 cells per mm3. At this level of CD4 cells, the immune system does not function adequately and is considered suppressed. Patients who have this CD4 count (fewer than 200 cells per mm3) are referred to as being immunosuppressed. A declining number of CD4 cells means that the HIV disease is advancing. Thus, a low CD4 cell count signals that the person is at risk for one of the many unusual infections (the so-called opportunistic infections) that occur in individuals who are immunosuppressed. In addition, the actual CD4 cell count indicates which specific therapies should be initiated to prevent those infections.

The viral load predicts whether or not the CD4 cells will decline in the coming months. In other words, those persons with high viral loads are more likely to experience a decline in CD4 cells and progression of disease than those with lower viral loads. Therefore, knowing the amount of virus can be used to predict the development of the disease. The viral load also is a vital tool for monitoring the effectiveness of new therapies and determining when drugs stop working. Thus, the viral load will decrease within weeks of initiating an effective antiviral regimen. If a combination of drugs is very potent, the number of HIV copies in the blood will decrease by as much as 100-fold, such as from 100,000 to 1,000 copies per mL of blood in the first 2 weeks and gradually decrease even further during the ensuing 12 to 24 weeks. Moreover, it has become increasingly clear that the greater the decline of the viral load after beginning therapy, the longer it will remain suppressed. The ultimate goal is to get viral loads to below the limits of detection by standard assays, usually less than 50 or 75 copies per mL of blood. When viral loads are reduced to these low levels, it is believed that the viral suppression may persist for many years.

Drug resistance testing also has become a key tool in the management of HIV-infected individuals. Details of these tests will be discussed later. Clearly, resistance testing is now routinely used in individuals experiencing poor responses to HIV therapy or treatment failure. In general, a poor response to initial treatment would include individuals who fail to experience a decline in viral load of approximately 100-fold in the first 8 weeks, have a viral load of greater than 500 copies per mL by week 12, or have levels greater than 50 or 75 copies per mL by week 24. Treatment failure would generally be defined as an increase in viral load after an initial decline in a person who is believed to be consistently taking his or her medications. More recent guidelines from the U.S. Department of Health and Human Services (DHHS) (www.hivatis.org) and International AIDS Society-USA (IAS-USA) have suggested that resistance testing be considered in individuals who have never been on therapy, particularly in the first months or even years of infection, to determine if they might have acquired HIV that is resistant to drugs. In fact, the most recent DHHS guidelines (May 4, 2006) formally recommend such testing be performed in all individuals starting therapy for the first time.

5.What are the key principles in managing HIV infection?


First of all, there is no evidence that people infected with HIV can be cured by the currently available therapies. In fact, individuals who are treated for up to three years and are repeatedly found to have no virus in their blood experience a prompt rebound increase in the number of viral particles when therapy is discontinued. Consequently, the decision to start therapy must balance the risk of an individual advancing to the stage of symptomatic disease against the risks associated with therapy. The risks of therapy include the short and long-term side effects of the drugs, described in subsequent sections, as well as the possibility that the virus will become resistant to therapy. This resistance then limits the options for future treatment.

A major reason that resistance develops is the patient's failure to correctly follow the prescribed treatment, for example, by not taking the medications at the correct time. In addition, the likelihood of suppressing the virus to undetectable levels is not as good for patients with lower CD4 cell counts and higher viral loads. Finally, if virus remains detectable on any given regimen, resistance eventually will develop. Indeed, with certain drugs, resistance may develop in a matter of weeks, such as with lamivudine (EpivirTM, 3TC), emtricitabine (EmtrivaTM, FTC) and the drugs in the class of nonnucleoside analogue reverse transcriptase inhibitors (NNRTI) such as nevirapine (ViramuneTM, NVP), delavirdine (RescriptorTM, DLV), and efavirenz (SustivaTM, EFV). Thus, if these drugs are used as part of a combination of drugs that does not suppress the viral load to undetectable levels, resistance will develop rapidly and the treatment will be ineffective. In contrast, HIV becomes resistant to certain other drugs, such as zidovudine (RetrovirTM, AZT), stavudine (ZeritTM, D4T), and protease inhibitors (PIs), over months. In fact, for some PIs whose effects are enhanced by giving them in combination with the PI, ritonavir (NorvirTM, RTV) to prevent their clearance by the body, resistance appears to be markedly delayed. These drugs are discussed in more detail in subsequent sections, but it is important to note that when resistance develops to one drug, it often results in resistance to other related drugs, so called cross-resistance. Nevertheless, HIV-infected individuals must realize that antiviral therapy can be very effective. This is the case even in those who have a low CD4 cell count and advanced disease, as long as drug resistance has not developed.

6.Factors to consider before starting antiviral therapy


One of the most controversial areas in the management of HIV disease is deciding the best time to start antiviral treatment. Clearly, therapy during the mildly symptomatic stage of the disease delays its progression to AIDS, and treating individuals with AIDS postpones death. Consequently, most experts agree that patients who have experienced complications of HIV disease, such as oral thrush (yeast infection in the mouth), chronic unexplained diarrhea, fevers, weight loss, opportunistic infections, or dementia (for example, forgetfulness) should be started on antiviral treatment even if the symptoms are mild. In patients who do not have symptoms, however, there is more uncertainty. Most recommendations for this group are based on the predictors of clinical progression, such as the number of CD4 cells and the viral load. Thus, several studies have demonstrated an increased risk of disease advancement in individuals with a CD4 cell count of less than 200 to 350 cells per mm3. Similarly, those with elevated viral loads, regardless of the CD4 cell count, are at increased risk for disease progression. Debate continues, however, regarding the best threshold level at which to set the viral load to trigger the beginning of drug treatment. In fact, it is likely that there will never be a proper study to answer this question. Therefore, the decision as to when to start treatment continues to be individualized, balancing the known benefits of therapy versus the risks, such as toxicity and the potential development of drug resistance. One can envision that as treatments become easier to take, better tolerated, and increasingly effective, that therapy will begin to be started earlier in the course of infection.

7. When to start antiviral therapy


Guidelines for starting antiviral therapy have been proposed by panels of experts from the DHHS and the IAS.- They recommend treating all patients who have symptoms and those who have CD4 cell counts of less than 200, and, perhaps, 350 cells per mm3 or in those with higher viral loads. Of late, there has been a trend towards focusing more on CD4 cell counts than viral loads in making the decision as to when therapy should be started in asymptomatic individuals. The DHHS guidelines have suggested that therapy be considered even in those with higher CD4 cell counts if viral load is greater than 100,000 copies per mL, or, at least, that CD4 cell counts be followed more closely in this group. The IAS-USA guidelines have tended to use a viral load cutoff for considering therapy in asymptomatic individuals with CD4 cells greater than 100,000 copies per mL. However, it should be kept in mind that the risk of developing short- and long-term toxicity from treatment, and the problem with getting patients to adhere to treatment, are major limitations of therapy that need to be considered before treatment is initiated in order to optimize the chances of success and to avoid the development of drug resistance. Other authorities, therefore, have proposed delaying therapy until the viral load is even higher. Regardless, all agree that HIV is a slowly progressive disease, and therapy rarely needs to be started abruptly. Therefore, there usually is time for each patient to carefully consider options prior to starting treatment.

Before starting treatment, patients must be aware of the short and long-term side effects of the drugs, including the fact that some long-term complications may not be known. The patients also need to realize that therapy is a long-term commitment and requires an extraordinary level of adherence to the regimen of drugs. In addition, clinicians and patients should recognize that depression, feelings of isolation, substance abuse, and side effects of the antiviral drugs can all be associated with the failure to follow the treatment program.

8.Initial therapy for HIV


Guidelines for using antiviral therapy have been developed and are updated on a regular basis by an expert panel assembled by the DHHS and the Henry J. Kaiser Foundation and the IAS-USA Panels. The DHHS guidelines are only one of several developed to provide recommendations for the treatment of HIV disease (www.hivatis.org). The most recent IAS-USA Guidelines were published in the Journal of the American Medical Association (JAMA) in the summer of 2004.

Antiviral treatment options have primarily included combinations of 2 nucleoside analogue reverse transcriptase inhibitors (NRTI), often referred to as "nucs," and 1 PI. In addition, together with 2 NRTIs, several combinations of 2 PIs have been used instead of a single PI because these regimens are easier to follow and/or have fewer side effects. Alternative preferred regimens include NRTIs with NNRTIs, often called "non-nucs." These NNRTI-containing combinations generally are easier to take than PI-containing combinations and tend to have different side-effects. Although there has been a great deal of interest in the possibility of using an all NRTI regimen, usually as 3 drugs from this class in combination, studies show that, at best, they are less potent than other treatment options. In addition, there are some triple NRTI combinations that have been shown not to be effective and that should be avoided, such as the nucleotide analogue RTI tenofovir (VireadTM, TDF) with 3TC and abacavir (ZiagenTM, ABC) and TDF, didanosine (VidexTM, ddI) and ABC. Results using combinations of 4 NRTIs are limited at this time.

9.What about treatment for HIV during pregnancy?


One of the greatest advances in the management of HIV infection has been in pregnant women. Prior to antiviral therapy, the risk of HIV transmission from an infected mother to her newborn was approximately 25-35%. The first major advance in this area came with studies giving ZDV after the first trimester of pregnancy, then intravenously during the delivery process, and then after delivery to the newborn for 6 weeks. This treatment showed a reduction in the risk of transmission to less than 10%. Although less data are available with more potent drug combinations, clinical experience suggests that the risk of transmission may be reduced to less than 5%. Current recommendations are to advise HIV-infected pregnant women regarding both the unknown side effects of antiviral therapy on the fetus, and the promising clinical experience with potent therapy in preventing transmission. In the final analysis, however, pregnant women with HIV should be treated essentially the same as non-pregnant women with HIV. Exceptions would be during the first trimester, where therapy remains controversial, and avoiding certain drugs that may cause greater concern for fetal toxicity, such as EFV.

All HIV-infected pregnant women should be managed by an obstetrician with experience in dealing with HIV-infected women. Maximal obstetric precautions to minimize transmission of the HIV virus such as avoiding scalp monitors, and minimizing labor after rupture of the uterine membranes. In addition, the potential use of an elective Caesarean section (C- section) should be discussed, particularly in those women without good viral control of their HIV infection where the risk of transmission may be increased. Breastfeeding should be avoided if alternative nutrition for the infant is available since HIV transmission can occur by this route. Despite the reduced risk of transmission associated with antiviral therapy, pregnant women with HIV need to be thoroughly counseled regarding all risks, as well as all options, including therapeutic abortions when appropriate. Updated guidelines for managing HIV-infected women are updated on a regular basis and can be found at www.hivatis.org.

10.What about treating people exposed to the blood or genital secretions of an HIV-infected person?


Recently, a great deal of interest has focused on preventing transmission to uninfected persons that are inadvertently exposed by the early administration of antiviral therapy. Because the risk of infection after most isolated exposures is relatively small, generally less than 5%, formal studies are difficult to perform. Animal studies and some human experience, however, suggest that post-exposure treatment may be effective. In fact, the current recommendation is that health care workers who experience a needlestick from an infected person take antiviral medication for 4 weeks in order to reduce the risk of infection. Extending that recommendation, many physicians have proposed similar preventive treatment for people with sexual exposures to HIV. Those individuals considering this type of preventative treatment must be aware that post-exposure treatment cannot be relied upon to prevent HIV infection. Second, such treatment is not always available at the time most needed and is probably best restricted to unusual and unexpected exposures, such as a broken condom during intercourse. Third, although regimens with 2 or 3 drugs generally are recommended for those exposed in the healthcare setting, the best therapy for sexual exposure still is unknown. Fourth, therapy probably will be most effective if started within the first 2 hours after an exposure. And finally, a 4-week supply of a three-drug combination of antiviral drugs costs approximately $1000 and generally is not covered by insurance. Updated guidelines are published and available at www.hivatis.org.

11.What can be done for people who have severe immunosuppression?


Although one goal of antiviral therapy is to prevent the development of immune suppression, some individuals are already immunosuppressed when they first seek medical care. In addition, others may progress to that stage as a result of resistance to antiviral drugs. Nevertheless, every effort must be made to optimize antiviral therapy in these patients. In addition, certain specific antibiotics should be initiated, depending on the number of CD4 cells, to prevent the complications (that is, the opportunistic infections) that are associated with HIV immunosuppression. Guidelines for the prevention of opportunistic infections can be found at www.hivatis.org.

In summary, patients with a CD4 cell count of less than 200 should receive preventative treatment against Pneumocystis carinii (the opportunistic bacteria that causes pneumonia and is now known as Pneumocystis jiroveci) with trimethoprim/sulfamethoxazole (BactrimTM, SeptraTM), given once daily or three times weekly. If they are intolerant to that drug, patients can be treated with an alternative drug such as dapsone, or atovaquone (MepronTM). Those patients with a CD4 cell count of less than 100 who also have evidence of past infection with Toxoplasma gondii, which is usually determined by the presence of toxoplasma antibodies in the blood, should receive trimethoprim/sulfamethoxazole. Toxoplasmosis is an opportunistic parasitic disease that affects the brain and liver. If a person is using dapsone to prevent Pneumocystis carinii (P. jiroveci), pyrimethamine and leucovorin can be added once a week to their regimen to prevent toxoplasmosis. Finally, patients with a CD4 cell count of less than 50 should receive preventive treatment for Mycobacterium avium complex (MAC) infection with weekly azithromycin (ZithromaxTM), or as an alternative, twice daily clarithromycin (BiaxinTM) or mycobutin (RifabutinTM). MAC is an opportunistic bacterium that causes infection throughout the body.

12.What is in the future for HIV-infected individuals and for those at risk to contract HIV?


Trends continue towards simplifying drug regimens to improve adherence and decrease side effects. In addition, many new drugs are being developed. These new drugs are in both the currently available classes of anti-HIV medications as well as in new classes of drugs, such as those that block the virus from entering cells or from incorporating itself into the human genetic material. Both of these actions prevent the virus from duplicating itself, thereby inhibiting an increase in the viral load. Perhaps even more importantly, researchers are attempting to enhance the body's natural defenses against HIV in order to control viral growth. An example of this approach is the use of an HIV vaccine, with or without antiviral therapy. Also, innovative studies are underway to try to purge or eliminate the HIV from the body. The rationale for purging is to allow for the withdrawal of therapy without a rebound increase in the number of viral particles in the blood. For example, drugs have been developed to stimulate HIV-infected CD4 cells, which then would be expected to undergo viral or immune self-destruction. Although all of this research is exciting and promising, the reality is that in the near future, patients will need to remain on antiviral therapy.

The good news is that the development of antiviral therapy has led to a marked decline in AIDS-related deaths in many parts of the world. The majority of infected individuals, however, do not have access to the expensive antiviral medications. Accordingly, the best hope for limiting the current epidemic of HIV around the world remains an effective vaccine. Unfortunately, despite increasing research in this area, the development of a vaccine continues to lag far behind the progress that has been made in antiviral therapy.


Updated guidelines for managing HIV-infected women are updated on a regular basis and can be found at www.hivatis.org.

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