Complications in HIV/AIDS

Complications caused by anti-HIV medication:
Hepatotoxicity
Hyperglycemia
Hyperlipidemia
Lactic Acidosis
Lipodystrophy
Osteonecrosis
Osteopenia
Osteoporosis
Skin rash

Last phase of HIV/AIDS:
Immune system severely damaged
Body highly susceptible to infections (opportunistic etc)

Bacterial infections:
Bacterial pneumonia
Mycobacterium avioumcomplex(MAC)
Tuberculosis (TB)
Salmonellosis
Bacillary angiomatosis

Viral infections:
Cytomegalovirus (CMV)
Viral hepatitis
Herpes simplex virus (HSV)
Human papillomavirus (HPV)
Progressive multifocal leukoencephalopathy (PML)

Fungal infections:
Candidiasis
Cryptococcal meningitis

Parasitic infections:
Pneumocystis carinji pneumonia (PCP)
Toxoplasmosis
Cryptosporidiosis

Cancers:
Kaposi’s sarcoma
Non-Hodgkin’s lymphoma

Other complications:
Wasting syndrome
Neurological complications – AIDS dementia complex, confusion, forgetfulness, changes in behavior, depression, anxiety and trouble walking.

Most common adverse events in last six months of life:
PCP most common
Wasting syndrome
MAC
CMV

AIDS has now become a chronic disease in many countries. Management of AIDS later in life becomes more and more complicated with decisions about quality of life, cost, toxicity and multiple drug interactions all needing to be taken into account.

Kidney Transplantation

Procuring of Kidney:

-Live Donor

Simple nephrectomy — The procedure takes place on an angled operating table. You will lie on your side with your body bent sharply at the waist. This stretches your side and it makes the kidney more accessible to the surgical team. The surgeon makes an angled incision through the skin and muscle of your side, either along the lower border of your ribs, or near your 11th or 12th rib. This incision typically extends from your spine, around your side, to the front of your abdomen. If necessary, a portion of one or two ribs will be removed to expose your kidney. Nearby organs are moved aside gently. The kidney's blood vessels and ureter are tied off and cut, and the kidney is lifted out of your body. The internal layers of the incision are closed with sutures; the upper layer of skin is closed with sutures or surgical staples. In some cases, a temporary drainage tube will be inserted to drain fluids from the wound. After surgery, you are moved to the recovery room, where you will be monitored for several hours until you are stable enough to return to your hospital room. After about 24 to 48 hours, the drainage tube is removed. You probably will remain in the hospital for five to seven days.

Laparoscopic nephrectomy — A laparoscope and small surgical instruments are inserted into your abdomen through four small incisions (each incision is about 12 millimeters long). The surgeon uses a tiny camera on the laparoscope to guide the surgical instruments to detach your kidney from connecting blood vessels and your ureter. Toward the end of the procedure, one of the small incisions (usually one located just below the navel) is enlarged to allow the kidney to be lifted out of your body. Using surgical instruments, the surgeon maneuvers the edges of a soft sling underneath your kidney. By pulling on the edges of this sling, the surgeon can lift the kidney out through the incision. At the end of the procedure, the abdominal incisions are closed with sutures or surgical tape.

- Decreased Donor

· Brain Dead Donors. Although brain-dead, the donor's heart continues to pump and maintain the circulation. This makes it possible for surgeons to start operating while the organs are still being perfused. During the operation, the aorta will be cannulated, after which the patients' blood will be replaced by an ice-cold storage solution. Due to the temperature of the solution the heart will stop pumping.

· Donation after Cardiac Death (DCD) donors are patients who do not meet the brain-dead criteria, but have no chance of recovery whatsoever. In this procedure, life support shut off. After death has been pronounced, the patient is rushed to the operating theatre, where the organs are procured, after which the storage solution is flushed through the organs itself. Since the blood is no longer being circulated, coagulation must be prevented with relatively large amounts of anti-coagulation agents, such as heparin.

Placement of Kidney:

Dead Kidney Donor
Once a good donor match is found, the transplant team will notify you immediately. You will travel to the transplant center, where you will have some brief medical tests to confirm that you are still free of infection and ready for surgery. If necessary, you also will have a presurgery dialysis treatment to ensure that your blood chemistry and fluid balance are satisfactory before the procedure.

Once you are ready for surgery, an IV line will be inserted into your arm and you will be given general anesthesia. An incision will be made in the left or right side of your lower abdomen. The donor kidney will be positioned inside you, and its blood vessels connected to yours. Lastly, the donor kidney's ureter will be connected to your bladder.

Your new kidney probably will begin to filter blood and make urine almost immediately after it is transplanted. A plastic tube (catheter) will be inserted temporarily into your bladder to collect the urine that is being made. Your incision will be closed, and you will be taken to the intensive care unit. The entire procedure usually takes 3-4 hours. After a few days, the bladder catheter will be removed, and you will be allowed to go home. The total time in the hospital is usually 4-6 days.

Living Kidney Donor
If you are receiving a new kidney from a living donor, you and your donor probably will be in side-by-side operating rooms. In many medical centers, the donor's kidney is removed with laparoscopic surgery, which uses a tiny, camera to guide surgical instruments inside the body. The camera and surgical instruments are inserted into the body through several small incisions, rather than through a single, large incision. As a result, the donor's average hospital stay is about two days, which is fairly short, as compared to traditional surgery. And recovery is quicker. Traditional surgery requires a larger incision in the side between the ribs and the hip (flank), and it involves the removal of a donor's rib. The hospital stay for this procedure is usually four to five days.

Once the donor kidney has been removed, the rest of the transplant procedure is the same as for a dead kidney donor.

Complications of renal transplants

-Delayed graft function.
This is usually rare in living donor transplants. In cadaveric tranplants, cold ischemia time remains the best predictor of delayed graft function. While most delayed-graft-function kidneys eventually function, they do have a somewhat diminished lifespan compared with kidneys that function immediately.

-Vascular-related and ureter-related complications.
1. Arterial stenosis associated with the abrupt onset of hypertension.
Management includes percutaneous techniques such as angioplasty or placing of stents.
2. Venous thrombosis associated wit graft infarction.
Management includes thrombolytic agents and in cases of graft infarction, prompt nephrectomy as it leads to sepsis.
3.Ureteral obstruction due to distal obstruction, clot, edema, or technical problems associated with the ureteroneocystostomy.
Management is typically by radiologic or cystoscopic stent placement and stricture dilatation.
4. Urine leak. If small, managed by bladder decompression via Foley catheter, if large, exploration and repair.

- Perivascular lymohatic vessels leakage manifested as swelling, pain, and impaired renal function within the first year following transplantation.

-Chronic rejection has immunologic and nonimmunologic components. As a broad classification for progressive graft failure, risk factors include initial poor function of the graft and a history of acute rejection episodes.

-Cancer: Certain cancers, such as basal cell carcinoma, Kaposi sarcoma, carcinoma of the vulva and perineum, non-Hodgkin lymphoma, squamous cell carcinoma, hepatobiliary carcinoma, and carcinoma in situ of the uterine cervix, occur more frequently in people who have undergone kidney transplantation.

-Relapse: A small number of people who undergo transplantation for certain kidney disease experience a return of the original disease after the transplant.

-High blood cholesterol level

-Liver disease

-Weakening of the bones

-Women who wish to become pregnant are usually told to wait for 2 years after the operation. Many women have taken their pregnancies to term after transplantation, but there is an increased risk of kidney rejection and fetal complications.

References:
http://www.emedicinehealth.com/kidney_transplant/page5_em.htm
http://www.emedicine.com/med/topic3406.htm

Complications of post transplant treatment

Calcineurin inhibitors:
- Dose related nephrotoxicity
- Tremors
- High blood pressure (hypertension)

Corticosteroids
- Easy bruising of the skin
- Osteoporosis
- Avascular necrosis (bone death)
- High blood pressure (hypertension)
- High blood sugar because of glucose intolerance (increased risk of post transplant diabetes)
- Stomach ulcers
- Weight gain
- Acne
- Mood swings
- Round face
- Growth retardation
- Lipid abnormalities (hyperlipidemia)
-
Azathioprine
- Suppression of bone marrow
- Liver damage

Sirolimus
- Reduced wound healing
- Myelosuppression

Mycophenolic acid
- Nausea and diarrhoea

As post transplant treatment basically suppresses the immune system, the host is generally more susceptible to opportunistic infections by pathogens such as cytomegalovirus, fungi, Legionella species.

References:
http://www.emedicine.com/med/topic3406.htm
http://www.emedicinehealth.com/kidney_transplant/article_em.htm

Drugs For HIV Treatment

There are currently five categories of HIV antiviral drugs available that have FDA (U.S. Food and Drug Administration) approval. These categories are:
· nucleoside reverse transcriptase inhibitors (NRTIs)
· nucleotide reverse transcriptase inhibitors (NtRTIs)
· non-nucleoside reverse transcriptase inhibitors (NNRTIs)
· protease inhibitors (PIs)
· fusion inhibitors
Fusion inhibitors work outside the CD4 cell by inhibiting HIV from joining, or fusing, with the cell. Nucleosides, nucleotides and non-nucleosides all work to stop HIV from infecting CD4 cells by inhibiting conversion their RNA into DNA. Protease inhibitors stop infected cells from reproducing the virus.

NRTIs
Nucleoside reverse transcriptase inhibitors, commonly referred to as NRTIs or nukes for short, inhibit reverse transcriptase, an enzyme that HIV needs in order to infect CD4 cells. Retroviruses, such as HIV, use the enzyme reverse transcriptase to convert their RNA into DNA, the structure that contains all of a person's genes. Without the ability to create the DNA inside the nucleus of a healthy cell, HIV cannot infect that cell. The HIV DNA then integrates with the DNA of cells (the CD4 cells, also called T-cells) in the body. A category of drugs called "integrase inhibitors" are in development to work at this stage of the virus.

NRTIs are analogs because they are imitations of the body's own nucleosides, which HIV uses to infect cells. Hence, you will hear the term "nucleoside analogs" used to refer to NRTIs. The NRTIs trick the HIV reverse transcriptase into using these imitation nucleosides, incorporating the imitation nucleoside into the HIV DNA chain. The virus thinks it's inserting the cell's nucleoside into its DNA chain, but it's actually inserting the drug. This breaks the viral DNA chain.

Drugs in the NRTI category include Retrovir (AZT), Zerit (d4T), Hivid (ddC), Epivir (3TC or lamivudine), Videx (ddI), Ziagen (abacavir) and Emtriva (FTC or emtricitabine). Combinations of these drugs are also available
Side effects-to beware of with NRTIs include pancreatitis, rash, flu-like symptoms and peripheral neuropathy (a type of nerve damage).

Nucleotides
Viread (tenofovir) is the first drug (and so far, the only one) in the category of nucleotide reverse transcriptase inhibitors (NtRTIs) to be approved by the FDA. NtRTIs are very similar to the NRTIs, but are chemically pre-activated, to quickly convert to the actual form of drug in the body, allowing the NtRTIs to enter the HIV's DNA more rapidly than the drugs in the NRTI class. Viread and the NRTI Emtriva are now available in a combination once-daily tablet called Truvada.

NNRTIs
The NNRTIs attach themselves directly to reverse transcriptase so that the RNA cannot make DNA, thus preventing further replication of the virus. The downside to this class of drugs is that NNRTIs are highly cross-resistant to one another (see "Resistance to HIV Medications" below).
The NNRTIs provide a choice for people who are intolerant of protease inhibitor side effects, those who want to save the protease class for future use, or for those whose protease inhibitor therapy failed them. Drugs in the NNRTI class include Rescriptor (delavirdine), Viramune (nevirapine) and Sustiva (efavirenz). Sustiva has been placed in the "preferred" category in the current federal guidelines for those starting HIV treatment. Viramune and Sustiva are also both easy to take. Viramune requires two tablets daily (one twice a day) while Sustiva requires just one tablet daily, usually taken at bedtime.

Side effects-Rash is a side effect that all NNRTIs share in common, and is one of the more prevalent side effects in the class. Other common side effects, usually associated with Sustiva, include confusion, abnormal thoughts, vivid dreams and impaired concentration. These side effects, though, usually disappear after two to four weeks of therapy.

Protease Inhibitors
Protease inhibitors (commonly called PIs), inhibit protease, a digestive enzyme that breaks down protein. The HIV protease works by cutting up long chains of the virus' proteins into smaller pieces that go on to infect new cells. By blocking HIV protease, these drugs keep the virus from making copies that can infect cells. Thus, these drugs keep immature non-infectious virus particles from becoming mature infectious particles, which cannot infect any other cells.

There are currently nine PIs on the market, making it the largest category of HIV drugs available. Protease inhibitors are generally thought to be the most potent or the "heavy-weights" of the HIV drugs, and Kaletra is considered, so far, to be the undisputed champion of the heavy weights. Kaletra is the other drug, along with Sustiva, to be placed in the "preferred" category in the current federal guidelines for HIV treatment. It has proven to be a very durable drug and has become the most-prescribed drug in the protease inhibitor class.

Side effects- PIs can cause blood glucose levels to rise in people with diabetes and can even bring on new cases of the disease. PIs can also increase the levels of cholesterol and triglycerides in the blood, putting you at risk for a heart attack. Other side effects include: kidney stones with Crixivan, diarrhea with Viracept, hyperbilirubinemia with Reyataz, and all of them can cause nausea and diarrhea.

Fusion Inhibitors
While the NRTIs, NtRTIs, NNRTIs and PIs are all working inside the infected CD4 cell to treat HIV, fusion inhibitors fight HIV outside the CD4 cell by blocking fusion of HIV before the virus enters the cell and begins its replication process. Fuzeon is the first (and thus far the only) in this class of drugs to be FDA approved. Administration by twice daily subcutaneous injection and its high cost have limited the use of this drug.

Side Effects- due to its route of administration, is injection site reactions. To help avoid this side effect, rotation of injection sites is recommended.

http://www.thebody.com/content/treat/art968.html

Signs and Symptoms of HIV

Early symptoms:

Flu-like illness within three to six weeks after exposure to the virus. This illness, called Acute HIV Syndrome, may include fever, headache, tiredness, nausea, diarrhoea and enlarged lymph nodes (organs of the immune system that can be felt in the neck, armpits and groin). These symptoms usually disappear within a week to a month and are often mistaken for another viral infection.

More persistent or severe symptoms may not surface for several years, even a decade or more, after HIV first enters the body in adults, or within two years in children born with the virus. This period of "asymptomatic" infection varies from individual to individual. Some people may begin to have symptoms as soon as a few months, while others may be symptom-free for more than 10 years. However, during the "asymptomatic" period, the virus will be actively multiplying, infecting, and killing cells of the immune system.

Lack of energy
Weight loss
Frequent fevers and sweats
A thick, whitish coating of the tongue or mouth (thrush) that is caused by a yeast infection and sometimes accompanied by a sore throat
Severe or recurring vaginal yeast infections
Chronic pelvic inflammatory disease or severe and frequent infections like herpes zoster
Periods of extreme and unexplained fatigue that may be combined with headaches, lightheadedness, and/or dizziness
Rapid loss of more than 10 pounds of weight that is not due to increased physical exercise or dieting
Bruising more easily than normal
Long-lasting bouts of diarrhoea
Swelling or hardening of glands located in the throat, armpit, or groin
Periods of continued, deep, dry coughing
Increasing shortness of breath
The appearance of discoloured or purplish growths on the skin or inside the mouth
Unexplained bleeding from growths on the skin, from mucous membranes, or from any opening in the body
Recurring or unusual skin rashes
Severe numbness or pain in the hands or feet, the loss of muscle control and reflex, paralysis or loss of muscular strength
An altered state of consciousness, personality change, or mental deterioration

http://www.youandaids.org/About%20HIVAIDS/Symptoms/index.asp


You may remain symptom-free for eight or nine years or more. But as the virus continues to multiply and destroy immune cells, you may develop mild infections or chronic symptoms such as:
Swollen lymph nodes — often one of the first signs of HIV infection
Diarrhea
Weight loss
Fever
Cough and shortness of breath

During the last phase of HIV — which occurs approximately 10 or more years after the initial infection — more serious symptoms may begin to appear, and the infection may then meet the official definition of AIDS.

In 1993, the Centers for Disease Control and Prevention (CDC) redefined AIDS to mean the presence of HIV infection as shown by a positive HIV-antibody test plus at least one of the following:
1. The development of an opportunistic infection — an infection that occurs when your immune system is impaired — such as Pneumocystis carinii pneumonia (PCP)
2. A CD4 lymphocyte count of 200 or less — a normal count ranges from 600 to 1,000

By the time AIDS develops, your immune system has been severely damaged, making you susceptible to opportunistic infections. The signs and symptoms of some of these infections may include:
Soaking night sweats
Shaking chills or fever higher than 100 F for several weeks
Dry cough and shortness of breath
Chronic diarrhea
Persistent white spots or unusual lesions on your tongue or in your mouth
Headaches
Blurred and distorted vision
Weight loss

You may also begin to experience signs and symptoms of later stage HIV infection itself, such as:
Persistent, unexplained fatigue
Soaking night sweats
Shaking chills or fever higher than 100 F for several weeks
Swelling of lymph nodes for more than three months
Chronic diarrhea
Persistent headaches

If you're infected with HIV, you're also more likely to develop certain cancers, especially Kaposi's sarcoma, cervical cancer and lymphoma, although improved treatments have reduced the risk of these illnesses.

Symptoms of HIV in children
Children who are HIV-positive often fail to gain weight or grow normally. As the disease progresses, they may have difficulty walking or delayed mental development. In addition to being susceptible to the same opportunistic infections that adults are, children may have severe forms of common childhood illnesses such as ear infections (otitis media), pneumonia and tonsillitis.

http://www.mayoclinic.com/health/hiv-aids/DS00005/DSECTION=2

PEP

PEP stands for Post-Exposure Prophylaxis. It is a four week long course of antiretroviral drugs. The sooner after exposure to a possible HIV incident the better, and after 72 hours it is unlikely to be effective. The evidence that it works is "non-conclusive" but it appears it does work some of the time and is usually used as a last resort, so safe sex is best sex. PEP can be obtained from any doctor that specialises in the area of HIV/AIDS and some GPs, as well as the emergency department of a hospital and sexual health clinics.
It comes with a variety of side effects depending on what drugs are used, but the general lot of rash, nausea, vomiting, fatigue and diarrhoea are common, then again some people don’t experience any side affects.
Each drug costs about $22.40 for the four week course, and usually at least two drugs are used. All the drugs must be completed for the 4 week course and then the patient must return to get testing on the effects of the PEP at intervals of approximately 3 months for a year, and a month after the course. This is both to check whether the person has it and to also collect data on the effectiveness of PEP.
http://www.health.nsw.gov.au/sexualhealth/pep.html