The Risks Resistance Clinical Problems AIDS

Viral resistance has to be anticipated whenever there is viral replication in the presence of suboptimal drug levels, and when resistant mutants have a selective advantage over the wild-type virus. As a result, there are concerns that resistance may develop particularly during the washout phase of medication (increasing viral replication with insufficient plasma levels) and on re-initiation of treatment (continued replication despite sufficient plasma levels). However, in the case of single...

Pregnancy and HIV

Therapy for mothers and prevention for neonates Perinatal (vertical) HIV infection has become rare since the introduction of antiret-roviral transmission prophylaxis and elective cesarean section. While the vertical HIV transmission rate ranged from 15 to 20 in the United States and Europe at the beginning of the nineties, it now amounts to only a few percent (Connor 1994, European Collaborative Study 2001, Marcollet 2002, Hollwitz 2004). Postpartum HIV infections are avoidable provided that...

Herpes zoster

Herpes zoster is the reactivation of an earlier infection with varicella virus, which subsequently resides lifelong in the spinal ganglia. Herpes zoster episodes occur even in HIV patients with relatively good immune status, and are also seen during immune reconstitution (Martinez 1998). With more advanced immunodeficiency, herpes zoster tends to become generalized. In addition to involvement of one or more dermatomes, dangerous involvement of the eye (affecting the ophthalmic branch of the...

Clinical manifestations

MtDNA-depletion may manifest clinically in one or several main target tissues (Fig. 1). In the liver mitochondrial toxicity is associated with increased lipid deposits, resulting in micro or macrovesicular steatosis. Steatosis may be accompanied by elevated transaminases. Such steatohepatitis may progress to liver failure and lactic acidosis, a potentially fatal, but fortunately rare complication. Although steatohepatitis and lactic acidosis were already described in the early 90s in patients...

The interaction of dendritic cells and BT cells

B and T lymphocytes may be regarded as the principle effector cells of antigen-specific immune responses. However, their function is under the control of dendritic cells. DC are able to pick up antigens in the periphery. These antigens are processed and expressed on the cell surface, together with co-stimulatory molecules that initiate T cell activation. B cells may recognize antigen after binding to the B cell receptor. Recognition of antigen by T cells requires previous processing and...

Maternofetal

In the absence of any intervention an estimated 15-30 of mothers with HIV infection will transmit the infection during pregnancy and delivery. In approximately 75 of these cases, HIV is transmitted during late pregnancy or during delivery. About 10 of vertical HIV infections occur before the third trimester, and 10-15 are caused by breastfeeding. In Western countries, perinatal (vertical) HIV infection has become rare since the introduction of antiretroviral transmission prophylaxis and...

Course of hepatitis B with concurrent HIV infection

In HIV-infected patients, chronic hepatitis B has an unfavorable course compared with monoinfected patients, and the risk of liver-associated mortality is significantly increased. Data from the Multicenter AIDS Cohort Study (MACS) have demonstrated the unfavorable influence of HIV infection on hepatitis B (Thio 2002). In approximately 5,000 patients observed over a period of 14 years, the risk of liver-associated mortality was 8 times higher than in HBs antigen negative HIV patients (14.2 1,000...

Malaria

Malaria does not behave like an opportunistic infection. Still, the details on the interaction between HIV and malaria are widely unknown. Malaria seems to increase HIV replication through proinflammatory cytokines. HIV infected pregnant women appear to have a higher malaria risk. Malaria-HIV coinfection in pregnancy is associated with increased parasitemia and a higher incidence of prematurity as well as low birth weight (Ayisi 2003, ter Kuile 2004). Until recently, the clinical influence of...

Treatment General

Treatment should be initiated immediately if there is clinical suspicion. In cases of mild PCP (BGA PO2 > 70-80 mm Hg), ambulatory treatment can be attempted oral medication can even be administered in very mild forms. This may well be possible in cooperation with a competent HIV nursing service. If such monitoring is not possible, if respiratory deterioration occurs, and in every case with resting dyspnea, immediate hospitalization is advised. If ventilation becomes necessary, patients have...

Dermatological examination and therapy in HIVinfected patients

HIV-infected patients with advanced disease often suffer from common skin diseases (Table 1), but they also present with rare dermatoses, unique to HIV infection. Careful dermatologic evaluation may lead to the diagnosis of serious systemic infections in this population such as cryptococcosis, bacillary angiomatosis, oral hairy leukoplakia, and Penicillium marneffei infections of the skin. Common dermatoses often present with atypical findings and may pose diagnostic dilemmas. For example,...

Avascular necrosis

Avascular necrosis occurs in approximately 0.4 of HIV patients, and is therefore significantly more frequent than in the general population (Cheonis 2002). The postulated association with PIs could not be confirmed (Miller 2002, Loiseau-Peres 2002). Risk factors for avascular necrosis are alcohol abuse, hyperlipidemia, steroid treatment, hypercoagulability, hemoglobinopathy, trauma, nicotine abuse and chronic pancreatitis. Virological (viral load) parameters are not associated with a risk of...

Antiretroviral agents in pregnancy

Nucleoside Reverse Transcriptase Inhibitors (NRTIs) Nucleoside analogs cross the placenta and can cause toxic damage not only to the mother but also to the child. The main problems are anemia and, when using combination therapy, lactate acidosis. On the basis of pregnancies observed to date, it can be maintained that frequently used nucleoside analogs such as AZT, 3TC and d4T, do not increase teratogenicity by more than twofold (Antiretroviral Pregnancy Registry 2004). Most of our experience is...

Virological Treatment Failure

Every change in treatment due to virological failure requires experience and a certain degree of finesse. But also decisiveness There are many possibilities for mistakes here. It is important to explain the reasons for change to the often skeptical patient (Shouldn't I save other drugs for later ). HAART should be rapidly changed in the case of insufficient viral suppression and or after an increase in plasma viremia, as suboptimal therapy always carries the risk of new resistance mutations,...

Sexual intercourse

Unprotected sexual intercourse is the most important transmission route of HIV infection worldwide. Although receptive anal sex is estimated to produce the highest risk of infection, infection after a single insertive contact has also been described. The presence of other sexually transmitted diseases markedly increases the risk of becoming infected with HIV. The lower the viral load, the less infectious the patient. A prospective study of 415 HIV-discordant couples in Uganda showed that of 90...

Asthma bronchiale

It could be supposed that an immunosuppressing disease such as HIV infection would at least protect patients from manifestations of exaggerated immune reaction such as allergies and asthma. However, the opposite is the case in a study from Canada concerning HIV-infected men, more than half of the interviewees had suffered an episode of wheezing within the previous 12 months, and nearly half of those showed evidence of bronchial hyperreactivity. These findings were particularly distinct among...

Chemotherapy

Chemotherapy harbors particular risks for HIV-infected patients. Bone marrow suppression, induced by chemotherapy, can lead to deterioration of existing, HIV-associated cellular immunodeficiency and occurrence of acute, life-threatening opportunistic infections. To maintain a high quality of life for the patient for as long as possible, HIV-associated KS should only be treated by chemotherapy in the presence of clinical symptoms (e.g. pain), rapid tumor progression and or visceral involvement....

Nausea and vomiting

If administration on an empty stomach leads to nausea and vomiting, most drugs can also be taken together with meals. When a drug (e.g. didanosine, indinavir, rif-ampin) has to be administered on an empty stomach, small quantities of low-fat salty crackers may lessen the nausea. Ginger, peppermint or chamomile teas or sweets may also be helpful, as well as frequent small meals. Care should be taken with fatty foods and dairy products. Coffee, smoking, alcohol, aspirin and very spicy foods...

Transmission risk

HIV is not a very contagious pathogen. The transmission rate after a high-risk contact is about 1 1000 to 1 100. Compared with HIV, the transmission rate for hepatitis C virus is 10 times higher, and 100 times higher for hepatitis B virus. Factors for the probability of transmission are the amount of incorporated virus and the exposure time. Contact with body fluids of a patient with a high viral load probably holds a higher risk of contagion than a similar contact with body fluids of a patient...

Renal problems Indinavir

Renal problems occur particularly on indinavir treatment, and are caused by indina-vir crystals, which may be found in the urine of up to 20 of patients. Approximately 10 of patients develop nephrolithiasis, which is not visible on X-ray, accompanied by renal colic. Nephrolithiasis is primarily caused by high indinavir levels in relation to a low body mass index (Meraviglia 2002), drug interactions and individual fluctuations of the drug plasma level. In one study, the intake of indina-vir...

Special case Needlestick injury or other occupational HIV exposure

Here, two aspects need to be considered testing of the index patient (the donor from whom the potential risk of infection arose) and testing of the exposed (the recipient). The national and local regulations pertaining to this must of course be followed, for legal and other reasons. If the index patient is known, he should be tested - after relevant counselling and consent ideally the injured individual's superior should be called in immediately -for HIV antibodies, HBsAg (do not forget...

Potential risks of PEP

The risks of PEP mainly concern the adverse effects of the antiretroviral substances. Most frequently this refers to gastrointestinal symptoms such as nausea, vomiting or diarrhea. Also possible are changes of hematology, transaminases or creatinine. There have been reports about elevated triglyceride and cholesterol levels and insulin resistance even in short term use of protease inhibitors. It is unknown whether the temporary use of antiretroviral substances may lead to long term side...

Signs and symptoms Diagnosis

Acute, usually high, fever and productive cough are typical. Breathing may be painful because of accompanying pleuritis, but real dyspnea is rare. Auscultation almost always allows distinction from PCP. If something can be heard, PCP is unlikely Chest radiography secures the diagnosis. CRP is significantly elevated, LDH usually normal. It is essential to take several blood cultures at body temperatures above 38.5 C before starting treatment. Sputum culture is a simple method allowing...

Chemokine receptors as coreceptors for HIV entry

A milestone for the characterization of the early events leading to HIV-1 entry was an observation by Cocchi and his co-workers in 1995. CD8+ T cells from HIV-infected patients are able to suppress viral replication in co-cultures with HIV-infected autologous or allogenic CD4 T cells, and this is independent from their cytotoxic activity (25). Cocchi identified the chemokines MIP-1a, MIP-1B and Rantes in supernatants from CD8+ T cells derived from HIV-infected patients, and was able to show...

Anamnesis

What previous illnesses has the patient had Someone who has suffered from PCP once has a higher risk of subsequent infection. A patient with hyperlipidemia and carotid stenosis might have coronary heart disease. What medication does the patient take Taking cotrimoxazole usually prevents PCP, and the risk of bacterial pneumonia may also be reduced (Beck 2001). In the case of PCP prophylaxis with pentamidine inhalation, however, atypical, often apically pronounced manifestations of PCP are to be...

NRTI and lipodystrophy

The patterns of fat redistribution in patients who are exclusively receiving NRTIs are unlike those observed in patients during PI therapy. Peripheral fat loss is the major symptom observed in NRTI therapy (particularly using stavudine and di-danosine combinations), although a few clinical studies have described a minimal intra-abdominal fat increase in these patients, which is clearly less than under PIs. Given that, commonly, only a mild increase in triglycerides has been observed, exclusive...

HIV and HCV Coinfection Epidemiology and Transmission

Coinfection with HIV and HCV occurs frequently, due to the fact that both are transmitted via the same pathways (parenteral, sexual, vertical). 240,000 people (30 of HIV-infected individuals) are estimated to be infected with both viruses in the USA. Several European countries have even higher rates of coinfection. In Spain, at least 50 of the 130,000 HIV-infected patients are also HCV-positive as a result of the high incidence of i.v. drug users. More than 90 of coinfected individuals are...

Diagnosis of HIV infection 18 months of age

The detection of anti-HIV antibodies does not prove an infection in infants. High titers of anti-HIV IgG are transferred transplacentally from mother to child. Maternal antibodies can be detected in children up to the age of 18 months. Therefore a direct method of detecting HIV is necessary. Identification by PCR is highly sensitive and specific. Detection of HIV can be achieved within the first 48 hours after birth in 38 of infected children, and within the first 2 weeks in 93 of children...

Other Important Aspects of HAART

Besides the goals described above - virological, immunological and clinical treatment success - several other aspects need to be considered. Cost reduction, prevention, and improving compliance remain a constant challenge for every HIV clinician. It is important for clinicians to be informed about the price of drugs which they prescribe and to rationalize in any way that would be cost beneficial to patients and health services. Antiretroviral therapies are expensive. Individual drugs cost...

Specific side effects Enfuvirtide T20

The typical side effect of enfuvirtide is an injection site reaction (ISR) with erythema, induration, nodules, pruritus, ecchymosis, pain and discomfort. Almost every patient is affected, most of them, however, only mildly. ISR, therefore, rarely limits treatment, and only 3 to 7 of patients discontinue therapy (Arasteh 2004, Lazzarin 2003). The practitioner and the patient have to get used to the injection technique and the management of ISR. Good injection technique (including aseptic...

Mega and GigaHAART Treatment Interruptions

Following the slogan the more, the bettef', several studies have shown that different intensified treatment combinations - often described as mega- or giga- HAART - may indeed be effective. The success of these mostly uncontrolled studies is debatable. On five- or six-drug regimens, sufficient suppression of viral load was achieved only in a variable percentage of patients (22-52 Grossman 1999, Miller 2000, Montaner 2001, Piketty 2002, Youle 2002). First and foremost, these studies indicate...

CDC Classification System

The most widely accepted classification system of HIV infection, initially published by the U.S. Centers for Disease Control and Prevention (CDC) in 1986, is based on certain conditions associated with HIV infection (see Table 1). This classification system was intended for use in conducting public health surveillance and it has been a useful epidemiological tool for many years. In 1993, the CDC classification was revised (CDC 1993b). Since then, the clinical definition of AIDS has been...

Vaccinations

A travel medicine consultation is an opportunity to check and complete routinely recommended immunizations such as tetanus diphtheria, pneumococcal, influenza, and hepatitis B vaccination. It has to be kept in mind that the southern hemisphere influenza season is from April to September, while in the tropics influenza can occur all year long. Additional immunizations have to be considered according to travel style, duration, and destination. Open immunization questions usually require the...

Ritonavir

Due to its gastrointestinal side effects, the therapeutic dose of ritonavir is hardly acceptable and rarely prescribed. However, ritonavir has become an important drug for boosting other protease inhibitors. In these combinations, when lower doses are used, side effects of ritonavir are tolerable. Numerous drug interactions must be considered. 100 mg soft gel capsules 80 mg ml oral solution Drug class protease inhibitor Manufacturer Abbott Indications HIV infection Oral dose in rare cases, in...

The HLA system and the immune response to HIV

CD8 T cells recognize their antigen (peptide) in context with HLA class I molecules on antigen-presenting cells, whereas CD4 T cells require the presentation of antigenic peptides in context with HLA class II molecules. The generation of an HIV-specific immune response is therefore dependent on the individual HLA pattern. Antigen-presenting cells may bind HIV peptides in different ways within grooves on the HLA class I molecules. Therefore, CD8 T cells can be activated in an optimal or...

Lymphatic tissue as the site of viral replication

Viral replication within the lymphatic tissue is already extensive in the early stages of the disease (50,51). During the initial phase of HIV-1 infection, there is a burst of virus into the plasma, followed by a relative decline in viremia. During this time, a strong HIV-1 specific cytotoxic T cell response is generated, which coincides with the early suppression of plasma viremia in most patients. Virions are trapped by the follicular dendritic cell (FDC) network within the lymphoid tissue....

Delavirdine

Delavirdine is rarely used, due to impractical dosing and drug interactions. However, the drug has theoretical potential. It is fairly well tolerated (no hepatotoxicity, no CNS problems), and increases levels of indinavir and saquinavir. Disadvantage It has the usual NNRTI cross-resistance, and high pill burden. Drug class non-nucleoside reverse transcriptase inhibitor (NNRTI) Manufacturer Pfizer Indications HIV infection Oral dose 400 mg tid Side effects rash, usually occurring within the...

Change Due to Concern over Longterm Toxicity

In the last few years, many clinicians have started to change virologically successful combinations out of concern for cumulative long-term toxicities. In particular PI- and d4T-containing combinations are sometimes replaced with NNRTIs and other nucleoside analogs. A large number of so-called switch studies have appeared in the last few years on this topic. The most important randomized studies are discussed below. It should be noted that a considerable number of these studies are not yet...

Bacillary angiomatosis

Bacillary angiomatosis was first described in the 1980s in HIV patients (detailed, freely accessible review Maguina 2000, http hiv.net link.php id 11). Bacillary angiomatosis is caused by the rickettsial species Bartonella henselae and Bartonella quintana (Rochalimaea until the beginning of the 1990s). Bartonella occurs far more frequently in North and South America than in Europe. In one study of 382 febrile HIV patients in San Francisco, Bartonella was found to be the causative organism in 18...

Asymptomatic Patients below 200 CD4 cellspl

There is general consensus that the available data provides clear evidence for initiation of therapy in these patients. 200 CD4 cells l is the cut-off, and one should not wait for values to drop below this level, as the risk for severe complications increases significantly with increasing duration of immunosuppression (Mellors 1997, Egger 2002). For patients with CD4 cells of 200 l and a high viral load, the six-month risk for AIDS is sometimes greater than 10 (Phillips 2004). It is therefore...

Structured Intermittent Treatment SIT at Fixed Intervals

In the initial phase following treatment interruption, the viral load usually continues to be very low. Plasma viremia only reaches pre-treatment levels after about four, sometimes even six weeks. The risk of developing resistance is presumably small at lower levels of viral replication (Bonhoeffer 2000). Does this indicate that ultrashort treatment interruptions could be utilized to reduce drugs, costs and long-term toxicity In an NIH pilot study on SIT (structured intermittent treatment), 10...

Histoplasmosis

Histoplasma capsulatum is a dimorphic mould, found mainly in moist soil and without a capsule despite its name. The South and Midwest of the USA are endemic areas, as are Central America and Africa. Inhalation of microconidia, the spores of H. capsulatum, can cause granulomatous disease in immunocompetent individuals. In HIV patients with impaired immunity (85 have less than 100 CD4 T cells l), infection leads to an acute, life-threatening disease with dry cough, fever, dyspnea and malaise...

Candidiasis

Candidiasis is an infection with yeast-forming fungi. Of the 150 Candida species known to date, only approximately 20 cause disease. By far the most frequent species is C. albicans. Other species such as C. tropicalis, C. glabrata and C. krusei are rare, but may respond less readily to treatment with azoles. Although it is commonly assumed that azole resistance is a problem particularly with albicans strains, this has not been the case to date (Sanglard 2002). Mucocutaneous candidiasis is...

Signs and symptoms

There are often prodromal signs with headache, malaise and photophobia, accompanied only rarely by fever. The affected areas are initially hypersensitive, and then become pruritic and or painful within hours or days. Pain can precede lesions by several days. Lesions often show segmental (always unilateral ) erythema with her-petiform blisters within one or more dermatomes. Lesions ulcerate, are often hemorrhagic, and gradually dry up. They should be kept dry and clean to avoid bacterial...

Direct detection of HIV

An HIV infection may also be diagnosed through the detection of virus, rather than indirectly through the detection of antibodies. Virus detection is only necessary in certain situations and, because of its higher cost, should only be undertaken if indicated. Virus isolation in cell cultures is reserved for special cases, as it is demanding, carries a certain risk and therefore requires the use of a high-security laboratory. Alternatively, assays for the detection of HIV-1 p24 antigen are...

Mechanism of action and efficacy

The HIV protease cuts the viral gag-pol polyprotein into its functional subunits. Inhibition of the protease, preventing proteolytic splicing and maturation, leads to the release of virus particles that are unable to infect new cells. With knowledge of the molecular structure of the protease encoded by the virus, the first protease inhibitors were designed in the early nineties these substances were modified in such a way that they fit exactly into the enzyme active site of the HIV protease...

How to Change HAART

The approach to changing a treatment regimen that is successful but intolerable due to side effects is usually straightforward. The suspected drug is replaced with another drug of the same class. However, difficulties can arise if alternate drugs are contraindicated because of potential toxicity or if resistance mutations against these drugs are suspected. In such cases, changes have to be individualized according to the situation of the patient. This chapter discusses two other important...

Therapy

Wasting syndrome always requires competent diet counseling. Exercise, if possible, is also good. Of course, both only have limited success. Supportive parenteral nutrition only helps if there are problems with absorption (Kotler 1990, Melchior 1996). Effective HAART is important, ideally without drugs that cause lipoatrophy such as d4T or ddI. Severe lipoatrophy may require complete omission of nucleo-side analogs (see chapter on Nuke sparing). Beyond this, many kinds of drug treatment have...

Pathogenesis of HIV1 Infection

Since the initial description of the human immunodeficiency virus type I (HIV-1) in 1983 (1, 2) and HIV-2 in 1986 (3), these two viruses have been identified for almost 20 years as the primary cause of the acquired immunodeficiency syndrome (AIDS). As HIV-1 is the major cause of AIDS in the world today, our discussion will be primarily limited to HIV-1 infection. Worldwide, the number of HIV-1 infected persons exceeds 40 million, the majority of whom live in the developing countries of...

Epidemiology

This is not the place for a detailed description of the epidemiological situation of the HIV pandemic. The prevalence and incidence of HIV AIDS vary considerably from continent to continent, from country to country, from region to region. Several countries in sub-Saharan Africa report infection rates of 30 , especially in urban areas. In other countries, HIV prevalence still remains low. However, low national prevalence rates can be misleading. They often disguise serious epidemics that are...

What is relevant in practice

With each and every HIV test, different important aspects need to be taken into account. Unfortunately and regrettably, careless and negligent actions still sometimes occur. It has to be realised Despite all therapeutic progress, a positive test result still has massive psychological consequences for the person concerned The meaning of a positive test result can hardly be overrated. Every patient therefore must be informed that he she is to be tested for HIV - in advance A routine pre-operative...

Sulfadiazine

Indications treatment and prophylaxis of cerebral toxoplasmosis, only in combination with pyrimethamine. Dose For treatment 2-3 500 mg tablets qid (daily dose 4-6 g). For prophylaxis halve the dose (500 mg qid) Renal insufficiency creatinine clearance 50-10 ml min halve dose. At values below 10 ml min administer one third of the dose. Side effects very frequently allergies with pruritus, fever and urticaria, often treatment-limiting. Rare Stevens-Johnson syndrome. Gastrointestinal complaints...

The safety of sperm washing

The technique of processing sperm from HIV-positive men prior to the insemination of their HIV-negative partners was first published by Semprini et al. in 1992. The first inseminations with sperm, washed free of HIV, were carried out in Italy and Germany as early as 1989 and 1991, respectively. Up to mid 2003, more than 1,800 couples had been treated in about 4,500 cycles, applying various techniques of assisted reproduction. More than 500 children have been born with no single seroconversion...

Conclusions

The dermatologist's role in the care of HIV-infected patients is to be familiar with HIV-associated skin and mucocutaneous diseases, their diagnoses, and management. It is also a part of the extensive interdisciplinary knowledge necessary for any physician who takes care of HIV-infected patients. Considering the lifelong duration of antiretroviral therapy with complications such as drug intolerance, development of epithelial tumors induced by UV-light exposure or oncogenic viruses, it is...

Nevirapine

Liver toxicity occurs more commonly on nevirapine than on other antiretroviral drugs. Clinically asymptomatic and symptomatic liver toxicity, including rapidly occurring fatal liver failure have been observed. Serious and fatal liver toxicity has been reported during post-exposure prophylaxis (MMWR 2001), but not after single doses of nevirapine. Females and patients with higher CD4 cell counts are at increased risk of liver toxicity with nevirapine. The risk of symptomatic hepatotox-icity for...

What Should Be Clarified Beforehand

Can the patient really take drugs several times a day Is this realistic with regard to the individual, professional or social situation If in doubt, a simpler regimen is preferable to one that is presumed to be more effective. Intravenous drug users, for example, may be unable to comply with a complicated or high pill burden regimen. In this situation, once-daily regimens for i.v. drug users (Proenca 2000, Staszewski 2001, Conway 2002), which are also suitable for DOT (Directly Observed...

Valvular Heart Disease

Valvular heart disease of HIV-infected patients occurs as a bacterial or mycotic endocarditis. The most frequent germ is staphylococcus aureus, being detected in more than 40 of HIV-infected patients with bacterial endocarditis. Further pathogens include streptococcus pneumoniae and hemophilus influenzae (Currie 1995). Mycotic forms of endocarditis, which may also occur in patients who are not intra venous drug abusers, mostly belong to aspergillus fumigatus, candida species or cryptococcus...

Protease inhibitors PIs

All protease inhibitors can be used in combination with 2 NRTIs. PIs differ from each other in respect to their tolerability and side effects. As with adults, dyslipide-mia is associated with the use of protease inhibitors (Lainka 2002). It includes elevated total cholesterol, triglycerides (TG), and low density lipoprotein cholesterol (LDL-c) and decreases in high density lipoprotein cholesterol (HDL-c) In lipodys-trophy, there is a loss of subcutaneous fat (lipoatrophy) and or a deposition of...

Atazanavir and Indinavir

Atazanavir and indinavir inhibit the hepatic enzyme UDP-glucuronosyltransferase, increasing the level of bilirubin in up to 47 of the patients. It is not usually associated with signs or symptoms of hepatocellular injury, and clinically resembles Gilbert's syndrome. Fewer than 2 of patients discontinue atazanavir therapy because of this adverse effect (Busti 2004). The levels of bilirubin return to normal following discontinuation of the drugs. If bilirubin is only mildly elevated (< 3 times...

Microsporidiosis

Microsporidiosis is an important cause of diarrhea in HIV patients. Microsporidia are obligate intracellular protozoa. At least four genera that are pathogenic in humans have been described. Of these, Enterocytozoon bieneusi is probably the most important. Even in Europe, microsporidia are among the most frequent diarrhea-causing microbes, and can be found in approximately one third of all patients and in two thirds of all HIV patients with chronic diarrhea (Sobottka 1998). Microsporidiosis is...

Specific interventions

Given the extensive indications that PIs are the culprits substantially contributing to the metabolic side effects, numerous attempts have tried to substitute the PI component of a regimen with nevirapine, efavirenz, or abacavir. Similarly, given the close association of stavudine-based therapy with lipoatrophy, replacement of this thymi-dine nucleoside analogue by, for example, abacavir or tenofovir has been evaluated in several studies. Indeed, these switch studies have demonstrated...

Cotrimoxazole Trimethoprimsulfamethoxazole

Manufacturer co-trimoxazole is manufactured by several different companies. Indications prophylaxis and treatment of Pneumocystis pneumonia (PCP). Prophylaxis and treatment (reserve drug) of cerebral toxoplasmosis. Dose PCP prophylaxis 80 400 mg qd or 160 800 mg trimetho-prim sulfamethoxazole 3 x week. PCP therapy 5 mg kg (based on trimethoprim) po or iv q 8 h x 21 days, therefore usually 5 to 6 ampules a 80 400 mg q 8 h. Toxo-plasmosis prophylaxis 1 tablet (160 800 mg) qd. Reduced renal...

Preconceptual counseling

The initial counseling of the couple should not only consider extensive information on all reproductive options available, diagnostics and prerequisites for reproductive treatment, but also the psychosocial situation of the couple. Important issues to discuss are the financial situation, current psychosocial problems, the importance of a network of social support from family or friends, and planning and perspectives about the future as a family, including possible disability or death of one of...

Hepatotoxicity

Elevated liver function tests are common with HAART, and severe hepatotoxicity occurs in up to 6 of patients (Becker 2004). Their occurrence depends on the drug classes or agents used as well as on pre-existing liver dysfunction. The level of liver toxicity ranges from mild and fully reversible liver enzyme elevation to rare but rapidly occurring, occasionally fatal, liver failure. Severe hepatotoxicity and hepatic failure have been observed during treatment with nevirapine and ritonavir (De...

HAART lipodystrophy syndrome and cardiovascular risk

The fat redistribution and disturbances in glucose and fat metabolism resemble a clinical situation that is known as the metabolic syndrome in HIV-negative patients. This condition includes symptoms such as central adipositas, insulin resistance and hyperinsulinemia, hyperlipidemia (high LDL, Lp(a) hypertriglyceridemia and low HDL) and hypercoagulopathy. Given the well-established cardiovascular risk resulting from this metabolic syndrome, there is growing concern about a potential...

Change Due to Acute Side Effects

Not every acute side effect requires immediate modification of the treatment regimen. A bit of nausea or diarrhea in the beginning can and should be tolerated. One should always remember that the number of available drugs is limited. Gastrointestinal side effects that occur during the first weeks are not dangerous and often improve spontaneously or can be treated symptomatically. The same is true for some allergic reactions and for relatively mild CNS disorders with efavirenz (mild allergies)....

Clinical course and pathogenesis

Course of hepatitis C in HIV HCV-coinfected patients The clinical course of hepatitis C and HIV coinfection is determined by the HIV-associated immunosuppression. Progression of immunosuppression accelerates the course of hepatitis C. This was first shown in data from the American Multicenter Hemophilia Cohort Study (MHCS), in which 10 of adult hemophiliacs with HCV coinfections developed hepatic failure after a latent period of 10-20 years, even before the onset of AIDS-defining opportunistic...

Two Nucleoside Analogs Plus an NNRTI

NNRTIs have an equal, if not presumably even superior effect on surrogate markers as PI combinations. NNRTIs have done well in numerous randomized studies efa- virenz-based regimens in studies such as 006, ACTG 384, ACTG 5095 or CLASS were superior to indinavir, nelfinavir, amprenavir r or triple nukes (Staszewski 1999, Robbins 2003, Gulick 2004, Bartlett 2002). The nevirapine-containing regimens in Combine or Atlantic were at least equivalent to nelfinavir and indinavir, and better than triple...

STI at the Patients Wish for Reduction of Toxicity

Interruption of therapy can have psychological advantages (Tuldra 2001). Quality of life improves (Moreno 2003), and many patients are relieved of the burden of continuous, lifelong therapy. Clinicians should take the wish for treatment interruption seriously. Presumably most patients expressing such a wish will interrupt sooner or later anyway so the interruption may as well be structured What about side effects Increased lipid levels (cholesterol, triglycerides) drop quite rapidly after...

Asymptomatic Patients above 350 CD4 cellspl

The cut-off level of 350 CD4 cells l is important in many guidelines. Above 350 CD4 cells l, it is usually recommended to defer therapy. In the MACS Cohort, not a single patient with more than 350 CD4 cells l and a viral load below 60,000 copies ml developed an AIDS illness within a year (Phair 2002). For patients with more than 350 CD4 cells l, the 2004 recommendations from the US and Germany have been slightly revised. At a viral load below 50,000 copies ml, both guidelines recommend...

Bacterial pneumonia

Bacterial pneumonia occurs even with relatively good immune status (above 200 CD4 T cells l). It is not as closely associated with immunodeficiency, and the decrease in incidence since the HAART era has been more moderate than for other opportunistic infections. Only recurring, radiologically and culturally detected acute pneumonia (more than one episode in the last 12 months) is considered AIDS-defining. As with HIV-negative patients, community-acquired pneumonia should be distinguished from...

Clinical manifestation

Lipodystrophy was originally described as a condition characterized by regional or generalized loss of subcutaneous fat. The non-HIV-associated forms, such as congenital or familial partial lipodystrophy, have a very low prevalence. Generally, these forms are associated with complex metabolic abnormalities and are difficult to treat. The term lipodystrophy syndrome in association with HIV, was introduced to describe a complex medical condition including the apparent abnormal fat redistribution...

HAART Influence on skin and mucocutaneous diseases

The introduction of HAART in 1996 revolutionized the dermatological management of HIV-infected patients. Opportunistic infections and the clinical manifestations of Kaposi's sarcoma abated to a level of 10 compared to the pre-HAART era (Reinmoller 1997, Schofer 1998, Sepkowitz 1998, Calista 2002). An Italian hospital reported that HAART had reduced the total number of HIV patients with skin problems by 40 . The percentage of patients with cutaneous infections dropped from 66 to 53 the...

Herpes simplex

Infections with herpes simplex viruses are a frequent and inconvenient problem for HIV-infected patients (Chang 1995). Two viruses should be distinguished. HSV-1 is transmitted by direct contact with mucosal membranes, as well as by kissing, and causes the typical, itchy perioral herpes blisters on the lips, tongue, gums or buccal mucosa. HSV-2 is sexually transmitted and leads to herpetiform lesions on the penis, vagina, vulva and anus. Herpes lesions have a tendency to spread with decreasing...

Management of Side Effects

Christiane Schieferstein, Thomas Buhk Patients on HAART commonly suffer from side effects. As a result, treatment of HIV infection has become a complicated balancing act between the benefits of durable HIV suppression and the risks of drug toxicity. About 25 of patients stop therapy within the first year on HAART because of side effects (d'Arminio Mon-forte 2000). About the same number of patients do not take the recommended dosages of their medication due to concerns regarding the side effects...

Other Routine Checks What Should Be Monitored

Besides the CD4 cell count and viral load, several other parameters should be monitored in the HIV patient. The following recommendations apply to clinically asymptomatic patients with normal results on routine laboratory evaluation, who have been on stable treatment for several months, or who are not taking antiretrovi-ral therapy. Of course, if treatment is started or changed, or if the patient develops complaints, more frequent monitoring is required. Depending on the problem, additional...

Pulmonary Complications Bacterial pneumonia

Bacterial pneumonia occurs more often in HIV-positive than in HIV-negative patients, and, like PCP, leaves scars in the lung. This often results in a restriction of pulmonary function which persists for years (Alison 2000). Although bacterial pneumonia occurs in the early stages of HIV infection, the risk grows along with increasing immunosuppression. A case of bacterial pneumonia significantly worsens the long-term prognosis of the patient (Osmond 1999). Thus, contracting bacterial pneumonia...

Symptomatic Patients

There is currently consensus that every symptomatic patient should receive antiret-roviral therapy. This is, of course, mainly true for patients in WHO Stage C (with AIDS), but also for all patients in Stage B. Although this should be correct in most cases, it may be advisable to consider the situation more closely in individual cases. To avoid misunderstanding all opportunistic infections indicative of severe immunodeficiency, such as CMV, MAC, toxoplasmosis or PCP, and also AIDS malignancies...

The Th1Th2 immune response

Depending on the secretion pattern of cytokines, CD4 T cells may be differentiated into TH1 and TH2 cells. TH1 CD4 T cells primarily produce interleukin-2 (IL-2) and IFNy, which represent the cytokines that support the effector functions of the immune system (CTL, NK-cells, macrophages). TH2 cells predominantly produce IL-4, IL-10, IL-5 and IL-6, which represent the cytokines that favor the development of a humoral immune response. Since TH1 cytokines are critical for the generation of CTLs, an...

HIV1 specific humoral immune responses

The association between an HIV-1-specific humoral immune response and the course of disease is less well characterized. In a SIV model, injection of an antibody cocktail consisting of various neutralizing antibodies is able to prevent SIV infection after a mucosal virus challenge (80), indicating that primary protection is mainly dependent on a broad humoral immune response. In contrast, B cell depletion by a monoclonal antibody directed against B cells in monkeys with already established SIV...

The structure of HIV1

HIV-1 is a retrovirus and belongs to the family of lentiviruses. Infections with len-tiviruses typically show a chronic course of disease, a long period of clinical latency, persistent viral replication and involvement of the central nervous system. Visna infections in sheep, simian immunodeficiency virus infections (SIV) in monkeys, or feline immunodeficiency virus infections (FIV) in cats are typical examples of lentivirus infections. Using electron microscopy, HIV-1 and HIV-2 resemble each...

Gastrointestinal side effects

Gastrointestinal side effects are the most common side effects of almost all antiret-roviral drugs - nucleoside analogs, NNRTIs and particularly protease inhibitors -and occur especially during the early stages of therapy. Typical symptoms include abdominal discomfort, loss of appetite, diarrhea, nausea and vomiting. Heartburn, abdominal pain, meteorism and constipation may also occur. Nausea is a common symptom with zidovudine-containing regimens diarrhea occurs frequently with zidovudine,...

Experiences from Daily Practice

Even if the indication for HAART seems obvious, a conversation with the patient should clarify whether he or she is indeed prepared to start treatment. The problem is not the initiation of HAART, but its continuity, day after day, month after month. The decision to initiate treatment is often made prematurely. In some cases, patients put themselves under pressure unnecessarily, or let others do so. A single lower CD4 count value, a prolonged case of flu seeming to indicate a weakened immune...

Consequences for the Further Course of Disease

In addition to the risk of death and disease progression, the controversy over the optimal time for starting therapy also raises other questions. Based on large cohorts, there have been repeated attempts to prove that the time point when therapy is started influences virological or immunological treatment success. The problems with such arguments are discussed below. Is virological response less durable with a low CD4 cell count and a high viral load At first glance, many cohort studies have...

Indinavir

Approved dose IDV 800 mg TID, IDV r 800 100 mg BID (an increased number of side-effects possibly suggests elevated IDV plasma-concentrations. Monitor for IDV toxicity by TDM) Metabolism Indinavir (IDV) is primarily metabolised by CYP3A4 and is an inhibitor of CYP3A4. For optimal adsorption an acidic gut ph is necessary, therefore IDV should be taken with a light meal 1 . IDV r 800 100 BID + EFV 600 QD IDV 1 19 (Cmin 48 j) 6 IDV r 800 100, probably higher doses for pre-treated patients are...

HIV and Pulmonary Diseases

The spectrum of lung diseases in HIV-infected patients encompasses complications typical for HIV such as tuberculosis, bacterial pneumonia, lymphomas and HIV-associated pulmonary hypertension, but also includes typical everyday pulmonary problems such as acute bronchitis, asthma, COPD and bronchial carcinomas (Table 1). Classical diseases such as PCP have become rarer as a result of HAART and chemoprophylaxis, so that other complications are on the increase. None other than acute bronchitis is...

Problems with Initial Therapies

Combinations generally considered to be suboptimal include all forms of mono-and dual therapy, especially two nucleoside analogs. Even one nucleoside analog plus one NNRTI is not good, as shown by the INCAS Trial (Montaner 1998). In addition, there are several typical mistakes that should be avoided if possible. When using nucleoside analogs, it is important to make sure that they are not competing for the same bases. Therefore, combination of thymidine analogs (AZT and d4T) or cytidine analogs...

Future Combinations

Future combinations need to be more effective, simple and tolerable. However, there is not always time to wait for new drugs to be developed As a result, there are three approaches being closely investigated with the currently available drugs combinations without any nucleoside analogs (nuke sparing) combinations that require only once-daily dosing and so-called induction therapies, comprised of intensive combinations using more than three active drugs or drugs from three different classes. All...

References

Update on chronic hepatitis C in HIV HCV-coinfected patients viral interactions and therapy. AIDS. 2003 Nov 7 17 2279-90. 2. Eyster ME, Diamondstone LS, Lien JM, et al. Natural history of Hepatitis C virus infection in multi-transfused hemophiliacs. Effect of coinfection with HIV. J AIDS 1993 6 602-10. 3. Greub G, Ledergerber B, Battegay M, et al. Clinical progression, survival and immune recovery during antiretroviral therapy in patients with HIV-1 and Hepatitis C virus coinfection....

Nelfinavir

NFV, Viracept Approved dose 1250 mg BID Metabolism Nelfinavir (NFV) is primarily metabolised by CYP2C19 more than CYP3A4 and CYP2D6. NFV is an inhibitor of CYP3A4. It is metabolised to an active metabolite M8 (approx. 30 of parent compound), with equal antiretroviral potency to NLF. M8 is metabolised by CYP3A4 1,2 . DDI fasting, NFV with a light meal No clinically significant interaction In this study no dose adjustment was necessary. NLF 1250 BID + ATV 400 QD Cmin NLF 57,4 t, M8 124 t, No...

Lactic acidosis

In comparison to asymptomatic hyperlactacidemia, which occurs in approximately 15 of NRTI-treated patients (Carr 2001, Hocqueloux 2003), lactic acidosis is a rare but life-threatening complication. NRTIs are thought to cause mitochondrial toxicity via inhibition of the mitochondrial DNA polymerase. The incidence is approximately 3.9 1000 NRTI patient years (John 2001) (see also chapter on Mitochondrial Toxicity of Nucleoside Analogs). It occurs most frequently on treatment with stavudine and...

Comedication

PIs are well known to increase plasma concentrations of comedications, resulting in an increased number and strength of side effects due to inhibition of CYP3A4. Common adverse events attributable to these interactions are illustrated in table 2. To avoid such side effects, the dosage of comedications should be adapted in specific combinations otherwise drugs with a low affinity for the cytochrome P450 system should be used in preference. Table 2 Common side effects caused by drug-drug...

Immune reconstitution inflammatory syndrome IRIS

For the first time, in mid-1997 and early 1998, two groups described atypical manifestations of CMV retinitis (Jacobsen 1997) and MAC disease with abscess formation (Race 1998) in HIV patients within a few weeks of initiation of HAART. Although the pathogens, pathogenesis and localization were very different, all these illnesses had a distinct inflammatory component and were associated with significant immune reconstitution in these patients. It was therefore suspected early on that these...

ELISA screening test

Many commercial ELISA tests are available as 96-well microtitre plates. Although the test may be carried out completely manually, they also allow automatisation and thus the safe and economical testing of large numbers of patient samples. Various other test kits based on similar formats are also available, often performed by large, fully automatic pipetting and analysing machines. Different ELISA formats can be distinguished they are all based on the principle of a specific antigen-antibody...

Therapeutic Drug Monitoring TDM When Should Plasma Levels Be Measured

Individual plasma levels of many antiretroviral drugs may vary quite considerably for differing reasons (e.g. compliance, metabolism, absorption). But, sufficient plasma levels are essential for success of virological treatment (Acosta 2000). In the VIRADAPT Study, adequate PI-concentrations were even more crucial than knowledge of resistance mutations (Durant 2000). The importance of sufficient plasma levels has also been shown for NNRTIs (Marzolini 2001, Veldkamp 2001). On the other hand,...

Acute treatment in psychiatric emergency

Most important de-escalation by talking down - this includes measures such as staying in contact with the patient, taking him seriously and adopting a non-confrontational position. Should the use of restraints be necessary, stay calm but act firmly. Always leave the patient the chance to correct inappropriate behavior and always use the least possible restrictive method of restraint. Table 5 Psychiatric emergency (Benkert 2003 Currier 2004) Acute intoxication with psychoactive drug Delirium due...

Fosamprenavir

Approved dose APV r 600 100 mg BID, FPV r 700 100 mg BID (where APV r alternatively FPV r are stated in the tables administered at their approved dose) Metabolism Fosamprenavir (FPV) is a prodrug of Amprenavir (APV) and is hy-drolysed in the gut epithelium by cellular phosphatases during absorption to the active compound. APV is metabolised by CYP3A4 and is an inhibitor of CYP3A4 (as potent as Indinavir and Nelfinavir). Additionally, there are reports suggesting that APV is also an inducer of...

T20 Enfuvirtide

T-20 is the prototype of a new drug class - the entry inhibitors. It has been licensed in the USA and Europe since 2003 for the treatment of HIV-1 infection in treatment-experienced adults and children above 6 years who have received at least one drug out of each of the antiretroviral drug classes (PI, NNRTI and NRTI) and developed treatment failure or intolerance. T-20 is well tolerated, but can only be administered subcutaneously as an injection. However, this drug is important in salvage...

Lifestyle changes

Dietary interventions are commonly accepted as the first therapeutic option for hy-perlipidemia, especially hypertriglyceridemia. Use of NCEP guidelines may reduce total cholesterol and triglycerides by 11 or 21 , respectively. Whenever possible, dietary restriction of the total fat intake to 25-35 of the total caloric intake should be a part of the treatment in conjunction with lipid-lowering drugs. Consultation with professional and experienced dieticians should be considered for HIV-infected...

Polyneuropathy and Polyradiculopathy

Peripheral neuropathies may complicate all stages of HIV infection. During the early asymptomatic stages peripheral neuropathies are uncommon, but electrodiag-nostic testing reveals subclinical evidence of peripheral nerve involvement in about 10 of cases. In later stages, symptomatic neuropathies occur in some 30-50 of patients. Neuropathological studies have shown pathological changes with a prevalence approaching 100 in patients with AIDS. The neuropathies can be classified as primary...

Three Nucleostide Analogs Triple Nuke

Triple nuke therapies, i.e. combinations of three nucleoside or nucleotide analogs, have several advantages few pills, few interactions, no side effects typical of PIs or NNRTIs, and the fact that two entire drug classes can be spared for later. A big disadvantage of triple nuke therapies is that they appear to be less potent than other combinations. The combination of AZT+3TC+ABC in a single tablet (Trizivir ) is the classic triple nuke combination and one of the simplest HAART regimen with...