Other Languages

2007
German

2006
Portuguese
Vietnamese

2005
Russian
Spanisch

2003
Persian (Farsi)

Thomas Weitzel

HIV patients are fond of traveling. In Europe and the USA, annually 10-15 % of HIV patients travel abroad, often to tropical regions and also to developing countries (Kemper 1995, Simons 1999). In the future, with increasing expectancy and quality of life, travel activities of HIV patients will further rise.

Travel preparations

HIV patients bear an increased risk of travel-associated infections, particularly if when CD4+ T-cell counts are below 200/µl. Furthermore, the effectiveness of vaccinations is reduced. Therefore, travel activities should be well prepared. An overview of travel recommendations can be accessed through different Internet sites. Especially before traveling to tropical or subtropical countries, it is recommended to obtain additional advice from travel medicine specialists. Long-term travelers should get informed on the medical infrastructure at their destination. A first-aid kit for HIV-infected travelers should contain, besides local antihistaminics, disinfectants, sun protection, analgesics, antipyretics, antiemetics, and antidiarrheals, an antibiotic for the empirical treatment of acute diarrhea (see below).

Antiretroviral therapy (ART)

Before traveling, ART should be proven to be effective and well tolerated for at least three months. Depending on the destination, planned activities, and possible compliance problems, which occur quite frequently during travel (Salit 2005), an interruption of therapy can be considered. If ART is being continued during traveling, the following aspects should be considered:

• A stockpile of antiretroviral drugs should be packed, preferably in the hand luggage, in case the suitcases get lost.
• The availability of the ART at destination should be checked beforehand. If necessary, prescriptions and a medical letter in English should be taken along.
• Because of some countriesŽ entry regulations (see below) it may be useful to pack antiretroviral drugs in neutral packages.
• Storage requirements for the drugs (refrigeration, etc.) must be kept in mind.
• Unplanned therapy interruption during travel should be discussed beforehand in detail.

More? HIV Medicine 2007, Chapter 17: Download

HIV Medicine
15th edition
818 pages
PDF, 3.7 MB

General precautions The higher risk of gastrointestinal infections in HIV patients demands adherence to the principles of food and water hygiene (Hayes 2003). The following food and drink are to be avoided: § Raw fruit or vegetables that are not peeled § Raw or undercooked meat or fish dishes § Tap water § Ice cubes made from tap water § Unpasteurized milk or milk products § Food prepared or distributed under insecure hygienic circumstances (e.g. by street vendors) Even brushing teeth or swimming carries the risk of swallowing small amounts of potentially contaminated water. In the lack of hygienic beverages, tap water should be boiled. In areas up to 2,000 meters above sea level, a boiling time of one minute kills all potential pathogens; at higher altitudes, the boiling time should be prolonged to three minutes. Chemical or filtration methods of water treatment are less reliable. Also protective measures against vector-transmitted infections are of special importance (see links). Those include: § Outdoors, long and bright clothes should be worn § Repellents (e.g. DEET based) should be applied to uncovered skin areas (sun protection has to be applied beforehand § Outdoor stays during dawn or night ought to be avoided § Sleeping areas should be mosquito safe (a mosquito net is the best repellent!) § Impregnation of clothes and mosquito nets with permethrine provides additional safety Since condoms and lubricants abroad are not always of reliable quality, a sufficient amount of these products should be brought, to guarantee safe sex during the holiday. Because of possible Strongyloides stercoralis infection (see below), direct skin contact to fecally contaminated soil should be avoided. It is wise to wear closed shoes and place a towel underneath when lying or sitting on the ground. Precautions against zoonotic infections such as salmonellosis or cryptosporidiosis include proper hand washing following animal contact. Vaccinations A travel medicine consultation is an opportunity to check and complete routinely recommended immunizations such as tetanus/diphtheria, pneumococcal, influenza, and hepatitis B vaccinations. 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 consultation of a specialized institution (see links for institutions in Germany). Further details on this issues are available in the chapter on vaccinations in this book. Malaria prophylaxis Interactions between antiretroviral drugs and drugs for malaria prophylaxis, such as chloroquine, mefloquine, doxycycline, and Malarone™ (atovaquone/proguanil), are inadequately evaluated (Khoo 2005). In healthy volunteers taking mefloquine (Lariam™) together with ritonavir, a 30 % reduction of the steady-state plasma level of ritonavir was reported; however, mefloquine did not change the ritonavir level after a single dose of ritonavir (Khaliq 2001). The explanation is probably a reduced bile production caused by mefloquine. No relevant interactions seem to occur if mefloquine is coadministered with nelfinavir or indinavir (Schippers 2000). Chloroquine is metabolized by CYP2D6, but is also excreted by the kidneys; explicit data on interactions of chloroquine with HIV drugs are lacking. In vitro, chloroquine inhibits HIV replication and shows synergistic effects together with protease inhibitors (Savarino 2004). On the other hand, PIs display an inhibitory effect on plasmodia in vitro and in animals. Whether these observations could have an impact on the clinical management of HIV infection or malaria is still uncertain. (Parikh 2005, Andrews 2006). Clinical data on the interactions of Malarone™ with HIV drugs are missing. In vitro data indicate that ritonavir and lopinavir reduce levels of atovaquone and that ritonavir increases the level of proguanil. Atovaquone decreases the indinavir level by 20 % and increases the AZT level by 30 %. Doxycycline is not metabolized by the cytochrome p450 system. Thus, relevant interactions with HIV drugs are not anticipated. Available data and clinical experience indicate that mefloquine as well as doxycycline and chloroquine can be safely and effectively used in patients taking antiretroviral therapy. Although clinical studies are lacking, the same applies for Malarone™. Thus, recommendations for malaria prophylaxis are not limited by concomitant HIV medication. Mefloquine, however, should not be used in HIV patients with neurological disturbances. Common drugs for malaria stand-by treatment are chloroquine, mefloquine, Malarone™, and Riamet™ (artemether/lumefantrine). Both components of Riamet™ are substrates of CPY3A4; due to incalculable increases in drug exposure, Riamet™ is contraindicated together with protease inhibitors (see Riamet™ product information). Entry regulations and travel insurance Although contentious as a measure of health policy and not recommended by the WHO, more than 150 countries, including the USA, refuse entry to HIV infected individuals. This particularly affects long-term stays in connection with work or study. To avoid problems, information on entry regulations should be obtained beforehand. Peter Wiessner and Karl Lemmen's brochure "Schnellfinder" provides an excellent and comprehensive overview on entry policies. In cooperation with David Haerry of the Swiss Aids Info Docu, a regularly updated version of this databank is available online (see links). The American foreign ministry also publishes a list of countries with HIV-specific entry restrictions (see links). Under certain circumstances, e.g. visits to conferences, family members, or business travel, journeys to the USA are possible for HIV patients if they apply for a "visa waiver". However, the procedure is time consuming and the passport endorsement can complicate further travel to the USA or other countries. Travel insurances usually exclude existing illnesses and often refuse HIV patients explicitly. Only in some countries, e.g. the UK and the USA, special HIV travel insurances are available. Special risks Enteric infections Reduced immunological defense and diminished gastric acid production increase the risk of gastrointestinal infections in HIV patients. Furthermore, bacterial enteric infections such as salmonellosis, shigellosis, and Campylobacter infections bear a high risk of bacteremia and relapse. Infections caused by Cryptosporidium sp., Isospora belli and microsporidia are dangerous due to their chronicity. Prophylactic use of antibiotics, although reducing the prevalence of travel-associated diarrhea, is not generally recommended in HIV patients. In certain situations though, e.g. HIV patients with advanced immunodeficiency traveling under poor hygienic conditions, prophylaxis with ciprofloxacin (500 mg per day) should be considered. In Southeast Asia, an increasing rate of quinolone resistance makes azithromycin a useful alternative. Because of widespread bacterial resistance, cotrimoxazole and doxycycline are insufficient. HIV patients should be advised to empirically self-treat travel-associated diarrhea for five to seven days with ciprofloxacin (500 mg per day) or alternatively azithromycin (400 mg per day). Malaria Synergistic interactions between HIV and malaria are subject to recent and ongoing research (Kublin 2006, Brentlinger 2006). Proinflammatory cytokines, released during plasmodial infection, increase HIV replication. On the other hand, HIV patients suffer malaria episodes with increased frequency and severity which has fatal consequences especially in African (Korenromp 2005, Kamya 2006). The efficacy of antimalarial therapy is not influenced by HIV. Accordingly, recommendations for malaria therapy generally apply to HIV patients. As described above though, drug interactions of antimalarial and HIV drugs are not well-established. The treatment of complicated malaria is problematic since the indicated drugs, quinine, quinidine, or artemisinin derivates, are all metabolized by CYP3A4. The coadministration of these drugs with CYP3A4 inhibitors as protease inhibitors, efavirenz, or delavirdine, requires intensive care monitoring and, if possible, drug level monitoring. Measles On a global scale, measles are a common infection. For 2005, the WHO reported more than 20 million measles cases with about 345,000 deaths worldwide. In HIV-infected patients, measles occur more frequently and more severely, and viral shedding is prolonged (Moss 2002). American studies showed a high mortality rate, mostly due to giant-cell pneumonitis (Kaplan 1996). Non-immune HIV patients should therefore consider active or passive immunization before traveling to areas with a high prevalence of measles (see chapter "Vaccinations and HIV"). Leishmaniasis Visceral leishmaniasis (kala azar) is a life-threatening infection complicated by limited therapeutic options. German data revealed that most imported cases were acquired in Mediterranean countries, that long-term travelers were affected more frequently, and that HIV patients had a higher infection risk than healthy travelers (Harms 2003, Weitzel 2005). Most frequently, HIV patients with CD4+ T-cell counts below 200/µl are affected (Kaplan 1996). Due to the infection's potentially extended latency period, symptoms can occur long after exposure. Diagnosis is challenging, mostly requiring cooperation with a specialized center. Cutaneous leishmaniasis does not seem to occur more frequently in HIV patients. Severely immunocompromised HIV patients must be informed of the risk of leishmaniasis even when traveling to Mediterranean countries. Preventive measures against mosquito bites should be followed to avoid leishmanial infections; because of the vector's small size, the use of an impregnated mosquito net of small mesh size is advisable. Tuberculosis Globally, tuberculosis is the most prevalent HIV-associated opportunistic infection. Many tropical and subtropical regions bear an increased tuberculosis risk compared to European and North American countries. Therefore, a tuberculin skin test should be performed before and after long-term travel to countries of high tuberculosis endemicity. Patients with a positive tuberculin skin reaction or with a known high risk exposure should receive a course of treatment for latent tuberculosis (see chapter "Tuberculosis"). HIV-infected individuals should avoid risk areas such as hospitals, prisons or homeless-shelters, or wear adequate facemasks. Endemic mycoses Endemic mycoses are rare infections. Nevertheless, they are able to cause life-threatening opportunistic infections in HIV patients even years after stays in endemic areas. Most agents of endemic mycoses are thought to enter the pulmonary tract after inhalation of infective spores. In areas endemic for Penicillium marneffei (South East Asia, Southern China) and Coccidioides immitis (south-west parts of the USA, parts of Central and South America), increased exposure to dust or soil should be avoided (e.g. construction sites, agriculture, garden work, excavations). Histoplasma capsulatum is prevalent worldwide in soil contaminated with bird and bat droppings. Exposure might happen during eco or adventure tourism and should be avoided by HIV-infected persons. In individual cases, e.g. severely immunocompromised HIV patients with a foreseeable contact to agents of endemic mycoses, primary prophylaxis can be considered. Depending on the expected pathogen, either fluconazole or itraconazole should be prescribed. Another fungus causing severe infections in HIV patients is Sporothrix schenkii. This pathogen, which occurs worldwide, enters the body through cutaneous lesions. Wearing gloves while working with plants, hay, or peat moss can reduce the sporotrichosis risk. Sexually transmitted diseases In travelers, the risk of sexually transmitted diseases is markedly increased (Richens 2006). It is estimated that 5 to 10 % of the HIV infections of German patients were acquired during holidays. HIV-positive travelers should be aware of the special risks that sexually transmitted diseases including HIV reinfection present to them. Other parasites The following parasitic pathogens are relevant for traveling HIV patients: § Strongyloides stercoralis is prevalent in most tropical and subtropical areas. The parasite is transmitted by cutaneous larval invasion after skin contact with fecally contaminated soil. In HIV patients, there is the risk of a "hyperinfection syndrome" with a high fatality rate (Gompels 1991). Besides HIV infection, corticosteroid use is an important risk factor, as these drugs seem able to increase larval maturation triggering a cycle of massive autoinfection. § Trypanosoma cruzi is endemic in large parts of Latin America. This protozoan causes Chagas disease and is transmitted by triatomine bugs. Chagas disease, which often persists asymptomatically for many years, can reactivate in severely immunocompromised HIV patients. In these cases, lesions radiologically resembling cerebral toxoplasmosis are often found in the central nervous system (Rocha 1994). § Babesia sp., tick-borne protozoa with a worldwide distribution, are able to cause infections in a broad spectrum of vertebrates. Severe infections, clinically resembling malaria, occur more frequently in severely immunocompromised HIV patients (Falagas et Klempner 1996). § Free-living ameba (Acanthamoeba sp. and Balamuthia mandrillaris) are ubiquitous, living in soil and water. In HIV-infected, these organisms can cause severe infections of the central nervous system (granulomatous encephalitis), as well as local infections of the skin and cornea (Sison 1995). Medical problems after traveling Because of the infections mentioned in this chapter, travel-associated diseases in HIV patients have to be diagnosed and treated in a timely manner. In temperate countries, where most tropical diseases are rare, diagnosis is often delayed. An analysis of imported visceral leishmaniasis revealed a median time span of 85 days until the diagnosis was established (Weitzel 2005). Furthermore, tropical diseases often manifest atypically in HIV patients (Karp et Neva 1999). The differential diagnosis of febrile syndromes in HIV-infected individuals is already very broad; after traveling the clinical situation can become even more complex needing close cooperation of HIV and Tropical Medicine specialists. References 1. Andrews KT, Fairlie DP, Madala PK, et al. Potencies of human immunodeficiency virus protease inhibitors in vitro against Plasmodium falciparum and in vivo against murine malaria. Antimicrob Agents Chemother 2006; 50: 639-48. http://amedeo.com/lit.php?id=16436721 2. Brentlinger PE, Behrens CB, Micek MA. Challenges in the concurrent management of malaria and HIV in pregnancy in sub-Saharan Africa. Lancet Infect Dis 2006; 6: 100-11. 3. Falagas ME, Klempner MS. Babesiosis in patients with AIDS: a chronic infection presenting as fever of unknown origin. Clin Infect Dis 1996; 22: 809-12. http://amedeo.com/lit.php?id=8722936 4. Gompels MM, Todd J, Peters BS, Main J, Pinching AJ. Disseminated strongyloidiasis in AIDS: uncommon but important. AIDS 1991; 5: 329-32. http://amedeo.com/lit.php?id=2059374 5. Harms G, Schonian G, Feldmeier H. Leishmaniasis in Germany. Emerg Infect Dis 2003; 9: 872-5. http://amedeo.com/lit.php?id=12890332 6. Hayes C, Elliot E, Krales E, Downer G. Food and water safety for persons infected with human immunodeficiency virus. Clin Infect Dis 2003; 36 (Suppl 2): S106-9. http://amedeo.com/lit.php?id=12652380 7. Kamya MR, Gasasira AF, Yeka A, et al. Effect of HIV-1infection on antimalarial treatment outcomes in Uganda: a population-based study. J Infect Dis 2006; 193: 9-15. 8. Kaplan JE, Hu DJ, Holmes KK, Jaffe HW, Masur H, De Cock KM. Preventing opportunistic infections in human immunodeficiency virus-infected persons: implications for the developing world. Am J Trop Med Hyg 1996; 55: 1-11. http://amedeo.com/lit.php?id=8702012 9. Karp CL, Neva FA. Tropical infectious diseases in HIV-infected patients. CID 1999; 28: 947-63. http://amedeo.com/lit.php?id=10452619 10. Kemper CA, Linett A, Kane C, Deresinski SC. Frequency of Travel of Adults Infected with HIV. J Travel Med 1995; 2: 85-8. http://amedeo.com/lit.php?id=9815367 11. Khaliq Y, Gallicano K, Tisdale C, Carignan G, Cooper C, McCarthy A. Pharmacokinetic interaction between mefloquine and ritonavir in healthy volunteers. Br J Clin Pharmacol 2001; 51: 591-600. http://amedeo.com/lit.php?id=11422019 12. Khoo S, Back D, Winstanley P. The potential for interactions between antimalarial and antiretroviral drugs. AIDS 2005; 19: 995-1005. 13. Korenromp EL, Williams BG, de Vlas SJ, et al. Malaria sttributable to the HIV-1 epidemic, sub-Saharan Africa. Emerg Infect Dis 2005; 11: 1410-9. 14. Kublin JG, Steketee RW. HIV infection and malaria - understanding the interactions. J Infect Dis 2006; 193: 1-3. 15. Moss WJ, Monze M, Ryon JJ, Quinn TC, Griffin DE, Cutts F. Prospective study of measles in hospitalized, human immunodeficiency virus (HIV)-infected and HIV-uninfected children in Zambia. Clin Infect Dis 2002; 35: 189-96. http://amedeo.com/lit.php?id=12087526 16. Parikh S, Gut J, Istvan E, et al. Antimalarial activity of human immunodeficiency virus type 1 protease inhibitors. Antimicrob Agents Chemother 2005; 49: 2983-5. http://amedeo.com/lit.php?id=15980379 17. Richens J. Sexually transmitted infections and HIV among travellers: a review. Travel Med Infect Dis 2006; 4: 184-95. http://amedeo.com/lit.php?id=16887740 18. Rocha A, de Meneses AC, da Silva AM, et al. Pathology of patients with Chagas' disease and acquired immunodeficiency syndrome. Am J Trop Med Hyg 1994; 50: 261-8. 19. Salit IE, Sano M, Boggild AK, Kain KC. Travel patterns and risk behaviour of HIV-positive people travelling internationally. CMAJ 2005; 172: 884-8. http://amedeo.com/lit.php?id=15795409 20. Savarino A, Lucia MB, Rastrelli E, et al. Anti-HIV effects of chloroquine: inhibition of viral particle glycosylation and synergism with protease inhibitors. J Acquir Immune Defic Syndr 2004; 35: 223-32. http://amedeo.com/lit.php?id=15076236 21. Schippers EF, Hugen PW, den Hartigh J, et al. No drug-drug interaction between nelfinavir or indinavir and mefloquine in HIV-1-infected patients. AIDS 2000; 14: 2794-5. 22. Simons FM, Cobelens FG, Danner SA. Common health problems in HIV-infected travelers to the (sub)tropics. J Travel Med 1999; 6: 71-5. http://amedeo.com/lit.php?id=10381957 23. Sison JP, Kemper CA, Loveless M, McShane D, Visvesvara GS, Deresinski SC. Disseminated acanthamoeba infection in patients with AIDS: case reports and review. Clin Infect Dis 1995; 20: 1207-16. http://amedeo.com/lit.php?id=7620001 24. Weitzel T, Muhlberger N, Jelinek T, et al. Imported leishmaniasis in Germany 2001-2004: data of the SIMPID surveillance network. Eur J Clin Microbiol Infect Dis 2005; 24: 471-6. http://amedeo.com/lit.php?id=15997368