C14 An HIV traveler

Introduction

As a result of the improved quality of life and survival benefits brought forth by the use of effective antiretroviral therapy, people living with HIV/AIDS (PLWHA) are leading relatively normal life. Travel is now more common for PLWHA, especially from developed countries to tropical and subtropical areas of the world.[1] This trend has created unique health concerns because of the defective immune response arising from low CD4 count and an increased risk of complications from exotic diseases acquired at their travel destinations.

Studies in North America had shown that only half of the PLWHA consulted with a physician prior to travel.[2] While travel medicine [Further reading A] and the concept of pre-travel health consultation are still at their developmental stage in Hong Kong, physicians should alert PLWHA of the importance of obtaining pre-travel advice, especially when planning for trips to developing countries where the infection risk is anticipated to be higher than the traveller’s home country. Likewise, HIV physicians need to counsel their clients with regard to a wide variety of health issues not only limited to infectious diseases, but also non-infectious aspects of travelling including time-zone changes, temperature extremes, altitude medicine, diving medicine, environmental hazards and personal safety. Constant update on destination-specific diseases and environmental conditions, and basic knowledge across the health specialties is desirable in order to offer individualised risk assessment and to discuss the prevention strategies and management plan with PLWHA. [Further reading B]

Basic principles of healthy travelling

Like any other travellers, an HIV traveller should plan ahead of his/her trip and seek not only general travel-related advice regarding infectious and non-infectious travel risks in their destination, but also specific advice in regards to one’s current health status. Visits should be made at least 4-6 weeks in advance of departure to allow for the consideration of vaccination and modification of treatment regimen and observing potential side effects of prophylactic treatment should these be required. [Algorithm 14]

Apart from obtaining routine travel information as listed in Box 14.1, physicians should also provide specific information on one’s health status, specifically the most recent CD4 count and its trend, the latest HIV viral load, the current highly active antiretroviral therapy (HAART) regimen and drug adherence. An integration of all these information could be used to assess the degree of immunocompromise and physical fitness of an HIV traveller for the journey and to offer general and specific health advice.

In the past, CD4 counts of less than 200 cells/μL and history of an AIDS-defining illness (ADI) were used to define a compromised immune system. But since most PLWHA in care these days are already on HAART to achieve viral suppression, those who have no replicating virus are not thought to be immunocompromised (unless CD4 cell count is severely diminished) and should be approached like uninfected travellers. For those with CD4 count <200 cells/μL who are not yet on treatment or with a detectable viral load, history of ADI, or those with clinical manifestations of symptomatic HIV, they are considered to have severe immunosuppression and should generally be advised to delay their travel whenever possible.[3] Such a delay is preferred when the individuals undergo immune reconstitution with the initiation of antiretroviral treatment, firstly because it is not uncommon for them to suffer from side effects of the treatment during the initial months; secondly, immunologic recovery will minimise the risk of acquiring new infections and potentially lead to a better response to vaccinations.

An HIV traveller on treatment should ensure an ample supply of antiretroviral medications to prepare for unanticipated delay during their trip. Special consideration has to be taken on dosing interval when travelling across time zones. Whenever possible, new medication change just prior to travel should be avoided. Medications are best kept in the original bottles in their carry-on luggage and not the check-in luggage. It is advisable to obtain a letter from the physician with a brief summary of the medical history and list of medications to expedite the customs process when crossing borders. Reliable medical institutions at the destination should be located before travelling so that prompt medical care can be sought if one becomes ill while travelling. Medical insurance coverage should be verified and evacuation insurance should be considered depending on the type of travel and itinerary.

As in the case of traveller’s diarrhoea, HIV travellers should be reminded that all of the preventive strategies against specific conditions do not guarantee a 100% protection. They should be advised to seek expert medical assistance early in case of any febrile illness during or after the trip.

Food- and water-borne disease and traveller’s diarrhoea

Immunocompromised HIV travellers are more prone to either chronic diarrhoea from parasitic enteric infections, e.g. Cyclospora, Cryptosporidium and Cystoisospora; or more severe diseases from associated bacteraemia with the bacterial pathogens, e.g. Campylobacter species, Shigella species, and Salmonella species. The same precautions against food and waterborne diseases for all travellers should be emphasised when counselling PLWHA. They should be advised to avoid any uncooked foods, raw fruits and vegetables, raw or undercooked seafood or meat, tap water, ice made from tap water, unpasteurised milk and dairy products, and food and beverages purchased from street vendors. Frequent hand washing and use of proper hand hygiene with water and soap or alcohol-based solutions should be reinforced and advised as the best prevention against enteric infections.

Water should be either boiled or bottled, and when these are not feasible, alternative methods including use of portable water filtration units together with chemical treatment with e.g. iodine, tetraglycine hydroperiodide tablets, and chlorine can be considered. However, travellers should be warned that all of these methods have caveats to their use, thus they should not be falsely reassured of their safety, and the basic precautions above should be vigilantly observed throughout the trip.

As some animals are known to be associated with infections e.g. Salmonella, Campylobacter, Cryptosporidium, Brucella etc., HIV travellers should be advised to wash their hands after handling pets, avoid contact with pet faeces, and refrain from contact with reptiles, birds, and young farm animals.

Traveller’s diarrhoea can occur despite strict adherence to the precautions as mentioned. Routine antimicrobial prophylaxis for traveller’s diarrhoea is not recommended for HIV travellers, due to concerns of adverse effects and the possibility of promoting drug resistance.[4] In the event of severe manifestations (severe diarrhoea, abdominal cramp and fever), treatment of traveller’s diarrhoea using oral rehydration solutions in combination with antidiarrhoeal agents and presumptive antibiotic regimen with azithromycin (but not clarithromycin) or a fluoroquinolone such as ciprofloxacin and levofloxacin may be considered. These agents are safe, as they are not known to have significant interactions with HAART drugs. Fluoroquinolones, however, should be used with caution as resistant strains of campylobacter have been increasingly reported in Southeast Asia. Rifaximin is a non-absorbable antibiotic that has been shown to be active against several enteric pathogens. However, it is not readily available in Hong Kong and its use is limited by its cost and inconvenient thrice-daily dosing schedule.

Other waterborne infections (e.g. cryptosporidiosis, giardiasis, schistosomiasis or leptospirosis) may also result from swallowing or even being exposed to some bodies of water during recreational activities. HIV travellers should be advised to limit their exposure to fresh water (including rivers and ponds) and be careful not to swallow water while swimming. They should wear shoes and protective clothing to limit their exposure to soil with possible faecal contamination. For those with unavoidable exposure to water potentially contaminated with leptospira, chemoprophylaxis with a weekly dose of doxycycline at 200mg is recommended.[5]

Vector-borne disease and malaria

General advice on preventing exposure

HIV travellers are more prone to severe sequelae of certain insect-borne illnesses, e.g. leishmaniasis and Chagas disease. They need to take personal protective measures to avoid bites from different insects, such as mosquitoes (vectors for malaria, dengue fever, Japanese encephalitis, yellow fever, West Nile virus, and other arboviral infections), sandflies (vectors for leishmaniasis and Bartonella bacilliformis), ticks/mites/lice/fleas (vectors for rickettsiosis). They should be advised to put on light-colored clothing that covers most of the body surface, to use repellent-impregnated mosquito nets and to avoid shrubby areas and other infested habitats. The most effective repellent against a wide range of arthropods is N, N-diethyl-3-methylbenzamide (known as DEET). Insect repellents that contain DEET at concentrations up to 50% (range from 30-50%) are recommended for adults, and DEET up to 30% has been shown to be safe when applied to children older than 2 months according to the directions on the product labels. Repeated applications are necessary as DEET can be washed off with perspiration or rain. Permethrin can be used to spray clothes and bed nets, and permethrin-treated bed nets and clothing are also available as alternatives. Combined use of all of these measures can reduce insect bites substantially.

Malaria

Existing data on the relationship between HIV infection and incidence or severity of malaria are complex, and malaria has not been regarded as an HIV-related opportunistic infection. However, recent evidence has shown that HIV RNA plasma levels are increased during malaria infection, and CD4 counts are lowered in patients on HAART. In vitro studies also indicate that immune activation mediated by proinflammatory cytokines may contribute to HIV disease progression. HIV infection has been associated with recurrent malaria parasitaemia and reinfections, with increased clinical severity.[6] A thorough discussion of malaria prevention should be included in the pre-travel consultation with travellers visiting malaria endemic areas.

Apart from personal protection measures against insect bites, an HIV traveller should be strongly urged to start chemoprophylaxis before the trip and be reminded of the importance of drug adherence. The regimen should be tailored according to the specific area of travel and the local resistance to antimalarial drugs. Special consideration, however, has to be taken for potential drug-drug interactions, e.g. between ritonavir (RTV) and atovaquone-proguanil, chloroquine, and mefloquine, between efavirenz (EFV) and atovaquone-proguanil and doxycycline, and between cobicistat (COBI)-boosted regimen with mefloquine, although no clinically relevant events have been reported and no dosage adjustments are recommended. Mefloquine carries the risk of additional neurological toxicity when used with EFV, and atovaquone-proguanil has been known to increase the level of zidovudine (ZDV), thus, close monitoring of haemoglobin level is warranted. The up-to-date regional prophylaxis recommendations from CDC can be found at https://www.cdc.gov/malaria/travelers/country_table/a.html. In general, doxycycline and atovaquone-proguanil are considered to be the drugs of choice for malaria prophylaxis among PLWHA receiving antiretroviral drug therapy in view of the safety profile, tolerability and lack of clinically significant drug interactions.[7]

In contrast, antimalarial treatment regimens, including artemisinin derivatives and quinine/quinidine, may have potential interactions with many non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), COBI-boosted regimen, and with the CCR5 receptor antagonist. Expert advice should be sought when treating patients for malaria who are also on HAART. [3] [7]

Vaccine issues in HIV travellers

Travel-related vaccines can be categorised into 3 main groups: (a) routine vaccines; (b) recommended vaccines, depending on the destination and travel itinerary; and (c) required vaccines to acquire visa/entry permission for certain countries. Physicians should take the opportunity to update routine immunisation and to offer required and recommended destination-specific vaccinations for their HIV clients during the pre-travel consultation after careful evaluation of the risk of disease acquisition versus the safety and efficacy of respective vaccines.

As a general rule, killed or inactivated vaccines are safe for use in PLWHA. Live vaccines should be avoided, especially when the CD4 count is <200/μL (except for highly selected circumstances that measles or yellow fever vaccine may be considered when the risk of acquiring the infection outweighs the potential risk of the vaccination). Besides, the degree of immunocompetence also correlates with the degree of immunologic response to vaccinations. Studies have demonstrated a suboptimal antibody titre following vaccination at lower CD4 counts. Revaccination is recommended at least 3 months after immune reconstitution with antiretroviral therapy for any vaccines given while CD4 counts are <200/μL.[3] Box 14.2 summarises the recommendations for specific vaccines relevant to adult HIV travellers.

Sexual health and blood-borne viral risks

It has been shown that sexual activity increases during international travel, with only a limited number of travellers reporting consistent use of condoms. A study on the practices of HIV travellers revealed that over 20% reported having had casual sexual activity with new partners while travelling.[8] Physicians should take the opportunity during the pre-travel consultation to provide counselling on risks of exposure to other sexually transmitted infections (STI) as well as the risk of transmitting HIV and acquiring a new strain of HIV, and remind PLWHA on safer-sex preventive strategies.

Entry restriction

Border regulations relating to HIV status are a unique and important part to consider while planning for international travel. Most countries do not have entry restrictions to PLWHA for short-term stay, so holidaymakers do not usually have any problems. USA has lifted the ban in 2010. But there are still countries that impose restrictions on the entry of PLWHA and immigrants. In case of doubt, HIV travellers should be advised to check with the embassies or consulates of destination countries to get the most up-to-date information and policy about HIV test requirements and other possible health-related visa requirements, e.g. vaccination requirement and proof of immunity, TB test and chest x-ray, etc.

Approach to post-travel management of HIV travellers

When a returning HIV traveller presents with illness for post-travel assessment, a detailed history including the onset of symptoms in relation to the itinerary, the exact arrival and departure dates, specific risk behaviours (e.g. intake of ‘high-risk’ food/drinks, contact/bites by animals, fresh water exposures, insect bites, new sexual partners, hospitalization in foreign countries etc.), history of any pre-travel vaccination and chemoprophylaxis and the adherence to such treatment during and after the trip should be obtained to determine the potential exposure to infectious agents and the likely incubation period.

Because of its complexity, any returning, febrile HIV traveller should be evaluated immediately, preferably by an infectious disease clinician or tropical medicine specialist. Physicians should be aware of the presence of HIV infection or AIDS, which can pose a diagnostic challenge as the natural history of infectious disease could be altered in different ways and that patients may present with atypical clinical manifestations. Apart from geographically focal infections for inclusion in the list of differential diagnoses, physicians should always consider commonly encountered infections.

For any febrile travellers returning from a malaria-endemic area, irrespective of the history of chemoprophylactic treatment and its adherence, all should be managed as medical emergency with a working diagnosis of malaria until proven otherwise. If chemoprophylaxis has been given, the same medicine should not be used for treatment.

References

Further reading