C09 The Primary care perspectives of HIV management

Introduction

HIV has become a chronic, manageable condition since the introduction of highly active antiretroviral therapy (HAART) which improved substantially the life expectancy of HIV-infected individuals. As a result, many people living with HIV/AIDS (PLWHA) who are infected early in the course of their lives are confronted with the similar effects of ageing as the general population. Non-AIDS diseases now account for the majority of deaths in PLWHA.[1] The risk of developing these chronic non-communicable diseases however, may differ from that of the general population as a result of immune activation due to HIV infection, lifestyle factors and the effects of HAART.

It is important for the primary care physicians to appreciate that they are important partners in the management of PLWHA in the community, and to recognise the similarities and differences in treatment strategies in areas such as, but not limited to non-communicable diseases, vaccination, prophylaxis and cancer screening. Diabetes mellitus, hyperlipidaemia and cardiovascular diseases are associated with HIV as well as HAART. Screening and management of these conditions also form part of the primary care aspects of HIV management. These are covered in a separate chapter “Metabolic problems and cardiovascular complications”.[Chapter C15]

Immunisation

The risk of suffering from infectious diseases is generally higher in the immunocompromised population compared to their immunocompetent counterpart. As a general rule, vaccinations are more efficacious in HIV-infected individuals when their immune function is relatively preserved, generally regarded as a CD4 count above at least 200/μL. CD4 counts above 500/μL are optimal. Patients should therefore consider vaccination before their CD4 count falls below 200/μL, or failing so, until immune reconstitution from HAART.

In general, live vaccines should be avoided in PLWHA, unless the benefits of prevention of an infection are outweighed by the risks of infection by the vaccine strain.Box 9.1 outlines vaccine recommendations in HIV-infected population.[2] [3]

Box 9.1. Vaccine recommendation in HIV-infected individuals

Vaccine against Remarks
Influenza Annual influenza vaccine for all HIV-infected individuals; use of inactivated vaccine recommended
Tetanus, diphtheria, pertussis (Td/Tdap) Routine vaccination as for the general population; substitute 1-time dose of Tdap for Td booster, then boost with Td every 10 years
Varicella Contraindicated for those with CD4 count <200/μL
Human papillomavirus 3 doses through age 26 years for both male and female. (As the vaccine is most effective if given to those before sexual debut, the benefits conferred by vaccinating those who have been sexually active remain unclear)
Zoster Contraindicated for those with CD4 <200/μL; no recommendation to-date for CD4 count ≥200/μL
Measles, mumps, rubella (MMR) Contraindicated for those with CD4 count <200/μL
Pneumococcus For those who have not received PCV13 or 23vPPV: administer PCV13 followed by 23vPPV at least 8 weeks apart; for those who have already received 23vPPV, PCV13 should be administered at least 1 year later; for those who have already received any PCV13, a single dose of 23vPPV should be administered at least 8 weeks later
Hepatitis A Recommended in all HIV-infected individuals without immunity, especially in chronic hepatitis B and C carriers and MSM
Hepatitis B Recommended in all HIV-infected individuals without immunity

Immunisation for HIV-infected travellers should follow the same general guidance as above. Routine vaccines should be updated and destination-specific immunisations and prophylactic medications advised.

Travel advice for HIV infected individuals are discussed in further details in Chapter C14: An HIV Traveller.

Prophylaxis against opportunistic infections

Pneumocystis pneumonia (PCP) is the commonest AIDS-defining illness in Hong Kong.[Chapter D25] In some patients, PCP is the presenting illness prompting an HIV test. The risk of PCP is greatly increased in persons whose CD4 count has dropped below 200/μL. Primary prophylaxis is indicated in those with CD4 count below 200/μL or with oropharyngeal candidiasis. Primary and secondary prophylaxis should be continued until immune reconstitution is achieved, defined as a CD4 count ≥200/μL for more than 3 months.

Latent tuberculosis infection (LTBI) predicts the future risk of developing active TB. As TB is endemic in Hong Kong, the current practice of screening for LTBI among asymptomatic HIV-infected individuals includes using either a tuberculin skin test (TST) or blood test for IFN-gamma release assay (IGRA). A positive TST is defined as an induration size ≥ 5mm in the HIV-infected, after ruling out active disease. In patients who had never been treated for active or latent TB and who tested positive on TST or IGRA, isoniazid preventive therapy (IPT) or other alternatives reduces the risk of developing active TB disease in the future. It is imperative to exclude active TB before initiation. IPT is also indicated in HIV-infected individuals who have been in close contact with another person harbouring active disease. Liver function tests should be monitored closely especially in those who have chronic hepatitis B or C infection. Details regarding the diagnosis of treatment of latent TB infection are discussed in Chapter D23.

Primary prophylaxis against disseminated Mycobacterium avium complex (MAC) disease is indicated in patients with a low CD4 count < 50/μL and in whom active MAC disease has been excluded. Secondary prophylaxis after completion of treatment should also be instituted unless immune reconstitution has occurred. Discontinuation of primary and secondary prophylaxis may be considered when there is sterilization of MAC and CD4 count rises to above 100/μL for more than 3 and 6 months respectively after HAART.[Chapter D22]

Toxoplasma gondii encephalitis [Chapter D27] may be prevented in the HIV-infected individual by the administration of cotrimoxazole. In patients who tested positive for Toxoplasma IgG, primary prophylaxis should be instituted when the CD4 count drop below 100/μL. Cotrimoxazole has the advantage of prophylactic activity against PCP. Primary and secondary prophylaxis may be discontinued when CD4 count rise above 200/μL for more than 3 and 6 months respectively in patients on HAART. Box 9.2 provides the details of prophylaxis against common opportunistic infections.

Box 9.2. Prophylaxis against opportunistic infections

Infection and indication Prophylaxis Alternative regimen
PCP
Primary prophylaxis TMP/SMZ^-DS* regimen provides cross-protection vs. toxoplasmosis[
1DS *daily po or
1SS# daily po
Dapsone 100mg daily po or
Aerosolised pentamindine 300mg via Respigard II nebuliser monthly or
Atovoquone 1500mg daily po
Secondary prophylaxis Same as primary prophylaxis Same as primary prophylaxis
Latent TB infection
Isoniazid preventive therapy (IPT) Isoniazid 300mg daily po for 9 months Rifampicin® 600mg daily po for 4 months or
Rifabutin (dosage adjusted base on concomitant ART) daily po for 4 months or
Rifapentin (weight-based. 900mg max#) once per week po + Isoniazid 300 mg once per week po
Disseminated MAC
Primary prophylaxis Azithromycin 1000mg weekly po or
Clarithromycin 500mg bd po or
Azithromycin 500mg twice per week po
Rifabutin 300mg daily po
Secondary prophylaxis Same as treatment regimen  
Toxoplasma gondii encephalitis
Primary prophylaxis TMP-SMZ 1 DS daily po Dapsone 50mg daily po + Pyrimethamine 75mg po weekly + leucovorin 25mg po weekly
Secondary prophylaxis Pyrimethamine 25-50mg daily po + sulfadiazine 2000-4000mg daily po (in 2-4 divided doses) + leucovorin 10-25mg daily po Clindamycin up to 450mg every 6-8 hours + Pyrimethamine 25-50mg daily po + leucovorin 10-25mg daily po or Atovaquone 750mg po every 6-12 hours +/- [(Pyrimethamine 25mg po daily + leucovorine 10mg po daily) or sulfadiazine 2000-4000mg daily po]
TMP-SMZ: trimethoprim-sulfamethoxazole
*DS: double strength
#: single strength
#32.1-49.9kg: 750mg; ≥50mg: 900mg
®watch out for potential drug-drug interactions between Rifampicin, Rifabutin, Rifapentin with ART

Cancer screening

Cancer has been the major cause of death in Hong Kong for the last 2 decades. In the HAART era, non-AIDS defining cancers outnumbered AIDS-defining cancers in PLWHA.[4] In one study, 71% of all observed cancers were non-AIDS defining cancers.[5] HIV-infected individuals are at a higher risk of developing these non-AIDS defining cancer than the general population (See Chapter E32 for more details).

The risks of cervical and anal cancers are greatly increased compared to the general population. Female patients should undergo cervical screening half-yearly at the first year of diagnosis, and thereafter, annual screening. The recommendation calls for more frequent screening than the general female population due to the increased risk of cervical dysplasia.

Anal cancer is also becoming more common among HIV-infected individuals as they age. This is of particular importance in the MSM population due to the high prevalence of infection by oncogenic HPV types through anal sex. In HIV-infected MSM, the rate of anal cancer is a few times higher than the HIV-uninfected MSM. Most strikingly, the HIV-infected MSM is almost 60 times as likely as the general population to develop anal cancer.[6]

It is unclear whether detection of anal dysplasia by anal cytology is useful to reduce the burden of anal cancer among MSM who are infected with HIV. Currently, there is no consensus on the screening strategies for this population. Abnormal anal cytology should be followed by high-resolution anoscopy and biopsy. There is a need to develop expertise skilled in interpreting anal cytology results and in managing anal dysplasia.

Screening of sexually transmitted infections (STI)

Sexually transmitted infections (STI) are frequently observed in HIV-infected individuals and represent a dual concern, as some STIs may increase the risk of HIV transmission; and HIV infection may alter the clinical manifestation of STIs.

Screening of HIV patients for STIs is advised (refer to Algorithm in Chapter D29). One useful approach is to screen for syphilis infection by serology every 3-4 months in MSM due to the high risk of co-infection, and annually in other patients. Urine, rectal or throat sample screening tests for Neisseria gonorrhoea or Chlamydia trachomatis by nuclei acid amplification test (NAAT) is convenient and improves the yield as some infections may be asymptomatic. In women, swabs for Chlamydia trachomatis and Neisseria gonorrhoea are routinely performed for females undergoing annual cervical smear. Hepatitis C could also be transmitted by unprotected sexual intercourse and hence interval screening of Hepatitis C antibody along with monitoring of liver function should be done.

Mental health

Mental health symptoms are commoner in HIV-infected individuals than the general population. Depression, anxiety, substance misuse and suicidality are but a few of the commoner conditions encountered.[7] These symptoms should be differentiated from non-psychiatric conditions associated with the infection or adverse events associated with treatment. These include HIV-associated dementia, neurosyphilis, Vitamin B12 deficiency, thyroid disease, adrenal insufficiency or hypogonadism. Primary care practitioners are first point of contact of HIV-infected individuals; and if equipped with the necessary tools to pick up early symptoms, may prevent the occurrence of debilitating disease. At the first and subsequent visits, symptoms of depression or anxiety, sleeping pattern, suicidal ideation and current or past use of alcohol or other psychotropic substances should be evaluated. Understanding the broader context of family circumstances and social support network aid in subsequent management. Prompt referral to specialist is warranted in some circumstances.

The use of recreational drugs, e.g. methamphetamine and gamma-hydroxybutyric acid, carries important implication in the sexual behaviours and mental health status of the HIV-infected individuals. It increases the risk of developing both STI and other mental health problems. Co-administration of recreational drugs with HARRT may also increase the risk of developing overdoses and toxicities,[8] further details of which are covered in Chapter F37 on Chemsex and its implications.

Smoking cessation

The proportion of daily cigarette smokers in Hong Kong stands at 10% in 2017, and a greater number is seen amongst males (18.1%) than females (2.7%). Smoking has been reported to be more prevalent in the HIV-infected population compared to the general public.[9]

The effects of tobacco smoking on HIV-infected patients are manifold. Apart from demonstrating a poorer virologic and immunologic response to HAART, HIV-infected smokers bear a higher toll of tobacco-related maladies than the HIV-uninfected, notably cancers affecting the lungs, head and neck region, cervix, anus; as well as oral candidiasis and oral hairy leukoplakia.[10]

Primary care physicians should include assessment of smoking status as part of day-to-day clinic management of PLWHA. It is the responsibility of the attending doctor or health care team to assess the patient’s readiness to quit smoking using, for example, the transtheoretical model of health behaviour change.[11] This model encompasses the hallmark five stages of behaviour change: pre-contemplation, contemplation, preparation, action and maintenance. Brief interventions by attending doctors improve abstinence rates of smokers. Motivational interviewing is another strategy which may be combined with the above for those who are not thinking of quitting.

Pharmacological interventions e.g. nicotine replacement therapy, are also used in the HIV-infected individuals. Both bupropion and varenicline may affect sleep and exacerbate psychiatric symptoms. They should be used with caution in patients taking efavirenz. Primary care physicians or attending doctors should familiarise themselves with potential drug interactions when considering these options.

References

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  2. Scientific Committee on Vaccine Preventable Diseases, Centre for Health Protection, Hong Kong. Updated Recommendations on the Use of Pneumococcal Vaccines for High-risk Individuals. Hong Kong: Department of Health, 2016. link
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  9. Mdodo R, Frazier EL, Dube SR, Mattson CL, Sutton MY, Brooks JT, Skarbinski J. Cigarette smoking prevalence among adults with HIV compared with the general adult population in the United States: cross-sectional surveys. Ann Intern Med 2015;162(5):335-44. link
  10. Crothers K, Goulet JL, Rodriguez-Barradas MC, Gibert CL, Oursler KA, Goetz MB, Crystal S, Leaf DA, Butt AA, Braithwaite RS, Peck R, Justice AC. Impact of cigarette smoking on mortality in HIV-positive and HIV-negative veterans. AIDS Educ Prev 2009;21(Suppl 3):40-53. link
  11. Aveyard P, Massey L, Parsons A, Manaseki, Griffin C. The effect of Transtheoretical Model based interventions on smoking cessation. Soc Sci Med 2009;68(3):397-403. link