Chapter 27: HIV/AIDS—could it be HIV?

HIV, the cause of the well-known AIDS, can rightly be included as one of the clinical masquerades of modern medicine. Public health measures in the Western world have limited the spread of the infection. By contrast, the incidence in Africa and Asia continues to rise at an alarming rate. The World Health Organization estimated that in 2010,¹ 34 million adults and children were living with HIV, including 23 million in sub-Saharan Africa and 25 000 in Australia, with 2.7 million newly infected and increasing, while 1.8 million people with HIV died. However, this figure reduced to 1.1 million in 2015.

In 2012, the average age of people newly diagnosed with HIV infection was 37 years and about 86% were male; most infections are in men who have sex with men (MSM). The conversion rate of HIV to AIDS has been 33% but it is improving with antiretroviral therapy (ART), which has dramatically changed people’s lives. HIV is now a chronic disease management problem. The introduction of combination treatment with the protease inhibitors in November 1995 changed the previously understood natural history of the disease.

The benefit of early diagnosis has become even more impressive since the discovery that HIV is not a latent infection throughout most of its course. Soon after initial infection, an explosive replication of HIV occurs, which is brought under control by the immune system in 6 to 8 weeks as the host-versus-virus interaction reaches an active and dynamic equilibrium. This dynamic situation continues throughout a person’s lifetime, with as many as 10 billion new viroids produced and up to 2 billion CD4 T lymphocytes destroyed and replaced daily. Clinical immunodeficiency develops when the body’s ability to replace CD4 cells is finally exhausted, resulting in further uncontrolled viral replication. Viral load assays based on molecular techniques have revolutionised our understanding of the natural history of HIV disease. These advances make it imperative to make the diagnosis early in the course of the disease in order to start combination treatment to lessen the viral load.

The management of HIV infection is a specialised field but the GP is central in prevention, diagnosis, counselling, monitoring and shared management of HIV disease. The GP must be alert to the benefits of early diagnosis as summarised in TABLE 27.1.

Occurrence and transmission

HIV can be isolated from blood, tissues, semen, saliva, breast milk, cervical and vaginal secretions and tears of infected persons. HIV is transmitted in semen, blood and vaginal fluids, transplanted organs and breast milk through:

• unprotected sexual intercourse (anal or vaginal) and in rare cases oral sex with an infected person

• infected blood entering the body (through blood transfusion or by IV drug users sharing needles/syringes)

• needle-stick injury

• artificial insemination, organ transplantation

• infected mothers (to babies during pregnancy, at birth or in breast milk)

Infection with HIV can occur via the vagina, rectum or open cuts and sores, including any on the lips or in the mouth. Social (non-sexual) contact and insect vectors have not been implicated in transmission.

Stages⁵

The clinical stages of HIV disease are summarised in TABLE 27.2.⁶

Acute (seroconversion) illness

At least 50% of patients have an acute illness associated with seroconversion. The illness usually occurs within 6 weeks of infection and is characterised by fever, night sweats, malaise, severe lethargy, anorexia, nausea, myalgia, arthralgia, headache, photophobia, sore throat, diarrhoea, lymphadenopathy, generalised maculoerythematous rash and thrombocytopenia. The main symptoms are headache, photophobia and malaise/fatigue. Neurological manifestations, including meningoencephalitis and peripheral neuritis, can occur. Acute HIV infection should be considered in the differential diagnosis of illnesses resembling glandular fever. This illness, which resembles infectious mononucleosis, is self-limiting and usually resolves within 1 to 3 weeks. However, chronic lethargy, depression and irritability may persist after the acute illness. Non-specific viraemic sequelae such as mucosal ulceration, desquamation, exacerbation of seborrhoea and recurrences of herpes simplex may occur (see FIG. 27.1).

Acute illness may be accompanied by neutropenia, lymphopenia, thrombocytopenia, and mildly elevated ESR and serum transaminases. During recovery lymphocytosis may occur with appearance of atypical mononuclear cells and an inversion of the CD₄⁺:CD₈⁺ ratio due to elevation of CD₈⁺ cells. It is seronegative for EBV.

Differential diagnoses are given in TABLE 27.3.

Subsequent stage

After the acute illness, HIV disease passes into an asymptomatic stage of variable length, up to several years, but 30% have persistent generalised lympathenopathy.

Later constitutional symptoms develop along with minor opportunistic infections such as oral candidiasis, herpes simplex and herpes zoster. This early symptomatic stage is referred to as AIDS-related complex and is regarded as a prodromal to AIDS.

AIDS-defining conditions

The original US Centers for Disease Control (CDC) classification has been modified with time to provide a more simplified scheme for defining AIDS. The HIV/AIDS case surveillance system simply specifies a list of clinical conditions associated with the late stages of HIV infection as being ‘AIDS-defining’.⁷

The AIDS-defining conditions are:

• candidiasis of bronchi, trachea or lungs

• candidiasis, oesophageal

• cervical cancer, invasive

• coccidioidomycosis, disseminated or extrapulmonary

• cryptococcosis, extrapulmonary

• cryptosporidiosis, chronic intestinal (>1 month’s duration)

• cytomegalovirus (CMV) disease (other than liver, spleen or nodes)

• CMV retinitis (with loss of vision)

• encephalopathy, HIV-related

• herpes simplex virus (HSV): chronic ulcer(s) (>1 month’s duration); or bronchitis, pneumonitis or oesophagitis

• histoplasmosis, disseminated or extrapulmonary

• isosporiasis, chronic intestinal (>1 month’s duration)

• Kaposi sarcoma

• lymphoma, Burkitt (or equivalent term)

• lymphoma, immunoblastic (or equivalent term)

• lymphoma, primary, of brain

• Mycobacterium avium complex of M. kansasii, disseminated or extrapulmonary

• Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary)

• Mycobacterium, other species or unidentified species, disseminated or extrapulmonary

• Pneumocystis jiroveci pneumonia (PJP)

• Salmonella septicaemia, recurrent

• toxoplasmosis of brain

• wasting syndrome due to HIV

The Australian AIDS surveillance case definition does not refer to the CD₄ cell count although in the US AIDS is also defined by a CD₄ cell count of <200/μL, regardless of clinical condition. At levels below this, people will become increasingly vulnerable to AIDS-defining conditions.

There is a multiplicity of clinical findings in HIV infection (see FIG. 27.1).

Fever

• Usually this is of unknown origin.

Weight loss

• Usually severe and muscle wasting

Respiratory

• Sinusitis

• Non-productive cough, increasing dyspnoea and fever: due to opportunistic pneumonias

More than 50% of patients present with PJP which may have an abrupt or insidious onset.⁶ With the insidious type of onset, examination and chest X-ray are often normal early. Many other agents (e.g. CMV, cryptococcosis and TB) can be responsible. Exclusion of PJP is important as this condition carries a high mortality if untreated.⁶

Gastrointestinal

• Chronic diarrhoea (many causes) with weight loss or dehydration

Neurological

• Headache

• Progressive dementia (HIV encephalopathy)

• Ataxia due to myelopathy

• Seizures

• Mononeuritis

• Guillain–Barré type mononeuropathy

• Toxoplasma encephalitis

• Cryptococcal meningitis

• Peripheral neuropathy

• Progressive visual loss (CMV retinitis)

• CNS lymphoma

Oral cavity

• Aphthous ulcers

• Angular cheilitis

• Periodontal/gingival disease

• Tonsillitis

• Oral candidiasis

• Oral hairy cell leukoplakia (frequently mistaken for candidiasis but affects lateral border of tongue)

Genitourinary

• Cervical dysplasia

• Vaginal candidiasis

• Various STIs (e.g. HSV, HPV)

Skin

• Impetigo

• Warts

• HSV

• Shingles, especially multidermatomal

• Seborrhoeic dermatitis

• Cutaneous mycoses

• Kaposi sarcoma (painless red-purple lesions on any part of the body including palms, soles, oral cavity and other parts of the GIT) (see FIG. 27.2).

Psychological

FIGURE 27.3 presents the chronology of HIV-induced disease correlated with time since infection and CD₄ cell levels.

Investigations and diagnosis⁶

The laboratory investigation of AIDS covers three broad areas:

1. Tests for HIV infection:

   • antigen–antibody test (ELISA screen) or HIV rapid test (at point of care). If positive—western blot technique (used for confirmation)

2. Tests of immune function:

   • CD₄ lymphocyte counts—the strongest predictor of possible clinical manifestations of HIV infection

   • low CD₄ cells (counts <500 cells/μL) = defective cell immunity^2,4

   • counts <200 cells/μL = severe immunodeficiency

3. Plasma HIV RNA (viral load): a measure of the serum level of RNA of the HIV virus—correlates with response to treatment and progression to AIDS and death

4. Genotype resistance (HLA B5701 if treatment with abacavir planned)

5. Tests for opportunistic infections and other problems, e.g. other STIs, EBV, CMV, hepatitis, Mantoux test

6. Routine general health tests, e.g. FBE, U&E, blood glucose, lipids, eGFR, LFTs

Management

Patients with HIV infection who invariably have to cope with profound psychological stress require considerable psychosocial support, counselling and regular assessment from a non-judgmental, caring practitioner. Best practice is referral to a specialist clinic for shared care.

The holistic approach

Most people with HIV infection will take ‘natural therapies’. This should be viewed as being complementary to the management suggested by the GP, and the patient should be encouraged to tell his or her doctors of the alternative medicines being taken. Anecdotal reports suggest that 75% of people with HIV regularly use ‘natural therapies’,⁸ and in the setting of the long-term nature of the condition it is important for doctors to be supportive and create a climate of acceptance around these practices.

Positive lifestyle factors include:

• a very healthy balanced diet: high fruit and vegetable intake, pure fruit juices, high fibre, low fat, high complex carbohydrates

• toxic avoidance: processed foods, caffeine, illicit drugs, alcohol, cigarettes

• relaxation and meditation (reduction and self-monitoring of stress levels)

• appropriate sleep and exercise

• consider supplementary antioxidants

• support groups and continuing counselling

Treatment (medication)^8,9,10

Optimal antiretroviral therapy (ART), which has dramatically changed the outlook, now depends on the use of combinations of drugs. Monotherapy is no longer accepted practice. The recommendations for the use of antiretroviral therapy are constantly changing. Updated guidelines can be found on the internet at www.hivatis.org, www.bhiva.org, www.ashm.org.au or www.aidsinfo.nih.gov/guidelines. Viral resistance is the limiting factor, no matter how potent an individual drug may be at reducing viral load initially. The trials of combined zidovudine and lamivudine demonstrated both a more sustained decrease in plasma viral load than either drug did alone, and a more delayed development of viral resistance. There are now many antiretroviral drugs available for use in Australia (see TABLE 27.4) and clinicians have a much wider scope of treatments available. However, many questions remain about combination therapy and further trials using viral load as a clinical endpoint should provide pointers for treatment. Currently the use of three drugs, referred to as highly active antiretroviral therapy (HAART), is favoured. There are many possible combinations. Side effects, which are often severe—including cardiovascular disease—and affect the quality of life, remain a problem. Resistance to HAART is now a problem. Effective (90%) results have been achieved with TRIO (etravirine, darunavir and raltegravir) therapy.¹¹ Investigators are evaluating the benefits of dual therapy through the SWORD-1 and SWORD-2 studies. Long-term treatment with fewer agents would be popular if of proven efficacy. Subcutaneous injections of interleukin-2 have been shown to boost immunity.

When to start^12,13

This is a controversial issue. CD₄ cell count guidelines:

• <350/μL—treat with ART

• 350–500/μL—strongly consider, offer or closely monitor

Current thinking favours early treatment. Refer to current international guidelines (see Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine: www.ashm.org.au). The most widely used and preferred regimen consists of 2 NTIs plus either an NNRI or a protease inhibitor,⁹ e.g. emtricitabine + tenofovir + efavirenz or rilpivirine.

Be aware of:

• drug interactions (www.hiv-druginteractions.org)

• contraindicated drug combinations⁹

• adverse effects⁹

• opportunistic infections

HAART (highly active antiretroviral therapy)

This is a combination of three (or more) agents with one or more penetrating the blood–brain barrier.

Pneumocystis jiroveci⁹

This is an important cause of pneumonia and not usually seen until the CD₄⁺ cell count is <200/μL. It is usually treated with trimethoprim + sulfamethoxazole (cotrimoxazole) oral or IV for 21 days depending on severity, which is also given orally as prophylaxis when the cell count reaches <200. Alternative agents are IV pentamidine or oral dapsone, clindamycin and atovaquone.

Acute HIV Infection

Treatment of seroconversion illness is not of proven clinical benefit (to date) but is optional and some clinics offer it.

Pre-exposure prophylaxis (PrEP)

This can be considered for those at risk. Selected tablets such as tenofovir or Truvada are taken around time of sex.¹⁴ Refer to your local sexual health clinic.

Post-exposure prophylaxis (PEP)

Undertake a risk assessment—PEP is not recommended for low-risk cases but those with significant high risk should be considered for PEP. It should be commenced within 72 hours of exposure and usually involves 2–3 antiretroviral agents taken daily for 28 days.¹⁵ Refer to ‘Needle-stick and sharps injuries’ for protocol (see CHAPTER 132).

The astute GP will use the opportunity of a request for an HIV test to explore preventive and sexual health issues. A full sexual history and drug history must incorporate the ‘three Cs’ of counselling, confidentiality and consent in the pre-test interview.

Many HIV-positive patients have described how the results left them bewildered and devastated, especially with an unexpected positive result. Part of the reason given was the lack of any form of pre-test counselling. Ideally, management involves shared care with an expert consultant, with whom close liaison is essential.

Initial consultation

• First establish why the patient is presenting ‘now’ for the test.

• Explore the ‘hidden component’ of the patient’s consultation.

• Take a full sexual, medical and drug-taking history. It is recognised that this can be embarrassing for both the doctor and the patient, but those experienced in this process advise the following approach:

  • – Establish a supportive, non-judgmental atmosphere. Encourage disclosure of history and patterns of partners and sexual practices in a gender-neutral situation. Make no assumptions about sexual preferences; they will be indicated by the patient as the history evolves, provided you allow this to happen; this will take time.

• Non-judgmental, matter-of-fact questions such as ‘Have you injected yourself with drugs?’ and ‘Do you have sex with men or women or both?’ may permit honest disclosure.

• Stress the importance of disclosure of prior, known infections with STIs. Assess the patient’s risk for an STI.

• Assess the patient’s coping strategies and social network.

Pre-test counselling

• Give information on the test (what it tells and does not tell).

• Explain about the false negative and ‘window period’.

• Give appropriate information about HIV disease and other STIs.

• Dispel any myths about transmission of infection.

• Give preventive advice on safer practices (sex and IV drugs).

• Assess the possible coping mechanisms of the patient.

• Assess the patient’s social support networks and interpersonal bonds.

• Reassure about confidentiality. This is a legal requirement.

• Discuss who to tell: informing sexual contacts.

• Offer tests other than STIs.

Finally:

• Discuss how the patient will cope with the test result.

• Discuss legal requirements (check with state laws).

• Advise of need for informed consent (not only for HIV test but other STIs).

• Make arrangements to discuss the test results face to face.

Consider the useful question: ‘How would your behaviour change, if at all, as a result of having this test today?’

Test result (about 2 weeks later)

This must be given in consultation (whether positive or negative): avoid the telephone.

The negative test result

• Provide reassurance.

• Emphasise the safe sex information.

• Counter any suggestion that current risk-taking behaviour is safe.

• Retest if in high-risk category or known HIV contact or in a ‘window period’ of 12 weeks.

• A test in 3 months helps rule out recent acquisition.

• Maintain confidentiality.

The positive test result

This is a very traumatic experience and good communication skills are essential. The result should be stated clearly. Good pretest history taking, risk assessment and counselling will make the task of informing the patient of a positive test result a lot easier. Being able to inform the patient of a greatly improved prognosis due to combination drug therapy is also of assistance in breaking the news. Be warm and open. Many patients want to be touched for reassurance. The words ‘you are not dying’ can be firmly stated a few times. Educate the patient about the difference between HIV infection and the acquired immunodeficiency syndrome. Discuss with the patient to whom he or she is going to tell the result and help the patient decide on the most supportive friend. Ask the patient what he or she is going to do after the consultation and make an appointment for the next day. Give the patient an HIV support line number for overnight telephone support if required. Discuss the issue of contact tracing briefly and in more depth at the next consultation, because sexual contacts should be notified. However, avoid an information overload.

Start immediate post-test counselling and education. Emphasise that an HIV-positive status does not equal AIDS and need not lead to it in the short term. Organise a consultant’s appointment and provide sound patient education material.

Interview and full clinical assessment

• Assessment of general health. Assess risk factors for cardiovascular disease and diabetes since ART can increase the overall risk at least two-fold.¹⁶

• Particular assessment of prior psychiatric history and confirm prior STIs and drugs

• Evidence of EBV (glandular fever), hepatitis B, HIV illness (acute seroconversion illness)

• Further counselling and discussion of specific problems

• Assessment of bonds and relationships with regard to support

Examination—to set a base level

• Full examination, skin, CNS—especially fundi, chest, abdomen and genitals; urine and lung function test

• Monitor temperature and weight

Blood tests—to set a base level and check immune status

• Repeat HIV antibody test (if any possibility of error)

• CD₄ cells with FBE and a differential WCC

• Viral load test

• G-6-PD screen for enzyme deficiency

• Serology for syphilis (RPR), hepatitis A, B and C (very important), toxoplasmosis, CMV

• Test for gonorrhoea and Chlamydia, herpes and thrush (if indicated)

• Mantoux test for tuberculosis

Encourage a holistic approach to health maintenance and enhancement. Explore the patient’s feelings, anxieties, fears and confidentiality concerns. Reinforce safer practices.

The second post-positive result consultation

• Give results of repeat HIV test and baseline tests.

• Explore patient’s understanding, feelings, coping abilities and spiritual issues (if appropriate).

• Some of the common questions that patients with HIV infection ask are:

  • – Am I going to get sick?

  • – How long will I live for?

  • – Are there any treatments available?

  • – Is there a cure?

  • – What is going to happen to me?

  • – Should I tell my friends?

  • – Should I tell my family?

  • – What are the social and legal issues?

It is worth pre-empting these questions and having ready appropriate answers for that particular patient.

• Give appropriate reassurance: prognosis is now much better, in respect of long remission, than appreciated.

• Discuss support systems.

• Check personal prophylaxis (safer sex and needle-sharing habits).

• Reinforce lifestyle strategies and suggest how patients can help themselves: give case examples.

• Recommend meditation, mindfulness and appropriate literature.

• Provide appropriate referrals (if needed): specialist counsellors, self-help and support groups, meditation classes.

• Advise patients about their legal and ethical responsibilities not to pass on the infection to others.

• Organise contact tracing.

• Address the difficult issue of telling sexual partners.

• If the patient is unwilling to inform sexual partners or is uncertain of who they may be, then contact-tracing organisations run through state government offices are of assistance in tracing sexual partners who may be at risk.

• If a patient refuses to inform a sexual partner of the risk, then the doctor may disclose this information to the patient’s partner in the following circumstances: if there is a clear risk of transmission; if the patient has been given education and counselling and this has been ignored; or if the doctor in the case has sought advice from colleagues and institutional ethics committee and before disclosure discussed it with the medical defence organisation. The doctor then should provide the patient with written advice that the patient must notify the partner, and if the patient still refuses to do so then the doctor has the right to do so.

• Discuss ‘safer sex’ guidelines. Condom usage is essential to prevent further viral loading and this needs to be explained, as well as the reason of protecting others.

• Advise on the importance of compliance with medication. There is rapid rebound of the virus when ART is stopped.

• Different criteria are used to guide treatment of children.

Continuing maintenance consultations

• Provide appropriate support, encouragement and counselling.

• Frequency depends on CD₄ cell count (e.g. 3–6 monthly).

• Examination:

  • – Check general condition, temperature and weight.

  • – Look for unusual lung infection, diarrhoea, skin lesions, tongue and oropharynx, fevers, wasting and neurological signs.

  • – Examine for signs of CMV retinitis (at risk if CD₄ count <100 cells/μL).

  • – Monitor for depressive illness.

  • – Look for early signs of AIDS-related dementia.

• Tests: CD₄ cell count and syphilis serology; viral load test; chest X-ray and induced sputum (if cough, shortness of breath), faeces microculture if diarrhoea persists, Candida mouth swabs and herpes swabs appropriately.

• Treat intercurrent illness.

• Prophylaxis—this is managed according to immune status: if CD₄ count <200 cells/μL use cotrimoxazole to prevent opportunistic infections, particularly PJP.

Contact tracing

Contacts of HIV-positive patients should be traced and offered testing with counselling.⁵ Patients with HIV infection must be advised of the risk they pose to seronegative sexual partners. A person who has HIV or is at risk of HIV infection must not make any blood, semen or tissue donation. Because of the probable association between genital ulcerative disease and HIV transmission, the effective management of STIs is part of the general strategy for HIV control.

Counselling the person at risk regarding ‘safer practices’

No effective vaccine has been developed. Modification of behaviour is the only valid strategy for prevention of HIV infection. Education programs to encourage sexual practices that reduce the exchange of genital secretions (safe sex) may achieve risk reduction for sexually active individuals. Condoms provide a barrier if used properly and consistently but may be too easily damaged to offer reliable protection during anal intercourse. A water-based lubricant such as K-Y gel or Lubafax should be used: oil-based lubricants such as Vaseline weaken condoms.

Discuss alternative sex practices, including touching, cuddling, body-to-body rubbing and mutual masturbation.

Emphasise the importance of being in control with drug taking, IV usage, safe sex practices and the needle-exchange program.

Of special importance is the finding that the most important biological risk factor for HIV transmission is the presence of other active STIs in either partner. This includes chlamydia, gonorrhoea, syphilis and genital herpes. Herpes is also likely to increase the risk of HIV transmission during both homosexual and heterosexual intercourse, even in the presence of condoms.^13,14,15

Health professionals

Care should be exercised whenever blood samples are taken or sharps have been used. Advise safe disposal of sharps and other disposables and appropriate sterilisation of material. Gloves should be worn for all invasive procedures. Management of needle-stick injuries and other at-risk exposures is described in CHAPTER 132. Blood donors need to be carefully screened.

Educating the community in a non-emotional, responsible way about AIDS should be a priority. While the personal, community and global benefits of effective AIDS education are generally acknowledged, the fear of addressing such a sensitive issue sometimes results in failure to act.^16,17 AIDS education in schools in particular can be an important strategy. People with HIV infection would be appropriate resource educators and the use of videos would be a most appropriate medium for education.

Most patients with HIV disease need referral to a specialist or clinic that can manage the patient expertly and sympathetically.

Referral should take place at the time of:

• onset of a life-threatening opportunistic infection

• the need to initiate antiretroviral drug therapy

• administration of prophylactic pentamidine therapy

• serious psychological problems related to HIV-positive status

Part of this text, including clinical manifestations, prevention and contact tracing is reproduced from the Handbook on Sexually Transmitted Diseases⁵ (copyright Commonwealth of Australia, reproduced by permission).

Hand-out sheets from Murtagh’s Patient Education 7th edition:

• HIV infection and AIDS

• HIV post-exposure prophylaxis