RECOMMENDATIONS FOR THE PREVENTION AND TREATMENT OF OPPORTUNISTIC AND HIV RELATED DISEASES IN ADULTS

Department of Health

Directorate: HIV and AIDS and STDs

LAUNCHED OCTOBER 2000

Table of Contents

Glossary

1. Introduction
2. General principles
3. Recommendations for the Prevention of Opportunistic Infections in HIV-infected Adults
4. Management of Common Respiratory Infections
5. Management of Tuberculosis in HIV-infected Adults
6. Management of Common Oral and Oesophageal Conditions
7. Management of Common Skin Conditions
8. Treatment of Herpes Virus Infections
9. Management of Human Papillomavirus Infection
10. Management of Genital and Sexually Transmitted Conditions
11. Management of Neurological Complications
12. Management of Central Nervous System Conditions
13. Management of Diarrhoeal Disease
14. Miscellaneous Conditions
15. HIV Complications at Various Degrees of Immunosupression
16. Antiretroviral Therapy

1. Introduction

This document provides recommendations for the medical management of people living with HIV infection and AIDS. The recommendations in this guide use medications that are listed as essential drugs (for primary and hospital care) by the Essential Drugs Programme within the Department of Health.

Currently, antiretroviral therapy is not available in the public sector. The Department of Health is investigating the possible use of antiretroviral medications for HIV positive persons and as a possible therapy to prevent mother-to-child HIV transmission. Guidelines for the use of antiretroviral therapy are therefore not presented in this document.

Separate guidelines exist for the management of sexually transmitted diseases and tuberculosis at primary health care level. Clinicians are best referred to those guidelines for information on clinical management of patients with these conditions.

Clinical science and the medical treatment of HIV positive and persons living with AIDS are developing rapidly. This guide is not intended to provide the state of the art medical care, but a practical approach for managing HIV and AIDS related diseases within health services in South Africa. Primary and secondary prevention of HIV infection are not addressed in this document but should be emphasised at all opportunities including during the treatment of HIV positive persons. The Department of Health would like to acknowledge the valuable contribution of Dr. Clive Evian who provided an early version of this guideline and the Southern African HIV and AIDS Clinician’s Society.

2. GENERAL PRINCIPLES

HIV causes immune system damage through the effects of ongoing viral replication and this ultimately leads to AIDS.

The rate at which the disease progresses differ between individuals, so treatment decisions should be individualised, guided by the clinical status and, if available, laboratory tests of plasma HIV RNA levels and CD4+ T-cell counts.

The time from infection to severe immunosuppression is variable, but usually takes up to 10-12 years in adults, unless the course of the infection is altered by therapeutic interventions.

Clinical course/Pathogenesis

The natural history of HIV infection is divided into the following stages:

1. Viral transmission
2. Primary HIV infection (Acute retroviral syndrome)
3. Seroconversion
4. Asymptomatic chronic infection with or without persistent generalized lymphadenopathy (PGL)
5. Symptomatic HIV infection
6. AIDS (Diagnosed by the presence of AIDS indicator clinical conditions)

The World Health Organisation (WHO) describes four clinical stages of HIV infection as follows:

Stage 1 Performance scale 1: asymptomatic normal activity Acute retroviral infection (seroconversion illness) Asymptomatic Persistent generalised lymphadenopathy

Stage 2 Performance scale 2: symptoms but fully ambulatory Unintentional weight loss < 10% of body weight Minor mucocutaneous (e.g. seborrhoea, prurigo, fungal nail infection, oral ulcers, angular chelitis) Herpes zoster within the last 5 years Recurrent upper respiratory tract infection (e.g., bacterial sinusitis)

Stage 3 Performance scale 3: bedridden < 50% of daytime Unintentional weight loss > 10% of body weight Chronic diarrhoea > 1 month Prolonged fever > 1 month Oral candidiasis Oral hairy leucoplakia Pulmonary tuberculosis (TB) in the last year Severe bacterial infections (pneumonia, pyomyositis) Vulvovaginal candida > 1 month or poor response to therapy

Stage 4 Performance scale 4: bedridden > 50% of daytime in prior month HIV wasting (weight loss plus chronic diarrhoea or fever) Pneumocystis carinii pneumonia CNS toxoplasmosis Cryptosporidiosis + diarrhoea > 1 month Isosporiasis + diarrhoea Cryptococcus – non-pulmonary Cytomegalovirus infection other than liver, spleen or lymph node Herpes simplex infection; visceral or > 1 month mucocutaneous Progressive multifocal leuconencephalopathy Disseminated mycosis Candida oesophageal / tracheal / pulmonary Atypical Mycobacteriosis disseminated Nontyphoidal Salmonella septicaemia Extra-pulmonary TB Lymphoma Kaposi's Sarcoma HIV encephalopathy

Principles for the medical management of HIV and AIDS

HIV infection is always harmful, and true long-term survival free of clinically significant immune dysfunction is extremely rare. Ideally, the therapeutic approach to managing people with HIV includes the following interventions:

• Monitoring the immune status of the body, the viral load, and clinical surveillance and diagnosis of opportunistic or HIV associated conditions.

• Immune boosting therapy

• Prophylaxis and treatment for common and serious opportunistic infections.

• Early and vigorous medical intervention for complications

• Promoting optimal health and well being and safer sexual practices

• Palliative and terminal care for severe and advanced end stage disease.

Current research also suggest that suppressing HIV viral activity and replication with anti-retroviral therapy (ART), or Highly Active Antiretroviral Therapy (HAART) combinations prolongs life and prevents opportunistic infections.

Psychosocial support is an important aspect of caring for HIV infected individuals and their families and partners. This will however, not be addressed in this document.

The goals of treatment for HIV infection should be to maintain immune function in as near a normal state as possible, prevent disease progression, prolong survival, and preserve quality of life by effectively suppressing HIV replication. For these goals to be accomplished, therapy should be initiated, whenever possible, before extensive immune system damage has occurred.

Laboratory monitoring

Where available, regular, scheduled monitoring of plasma HIV RNA levels and CD4+ T-cell counts assists in predicting the risk of disease progression in an HIV-infected individual and serves as a guide to initiating or modifying prophylactic and antiretroviral treatments. Although these laboratory tests are helpful, they are not required to be able to manage people living with HIV and AIDS at the primary health care level.

Laboratory tests that measure plasma HIV RNA levels indicate the magnitude of HIV replication. Higher levels of circulating virus lead to more rapid CD4+ T-cell destruction. The CD4+ T-cell count is a measure of the extent to which HIV-induced immune damage has already occurred. The optimal schedule for monitoring depends on the stage of the disease and whether the patient is on Antiretroviral therapy. Separate guidelines are available that recommend optimal monitoring schedules and assist with interpreting the results of the laboratory tests.

Management of HIV-Infected adults according to the stage of disease at primary care level

HIV-infected adults can be managed at primary health care level according to the WHO clinical staging system for HIV infection as follows:

First Visit
Clinical	Take full history of previous illnesses and current symptoms Do full physical examination of all systems Determine patient's clinical stage
Laboratory tests	If no documentation of HIV test result, repeat HIV test Full blood count (FBC) and differential; RPR; PAP smear for women; Anti-HBc
Prophylaxis	Influenza vaccine 0.5 ml IM before influenza season Trimethoprim-Sulphamethoxazole (TMP-SMX also known as co-trimoxazole or Bactrim® or Septran ®) for patients who are clinically stage 2, 3 or 4 PEM (protein energy malnutrition) scheme and multivitamins if losing weight, malnourished or with diarrhoea
Frequency of visits for review	Review results of tests in one week so that results can be acted on: e.g., Give Penicillin 2.4 million units IM if RPR positive Refer if abnormal PAP smear Give Hepatitis B vaccine if anti-HBc negative

 

Stage 1
Clinical	Patient is generally asymptomatic Conduct review of systems and physical examination
Laboratory tests	PAP smear annually for women
Prophylaxis	Reinforce health lifestyle choices
Frequency of visits for review	6 monthly
Stage 2
Clinical	Patient may be suffering from minor weight loss, skin rashes, upper respiratory tract infections Conduct review of systems and physical examination concentrating on the mucocutaneous system
Laboratory tests	PAP smear annually for women
Prophylaxis	Reinforce healthy lifestyle choices Trimethoprim-Sulphamethoxazole 2 single strength (80/400mg) or 1 double strength tablet (160/800 mg) PO daily for life Influenza vaccine 0.5 ml IM annually prior to influenza season
Frequency of visits for review	3 to 6 monthly Refer for social support grants if required

 

Stage 3
Clinical	Patient is starting to feel ill - may stay in bed because not feeling well - weight loss, candida, diarrhoea, fever, TB, pneumonia Conduct review of systems and full physical examination
Laboratory tests	PAP smear annually for women
Prophylaxis	Reinforce healthy lifestyle choices Trimethoprim-Sulphamethoxazole 2 single strength (80/400mg) or 1 double strength tablet (160/800 mg) PO daily for life Influenza vaccine 0.5 ml IM annually prior to influenza season
Frequency of visits for review	3 monthly / as clinically indicated Refer for social support grants, if required

 

Stage 4
Clinical	Patient is now sick- may be bedridden for most of the day - severe opportunistic infections may be present that need referral for investigation and treatment
Laboratory tests	PAP smear annually for women
Prophylaxis	Reinforce healthy lifestyle choices Trimethoprim-Sulphamethoxazole 2 single strength (80/400mg) or 1 double strength tablet (160/800 mg) PO daily for life Influenza vaccine 0.5 ml IM annually prior to influenza season
Frequency of visits for review	Monthly to 3 monthly / as clinically indicated

Appropriate Levels of Care for HIV-Infected Adults

• The increasing need for health care by HIV-infected individuals requires a coordinated system of care.

• Health services will cope better with rising numbers of patients if they are organised within a comprehensive framework linking hospitals, clinics, home- and community-based care providers, NGOs, and other community services.

• Hospitals should be aware of community resources available and actively plan and manage how their services are utilised to reduce the HIV patient load.

• Communication between different levels of care is essential. It provides continuity and consistency of management between the different service providers. This is especially important when decisions about terminal care are made.

• Standardised communication protocols and forms could be used.

• Having access to the results of TB and other investigations or recent HIV tests saves health workers time and money and these must be communicated to other health facilities involved in the patient’s care, while respecting confidentiality.

• Some of the drugs listed in these guidelines will not be available at primary health care clinics at this stage.

Primary Care

Most of the conditions affecting adults with HIV infection can be managed in the primary care setting, and this is also likely to be most convenient and cost-effective for the individual and their family.

The proposed scope of practice for primary care management of HIV-infected individuals and their families includes:

• HIV and STD detection, diagnosis and follow-up

• Education about safer sex, healthy living and caring for HIV-infected friends and relatives

• Pre and post-test counselling

• Taking blood for HIV testing and reporting the results to the patient

• Psychosocial support to families affected by HIV

• Provision of advice about hygiene, nutrition and self-management of minor ailments

• Treatment of minor ailments and opportunistic infections

• Supply of prophylactic medication e.g. Trimethoprim-sulphamethoxazole (Bactrim®), including commencing such prophylaxis, following the guideline recommendations

• Supervision of palliative care for patients with late-stage HIV disease

• Referral of acutely ill patients and those requiring further investigation for complex medical problems

• Consultation with referral centres e.g. telephonic contact for advice on management (hospitals may wish to have designated doctors "on-call" to advise peripheral centres)

• Follow-up of patients discharged from hospital

• Investigation for TB as per Department of Health protocols

• Supervision of TB therapy and tracing of contacts where applicable

• Issuing of condoms and family planning advice

• Access to more sophisticated diagnostics tests (such as CD4+ lymphocyte counts) will generally not be available at primary health care clinic level.

Hospital Care

Individuals who present with difficult clinical problems and seriously ill patients who require active treatment should be dealt with either in consultation with experienced health care workers or by referral to the hospital setting.

Referral to hospital may be necessary if:

• The patient is severely ill and requires admission, based on the same criteria as for other patients, such as in cases of hypoxia, dehydration, reduced level of consciousness etc.

• The individual is not responding to conventional therapy for a specific clinical problem

• Unexplained persistent fever, if investigation is not available at primary care level

• Unusual complications, if treatment is not available at primary care level

• Investigations that are required but not available at primary care level

• Palliative care is required and is not available at primary care level

• The individual is not coping at home and requires assistance in finding palliative care.

Hospital Admission for In-Patient Management

Admission to hospital should occur only when the individual would clearly benefit and where there is a specific, defined indication, such as the management of a reversible or treatable condition or initiation of palliative care. All admissions should be properly managed to ensure that hospital resources are utilised efficiently.

Hospital Outpatient Clinics

There are a few specialist HIV clinics at referral centres (mostly Academic Hospitals) where individuals who have unusual HIV-related problems may be seen. Patients will usually only be seen at specialist clinics on an appointment basis.

• Access to more sophisticated diagnostics tests (such as CD4+ lymphocyte counts) will not be available at many hospitals.

Tertiary referral

Very infrequently, specialist referrals may be required to departments such as Oncology; Neurology or Ophthalmology and these should normally be initiated within the referral hospital.

ICU care

Individuals who are HIV-infected should not automatically be excluded from access to Intensive Care. The decision to admit a patient to the ICU should be based on the indication for which they require this level of care, as well as their prognosis – based on the condition for which they are being managed and their underlying immune status (stage of HIV infection). ICU admission policies may vary, depending on the availability of resources and on local management protocols. Ideally, all patients being admitted to ICU should have their HIV status assessed prior to admission, as infection with HIV may have implications for their clinical management and prognosis.

3. RECOMMENDATIONS FOR THE PREVENTION OF OPPORTUNISTIC INFECTIONS (OIs) IN HIV-INFECTED ADULTS

• Preventive therapy against common opportunistic infections has beneficial effects for the well-being and survival of individuals infected with HIV.

SUMMARY: Prevention of opportunistic infections in HIV-infected adults:

Agent/Intervention	Dosage/Schedule	Indication	Disease Prevented
Trimethoprim-Sulfamethoxazole (TMP-SMX also known as Co-trimoxazole or Bactrim ® or Septran ®)	2 single strength (80/400mg) or 1 double strength tablet (160/800 mg) PO daily for life	All symptomatic HIV infected individuals (WHO clinical stage 2, 3 or 4) or CD4+ T-lymphocyte count below 200/µL or if there has already been an active infection of Pneumocystis carinii or toxoplasmosis	Pneumocystis carinii pneumonia, toxoplasmosis, bacterial pneumonia, Diarrhoea
PAP smear	At first presentation and annually thereafter	All HIV-infected women	To detect human papillomavirus-associated genital epithelial cancers- abnormal PAP smear results should be followed up in accordance with current accepted best practices.
Hepatitis B vaccine	0.5 ml IM injection x 3 doses according to manufacturer's instructions	All susceptible (anti-HBc-negative) HIV infected individuals	Hepatitis B
Influenza vaccine	0.5 ml IM injection annually prior to the influenza season	All HIV infected individuals	Influenza

NB Shaded sections are interventions that are recommended at primary care level.

Prevention of Pneumocystis carinii pneumonia (PCP)

Condition	Management	Indications	Comments
Primary Prophylaxis for PCP	Trimethoprim/sulpha-methoxazole (TMP-SMX single strength 80/400 mg) 2 tablets PO daily OR TMP-SMX double-strength (160/800 mg) 1 tablet PO daily OR TMP-SMX 1 single-strength tablet PO daily (which is better tolerated by some but is not effective as prophylaxis for toxoplasmosis)	Adults and adolescents who have HIV infection (including pregnant women and those on HAART) with: Symptomatic HIV disease (WHO clinical stage 2, 3 or 4) CD4+ T-lymphocyte count of less than 200/µL Or if there has already been an active infection with Pneumocystis carinii	TMP-SMX at a dose of one double-strength tablet per day confers cross-protection against toxoplasmosis and some common respiratory bacterial infections Intolerance to TMP-SMX is experienced by 25-50%, mostly as skin rashes ± fever Secondary Prophylaxis Chronic maintenance therapy should be continued after treating a confirmed episode of PCP using the same protocol as for Primary prophylaxis, except this should not be discontinued
Prophylaxis for PCP in individuals who are sensitive to TMP-SMX             Discontinuation of Primary Prophylaxis for PCP	Consider re-introduction of TMP-SMX, if feasible (see note) Alternative: Dapsone 100mg PO daily           Optimal criteria for discontinuing PCP prophylaxis are still being assessed	As above             It may be possible to discontinue prophylaxis when patients have sustained a CD4+ count of greater than 200 cells/µL for at least 3-6 months, or a sustained reduction in viral load for at least 3-6 months	For patients who have an adverse reaction that is not life threatening, treatment with TMP-SMX should be continued if clinically feasible; for those who have discontinued such therapy because of an adverse reaction, reinstitution of TMP-SMX should be strongly considered after the adverse event has resolved. Patients who have experienced adverse events, especially fever and rash, might better tolerate reintroduction of the drug with a gradual increase in dose (desensitisation) or reintroduction of TMP-SMX at a reduced dose or frequency; up to 70% of patients can tolerate reinstitution of therapy in this way Mostly advised when discontinuation of primary prophylaxis (no prior episode of PCP) is considered for individuals on protease inhibitor-containing regimens, who meet the criteria described.
Restarting Primary Prophylaxis for PCP	As for Primary Prophylaxis recommendations	As for Primary Prophylaxis recommendations	No data available to demonstrate that this should differ from Primary prophylaxis
PCP prophylaxis for Pregnant Women	As for other adults		TMP-SMX may exacerbate folate deficiency and increase the risk of neural tube defects. For this reason, pregnant women should preferably be given TMP-SMX after the first trimester and should also receive folate supplements

Prevention of Toxoplasma gondii infection

Condition	Management	Indications	Comments
Primary Prophylaxis for Toxoplasma encephalitis (TE)	Advise against eating undercooked meats, about safe food handling procedures and appropriate pet care for cats Trimethoprim/sulphamethoxazole (TMP-SMX single strength 80/400 mg) 2 tablets PO daily OR TMP-SMX 1 double-strength tablet PO daily	Toxoplasma seropositive adults and adolescents who have HIV infection (including pregnant women and those on HAART) with CD4+ T-lymphocyte counts of less than 100/µL who are not taking PCP Prophylaxis that includes double strength TMP-SMX	The double strength TMP-SMX regimens advised for PCP Prophylaxis are also effective against Toxoplasma. Individuals who do not know their Toxoplasma serology status, or are seronegative, who are not taking a PCP prophylactic regimen known to be active against TE should be retested for IgG antibody to Toxoplasma when their CD4+ T-lymphocyte count declines below 100/µL to determine whether they have seroconverted and are therefore at risk for TE Secondary Prophylaxis Individuals who have had TE should be administered lifelong suppressive therapy (secondary prophylaxis / chronic maintenance therapy) with drugs active against Toxoplasma to prevent relapses
Prophylaxis for Toxoplasma in individuals who are sensitive to TMP-SMX	Non-drug measures, as above Dapsone 100mg PO daily (± pyrimethamine 50 mg PO weekly)	Adults and adolescents who have HIV infection (including pregnant women and those on HAART) with CD4+ T-lymphocyte count of less than 100/µL and are Toxoplasma seropositive	Prophylactic monotherapy with dapsone, pyrimethamine, azithromycin, or clarithromycin cannot be recommended on the basis of current data It is advisable to check Toxoplasma serology in these patients to guide therapy
Discontinuation of Primary Prophylaxis for Toxoplasmosis	Limited data suggest that discontinuing prophylaxis for patients whose CD4+ T-lymphocyte counts increase to greater than 100 cells/µL in response to HAART is associated with low risk of TE		Prophylaxis for PCP should continue if it is still indicated
Toxoplasma prophylaxis for Pregnant Women	Pregnant HIV-infected women who have evidence of prior Toxoplasma exposure can be administered TMP-SMX for prophylaxis against TE as described for PCP		NB: Primary toxoplasmic infection or active toxoplasmosis (including TE) should be evaluated and managed during pregnancy in consultation with appropriate experts

Prevention of Bacterial Respiratory Infections

Condition	Management	Indications	Comments
Pneumococcal prophylaxis	Single dose of Pneumococcal vaccine	Not currently recommended for HIV infected individuals in South Africa	There is controversy over whether this vaccine should be given because a clinical trial in Uganda showed that HIV infected individuals who were vaccinated had an increased risk of pneumonia.
Haemophilus influenzae prophylaxis	H. influenzae type B vaccine is not generally recommended for adult use		TMP-SMX, given for PCP prophylaxis, may reduce the frequency of bacterial respiratory infections, but TMP-SMX should not be prescribed solely to prevent bacterial respiratory infections, as this may lead to antibiotic resistance

Prevention of Fungal Infections

Condition	Management	Indications	Comments
Candida (Thrush)	Emphasise the importance of oral hygiene, with the use of mild mouthwashes. Routine primary prophylaxis is not recommended.		Routine primary prophylaxis is not recommended because of the effectiveness of therapy for acute disease, the low mortality associated with mucosal candidiasis, the potential for resistant Candida organisms to develop, the possibility of drug interactions, and the long-term cost of prophylaxis
Cryptosporidiosis	Advise about appropriate hygiene, food and water safety measures. No specific agents have been proven to be effective as chemoprophylaxis against cryptosporidiosis
Cryptococcosis	Antifungal prophylaxis should not be used routinely because of the relative infrequency of cryptococcal disease, the lack of survival benefits associated with prophylaxis, the possibility of drug interactions, the potential development of antifungal drug resistance, and cost. When indicated: Fluconazole 100-200 mg daily	Primary prophylaxis is indicated for special cases only: CD4+ T-lymphocyte count less than 50 cells/µL with unusually high additional risk of Cryptococcosis, or if considered as part of the decision to treat other concomitant fungal infections	Fluconazole and Itraconazole should be avoided in pregnancy and effective birth control measures should be recommended to all HIV-infected women on prolonged azole therapy. Secondary Prophylaxis: After recovery from a confirmed diagnosis of Cryptococcal disease, ongoing Fluconazole should be administered as prophylaxis against recurrence.

Prevention of Mycobacterial Infections

Condition	Management	Indications	Comments
Mycobacterium tuberculosis Tuberculosis Preventive Therapy (TBPT)	Not currently recommended at primary health care level in South Africa When indicated: Isoniazid 300 mg PO daily for 6 months	HIV-infected adults with no signs or symptoms of TB and a normal chest x-ray. Tuberculin skin test-positive patients show greater benefit. It is extremely important to rule out active TB before initiating TBPT to prevent the development of isoniazid resistance.	The feasibility of providing TBPT at primary health care level is currently being assessed in TB/HIV pilot districts. Only health services with well functioning TB services and the ability to follow patients monthly should consider providing TBPT. It may be considered in occupational health services (e.g., mines), in prison health services and for health workers. For more information about TBPT contact your Provincial TB Coordinator.
M. avium complex (MAC) Prophylaxis	Routine prophylaxis is not cost-effective In highly selected cases: Azithromycin 1,200 mg PO weekly or clarithromycin 500 mg PO daily	CD4+ count <50/µL (selected cases only)

Prevention of Viral Infections

Condition	Management	Indications	Comments
Cytomegalovirus (CMV) CMV Retinitis	Recognition of the early manifestations of the disease is the most important method for preventing severe CMV. Oral Ganciclovir is the only effective antiviral for CMV prophylaxis, but is not recommended for routine use due to its lack of cost-effectiveness	Risk increases at CD4+ T-lymphocyte counts of less than 50 cells/µL	Individuals should be educated about the significance of increased floaters in the eye and should be advised to assess their visual acuity regularly by using simple techniques such as reading newsprint.
Herpes Simplex Virus (genital or orolabial)	Primary infection can be prevented through safer sex (condom usage) at all times and specific avoidance of contact with herpetic lesions (genital or orolabial). Drug prophylaxis of initial episodes of HSV disease is not recommended		Individuals with frequent or severe recurrences can be administered daily suppressive therapy with oral acyclovir or famciclovir
Varicella-Zoster Virus (VZV)	Individuals who have no history of chickenpox or shingles should avoid exposure to persons who are infected with chickenpox or shingles. Data are lacking on the effectiveness of acyclovir for preventing chickenpox in susceptible individuals. No preventive measures are currently available for shingles		Pregnant women: VZIG (Varicella Zoster Immune Globulin) is recommended for VZV-susceptible, HIV-infected pregnant women within 96 hours after exposure to VZV
Human Papillomavirus Infection	Prevent exposure: safer sex practices (use of condom at all times) should be advised. Prevention of HPV-associated Genital Epithelial Cancers in HIV-infected Women: Pelvic examination and a Pap smear at first presentation and annually thereafter if this is normal.	All HIV-infected women	Abnormal PAP smear results should be followed up in accordance with current accepted best practices.
Influenza virus	Influenza vaccine 0.5ml intramuscularly annually	All HIV infected individuals annually prior to the Influenza season	Amantadine 100mg PO twice a day is an alternative for selected susceptible (unimmunised) individuals who are acutely exposed to Influenza
Hepatitis B virus	Hepatitis B Vaccine 0.5 ml IM injection 3 doses according to manufacturer's instructions	All susceptible (Anti-HBc-negative) HIV-infected individuals

4. MANAGEMENT OF COMMON RESPIRATORY INFECTIONS ASSOCIATED WITH HIV

Condition	Recommended Treatment	Comments
Community acquired Pneumonia	Exclude PCP and active pulmonary TB. In many cases, empirical therapy needs to be started, pending the results of investigations. Severe infections require hospitalisation for Parenteral antibiotics and supportive therapy (Bed rest, oxygen, IV fluids and nutrition) Frequent monitoring of temperature, blood pressure and pulse rate in order to detect complications early and to monitor response to therapy. CXR and pre-treatment cultures of blood and sputum are required. Treatment of specific organism is ultimately guided by the results of investigations and culture sensitivities, as well as clinical response to first-line treatment.	Severe infections are suggested when there is: Moderate/severe respiratory distress; fever higher than 39.50C; hypoxia; confusion; dehydration; hypotension; heart rate >120; extensive pneumonia (bilateral / more than 1 lobe involved on CXR) or complicated pneumonia (such as empyema) A control post treatment chest X-ray is always indicated to ensure complete resolution of the pneumonia. With an uncomplicated clinical course this should only be done after 4–6 weeks, as radiological resolution may be delayed. Follow-up X-rays are indicated earlier only when complications are suspected (e.g. empyema, abscess or pneumothorax). At the onset of the pneumonia the X-ray changes may be unimpressive, and may only develop fully after a few days. Prolonged fever and clinical signs may be due to any of the complications, to the incorrect choice of antibiotic, or due to an underlying bronchus obstruction (foreign body or carcinoma). These patients should be further investigated.
‘Usual’ pneumonia pathogens suspected (S. pneumoniae / H. influenzae)	Oral: Amoxicillin 250-500mg 8 hourly until infection resolves. Duration of antibiotic therapy is guided by clinical response, but should not be less than 7–10 days. Where there is likely Penicillin/Ampicillin resistance: Amoxicillin/clavulanic acid (e.g. Augmentin®) 250/125 mg (375 mg tablet) PO 8 hourly should be first choice Penicillin allergic patients: Erythromycin 500mg PO 6 hourly Parenteral antibiotic therapy Depends on the causative organism. Empirical treatment could be started with Benzyl penicillin, IV, 2 MU 6 hourly for 10 days (or combination therapy with Gentamicin IV, if a gram negative infection is suspected; or an appropriate Cephalosporin)	Common at all stages of HIV infection. Clinically lobar or bronchopneumonia ± effusion. Penicillin/Ampicillin resistance is increasing, so alternative treatment might be required.
Suspected ‘Átypical’ pneumonia (Mycoplasma/ Legionella)	Erythromycin 500mg PO 6 hourly for 10-14 days

Treatment of Pneumocystis carinii Pneumonia (PCP)

Condition	Recommended Treatment	Comments
Acute PCP Infection Hypoxic patients Patients intolerant to Trimethoprim/ Sulphamethoxazole	Trimethoprim/sulphamethoxazole, 20/100 mg/kg/day in 4 divided doses. The duration of treatment is 21 days. If at all possible, this should be given orally. IV Trimethoprim/sulphamethoxazole may be used in patients not able to swallow. Prednisone, 40 mg/day should be continued for the duration of antibiotic treatment and withdrawn in a decreasing dose regimen. Clindamycin 600 mg PO or IV 6 hourly OR Pentamidine isethionate 4 mg/kg IV daily.	PCP often presents as an acute/sub-acute non-productive cough, with dyspnoea. Diagnosis further suggested by: CD4+ < 300/mm3; normal-looking X ray in early stages, or ‘ground-glass’ interstitial infiltrates and other atypical radiological findings; Relative hypoxia (pO2<80%) Moderately severe or severe disease is present when the patient is hypoxic (PaO2<70 mm Hg). Steroid therapy can further compromise the individual's immunity and other opportunistic infections (such as Candidiasis, TB and Herpes) should be anticipated

5. MANAGEMENT OF TUBERCULOSIS IN HIV-INFECTED ADULTS

TB/HIV Interaction

TB is the most common opportunistic infection and the biggest killer of people living with HIV in South Africa. Approximately 50% of TB patients in South Africa are infected with HIV. HIV increases the lifetime risk of progressing from TB infection to TB disease from 10% to about 50%. TB also accelerates HIV disease. TB is associated with decreased survival in HIV-positive individuals possibly through immune activation, expression of cytokines and increased viral replication.

Several clinical trials have shown that TB preventive therapy (e.g., isoniazid 300 mg daily for 6 months) decreases the incidence of TB in HIV-positive individuals who are not already sick with TB. The feasibility of providing TB preventive therapy in the public health system is currently being assessed in TB/HIV pilot districts. TB preventive therapy is not currently recommended in all primary health care services until this assessment is completed but may be considered in occupational health services (including mines), in prison health services and for health workers. To get more information about TB preventive therapy and how it should be administered, contact the TB coordinator in your province.

The diagnosis of pulmonary TB in HIV-infected individuals should be done following the diagnostic flow chart described in "The South African Tuberculosis Control Programme Practical Guidelines 2000". The cornerstone of diagnosis remains sputum microscopy for acid-fast bacilli (TB microscopy). If TB is suspected in a smear-negative patient who has not responded to a one-week course of broad-spectrum antibiotics, a chest x-ray and TB culture may be useful to confirm TB. Although smear-positive pulmonary TB remains the most common form of TB in HIV-positive patients, smear-negative and extrapulmonary TB are more common in HIV-positive than in HIV-negative patients. The clinical presentation of TB in early HIV infection is similar to the presentation in HIV-negative patients. HIV-positive patients with more advanced immunosuppression have a higher likelihood of hilar adenopathy, pleural or pericardial effusions and diffuse lung infiltrates rather than cavity formation in the lungs on chest x-ray. Diagnosis of extra-pulmonary TB is often difficult, so diagnosis may be presumptive after excluding other conditions. The most common types of extra-pulmonary TB are: TB meningitis, TB lymphadenitis, miliary TB, tuberculous pleural effusion, tuberculous empyema, tuberculous pericardial effusion, TB peritonitis and TB of bones and joints.

Given that such a large proportion of TB patients are HIV-positive, voluntary HIV counselling and testing should be offered to every TB patient.

Standard short course treatment also effectively cures TB disease in HIV infected individuals and the standard National TB Control Programme protocols should be followed, as described below. Sputum conversion and cure rates are the same in HIV-positive and HIV-negative patients treated with rifampicin-containing regimens. However, HIV-infected TB patients are more likely to develop side effects to anti-TB drugs and have a 2-3 fold higher mortality.

Since 1996, the National TB Control Programme has been implementing the internationally recommended DOTS (Directly Observed Treatment Short-course) strategy. The first priority of the DOTS strategy is to cure infectious (smear-positive) TB patients. The core elements of the DOTS strategy are:

• Government commitment to sustain TB control activities

• Sputum smear microscopy to detect infectious cases

• Standardised short-course anti-TB treatment regimens with direct observation of treatment

• An uninterrupted supply of TB drugs

• A standardised recording and reporting system which allows assessment of treatment outcomes.

Direct Observation of Treatment and Patient Centred Care

The implementation of DOTS ensures that every TB patient should have the support of another person to ensure that they swallow their medication daily. The most important factor in whether the patient will complete treatment or not is their relationship with the treatment supporter. The treatment supporter does not have to be a professional health worker, but can be any responsible member of the community who the patient trusts. Employers, colleagues and community health workers are examples of possible treatment supporters. Using family members is often problematic but has been successful in exceptional cases. Treatment supporters should keep the drugs and the treatment card, supply the medication, witness the patient swallowing the treatment and sign accordingly. They should know the symptoms of TB, side effects of TB drugs and the importance of taking TB medication regularly. They should motivate and empower patients and their families and provide them with a better understanding of TB and the importance of cure. TB treatment supporters should also educate people about the link between TB and HIV, how to prevent HIV, the importance of knowing your HIV status and the fact that TB can be cured whether you’re HIV-positive or not. A private practitioner may elect to monitor the progress of the patient personally. In this case, the patient should remain on the clinic TB patient register and follow-up results should be recorded.

Treatment supporters should sympathetically explain the importance of completing treatment. In order to foster an appropriate relationship, feelings, expectations and potential barriers/problems that will prevent success should be clearly discussed when treatment is started. Patients at the time of their first appointment are often able to predict their own compliance accurately, taking their lifestyle, habits and past experience into account. Extra help could be offered at this stage as necessary. If at all possible the same health worker should listen to the patient, monitor, encourage and provide feedback on progress. This is the best way to develop and maintain the effective bond that ensures completion of treatment, Should more than 2 doses of treatment be missed, extra effort should be made to help the patient mobilise support to manage any problems.

Multiple drug resistant (MDR) TB

This is diagnosed when there is resistance to rifampicin and isoniazid on sputum culture sensitivity testing. MDR-TB is often the result of poor adherence to treatment. It is difficult and expensive to treat. Currently, the cure rate is less than 50%. MDR-TB cases should be referred to an MDR TB unit where experienced clinicians can treat the patient according to the "Guidelines for the Management of Drug-resistant Tuberculosis Patients in South Africa". The best way to prevent MDR TB is to treat TB patients with appropriate regimens and to ensure patient adherence by providing directly observed treatment.

Co-trimoxazole prophylaxis

All HIV-infected TB patients are classified as WHO clinical stage 3 or 4 and should therefore be given prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX = co-trimoxazole = Bactrim ® = Septran ®) single strength 80/400 mg 2 tablets PO daily or double strength 160/800 mg 1 tablet PO daily for life. This has been shown to decrease hospitalisations and mortality in HIV-positive TB patients. If the patient did not take TMP-SMX before being diagnosed with TB, delay initiation of TMP-SMX until completion of one month of anti-TB treatment. This is to be better able to differentiate side effects to anti-TB drugs from side effects to TMP-SMX.

Chemoprophylaxis

Children under the age of 5 years in close contact with a smear-positive pulmonary TB patient or who are tuberculin skin test positive should be given prophylaxis (isoniazid 5mg/kg daily for 6 months). Chemoprophylaxis for contacts older than 5 years is not recommended.

Administration of treatment

The total daily amount of every drug should be administered in one dose and not divided.

The use of tobacco and alcohol should be strongly discouraged during treatment.

If the patient is underweight or has an alcohol problem, pyridoxine should be given routinely to TB patients. The dose is 25 mg in the mornings that TB drugs are taken.

Important drug interactions

Rifampicin reduces the efficacy of oral and injectable contraceptives. The result may be unplanned pregnancies. Therefore it is very important when introducing new patients to treatment to

• ask about contraception

• explain the problem

• if necessary, alter the oral or injectable contraceptive or suggest an IUCD.

Drug interaction between rifampicin and some protease inhibitors and non-nucleoside reverse transcriptase inhibitors require special caution if highly active antiretroviral therapy (HAART) is provided to patients on TB treatment. However, ritonavir and efavirenz may be concomitantly administered in HIV-infected patients.

Side effects of anti-TB drugs

The recommended TB drugs are safe, but the following should be noted:

• Streptomycin should not be used in pregnancy or over 65 years of age.

• Ethambutol should not be given to children under 8 years of age.

• Patients should be warned that their urine, and sometimes saliva, will be discoloured red (by rifampicin).

• Patients with impaired renal function should not be given ethambutol or streptomycin. Refer such patients.

Minor side effects:

• gastro-intestinal discomfort (any anti-TB drug)

• mild skin reactions (isoniazid and rifampicin)

• joint pains (pyrazinamide)

• flu-like symptoms (rifampicin)

These minor side effects are most common in the first month. Patients should be reassured that they are temporary and the importance of tolerating them should be explained. Additionally:

• Gastrointestinal symptoms may be minimised by taking the drugs with food, although drugs are best taken on an empty stomach.

• Symptoms may be less noticeable if drugs are taken before sleeping.

• Joint pains usually respond well to paracetamol.

Serious side effects of anti-TB drugs include:

• jaundice and hepatitis (isoniazid, rifampicin, pyrazinamide)

• rash and fever (isoniazid, rifampicin)

• bleeding tendency, shock and renal failure (rifampicin)

• impaired visual acuity and colour perception (ethambutol)

• giddiness, unsteadiness, ringing in the ears, deafness (streptomycin)

If patients develop any of the above serious side effects, stop drugs immediately and refer.

Tuberculosis Treatment Protocols

Three times per week regimens

Treatment should be given five times per week in both the intensive and continuation phases. However in special circumstances, treatment may be given three times per week, in the continuation phase provided it is supervised. There are areas in South Africa where circumstances may necessitate a 3 times per week regimen. Since increased dosages are involved, to avoid mistakes the regimen should be applied to all patients at particular facilities. Furthermore, since different packaging is involved, the use and packing of 3 times per week regimens should be approved and co-ordinated at provincial level.

New adult patients (Regimen 1):

New smear or culture positive and other serious pulmonary and extra pulmonary tuberculosis

2 Months Initial Phase (treatment given 5 times a week)		4 Months Continuation phase (treatment given 5 times a week)
Combination tablet RHZE 120/60/300/200 mg*		Combination tablet RH 150/100 mg	Combination tablet RH 300/150 mg
<50 kg	4 tabs		3 tabs
>50 kg	5 tabs			2 tabs
1. Combination tablets contain currently approved doses of component drugs
2. In hospital, drugs should be given 7 days a week in the above dosage

 

2 Months Initial Phase (treatment given 5 times a week)		4 Months Continuation phase (treatment given 3 times a week)
Combination tablet RHZE 120/60/300/200 mg		Combination tablet RH 150/100 mg	H 100 mg	Combination tablet RH 300/150 mg		H 100 mg
<50 kg	4 tabs		3 tabs	1 tab
>50 kg	5 tabs				2 tabs	3 tabs

R=rifampicin: H=isoniazid (INH): Z=pyrazinamide: E=ethambutol: S=streptomycin

*Ethambutol 225 mg in combination is also acceptable

Retreatment adult cases (Regimen 2): smear positive retreatment cases (failure, relapse and return after interruption)
2 Months Initial Phase (treatment given 5 times a week)		3rd Month (5 times a week)	5 Months Continuation Phase (5 times a week)
RHZE 120/60/300/ 200 mg*	Streptomycin	RHZE	RH 150 / 100mg	E 400mg	RH 300 / 150mg	E 400mg
<50 kg	4 tabs	750 mg	4 tabs	3 tabs	2 tabs
>50 kg	5 tabs	1 000 mg	5 tabs			2 tabs	3 tabs
Note: Streptomycin should be reduced to 750 mg per day to those older than 45 years and not be given to those over 65 years. It should also not be given during pregnancy.

 

2 Months Initial Phase (treatment given 5 times a week)		3rd Month (5 times a week)	5 Months Continuation Phase (3 times a week)
RHZE 120/60/300/ 200mg*	Streptomycin	RHZE	RH 150 / 100 mg	H 100 mg	E 400 mg	RH 300/150 mg	H 100 mg	E 400 mg
<50 kg	4 tabs	750 mg	4 tabs	3 tabs	1 tab			2 tabs
>50 kg	5 tabs	1 000 mg	5 tabs				2 tabs	3 tabs	4 tabs
R=rifampicin: H=isoniazid (INH): Z=pyrazinamide: E=ethambutol: S=streptomycin *Ethambutol 225 mg in combination is also acceptable The Fixed Dose Combinations reflected here represent the current International recommendations. These will be subject to continuous review in the light of new information.

6. MANAGEMENT OF COMMON ORAL AND OESOPHAGEAL CONDITIONS ASSOCIATED WITH HIV

7. MANAGEMENT OF COMMON SKIN CONDITIONS ASSOCIATED WITH HIV

All types of skin problems occur more commonly in association with HIV infection. Conditions that usually occur in non-HIV infected individuals should generally be managed in the same way, in accordance with Standard Treatment Guidelines.

Condition	Recommended Treatment	Comments
Molluscum contagiosum	Topical application of tincture of iodine or 1% phenol to individual lesions OR Cryotherapy with liquid nitrogen OR Surgical excision / curettage or electrosurgery.	For extensive lesions, which usually indicate severe immunodeficiency and are too widespread for topical treatment, systemic retinoid may be effective. This requires specialist supervision.
Seborrhoea	Skin Steroid cream (hydrocortisone 1%) and/or topical azole cream (e.g. Miconazole 2% cream), or Terbinafine cream, applied twice a day Scalp 2% selenium sulphide suspension - apply weekly by lathering on scalp and rinse off after 10 minutes OR Shampoos (e.g. Selsun®) containing selenium sulfide, zinc pyrithiore, ketoconazole, salicylic acid or coal tar, used daily
Folliculitis (including S. aureus; Eosinophilic inflammation; Pityrosporum ovale)	Depends on aetiology: Staphylococcal folliculitis: Topical cleansing with antiseptic lotions (e.g. chlorhexidine gluconate 2% or Hibiscrub®); Topical 2% sulphur cream twice a day. Consider short course antibiotic therapy: Flucloxacillin 500 mg PO four times a day for 10 days In pregnant and/or penicillin-allergic patients: Erythromycin 500 mg 4 times daily for 10 days Recurrent disease: chronic antibiotic (clindamycin 150 mg four times a day or TMP-SMX 1 DS four times a day)+/-nasal mupirocin Fungal: Miconazole 2% cream applied twice daily or other topical antifungal or systemic antifungal agents Eosinophilic: Topical steroids and anti-pruritics (such as promethazine or hydroxyzine) Phototherapy with UVB and/or PUVA is sometimes effective	A group of acne-like conditions that present as pruritic follicular papules and pustules on face, trunk and extremities at lower CD4+ counts. Spontaneous remissions and exacerbations occur.
Fungal skin / nail infections	Skin 6% benzoic acid and 3% salicylic acid ointment twice daily for 4 weeks OR 2% miconazole cream applied topically twice daily for 4 weeks or other topical antifungal agents such as coltrimazole For severe nail infections, consider: itraconazole 400 mg PO daily for 7 days repeated monthly x 2 months (fingernails) and 3 months (toenails).
Drug-related skin reactions	Depends on severity and the need for the implicated drug. Discontinue suspected drug Antihistamines such as chlorpheniramine 4 mg PO 3-4 times daily ± topical steroids such as hydrocortisone 1% cream applied twice daily. Severe reactions: discontinue all drugs Systemic steroids are not useful	Morbilliform exanthema are more common; most frequent onset 7-10 days after starting new drug. Diagnosis on basis of clinical features, past history of drug eruptions and history of new drug exposure. Response to stopping drug should be noticed within 3-5 days. It may be possible to re-introduce the drug, if necessary, if the reaction was not severe
Psoriasis	Salicylic acid 2% in white soft paraffin 3 times daily to local plaques or other topical treatments with emollients, topical steroids, coal tar, vitamin A, vitamin D derivatives, salicylic acid Phototherapy	Avoid methotrexate and prednisone
Kaposi’s sarcoma	Depends on symptoms and cosmetic concerns, staging based on tumour bulk and CD4 count Local: radiotherapy, intralesional vinblastine, surgical excision, or cryotherapy Cytotoxic chemotherapy may be considered	Treatments should be performed by an expert

8. TREATMENT OF HERPES VIRUS INFECTIONS

Condition	Recommended Treatment	Comments
Herpes simplex virus (HSV)
Initial treatment of mild skin or genital HSV	Aciclovir 200 PO 5 times a day (4 hourly while awake) or 400 mg PO 3 times a day OR Famciclovir 250 mg PO 3 times daily OR Valaciclovir 1 gm PO twice a day All administered for 7-10 days	Herpes is a recurrent viral disease that has no cure. Two serotypes of HSV have been identified: HSV-1 and HSV-2. Most cases of recurrent genital herpes are caused by HSV-2. It is a sexually transmitted disease. Antivirals do not cure the infection or prevent transmission. These drugs may shorten the time to clinical remission
Recurrent HSV	Aciclovir 400 mg PO three times a day or 800 mg PO twice a day OR Famciclovir 125 mg PO twice daily OR Valaciclovir 500 mg PO twice daily All administered for 5 days	Early treatment of initial infections is much more effective than treating recurrent infections. Most patients with first episode genital HSV-2 infection will have recurrent episodes of genital lesions. Initiate therapy at first sign of prodrome or genital lesions. Relapses after treatment of acyclovir-resistant strains often involve acyclovir-sensitive strains
Severe or refractory HSV Infection	Consider Aciclovir 5-10 mg/kg IV 8 hourly infused over 1 hour for 5-7 days OR Aciclovir 400-800 mg PO 5 times a day for 7-14 days OR Valaciclovir 1 gm PO 3 times a day for 7-14 days	· If failing to respond, or for disseminated HSV, give aciclovir 30 mg/kg/day IV and test sensitivity of isolate to acyclovir; · Resistant HSV: foscarnet 40 mg/kg IV 8 hourly, topical trifluridine, oral valaciclovir, or high-dose IV aciclovir (12-15 mg/kg IV 8 hourly or by continuous infusion)
Varicella zoster virus (VZV) / Shingles		VZV infections in immunocompromised patients should be treated with appropriate anti-viral drugs. However drug therapy is expensive and unlikely to be of advantage to patients with lesions that have healed (crusted phase).
Dermatomal VZV	Aciclovir 800 mg PO 5x/day at least 7 days (until lesions crust) OR Famciclovir 250 mg PO tid OR Valaciclovir 1 gm PO tid	Treatment can be started long as new lesions are forming Postherpetic neuralgia is less common in young patients No maintenance therapy is recommended Antiviral therapy has not been shown to be effective beyond 7 days of acute therapy
Disseminated, opthalmic nerve involvement, corneal or visceral infection (life or vision threatening) VZV	Acyclovir, IV, 5-10 mg/kg over 1 hour at 8 hourly intervals for at least 7 days OR Foscarnet 40 mg/kg IV 8 hourly or 60 mg/kg 12 hourly For corneal disease in addition to parenteral (IV therapy): Topical acyclovir eye drops 3% ointment, 4 hourly for 14 days For VZV pneumonia consider adding: Hydrocortisone 200 mg IV 6 hourly for 7 days	To be prescribed by a specialist only. The dose must be adjusted according to renal function.
Pain control Acute phase of infection	Ibuprofen 400 mg PO 3 times daily or Paracetamol 1 000 mg PO (4–6 hourly) plus Amitriptyline 25–50 mg PO at night.	Pain is often very severe and requires active control usually with a combination of non-steroidal, opiate analgesics and amitriptyline.
Chronic management of Zoster Associated Pain	Amitriptyline 25-50 mg PO at night +/- Carbamazepine 100-400 mg PO twice daily	If pain remains severe after 4 weeks, refer.

9. MANAGEMENT OF HUMAN PAPILLOMAVIRUS INFECTION

Condition	Recommended Treatment	Comments
Non-drug treatment	Surgical removal - tangential scissor excision, tangential shave excision, curettage, or electrosurgery. OR Cryotherapy with liquid nitrogen or cryoprobe. Repeat applications every one to two weeks	This is a sexually transmitted disease Note: The removal of warts does not necessarily decrease infectivity. It is advisable to treat sexual partners as well. Surgical removal of warts has the advantage over other modalities of rendering the patient wart-free, usually with a single visit. An expert should do this.
Drug Treatment For warts in general	Podophyllin resin 10–25% in compound tincture of benzoin. A small amount should be applied to each wart and allowed to dry. To avoid the possibility of problems with systemic absorption and toxicity, some experts recommend that application be limited to <0.5 ml of podophyllin or <10 cm2 of warts per session. Repeat weekly if necessary. or Trichloracetic acid (TCA) or bichloracetic acid (BCA) 80–90%. Apply a small amount only to warts and allow to dry, at which time a white "frosting" develops; apply talc or sodium bicarbonate to remove unreacted acid if an excess amount is applied. Repeat weekly if necessary.	The use of podophyllin is contraindicated during pregnancy. Podophyllin is caustic and should be used with care. Avoid contact with healthy skin. After visible genital warts have cleared, follow-up is not mandatory. Re-occurrence is most frequent during the first three months. Patients should be warned that scarring in the form of persistent hypo-or hyperpigmentation is common with ablative modalities.
Vaginal warts	TCA or BCA 80–90% applied only to warts. Apply a small amount only to warts and allow to dry at which time a white "frosting" develops; apply talc or sodium bicarbonate to remove unreacted acid if an excess amount is applied. Repeat weekly if necessary. or Podophyllin 10–25% in compound tincture of benzoin applied to a treated area that must be dry before removing the speculum. Treat less than or equal to 2 cm2 per session. Repeat application at weekly intervals.	The use of a cryoprobe in the vagina is not recommended because of the risk of vaginal perforation and fistula formation. Because of concern about potential systemic absorption, some experts caution against vaginal application of podophyllin. Podophyllin is contraindicated during pregnancy.
Cervical warts		For women with exophytic cervical warts, a high-grade squamous intraepithelial lesion (SIL) must be excluded before treatment is begun. Management should be carried out in consultation with an expert.
Urethral meatus warts	Podophyllin 10–25% in compound tincture of benzoin. The treatment area must be dry before contact with normal mucosa. Podophyllin must be applied weekly if necessary. OR Cryotherapy with liquid nitrogen or cryoprobe.	The use of podophyllin is contraindicated in pregnancy     To be performed by a specialist only
Anal warts	TCA or BCA 80–90% applied to warts. Apply a small amount only to warts and allow to dry at which time a white "frosting" develops; apply talc or sodium bicarbonate to remove unreacted acid if an excess amount is applied. Repeat weekly if necessary. OR Cryotherapy with liquid nitrogen or surgical removal	Management of warts on rectal mucosa should be referred to an expert.   To be performed by a dermatologist only
Oral Warts	Cryotherapy with liquid nitrogen or surgical removal	To be performed by a dermatologist only

10. MANAGEMENT OF GENITAL AND SEXUALLY TRANSMITTED CONDITIONS

Sexually transmitted diseases should be managed syndromically following the Department of Health "Protocols for the management of a person with sexually transmitted diseases" with the following considerations:

• Urethral Discharge – unchanged

• Genital ulcers – if painful vesicular lesions, see "Treatment of Herpes virus infections"

• Vaginal Discharge – unchanged but for vulvo-vaginal candidiasis, see below

Condition	Recommended Treatment	Comments
Genital Herpes Simplex Virus	See "Treatment of Herpes Virus Infections".
Vulvo-vaginal Candidiasis (Thrush)	Clotrimazole vaginal tablet 500 mg pessary at night as a single dose or vaginal cream, nightly for 7–10 nights. For more severe cases, use systemic therapy with Fluoconazole 150mg PO twice weekly until symptoms resolve OR Ketoconazole, oral, 200- 400 mg daily, for 5- 7 days	More prolonged therapy may be required in severely immune-deficient women.
Pelvic Inflammatory Disease (PID)	All patients with stage II-IV and severely ill patients with stage I must be hospitalised for parenteral antibiotic therapy. All patients must receive adequate therapy for both gonococcal and chlamydial infection.	Adequate fluid replacement, analgesics and antipyretics should be provided. Patients should be tested for syphilis and other STDs. In stage III, surgery is indicated if the diagnosis is uncertain, if rupture seems imminent, if there is no adequate response after 48 hours of appropriate therapy, if the patient deteriorates on treatment or if after 4–6 weeks there still is a large or symptomatic pelvic mass. Contact tracing Remember that PID is usually a sexually transmitted and that sexually partners should be offered treatment for their own health and to prevent re-infection and spread of the infection to other partners. Intra-uterine contraceptive devices are a risk factor for PID and should be removed after commencement of antibiotic therapy. Alternative contraceptive choices should be offered.
Stage I Acute (uncomplicated) salpingitis	Ciprofloxacin 500 mg as a single oral dose (Alternative to ciprofloxacin: Ceftriaxone 250 mg IM single dose) PLUS Doxycycline, 100 mg PO 12 hourly (with meals) for 14 days PLUS Metronidazole 400 mg PO 12 hourly for 14 days	Characterised clinically by local adnexal tenderness, but no peritoneal tenderness.
Stage II Salpingitis + peritonitis	Cefoxitin 2 g IV 6 hourly plus Doxycycline 100 mg IV 12 hourly PLUS Metronidazole, 400 mg PO 12 hourly, if there is no vomiting, otherwise per rectum 500 mg 8 hourly initially for 3- 5 days. This regimen is given for at least 48 hours after the patient clinically improves. After discharge from hospital, the patient continues with oral therapy with: Doxycycline 100 mg PO 12 hourly PLUS Metronidazole 400 mg PO 12 hourly until a total of 14 days of therapy has been completed.	Characterised clinically by local adnexal tenderness and peritoneal irritability (rebound, guarding, etc) Contact tracing Remember that PID is usually a sexually transmitted and that sexually partners should be offered treatment for their own health and to prevent re-infection and spread of the infection to other partners.
Stage III Tubal occlusion + pus + distention	Clindamycin 900 mg intravenously 8 hourly PLUS Gentamicin, IV, for at least 48 hours at a loading dose of 2 mg/kg, followed by 1.5 mg/kg 8 hourly This regimen is given for at least 48 hours after the patient clinically improves. After discharge from hospital, the patient continues with oral therapy with: Doxycycline 100 mg orally 12 hourly PLUS Metronidazole, oral, 400 mg 12 hourly until a total of 14 days of therapy has been completed. OR Clindamycin 450 mg four times daily until a total of 14 days of therapy has been completed.	Characterised clinically by peritonitis Gentamicin therapy should preferably be monitored by blood drug levels in patients with impaired renal function Contact tracing Remember that PID is usually a sexually transmitted and that sexually partners should be offered treatment for their own health and to prevent re-infection and spread of the infection to other partners.
Stage IV Rupture to peritoneal cavity	Antibiotics as stage III Rapid surgical exploratory laparotomy	Characterised by septicaemia, collapse. Contact tracing Remember that PID is usually a sexually transmitted and that sexually partners should be offered treatment for their own health and to prevent re-infection and spread of the infection to other partners.

Treatment of Syphilis

Condition	Recommended Treatment	Comments
Primary or secondary syphilis	Benzathine penicillin, IM, 2.4 MU as a single dose	Parenteral benzyl penicillin is the preferred drug for treatment of all stages of syphilis. The preparation(s) used (i.e., benzathine, aqueous procaine, or aqueous crystalline), the dosage, and the length of treatment depend on the stage and clinical manifestations of disease. Parenteral benzyl penicillin is effective in achieving local cure (healing of lesions and prevention of sexual transmission) and in preventing late sequelae.
Early latent syphilis	Benzathine penicillin, IM, 2.4 MU as a single dose.	Follow up serology tests for 6 months
Late latent syphilis or latent syphilis of unknown duration	Benzathine penicillin, IM, 7.2 MU total, administered as 3 doses of 2.4 MU each, at weekly intervals Non-pregnant penicillin-allergic patients: Doxycycline, oral, 100 mg twice daily, for 2 weeks if duration of infection <one year, otherwise, for 4 weeks, with close follow-up.	Pregnant patients with penicillin allergy: see above.
Tertiary syphilis	Benzathine penicillin, IM, 7.2 MU total, administered as 3 doses of 2.4 MU at weekly intervals.

11. MANAGEMENT OF NEUROLOGICAL COMPLICATIONS ASSOCIATED WITH HIV

Condition	Recommended Treatment	Comments
HIV-associated Dementia (HAD)	Possible benefit from antiretroviral regimens with agents that penetrate the CNS (AZT, d4T, hydroxyurea (+ ddI), ABC, nevirapine; less penetration – efavirenz, ddI, 3TC, indinavir)	AZT at higher dose for mild or moderately severe HAD has been shown beneficial. Anecdotal experience suggests some individuals respond to HAART. Monitor the effectiveness of therapy with neurocognitive tests.
Myopathy (inflammatory)	Consider discontinuing AZT for 3 weeks (if applicable) Non-steroidal anti-inflammatory agents sometimes useful Prednisone 40-60 mg/day (for severe case, preferably with biopsy-proven inflammation)	Indication for treatment is proximal muscle weakness plus elevated creatine kinase Often unclear whether due to HIV or AZT so use "drug holiday" if patient is taking AZT-containing regimen and monitor clinical and CPK response
Peripheral neuropathy	Neuropathic pain can be difficult to relieve. Consider Ibuprofen 400-800 mg PO three times a day PLUS Amitriptylline 25-50 mg PO at night or other tricyclic antidepressants Alternatives: Carbamazepine 200-400 mg PO twice a day	Peripheral neuropathy may be HIV-related but it may also be a side effect of several drugs such as isoniazid, ddI, d4T and ddC. If using Tricyclic antidepressants, increase doses incrementally (e.g.. Nortriptyline started at 10 mg at night, increasing the dose by 10 mg every 5 days to maximum of 75 mg daily or 10-20 mg three times a day until effective).

12. MANAGEMENT OF CENTRAL NERVOUS SYSTEM INFECTIONS ASSOCIATED WITH HIV

Condition	Recommended Treatment	Comments
Toxoplasmosis Acute Toxoplasma infection – encephalitis	Pyrimethamine 100-200 mg loading dose, then 50-100 mg/day PO + folinic acid 10 mg /day PO (or folic acid)+ sulfadiazine 4-8 gm/day PO (or replace sulfadiazine with clindamycin 300-450 mg PO 6 hourly) for at least 6 wks Corticosteroids if significant oedema/mass effect is present (Decadron® 4 mg PO or IV four times a day) Consider serial lumbar puncture to lower raised intracranial pressure	Anticipated response is clinical improvement within one week and improvement by CT scan within 2 weeks Patients who respond to primary therapy should receive life-long suppressive therapy (see below) The role of immune reconstitution (effective HAART) in modifying this rule is unclear
Maintenance therapy (after successful response to treatment of acute episode of Toxoplasma infection)	Pyrimethamine 25-50 mg/d PO + folinic acid 5 mg/day (or Folic acid) + sulfadiazine 2-4 gm/day PO (or replace sulfadiazine with clindamycin 300-450 mg PO 6-8 hourly)

Management of Cryptococcal Meningitis

Cryptococcal Meningitis occurs in significant numbers of individuals that have advanced HIV disease and severe immunocompromise, with a poor prognosis if therapy is not provided.

Diagnosis is made by lumbar puncture if history of subacute meningitic illness. If there are focal neurological signs, a CT scan may be indicated. CSF findings consistent with cryptococcal infection include positive Cryptococcal antigen, Indian ink stain or Cryptococcal culture. In rare instances where cryptococcus is isolated from other sites of infection, therapy should also be initiated due to the high risk of CNS dissemination.

Successfully treated cases of cryptococcal meningitis require life-long ongoing secondary prophylaxis therapy with fluconazole.

The majority of patients presenting with suspected Cryptococcal meningitis can be managed at secondary level hospitals, if there is the facility for lumbar puncture and laboratory CSF investigation. Ongoing secondary prophylaxis therapy can be provided at clinic level through selected clinics. Referral to higher levels of care may be necessary if the patient requires a CT Scan.

Poor initial prognostic factors include:

• Delayed presentation

• Significant co-morbidity (such as sepsis, pneumonia or TB)

• Depressed level of consciousness or impaired mental state

• Low CSF white cell count; CSF Cryptococcal Antigen titre > 1:1024, abnormal CSF glucose

• Localising signs, with raised intracranial pressure

The initiation of therapy in individuals that have very poor prognosis, or preceding poor functional status, needs to be carefully considered (preferably in consultation with the patient’s family/care-givers).

Patients who have been receiving antiretroviral therapy, or who begin this therapy after an episode of cryptococcal meningitis, may require some modification of the recommendations below.

Caution should be exercised in prescribing Fluconazole to patients who are taking Rifampicin; Protease Inhibitors; Warfarin; oral contraceptives; oral Sulphonylureas or Phenytoin.

Condition	Recommended Treatment	Comments
Cryptococcal meningitis	Initial treatment: Amphotericin B 0.7mg/kg/day IV for 14-21 days Changing to fluconazole 800 mg PO stat, then 400 mg PO daily for 4 weeks OR Fluconazole 800 mg PO stat, then 400 mg/d PO for 6-10 wks Management of raised intracranial pressure: Serial therapeutic lumbar puncture, preferably with manometry: Measure initial opening pressure by manometry Remove ± 20mL CSF if intracranial pressure is raised Repeat daily until opening pressure is normal	Amphotericin B is preferred for initial treatment, but total dose prior to fluconazole maintenance is arbitrary. Change to fluconazole earlier if Amphotericin intolerance or if ongoing IV administration becomes impossible. Fluconazole is acceptable as initial treatment only for patients with normal mental status     Individuals who remain symptomatic of raised intra-cranial pressure (without focal neurological signs), should be considered for therapeutic lumbar puncture.
	Maintenance therapy Fluconazole 200 mg PO daily.	Life-long maintenance therapy (secondary prophylaxis) is required. The importance of patient education to encourage adherence must be stressed.
	Primary prophylaxis is not recommended. Secondary prophylaxis should be given to all individuals who have documented previous cryptococcal meningitis, even if therapy was interrupted.
Neurosyphilis	Benzathine penicillin, IV, 18–24 MU daily, administered as 3–4 MU 4 hourly, for 10–14 days. Alternative Regimen: Procaine penicillin, IM, 2.4 MU daily, for 10–14 days plus Probenecid, oral, 500 mg 4 times a day, for 10–14 days.	These regimens are shorter than that of the regimen used for late syphilis in the absence of neurosyphilis. Therefore, some experts administer benzathine penicillin, IM, 2.4 MU after completion of these neurosyphilis treatment regimens to provide a comparable total duration of therapy. Parenteral penicillin is the only therapy with documented efficacy for neurosyphilis. Patients with neurosyphilis who report penicillin allergy should always, if possible, be treated with penicillin, after desensitization.

13. MANAGEMENT OF DIARRHOEAL DISEASE IN HIV

Chronic or recurrent diarrhoea is a common and debilitating condition that can have serious consequences on the individual’s well-being. It can be challenging to manage and often requires non-drug measures such as hydration and dietary changes.

Many infective causes of diarrhoea that affect non-HIV infected individuals occur commonly in HIV and should be managed in the same way as they are treated in non-HIV patients.

Basic food, water and personal hygiene, as well as infection control procedures should be emphasised.

Ensure hydration with home made sugar and salt solution: 1 level teaspoon of salt and 8 level teaspoons of sugar dissolved in 1 litre of boiled then cooled water

Condition	Recommended Treatment	Comments
Symptomatic treatment of diarrhoea	Loperamide, oral, 4 mg immediately, followed by 2 mg after each loose stool, up to 16 mg/day for severe diarrhoea. OR Codeine syrup/tablets 15-30mg PO 3-5 times a day (as required)	Loperamide and codeine should not be given if infective diarrhoea is suspected (e.g. fever, blood in stool). Oral rehydration should be prescribed if the diarrhoea is severe. Diet modification includes: low fat, no caffeine, no milk or milk products. Codeine usage can become addictive.
Infective diarrhoea	Usual infective diarrhoea should be managed in the same manner in HIV and non-HIV infected individuals.	Infective diarrhoea may be suspected, or confirmed on stool microscopy, culture and sensitivity
Non- invasive bacterial infections (food poisoning)	Replace electrolytes and fluids Treat vomiting symptomatically Antibiotics are mostly of no value, except for Enterotoxic E coli and for Cholera, in which cases, treat with: Trimethoprim/sulphamethoxazole (80/400), oral, 2 tablets twice daily OR Doxycycline, oral, 100 mg twice daily for 5 days.	Food Poisoning is a Notifiable Disease Outbreaks often occur in institutions.
Invasive bacterial infections causing diarrhoea	Trimethoprim/sulphamethoxazole (80/400), oral, 2 tablets twice daily for 7 days PLUS Metronidazole, oral, 400 mg 8 hourly for 7 days. Fluid and electrolyte replacement	Attempt to identify the specific causative agent and antibiotic sensitivity and give a