HIV Infection and AIDS (Acquired Immunodeficiency Syndrome)

The WHO Clinical Staging of HIV for adults and children in the tables below shows the typical clinical features of HIV infection. The staging is based on demonstration of one or more opportunistic infections or key findings and correlates with disease progression and prognosis. Clinical staging should be performed at HIV diagnosis, on entry into HIV care, at ART initiation and at every visit hereafter to help guide patient care and monitor disease progress.

WHO Staging for HIV Infection and Disease in Adults and Adolescents

Clinical Stage I: Asymptomatic

1. Asymptomatic
2. Persistent generalised lymphadenopathy

Performance Scale 1: asymptomatic, normal activity

Clinical Stage II: Mild

1. Moderate weight loss (< 10% of presumed or measured body weight)
2. Minor mucocutaneous manifestations (seborrheic dermatitis, popular pruritic eruptions, fungal nail infections, recurrent oral ulcerations, angular cheilitis)
3. Herpes zoster
4. Recurrent upper respiratory tract infections (e.g. bacterial sinusitis, tonsillitis, otitis media, and pharyngitis)

And/or performance scale 2: symptomatic but normal activity

Clinical Stage III: Advanced

1. Severe weight loss (more than 10% of presumed or measured body weight)
2. Unexplained chronic diarrhoea for longer than 1 month
3. Unexplained persistent fever (intermittent or constant for longer than 1 month)
4. Persistent oral candidiasis
5. Oral hairy leukoplakia
6. Pulmonary tuberculosis
7. Severe bacterial infections (such as pneumonia, pyomyositis, empyema, bone or joint infection, bacteraemia, meningitis)
8. Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis
9. Unexplained anaemia (< 8 g/dl), neutropenia (< 0.5×10⁹ per litre), or chronic thrombocytopenia (< 50× 10⁹ per litre)

And/or performance scale 3: Bed ridden for less than 50% of the day during the last month

Clinical Stage IV: Severe

• HIV wasting syndrome
• Pneumocystis jirovecii pneumonia (PCP)
• Recurrent severe bacterial pneumonia (>2 episodes within 1 year)
• Toxoplasmosis of the brain
• Cryptosporidiosis with diarrhoea for longer than 1 month
• Chronic isosporiasis
• Extrapulmonary cryptococcosis including meningitis
• Cytomegalovirus infection (retinitis or infection of other organs other than liver, spleen or lymph nodes)
• Chronic oro-labial, genital or ano-rectal herpes simplex virus (HSV) infection of >1 month
• Progressive multifocal leukoencephalopathy (PML)
• Any disseminated endemic mycosis such as histoplasmosis, coccidioidomycosis
• Candidiasis of the oesophagus, trachea, bronchi, or lungs
• Disseminated non-tuberculous mycobacterial infection
• Recurrent septicaemia (including non-typhoid salmonella)
• Extrapulmonary tuberculosis
• Lymphoma (cerebral or B-cell non-Hodgkin)
• Invasive cancer of the cervix
• Kaposi sarcoma
• HIV encephalopathy 
• Atypical disseminated leishmaniasis
• Symptomatic HIV-associated nephropathy or symptomatic HIV associated cardiomyopathy

And/or performance scale 4: Bed-ridden for more than 50% of the day during the last month

Differential diagnosis

• TB
• Untreated diabetes mellitus
• Malnutrition
• Cancer
• Other chronic diseases

HIV testing is the point of entry into comprehensive care HIV services. The aim of HIV Testing Services (HTS) is to promptly identify HIV status to ensure early linkage to prevention, treatment, and support services. Early diagnosis is fundamental for early treatment, good prognosis and reduction in transmission. HTS should be availed to all persons at risk of HIV infection using cost-effective and high impact approaches. HTS should be differentiated to subpopulations and geographical locations because less than 20% of PLWHIV aged 15 years and above do not know their status. Uganda is currently implementing targeted HIV testing to optimize HIV case identification and linkage to care. People at high risk of HIV acquisition include: being in a sexual relationship with multiple concurrent partners; belonging to a key/priority/vulnerable population (e.g., children, adolescent girls and young women, pregnant or breastfeeding women); being a sexual contact to an index client; being a biological child to an HIV positive client; not knowing your partner's HIV status; or being in a sero-discordant relationship.

1. The following approaches are utilized in targeted HIV testing:

• Screening for HIV testing eligibility for children, adolescents and adults.
• Index Client Testing (ICT), including Assisted Partner Notification (APN) and testing for biological children / Know Your Child Status (KYCS)
• Social Network Strategy (SNS)
• HIV Self-Testing (HIVST)

2. Pre and post counselling and consent are needed except in the following situations:

• Diagnostic testing: test carried out on very sick, unconscious, symptomatic or mentally ill by attending health care team for the purpose of better patient management

• Routine testing: for individuals likely to pose a risk of HIV infection to others e.g. pregnant and breastfeeding mothers, sexual offenders and survivors, blood or body tissue or organ donors. Individuals tested using this approach must be given an opportunity to know their status

If a patient is positive, he/she must be IMMEDIATELY connected to HIV care services.

In adults and children >18 months, testing is based on serological (antibody) testing.

Due to the window period between infection and production of detectable levels of antibodies, patients who are negative should be re-tested after three months if they had a possible exposure in the 3 months before the test.

Serial HIV Testing Algorithm for testing persons above 18 months of age in Uganda.

HIV Testing Algorithm using the HIV-Syphilis Duo Kit in MCH Settings

Serological testing is available from HC2 level.

In children below 18 months, testing is virological, that is based on direct detection of viral DNA (DNA-PCR).

Virological testing (DNA-PCR and viral load) is done on DBS (dried blood spots) samples which can be collected from HC2 and are sent to a central national laboratory through the hub system.

HIV testing in children less than 18 months

The recommended test for children <18 months is virological (DNA-PCR) testing, since antibody tests will detect antibodies passed to the child from the mother (so the test can give a false positive).

If the mother is HIV negative:

• The child is classified as HIV negative

If the mother if positive:

• Do DNA PCR at 6 weeks of age or at an earlier opportunity thereafter
  • Start cotrimoxazole prophylaxis and Niverapine syrup  till HIV status is confirmed
• If PCR is positive, enroll child for ART
• If PCR is negative and child never breastfed: child is negative
  • Stop cotrimoxazole and Niverapine syrup
  • Follow up every 3 months and do HIV rapid test (serological) at 18 months
• If PCR is negative BUT child is breastfeeding/has breastfed in the last 6 weeks, re-check PCR 6 weeks after cessation of breastfeeding

If mother’s status is unknown:

• Test the mother and continue management according to the result

If mother unavailable:

• Perform rapid antibody testing on the child. The result will give indication on the mother’s status:
  • If the test is negative: child negative
  • If the test is positive, follow algorithm for managing a child from an HIV positive mother

Other tests in HIV management

If an infant with a Negative previous PCR is symptomatic while still breastfeeding, take off a PCR sample at that point in time. If negative, another PCR sample must be taken according to the algorithm either 9 months or 6 weeks after breastfeeding. 

If mother's status cannot be ascertained, may use rapid test in babies to determine HIV exposure status, should perform DNA PCR for baby who is symptomatic, malnourished or has TB as routine. 

If breastfeeding is stopped before 9 months then a final DNA PCR can be done at any point 6 weeks after cessation of breastfeeding. 

For infants whose mothers are filling on any regimen: take off 2 DBS at the time of confirming the positive test- one for confirmation and one for HIVDR testing. 

Initial evaluation checklist for patients starting ART

Before initiating ART, a full evaluation of the patient must be done. This includes:

• Assessment of the history, physical exam and baseline laboratory tests to assess disease progression and any other conditions
• Staging the patient’s stage using WHO clinical staging
• Counselling and assessing patient’s readiness to start ART

Assessment of patient’s history

• Level of understanding of HIV/AIDS
• Length of time since the diagnosis of HIV infection
• Demographics and lifestyle: whether employed and nature of work
• History of previous ART, prior use of nevirapine during pregnancy
• Pregnancy risks: contraception options and choices, current or planned pregnancy, access to contraceptive services
• Sexual risks and disclosure: willingness to practice safer sex, disclosure of HIV serostatus, use of condoms, HIV counselling, and testing of sex partners and children
• Symptoms of chronic pain and depression
• History of opportunistic infections and other significant illnesses g. TB and STIs, hospitalisations, and surgeries
• Current medications (including anti-TB drugs, traditional therapies, )

Physical exam

• Weight
• Nutritional status
• Functional capacity and level of disability
• Vital signs, skin, eyes, oropharynx (presence of thrush), lymph nodes, lungs, heart, abdomen, genital tract (STIs), extremities, nervous system

Baseline laboratory tests to assess immunosuppression and disease aggressiveness

• Confirming HIV serostatus
• CD4 testing
• Pregnancy test
• Full blood count particularly for patients starting on a AZT-containing regimen

Baseline Labs to assess general health and diagnose any pre-existing HIV complications

• Sputum smear for AFB for patients who have coughed for > 2-3 weeks and a chest X-ray for patients who have unproductive cough or whose AFB smears are negative
• Urine analysis for proteinuria, particularly for patients starting on TDF-containing regimen
• Syphilis screening
• Hepatitis B screening
• Liver and renal function tests if available
• Cryptococcal antigen screening for patients whose CD4 count is < 100 cells/ml
• Symptom-directed lab tests to diagnose pre-existing illnesses

Staging of disease

• Using WHO clinical criteria (see tables above)

Counselling and assessment of patient’s readiness to start therapy

• Assess for education, information or counselling support needs
• Develop an adherence plan

Background of ART

A cure for HIV is not yet available, but by using highly active antiretroviral therapy (HAART), it is possible to promote growth in children and prolong the survival of all HIV infected patients, reduce their morbidity, and improve their quality of life.

Highly active antiretroviral therapy (HAART) is defined as therapy which is potent enough to suppress HIV viraemia to undetectable levels (< 50 copies/mL), and is durable in its virologic effect.

• HAART conventionally includes three or more medicines from at least two classes to achieve full and durable suppression of viral load
• Known sub-optimal regimens, e.g. monotherapy, double nucleoside, or certain triple nucleoside combinations are not HAART and are contraindicated in HIV disease

Goals of treatment with antiretroviral medicines are to:

• Inhibit viral replication as reflected in plasma HIV concentration to as low as possible and for as long as possible. This promotes restoration of the immune system.
• Preserve or enhance the immune function (CD4 restoration), which prevents/delays the clinical progression of HIV disease
• Minimise toxicities and side effects associated with the medicines
• Improve quality of life and reduce HIV-related morbidity and mortality
• Promote growth and neurological development in children

Tools to achieve the goals of therapy

• Maximisation of adherence to ART: adequate support to patient to adhere to treatment and/or access to community/facility level adherence counselling
  • Disclosure of HIV serostatus reinforces patient’s adherence to ART
• Rational sequencing of medicines to preserve future treatment options
• Use of ARV medicine resistance testing when appropriate and available
• Use of viral load estimates for monitoring

Principles of ART

Antiretroviral therapy is part of comprehensive HIV care. The guiding principles of good ART include:

• Efficacy and durability of the chosen medicine regimens
• Freedom from serious adverse effects; low toxicity
• Ease of administration including no food restrictions, better palatability, and lower pill burden
• Affordability and availability of medicines and medicine combinations
• Organised sequencing – spares other available formulations for use in second line while allowing for harmonisation of regimens across age and population
• Ongoing support of the patient to maintain adherence

Limitations of ART

• Antiretroviral medicines are not a cure for HIV but greatly improve quality of life when used appropriately
• ARVs are relatively expensive, require an adequate infrastructure, and knowledgeable healthcare workers
• Medicine interactions and resistance may decrease the potency of ARVs
• Patients may develop adverse medicine reactions
• Patients have to take at least 95% of their pills in order to respond well (adherence is key to successful therapy)
• The medications have to be taken for life
• Some patients may not respond (benefit) to treatment and continue to regress in spite of high adherence
• Children are dependent on adults for adherence to ART

Available agents for ART

At present, antiretroviral medicines come in six classes, which attack different sites and stages of the HIV life cycle, thereby interfering with its reproduction.

Initiation of ART

It is recommended to initiate ART at the earliest opportunity in all documented HIV-infected adults, adolescents and children regardless of CD4 count and WHO clinical staging (Test and Treat)

Evidence and programmatic experience have shown that early initiation of ART results in reduced mortality, morbidity and HIV transmission outcomes. However, priority should be given to patients with lower CD4 counts as well as those who are symptomatic.

A CD4 count is not necessary for initiation but it can be useful to assess risk of opportunistic infections.

ART in children

The vast majority (about 90%) of infants and children with HIV acquire the infection through mother-to-child transmission.

HIV infection follows a more aggressive course among infants and children than among adults; 30% die by age 1 year and 50% die by age 2 years without access to life-saving medicines, including ART and preventive interventions, such as cotrimoxazole prophylaxis.

Early HIV diagnosis and ARV treatment is critical for infants. A significant number of lives can be saved by initiating ART for HIV-positive infants immediately after diagnosis within the first 12 weeks of life.

General principles

• ARV doses need to be adjusted from time to time as the children grow quickly and thus, their weight
• Before a child begins ART, the following assessments must be made:
  • Readiness of parents/caretakers or child (if older) to start ART
  • Complete pre-treatment baseline assessment (see previous sections)

HIV management guidelines are constantly being updated according to evidence and public policy decisions. Always refer to the latest official guidelines. The current edition of UCG comes just before the new ART guidelines are being rolled out. Prescribers should continue to use the 2014 guidelines where drugs prescribed in the 2016 guidelines are not available.

ART regimens in children are age and weight dependent. When children grow, doses and regimens have to be changed according to guidelines below. E.g. a child started at age 2 on ABC+3TC+LPV/r will transition to ABC+3TC+EFV when age >3 and weight >15 kg.

Notes

• 1. TDF/3TC/EFV has low toxicity, once daily administration, and is effective against hepatitis B. It is a relatively inexpensive regimen and does not cause anaemia as AZT (which can then be reserved for second line). EFV has less risk of treatment failure than NVP.
• 2. Contraindications for EFV:
  • Severe clinical depression or psychosis
  • Patient receiving Benzodiazepines or Carbamazepine
  • Ongoing complications of neurological disease that block ability to assess side effects of EFV
  • Age < 3 yrs or weight < 15 kg
• 3. Contraindications for TDF
  • Renal disease and/or GFR < 60
  • Adolescents below 35 kg
• 4. Children unable to swallow pellets can start on nevirapine and then be switched to LPV/r when able to swallow

Triple NRTI regimens are now discouraged due to high virological failure rates and decrease of patient's future ART options

Important Drug Interactions

• Oral contraceptives: EFV/NVP increase their metabolism causing possible increased risk of contraceptive failure. Use additional barrier method
• Injectable progesteron-only contraceptives and IUDs: there is no significant interaction with ARVs and can be used effectively
• Levonorgestrel implants: effect reduced by EFV and NVP, use additional barrier method
• For emergency contraception: double the dose
• Rifampicin: increase metabolism of PI/nevirapine. See Tuberculosis and HIV Co-infection section below

The purpose of monitoring patients on ART is to assess:

• Response to ART and early detection of treatment failure
• Side effects and toxicity
• Adherence

The schedule of monitoring visits follow a pre-set calendar for the 1st one year after initiation of ART, i.e:

• At 1, 2 and 3 months from start of ART
• At 6, 9, 12 months

After 12 months from initiation of ART, the Differentiated Model of Care Delivery is followed, in which schedule and modalities of periodic checks are based on individual needs and characteristics of the patient.

The aim of this model is:

• A client centered approach, so that stable patients have spaced checks and fast tracks drug pick ups
• More efficient use of resources by avoiding overcrowding and long waiting times
• More focus on unstable/complex patients

(Refer to MOH HIV/ART guidelines for more details).

ARV drugs can cause a wide range of toxicities, from mild to life threatening.

Active monitoring and management of toxicities and side effects is important not only to avoid negative medical outcome but also to ensure that they do not negatively affect adherence.

Patients may need to be swiched to second line regimens in case of treatment failure, and to third line if they fail on second line drugs. Third line regimens require resistance testing to inform the choice of appropriate drugs, and needs referral to specialised ART centres.

Factors involved in treatment failure are poor adherence, inadequate drug levels or prior existing drug resistance.

Before switching therapy, it is essential to assess and address adherence issues, and provide intensive adherence counselling if necessary.

Criteria for defining treatment failure are presented in the following table:

Paediatric ARV Dosing Tables

Adult ARV Dosing Tables

Approximately one-third of the women who are infected with HIV can pass it to their babies.

Cause

Time of transmission

• During pregnancy (15-20%)
• During time of labour and delivery (60%-70%)
• After delivery through breast feeding (15%-20%)

Pre-disposing factors

• High maternal viral load
• Depleted maternal immunity (e.g. very low CD4 count)
• Prolonged rupture of membranes
• Intra-partum haemorrhage and invasive obstetrical procedures
• If delivering twins, first twin is at higher risk of infection than second twin
• Premature baby is at higher risk than term baby
• Mixed feeding carries a higher risk than exclusive breastfeeding or use of replacement feeding

Investigations

• Blood: HIV serological test
• HIV DNA PCR testing of babies (see Diagnosis and Investigation of HIV above)

Management

All HIV services for pregnant mothers are offered in the MCH clinic. After delivery, mother and baby will remain in the MCH postnatal clinic till HIV status of the child is confirmed, then they will be transferred to the general ART clinic.

The current policy aims at elimination of Mother-to-Child Transmission (eMTCT) through provision of a continuum of care with the following elements:

• Primary HIV prevention for men, women and adolescents
• Prevention of unintended pregnancies among women living with HIV
• Prevention of HIV transmission from women living with HIV to their infants
• Provision of treatment, care and support to ALL women infected with HIV, their children and their families

Key Interventions for eMTCT

• Routine HIV Counseling and Testing during ANC (at 1st If negative, repeat HIV test in the third trimester/ labour.
• Enrolment in HIV care if mother is positive and not yet on treatment
• If mother already on ART, perform viral load and continue current regimen
• ART in pregnancy, labour and post-partum, and for life – Option B+

Management

Treatment

Recommended ARV for option B+

• One daily Fixed Dose Combination (FDC) pill containing TDF + 3TC + EFV started early in pregnancy irrespective of the CD4 cell count and continue during labour and delivery, and for life

Alternative regimen for women who may not tolerate the recommended option are:

• If TDF contraindicated: ABC+3TC+EFV
• If EFV contraindicated: TDF + 3TC + ATV/r (see Management of HIV Infection section above)

Prophylaxis for opportunistic infections

• Cotrimoxazole 960 mg 1 tab daily during pregnancy and postpartum
• Mothers on cotrimoxazole DO NOT NEED IPTp with SP for malaria

Notes

• TDF and EFV are safe to use in pregnancy
• Those newly diagnosed during labour will begin HAART for life after delivery

Caution

• In case of low body weight, high creatinine, diabetes, hypertension, chronic renal disease, and concomitant nephrotoxic medications: perform renal function investigations before starting TDF
• TDF is contraindicated in advanced chronic renal disease

HIV-exposed infants should receive care at the mother-baby care point together with their mothers until they are 18 months of age. The goals of HIV-exposed infant care services are:

• To prevent the infant from being HIV infected
• Among those who get infected: to diagnose HIV infection early and treat
• Offer child survival interventions to prevent early death from preventable childhood illnesses

The HIV Exposed Infant and the mother should consistently visit the health facility at least nine times during that period.

The visits are synchronised with the child’s immunisation schedule (i.e., at 6, 10 and 14 weeks, then at 5, 6, 9, 12, 15 and 18 months).

Management

Treatment

Nevirapine prophylaxis

• Provide NVP syrup from birth for 6 weeks
• Give NVP for 12 weeks for babies at high risk, that is breastfeeding infants who mothers:
  • Have received ART for 4 weeks or less before delivery; or
  • Have VL >1000 copies in 4 weeks before delivery; or
  • Diagnosed with HIV during 3rd trimester or breastfeeding period (Postnatal)
• Do PCR at 6 weeks (or at first encounter after this age) and start cotrimoxazole prophylaxis
  • If PCR positive, start treatment with ARVs and cotrimoxazole and repeat PCR (for confirmation)
  • If PCR negative and baby never breastfed, child is confirmed HIV negative. Stop cotrimoxazole, continue clinical monitoring and do HIV serology test at 18 months.
  • If PCR negative but baby has breastfed/is breasfeeding, start/continue cotrimoxazole prophylaxis and repeat PCR 6 weeks after stopping breastfeeding
• Follow up any exposed child and do PCR if they develop any clinical symptom suggestive of HIV at any time and independently of previously negative results
• For negative infants, do serology at 18 months before final discharge

Dosages of nevirapine

• Child 0-6 weeks, 2-2.5 Kg: 10 mg once daily (1 ml of syrup 10 mg/ml)
• Child 0-6 weeks, >2.5 kg: 15 mg once daily (1.5 ml of syrup 10 mg/ml)
• Child 6 weeks – 12 weeks: 20 mg once daily (2 ml)

Cotrimoxazole prophylaxis

• Provide cotrimoxazole prophylaxis to all HIV- exposed infants from 6 weeks of age until they are proven to be uninfected. Dosages:
  • Child <5 kg: 120 mg once daily
  • Child 5-14.9 kg: 240 mg once daily
• Infants who become HIV infected should continue to receive cotrimoxazole prophylaxis for life
• If cotrimoxazole is contraindicated, offer dapsone at a dose of 2 mg/kg once daily ( up to 100 mg max)

Isoniazid (INH) preventive therapy (IPT)

• Give INH for six months to HIV-exposed infant who are exposed to TB (close contact with PTB case) after excluding TB disease
• Dose: Isoniazid 10 mg/kg + pyridoxine 25 mg daily
• For newborn infants, if the mother has TB disease and has been on anti-TB drugs for at least two weeks before delivery, INH prophylaxis is not required.

Immunisation

• Immunise HIV exposed children as per national immunisation schedule
• In case of missed BCG at birth, do not give if child has symptomatic HIV
• Avoid yellow fever vaccine in symptomatic HIV
• Measles vaccine can be given even in symptomatic HIV

Counselling on infant feeding choice

• Explain the risks of HIV transmission by breastfeeding (15%) and other risks of not breastfeeding (malnutrition, diarrhoea)
• Mixed feeding may also increase risk of HIV transmission and diarrhoea
• Tell her about options for feeding, advantages, and risks
• Help her to assess choices, decide on the best option, and then support her choice

Feeding options

• Recommended option: Exclusive breastfeeding then complementary feeding after child is 6 months old
• Exclusive breastfeeding stopping at 3-6 months old if replacement feeding possible after this
• If replacement feeding introduced early, mother must stop breastfeeding
• Replacement feeding with home-prepared formula or commercial formula and then family foods (provided this is acceptable, feasible, safe, and sustainable/ affordable)

If mother chooses breastfeeding

• The risk may be reduced by keeping the breasts healthy (mastitis and cracked nipples raise HIV infection risk)
• Advise exclusive breastfeeding for 3-6 months

If mother chooses replacement feeding

• Counsel and teach her on safe preparation, hygiene, amounts, times to feed the baby
• Follow up within a week from birth and at any visit to health facility.

Tuberculosis and HIV Co-Infection

Active TB may be present when ART needs to be initiated or it may develop during treatment.

TB and HIV care for co-infected patients should be provided in an integrated manner under one roof by one care team (one-stop-shop).

Co-management of TB and HIV is complicated by:

• Drug interactions between rifampicin and both the NNRTI and PI classes
• Immune reconstitution inflammatory syndrome (IRIS)
• Pill burden, overlapping toxicities and adherence

Management

ART should be initiated in all TB/HIV co-infected people irrespective of their clinical stage or CD4 count. However, the timing of initiation of treatment may differ based on whether the patient is diagnosed with TB before or after initiating ART.

ARV regimen in ART-naive patients on TB treatment

ARV regimen substitution for patients initiating TB treatment while on ART

Second line ART for patients with TB

• There are significant drug interactions with PIs and rifampicin. 
• If rifabutin is available, it may be used in place of rifampicin with ATV/r or LPV/r, but it is contraindicated in patients with WBC counts below 1000/mm³.
• Maintaining PI in second line regimens while switching from Rifampicin to Rifabutin (if available) is ideal

TB prevention

• BCG immunisation: it protects children against severe forms of TB. It can be given at birth. If delayed, avoid in symptomatic HIV
• IPT (Isoniazid Preventive Treatment) see Tuberculosis

Crytococcal meningitis is an opportunistic infection caused by a fungus Cryptococcus neoformans.

In Uganda, cryptococcal meningitis (CM) associated mortality is up to 39%. Patients with a CD4 cell count of <100 are at the highest risk, so early screening and management is critical.

Screening In ART-Naive Patients

• Screen routinely for Cryptococcal Meningitis with the cryptococcal antigen (CrAg) test (a bedside finger prick test):
  • All ART naive individuals with CD4 <100 cells/µL
  • Patients on ART with viral load (VL >1000 copies/ml) or clinical (stage 3 or 4 disease) failure
• If serum CrAg negative and no signs of meningitis: start ART immediately (or switch regimen)
• If CrAg positive and/or signs or symptoms of meningitis (headache, presence of seizures, altered consciousness, photophobia, neck stiffness, and a positive Kernigs’ sign)
  • Perform lumbar puncture and test for CSF CrAg (culture if possible)
• If CSF CrAg positive, diagnose and treat for Cryptococcal Meningitis
• If CSF CrAg negative but blood CrAg positive, give pre emptive treatment for asymptomatic cryptococcal disease or non CNS cryptococcal disease

Cryptococcal screening algorithm

Management

Pre-emptive treatment for cryptococcoal disease

Treatment 

Induction Phase

• Fluconazole 800 mg for 2 weeks or 12 mg /kg/day for individuals below 19 years

Consolidation Phase

• Fluconazole 400 mg (or 6 mg/kg/day up to 400 mg) for 8 weeks

Maintenance dose

• Fluconazole 200 mg for 14 weeks

Cryptococcal Meningitis

• It commonly presents with headache, fever, malaise developing over 1-2 weeks, progressing into confusion, photophobia, stiff neck
• Diagnosis is through identification of the microorganism in the CSF with Indian Ink stain, antigen in CSF or culture

Management

Treatment

Induction phase (2 weeks)

Recommended:

Amphotericin B 0.7-1 mg/kg/day +

Flucytosine (100 mg/kg/day in four divided doses)

OR

High-dose fluconazole 800 mg/day (12 mg/kg in children)

OR

Amphotericin B short course 5-7 days + high-dose fluconazole 800 mg/day, (12 mg/kg in children)

Alternative:

Fluconazole 1200 mg/day (12 mg/kg/day in children and adolescents <19kg)

Consolidation phase (8 weeks)

• Fluconazole 400-800 mg/day (or 6-12 mg/ kg/day in children) if Amphotericin is used in induction phase
• Fluconazole 800 mg (12 mg/kg/day) if amphotericin short course-high dose fluconazole regimen used
• Initiate ART 4-6 weeks after starting CM treatment and there is clinical response to antifungal therapy

Maintenance phase

• Fluconazole 200 mg/day (or 6 mg/kg/day max 200 mg for children)

Criteria for stopping after 1 year of maintenance phase

• Adults VL <1,000 copies/mm³ & CD4 ≥100 for 6 months or CD4 ≥200 if viral load not available.
• Children: If CD4% >25% or suppressed viral load

Adequate control of elevated CSF pressure

• Control of increased intracranial pressure improves survival by 25% in persons with cryptococcal meningitis
• All patients with a CSF Pressure >250 mmHg will need a therapeutic LP the following day to reduce the CSF pressure to < 200 mmHg
• In the absence of a manometer, one may use an IV giving set to create an improvised manometer measuring the height with a meter stick
• Removing 20-30 mL of CSF (even in the absence of a manometer) may be adequate to decrease CSF pressure. Most patients will need 2-3 LPs during the induction phase

Preventing Amphotericin toxicity:

• To prevent nephrotoxicity and hypokalaemia, do:
  
  • Pre-hydration with 1 L Normal saline before starting the daily amphotericin dose;
  • Monitor serum potassium and creatinine levels at initiation and at least twice weekly to detect changes in renal function;
  • Routine administration of 40 mEq/day of potassium chloride can decrease the incidence of amphotericin-related hypokalaemia;
  • Consider alternate day amphotericin if creatinine is >3 mg/dl
• Other options for treatment are a combination of Flucytosine (100 mg/kg/day in four divided doses) and fluconazole 800-1200 mg daily
• Fluconazole dose should be increased by 50% for patients on rifampicin
• Amphotericin and fluconazole are not recommended during pregnancy but use if benefit to mother outweighs risk. Avoid Flucytosine

Relapse Cases

• Present with a recurrence of symptoms of meningitis and have a positive CSF culture following a prior confirmed diagnosis of cryptococcal meningitis
• Evaluate for drug resistance:
• Send CSF to Microbiology reference laboratory (CPHL or Makerere University) for Culture and sensitivity testing
• If there are no drug resistance results, re-initiate the induction therapy for 2 weeks and complete other phases of treatment.

• Hepatitis B virus (HBV) is the leading cause of chronic liver disease among HIV patients. In Uganda, the prevalence of Hepatitis B among HIV patients is estimated to be at 17%. (see Chronic Hepatitis B Infection for more details)
• All HIV-infected patients initiating and those failing ART should be routinely screened for HBV infection using Hep B surface Antigen (HBsAg)
• People living with HIV with a positive HBsAg should have other complementary tests at baseline and repeated every 6 months and these include:
  • A complete blood count
  • Liver function tests: ALT, AST, albumin, bilirubin, PT-INR
  • Liver ultrasound scan: to assess stage of liver fibrosis
• Repeat tests every 6 months since patients with chronic HBV infection are at increased risk for hepatocellular carcinoma

Management of HBV/HIV co-infection

The goal of HBV/HIV treatment is to prevent dual disease progression and to reduce HBV-related morbidity and mortality.

Treatment

Preferably ART regimen containing:

• TDF 300 mg + 3TC 300 mg PO once daily for life
• After 6 months of treatment, patients should be evaluated for HBV treatment failure

If jaundice, malaise and abdominal right upper quadrant pain are present or if liver function tests are abnormal

• Do HBV DNA (hepatitis viral load) if any of the above is present

Treatment Failure

• Patients with HB VL >2000 IU/ml at 24 weeks of therapy should be referred for further evaluation and management

Prevention of HBV infection

• Counseling: emphasize sexual transmission as well as the risks associated with sharing needles and syringes, tattooing or body-piercing
• Advise patients with chronic HBV disease to avoid alcohol consumption
• All household members and sexual partners of people living with HIV with HBV should be screened for HBsAG
• HBV Vaccination is the most effective way to prevent HBV infection and its consequences
  • All HIV-infected patients who test negative on HBsAg should be vaccinated with HBV vaccine
  • All sexual partners and contacts should receive HBV vaccination regardless of whether they are HIV-infected or not

Interstitial pneumonitis caused by the parasite Pneumocystis jirovecii (formerly carinii). It is common in severely immunosuppresed patients (e.g. in HIV).

Clinical features

• Fever
• Dry cough
• Shortness of breath (significant hypoxemia)

Investigations

• Chest x-ray shows characteristic bilateral interstitial infiltrates

Management

Treatment

Pneumocystis Jirovecii pneumonia

• Give oxygen if SpO2 <94%
• Cotrimoxazole 120 mg/kg/daily in 2-4 divided doses for 21 days
  • For example cotrimoxazole 480 mg tablets:
  • If patient is < 60 kg: give 3 tablets
  • If patient >60 kg: give 4 tablets
• Plus prednisolone 2 mg/kg daily in 3 divided doses for 5 days, then reduce dose to complete 21 days of treatment

Or (in patients who cannot tolerate or do not respond to cotrimoxazole)

• Pentamidine 4 mg/kg by IV infusion daily for 21 days
  • Reduce dose in renal impairment
  • Avoid direct bolus injections whenever possible but if unavoidable, never give rapidly

Alternative regimen (21-day course) if above not available/ tolerated

• Clindamycin 600 mg every 8 hours
• Plus dapsone 100 mg daily

Prophylaxis

Give to all patients with history of PCP infection and consider also for severely immunocompromised patients

• Cotrimoxazole 960 mg daily or
• Dapsone 100 mg daily
• Continue until immunity recovers sufficiently

People living with HIV are at higher risk of acquiring any other infection and diseases, including non-communicable diseases, due to HIV itself and drug side effects.

• Treat any other infection (e.g. malaria, STI) as per guidelines for the general population
• Screen regularly for NCD (diabetes, hypertension and depression)
• Screen women at enrolment in HIV care and then annually for cervical cancer using Visual Inspection with Acetic Acid (VIA)

Behavioural change

• Always follow safe sex practices (e.g. use condoms; avoid multiple sexual partners)
• Never share used needles, syringes, razors, hair shavers, nail cutters, and other sharp objects
• Avoid tattooing, body-piercing, and scarification unless carried out under strictly hygenic conditions in properly controlled premises
• Delay start of sexual activity in adolescence
• Discourage cross generational and transactional sex
• Avoid violence and abuse

Biomedical prevention interventions

• PMTCT
• Safe Male Circumcision
• ART with viral suppression
• PEP (Post Exposure Prophylaxis)
• PrEP (Pre Exposure Prophylaxis)
• Blood transfusion safety
• STI screening and treatment
• Safe infusion and injection practices
• Adherence to infection control procedures

Post-Exposure Prophylaxis  Post-exposure prophylaxis (PEP) is the short-term use of ARVs to reduce the likelihood of acquiring HIV infection after potential occupational or non-occupational exposure.

Types of Exposure:

• Occupational exposures: Occur in health care settings and include sharps and needlestick injuries or splashes of body fluids to the skin and mucous membranes
• Non-occupational exposures: Include unprotected sex, exposure following assault like in rape & defilement, road traffic accidents and injuries at construction sites where exposure to body fluids occur

Steps in providing PEP

Treatment

Step 1: Rapid assessment and first aid

Conduct a rapid assessment of the client to assess exposure and risk and provide immediate care

Occupation exposure:

After a needle stick or sharp injury:

• Do not squeeze or rub the injury site
• Wash the site immediately with soap or mild disinfectant (chlorhexidine gluconate solution) or, use antiseptic hand rub/ gel if no running water (do not use strong irritating antiseptics (like bleach or iodine)

After a splash of blood or body fluids in contact with intact skin/broken:

• Wash the area immediately or use antiseptic hand rub/ gel if no running water (don’t use strong irritating antiseptics)

After a splash of blood or body fluids contact with mucosae:

• Wash abundantly with water

Step 2: Eligibility assessment

Provide PEP when:

• Exposure occurred within the past 72 hours; and
• The exposed individual is not infected with HIV; and
• The ‘source’ is HIV-infected or has unknown HIV status or high risk

Do not provide PEP when:

• The exposed individual is already HIV positive;
• When the source is established to be HIV negative;
• Exposure to bodily fluids that do not pose a significant risk: e.g. to tears, non-blood-stained saliva, urine, and sweat, or small splashes on intact skin
• Exposed people who decline an HIV test

Step 3: Counseling and support

Counsel on:

• The risk of HIV from the exposure
• Risks and benefits of PEP
• Side effects of ARVs
• Provide enhanced adherence counseling if PEP is prescribed
• Link for further support for sexual assault cases (see below)

Step 4: Prescription

• PEP should be started as early as possible, and not beyond 72 hours from exposure
• Recommended regimens:
  • Adults : TDF+3TC+ATV/r
  • Children: ABC+3TC+LPV/r
• A complete course of PEP should run for 28 days
• Do not delay the first doses because of lack of baseline HIV Test

Step 5: Follow up

• To monitor adherence and manage side effects
• Discontinue PEP after 28 days
• Perform follow-up HIV testing 6-week, 3 and 6 months after exposure
  • If HIV infected, provide counseling and link to HIV clinic for care and treatment
  • If HIV uninfected, provide HIV prevention education/risk reduction.

Post-rape care (see also Sexual Assault/Rape)

Health facilities should provide the following clinical services as part of post-rape care:

• Initial assessment of the client
• Rapid HIV testing and referral to care and treatment if HIV-infected
• Post-exposure prophylaxis (PEP) for HIV
• STI screening/testing and treatment
• Forensic interviews and examinations
• Emergency contraception – if person reached within the first 72 hours
• Counselling

The health facility should also identify, refer and link clients to non-clinical services

• Some of the services include the following:
• Long term psycho-social support
• Legal counseling
• Police investigations, restraining orders
• Child protection services (e.g. emergency out of family care, reintegration into family care or permanent options when reintegration into family is impossible)
• Economic empowerment
• Emergency shelters
• Long-term case management

Reporting: Health facilities should use HMIS 105 to report Gender Based Violence (GBV)

HIV positive persons benefit greatly from the following support after the first impact of the test result is overcome:

• Provide of emotional support
• Help the person understand the social, medical, and psychological implications for him/herself, the unborn child (in the case of a pregnant woman), and any sexual partners
• Connect the person with support services, including (religious) support groups, orphan care, income- generating activities, home care and others
• Help the person find strategies to involve his/her partner and extended family in sharing responsibility
• Help the person identify someone from the community to support and care for him/her
• Discuss with HIV positive mothers how to provide for the other children in the family
• Help him/her identify a person from the extended family or community who will provide support
• As appropriate, confirm and support information given in HIV counselling and testing on mother-to-child transmission, possibility of ARV treatment, safer sex, infant feeding and FP advice
• Help the person to understand and develop strategies to apply new information within daily life.