Human Immunodeficiency Virus (HIV) is a retrovirus, which infects primarily CD4 T cells (T helper cells).
Infection leads to a progressive destruction of the immune system with a consequent myriad of opportunistic infections and the development of certain malignancies.
Acquired Immuno Deficiency Syndrome
(AIDS) is defined as the presence of an AIDS defining illness with a positive antibody test for HIV
- Sexual transmission through vaginal and anal sex is the commonest route globally accounting for about 80%.
- Transfusion of infected blood and blood products
- Use of contaminated instruments;
sharing needles, tattooing and occupational exposures
- Mother-to-child transmission of
HIV: from an infected mother to her baby during pregnancy, at delivery and, after birth through breast-feeding
Clinical Course of HIV Disease:
1. Acute (Primary) HIV infection:
This occurs 1-4 weeks after infection during which infected people experience transient flu-like symptoms, which mayb include:
- Mild fever
- Muscle aches and pains
- Enlargement of lymph nodes
- Sore throat
- Skin rash
This stage is difficult to diagnose by standard laboratory assays.
- This usually occurs within 4 weeks.
- Patients develop antibody response, which is detectable by a positive HIV Ab test.
3. Asymptmatic infection:
- The individual feels well despite on-going viral replication. Usually last a variable amount of time and is marked by a gradual decline in CD4 cell counts.
4. Early Symptomatic infection:
- Generalized lymphadenopathy
- Weight loss
- Night sweats
- Pruritic skin rash
- Unexplained fever
- Chronic diarrhea
- Oral candidiasis
- Oral hairy leukoplakia
- Herpes zoster
- Pneumococcal infections
- Pulmonary Tb
5. Late Disease/AIDS defining Illness:
- This period is marked by the appearance of opportunistic infections and neoplasms
- Pulmonary/extrapulmonary tuberculosis and Disseminated TB
- Pneumocytis jiroveci (carinii) pneumonia.
- Cryptococcal meningitis
- Recurrent bacterial pneumonia
- Candida oesophagitis
- CNS toxoplasmosis
- Kaposi sarcoma
- Non-Hodkin’s lymphoma
- coccidiomycosis, crytococcosis or histoplasmosis
- Chronic (> 1month) intestinal cryptosporidiosis or isosporiasis
- Disseminated extrapulmonary mycobacteria (non-tuberculous)
- Progressive multifocal leukoencephalopathy (PML)
- Recurrent salmonella septicaemia
- HIV wasting syndrome
Staging of HIV/AIDS
WHO Staging System for HIV Infection and Disease in Adults and Adolescents
Clinical Stage I:
- Generalised lymphadenopathy
- Performance scale 1: asymptomatic, normal activity
Clinical Stage II:
- Weight loss <10% of body weight
- Minor mucocutaneous manifestations (seborrhoeic dermatitis, prurigo, fungal nail infections, recurrent oral ulcerations, angular cheilitis)
- Herpes zoster within the last five years
- Recurrent upper respiratory tract
infections (i.e. bacterial sinusitis)
- And/or performance scale 2:
symptomatic, normal activity
Clinical Stage III:
- Weight loss > 10% of body weight
- Unexplained chronic diarrhoea, > 1 month
- Unexplained prolonged fever (intermittent or constant) >1month
- Oral candidiasis (thrush)
- Oral hairy leucoplakia
- Pulmonary tuberculosis within the past year
- Severe bacterial infections (i.e. pneumonia, pyomyositis)
- And/or performance scale 3: bedridden <50% of the day during last month
Clinical Stage IV:
- HIV wasting syndrome
- Pneumocystic carinii pneumonia.
- Toxoplasmosis of the brain
- Cryptosporidiosis with diarrhoea > 1 month
- Cryptococcosis, extrapulmonary
- Cytomegalovirus disease of an organ other than liver, spleen or lymph node (e.g. retinitis)
- Herpes simplex virus infection, mucocutaneous (>1month) or visceral
- Progressive multifocal leucoencephalopathy
- Any disseminated endemic mycosis
- Candidiasis of oesophagus, trachea, bronchi
- Atypical mycobacteriosis, disseminated or lungs
- Non-typhoid salmonella septicaemia
- Extrapulmonary tuberculosis
- Kaposi sarcoma 2
- HIV encephalopathy
- And/or performance scale 4: bedridden > 50% of the day during last month
- Weight loss of > 10% plus either unexplained chronic diarrhoea> 1 month, or
chronic weakness and unexplained prolonged fever > 1 month.
- Clinical findings of disabling cognitive and/or motor dysfunction interfering with
activities of daily living, progression over weeks or months in absence of concurrent illness or condition other than HIV infection that could explain the finding
- Weight loss of > 10% plus either unexplained chronic diarrhoea> 1 month, or
- Diabetes mellitus
- Other wasting syndromes
- Full Blood Count and differentials
- VDRL (or RPR)
- Tuberculin test (PPD)
- Sputum smears for TB Electrolytes,
- Urea and Creatinine
- Blood glucose
- Liver function tests
- Lipid studies (fasting trigycerides, LDL, HDL)
- HBV, HCV serology
- Cervical (PAP) smears
- CD4 T cell counts
- HIV RNA level (viral load)
- HIV DNA (paediatric diagnosis <18 months of age)
- Genotype and phenotype assays for
- Clinical: prevent disease progression
- Immunological: restore immunity
- Virological: control or suppress viral replication
- Public health: reduce infectivity
Criteria for initiating ART
All HIV infected individuals are eligible for ART.
Early initiation of combination treatment (ART) is associated with health benefits in terms of reduced morbidity and mortality in all age groups.
Antiretroviral therapy (ART) has dramatically reduced HIV associated morbidity and mortality and has transformed the HIV disease into a chronic, manageable condition.
In addition, treatment of HIV infected individuals with ART is highly efficient at preventing transmission to sexual partners and mother to child transmission (MTCT).
From the moment a patient tests HIV positive, he/she should be linked to the Care and Treatment Clinic (CTC).
In health facilities where ART is being initiated at RCH and TB clinics, patients can be managed at those clinics.
Mobile outreach clinics can also be used for key and vulnerable population and hard to reach areas.
- In patients with dual TB/HIV disease, TB treatment should be initiated first, followed by ART as soon as possible thereafter (and within the first eight weeks of initiating TB treatment).
- For those with a CD4 count less than 500 cells/ mm3, ART should be provided within two weeks of starting TB treatment.
- Severe chronic liver disease includes cirrhosis and end-stage liver disease and is categorized into compensated and decompensated stages.
- Decompensated cirrhosis is defined by the development of clinically evident complications of portal hypertension (ascites, variceal haemorrhage and hepatic encephalopathy) or liver insufficiency (jaundice).
Antiretroviral Therapy in Adults and Adolescents
The second line NRTI choice for adults and adolescents depends on the first line regimen.
- For patients on TDF based regimens in first line, the preferred second line option is AZT plus 3TC combined with a ritonavir-boosted Pl, preferably ATVir because it is dosed once daily and has fewer metabolic complications and side effects.
- The same NRTIs, with exception of 3TC and FTC used previous regimen should not be used in subsequent regimens during switching due to treatment failure.
- LPV/r can be used as an alternative to ATV/r in patients using anti-TB drugs (with ritonavir super boosting) and children below six years.
- Also, ATVIr (300/100mg) cannot be used in children below 30kg.
- For patients who were on AZT and had never used TDF regimen, the default second line option will be TDF or ABC based regimen combined with a boosted PI (TDF+FTC+ATV/r).
- For patients who were introduced to TDF in first line due to AZT toxicity, the default second line option is to use ABC plus 3TC combined with a ritonavir-boosted PI ATV/r or LPV/r. (ABC+3TC + LPV/r or ATV/r). However, ABC may be rendered ineffective due to cross resistance with TDF associated resistance mutations.
Patients failing 2nd line regimens may have extensive NRTI and NNRTIs associated resistance mutations (RAMS) which preclude/minimise their use in third-line regimens.
Therefore, 3rd line regimens, in order to have at least two or preferably three effective drugs, need to be constructed using other new classes of drugs or second-generation formulations of previous drugs.
These second-generation drugs usually have a higher genetic barrier to resistance and their efficacy is not compromised by RAMS associated with the first-generation formulations.
Therefore, this guideline recommends the use of Integrase Strand Transfer Inhibitors (INSTIS) or Integrase Inhibitors Dolutegravir 50mg (DTG) and Raltegravir 400mg (RAL), Second generation Pls Darunavir 800mg /Ritonavir 100mg (DRV/r),
- DTG in third line regimen should be given twice daily for clients who were previously exposed to INSTIS.
- For TB and HIV co-infected patients on LPV/r should be switched to DRV/r after completion of TB treatment
- For second- and third-line regimens which are non TDF based, in case of new Hepatitis B co-infection TDF with FTC should be added to the new regimen as treatment of Hepatitis B.
ART in Women of Childbearing Potential or Pregnant Women
Mother-to-child transmission (MTCT) of HIV refers to the transmission of HIV infections from HIV infected mothers to their infants.
MTCT can occur during pregnancy, labour and delivery, and breast-feeding. Without intervention, the overall risk of MTCT is approximately 20%-45%.
However, with interventions, this risk can be reduced to less than 5%.
Transmission of HIV from mother to her child accounts for over 90% of all HIV infections in children aged below 15 years.
Prevention of Mother to Child Transmission
All HIV infected pregnant women and lactating mothers are eligible for ART regardless of CD4 cell count and clinical stage.
The pregnant or breast-feeding women with HIV should be started on lifelong ART at the time of diagnosis.
The recommended first line regimen is once a day fixed dose regimen of TDF + 3TC + DTG.
Although TDF+ 3TC + EFV may be an option for use during the pre-conception period through the first eight weeks of pregnancy to avoid potential risk of neural tube defects.
Then TLD should be continued postpartum
- A women-centered approach is adopted. Women of childbearing potential including those who are using long term effective contraception should be given adequate information to enable making informed decision and choice.
- Women should receive on-going counselling support to continue with HIV care and treatment in order to maintain good health and to reduce the risk of HIV transmission to others.
Available alternative first-line ART regimen includes
A: TDF+FTC+EFV600mg (FDC)
A: ABC+3TC+EFV600 or DTG OR
A: AZT+3TC+EFV600 or DTG
Prophylaxis for HIV Exposed Infants
Administer NVP syrup immediately after birth to all HIV exposed infants and continue until six weeks of age.
In case a high risk HIV exposed infant is identified, administer duo prophylaxis containing NVP syrup (once daily) and AZT syrup (twice daily) for the first weeks of life, then continue with daily NVP alone up to 12 weeks of life.
High-risk infants are those who are:
- Born to women diagnosed to be living with HIV during current pregnancy or breast feeding period,
- women known to be HIV positive but not yet on ART or already on ART but with high viral load (250/UL of blood)
Infant prophylaxis is most effective when given as soon as possible after birth, preferably within 6-12 hours.
HIV exposed infants identified beyond the age of 4 weeks should not be given ARV prophylaxis.
NVP Dosing Recommendation
Birth to 6 weeks:
- Birth weight 2000-2499g: 10mg (1 ml) once daily
- Birth weight ≥ 22500g: 15mg(1.5ml) once daily
Based on the dosing required to sustain exposure in the infant of >100 ng/mL with the fewest dose changes.
Low birth weight infants <2000g should receive mg/kg dosing: suggested starting dose is 2mg/kg once daily.
Antiretroviral Therapy in Children and Adolescents Living with HIV
ART in children has been proven to increase survival and decrease HIV-related morbidity and mortality.
Children should be started on ART as soon they are diagnosed including those who are presumably diagnosed.
When to start ART in children under 15 years
1st line: First line ARV Regimen in infants and children under 15 years
Note: Children with weight above 30kg can use TDF as a fixed dose combination with 3TC.
Special Considerations for LPVir syrup, granules and tablets
- The LPV/r liquid requires a cold chain only during storage at the facility
- After dispensing, the liquid is stable at room temperature for 1 month so patients should be given a maximum of 1-month supply
- Patients do not have to refrigerate the LPV/r liquid
- LPV/r granules for infants who can safely swallow LPV/r granules but who are unable to swallow LPV/r tablets whole.
- LPV/r tablet is heat stable but must be swallowed whole and should not be split or crushed as it loses effectiveness
Changing ART in Children Under 15 Years
- Drug toxicity
The principles for changing ARVS and the managing drug toxicity in children are like those applied to adults.
- Treatment failure
- Virological treatment failure: Viral load is the most reliable method to detect early treatment failure. Virological treatment failure is recognized if the child is adherent to the current ART regimen, for 6 months or more and has two consecutive viral load measurements over 1000 copies/ml at 3 months apart.
- Immunological treatment failure: If adherence is good, immunological criteria indicating that change to second-line therapy is warranted where/when HVL test is not available includes the following:
CD4 cell percent should not be measured during an inter-current infection but can be determined when the child has recovered.
If there is a modest decline in CD4 cell count or percent (<5%); and if there is no failure to thrive do not change medication, instead maintain close monitoring.
Clinical Treatment Failure: Clinical conditions indicating that a change to second-line therapy is warranted include:
- Poor growth (failure to gain weight, declining or stagnant weight) over a 6-month period, after excluding other causes, such as TB, feeding problems and food insecurity
- No improvement of neuro-developmental milestones
- Development of HIV encephalopathy
- Recurrent infections, such as oral candidiasis, persistent diarrhoea, recurrent severe bacterial pneumonia
- Advancement from one clinical stage to another or new evidence of new WHO stage 3 or 4 disease
- Short inter-current episodes of pneumonia, LRTI and gastroenteritis should not be regarded as clinical failure
- Pulmonary or lymph node TB, which are clinical stage 3 conditions, are not indications of treatment failure, and thus may not require consideration of second-line therapy
- The response to TB therapy should be used to evaluate the need for switching therapy
- Before an ARV regimen is thought to be failing based on clinical criteria, the child should have received the regimen for at least 6 months.
- The condition must be differentiated from immune reconstitution inflammatory syndrome.
Assessment of Infants and Children receiving ARV Therapy
Important clinical signs of response to ARV therapy in children include improvement in growth & development and decreased frequency of infections (bacterial infections, oral thrush, and/or other opportunistic infections).
Clinical monitoring of ARV treatment in children should include:
- Feeding practice and nutritional status
- Growth monitoring: weight, height, MUAC (mid-upper arm circumference)
- Head circumference should be monitored in children under 3 years old
- Neurologic symptoms & developmental milestones
- Cotrimoxazole prophylaxis taken daily
- Adjustment of ARV dose based on weight
- WHO disease clinical staging
- Immunization status
- Other medical conditions
- Screening for malaria and TB.
Infant and children take longer time to attain adequate viral suppression. Before confirming treatment failure, calculate drop in VL (using 0.5 log two years and above, 0.7log below 2 years for further details on how to convert VL into numbers.
ATV/r can be used as an alternative to LPV/r in children above 6 years old if paediatric formulation is available but adolescents >30kg can take adult formulation.
Third-Line ARV regimens in children under 15 years and adolescents
Clients failing 2nd line regimen have extensive NRTI and NNRTIs associated resistance mutations which minimise their use in third-line regimens.
Third-line regimen is constructed using new classes of drugs or second-generation formulations, in order to have at least two or three effective drugs.
For examples, Darunavir (DRV) is a second-generation Pl without cross resistance to Lopinavir/r used in the previous regimens.
Criteria for Change to Third line Failing any 2nd line regimen Referral to specialist care is recommended where third line regimen can be chosen according to genotype resistance testing and managed by an expert panel at tertiary care facilities.
The criteria for diagnosing second-line failure are the same as those used for diagnosing first-line failure.
Eligibility for Third Line Evaluation:
- All clients should have undergone an Enhanced Adherence Counselling (EAC)
- Failing 2nd line regimens
- Documented virologic failure (VL> 1000) on a PI regimen; except children below 3 years
Third-line Regimens for Children and Adolescents
Selection of third-line regimen should consider genotype resistance test results as well as treatment history.
Definition of clinical, immunological and
Post Exposure Prophylaxis (PEP)
Post Exposure Prophylaxis PEP) is the immediate provision of preventive measures and medications following exposure to potentially infected blood or other bodily fluids in order to minimize the risk of acquiring infection.
Several clinical studies have demonstrated that HIV transmission can be reduced by 81% following immediate administration of antiretroviral agents.
Effective post-exposure management entails the following elements:
- Management of exposure site
- Exposure reporting Assessment of infection risk
- Appropriate treatment
- Follow-up and counselling.
When an exposure occurs, the circumstances and post exposure management procedure applied should be recorded in the exposed person’s confidential form for easy follow up and care.
Evaluation of the Exposed Individuals
Individuals exposed to HIV should be evaluated within two hours and no later than 72 hours.
A starter pack should be initiated within 2 hours after exposure and before testing the exposed person.
Exposed healthcare workers should be counselled and tested for HIV at baseline in order to establish infection status at the time of exposure.
PEP should be discontinued if an exposed healthcare worker refuses to test. Vaccination against Hepatitis B should be considered.
In addition, rape survivors should be:
- Offered counselling, crisis prevention and provision of an on-going psychosocial support to reduce/minimize immediate rape trauma disorder and long-term post-traumatic stress disorder should be offered.
- Referred to mental care, police and legal services, according to the law and regulations.
Evaluation of the Source Person
Evaluation of the source person should be performed when the exposed individual agrees to take PEP
- If the HIV, HBV and HCV status of the source person is unknown perform these tests after consent from the source person.
- If the source person is unknown, evaluation will depend on other risk criteria.
ARVS used for HIV PEP
A: TDF 300mg+3TC 300mg+DTG 50mg (FDC) (PO) 24 hourly for 4weeks
Children (based on body weight)
A: AZT+3TC+LPVr 12hourly for 4weeks
Children whose weight is more than 20kg, DTG can be used instead of LPV/r and maintain AZT+3TC
If the source is using PI based regimen, then the PEP regimen should be PI based. (Similar to the source’s regimen.)
Follow-up of HIV Exposed individuals
HIV antibody tests should be performed at least after 4-6 weeks’ post-exposure (i.e. at 6 & 12 weeks).
HIV testing should also be performed for any exposed person who has an illness that is compatible with an acute retroviral syndrome, irrespective of the interval since exposure.
If PEP is administered, the exposed person should be monitored for drug toxicity at baseline and 2 weeks after starting PEP.
Minimally, it should include a Full Blood Count (FBC), renal function test (RFT-Serum creatinine & urinalysis) and hepatic function tests (LFT- ALT).
Exposed persons should be re-evaluated within 72 hours, after additional information about the source of exposure including serologic status, viral load, current treatment, any resistance test results (if available) or information about factors that would modify recommendations, is obtained.
PEP should be administered for 4 weeks if tolerated. If not tolerated manage symptoms accordingly and if intolerance persists, change to more tolerable PI based regimen.
If the patient seroconverts. and the exposed person becomes HIV infected, he/she should be referred to a CTC for proper care and treatment service.
Pre-Exposure Prophylaxis (PrEP)
Pre-Exposure Prophylaxis (PrEP) is the use of ARV drugs daily by HIV uninfected persons to prevent acquisition of HIV before the person becomes exposed to HIV.
PrEP is used by people who are at substantial risk for HIV acquisition to lower their chances of getting HIV infection.
Eligible clients for PrEP
- Aged 15 years and older
- HIV sero negative
- At substantial risk of HIV infection
- Creatinine clearance >60ml/min
- No suspicion of acute HIV infection
- Willingness to consent for and use PrEP as prescribed
Substantial risk of HIV infection means:
- Vaginal or anal sex without a condom with more than one partner
- History of a new sexually transmitted infection
- Use of post exposure prophylaxis for sexual exposure
- Has a known HIV positive sexual partner(s) who is not on ARTI on
- ART less than six months or refuses to report a risk category but still requests PrEP
Clients who are not eligible for PrEP include:
- Acute HIV Infection (AHI)
- Client with eGFR <60ml/min
- Significantly mobile persons that will not be able to attend visits as prescribed. For example:
- clients who will not be in a region where PrEP can be provided at the next visit
- clients who do not have contact information
- Unwilling/unable to take daily medication
- Allergy or contraindication to any medication within PrEP regimen.
ARVS used for PrEP
The recommended PrEP regimen is: (See your national guideline)
A: Emtricitabine200mg+Tenofovir Disoproxil Fumarate300mg (PO) 24hourly.
Indications for PrEP discontinuation
Individuals taking PrEP require ongoing risk assessment and PrEP can be discontinued if individuals acquire HIV infection, are no longer at substantial risk for HIV infection or decide to use other effective prevention methods and poor adherence.
Before discontinuation of PrEP, clients should be provided for at least 28 days after the last possible exposure to HIV.
The client should return after completing the final prescription for an HIV test to confirm status. Refer the client to other relevant prevention services.
Notable adverse drug reactions, caution and Contraindications
- Life-threatening skin rash (Stevens
Johnson syndrome); occurs in < 5% ofpatients, usually within 8 weeks oftreatment
- DRESS syndrome (drug rash, eosinophilia and systemic symptoms): manifests as fever, athralgia, etc
- Hepatitis and jaundice reported
- Morbilliform rash may appear; usually not life-threatening
- CNS side effects in about 50% of patients (usually self-limiting)
- Abnormal dreams.
- Abnormal thinking
For these reasons, EFV is contraindicated in patients who already have psychiatric
Foetal abnormalities observed in animal models; efavirenz should not be used in pregnant women or women who might become pregnant while on therapy
Bone marrow suppression resulting in:
- Anaemia with macrocytosis
- Gastro-intestinal intolerance is fairly common: hypersalivation, nausea, abdominal discomfort
- Peripheral neuropathy presenting with painful sensations in the lower limbs more than the upper limbs
- Lactic acidosis with hepatic steatosis
- Stop treatment or switch to a drug less toxic to mitochondria (worse when d4T is used in combination with ddl)
- Peripheral fat atrophy
- Ascending motor weakness resembling
- Guillain-Barre syndrome
- No major side effect but class side effects may occur
- Dose-related pancreatitis; worse when combined with hydroxycarbamide (hydroxyurea)
- Peripheral neuropathy; worse if combined with d4T
- Lactic acidosis (a class adverse effect)
- Infrequent; not more than what is
observed in placebos in controlled trials
- Renal insufficiency and bone demineralization
- Life-threatening hypersensitivity in 3 -9% of patients
- Lactic acidosis with or without hepatic steatosis
- Class-specific events
- Nephrolithiasis with or without
haematuria in 10 – 28% of patients; (fluid intake should be increased)
- Diarrhoea: 10-30% of patients; (should be managed with agents such as loperamide)
- Fat accumulation
Well tolerated except for occasional class adverse reactions:
- Hepatic transaminitis especially in patients with hepatitis B or C
- Fat accumulation
GIT intolerance in 5-30% leading to:
- Abdominal pain
- Class adverse effects
- GIT intolerance; oral paraesthesia in 28% of patients
Oral solution contains propylene glycol which may precipitate:
- Lactic acidosis
- Renal failure
Oral solution is contraindicated in children below 4 years; should be changed to capsules as soon as possible
- Class side effects
- Perversion of taste
- Circumoral and peripheral paraesthesia
- Unconjugated hyperbilirubinaemia
- Gastrointestinal effects
- No effect on lipids
Note: Refer to standard texts for possible drug-drug interactions in all cases.
- A: Abstinence
- B: Be faithful (mutual fidelity to infected
- C: Consistent and correct use of male and female condoms
- D: Delay onset of sexual activity
- E: Examine yourself
- F: Find out your status
Screening and treatment of sexually transmitted infections
- Encourage Partner Disclosure and Voluntary
- Confidential Couple Counselling (VCCCT)
- Promote the rights and protection of children and infusion women.