HIV Infection

Introduction

HIV (Human immunodeficiency virus) is an enveloped, single-stranded RNA virus that was recognized as the causative agent of AIDS (acquired immune deficiency syndrome).

If HIV is left untreated, the virus will cause progressive weakening of the immune system, a process which occurs at different rates in different people.
2 types of human HIV exist: HIV-1 and HIV-2. HIV-1 has worldwide distribution, whereas HIV-2 infection is endemic in West Africa.

NOTE: AIDS is diagnosed if the CD4 cell count is <200 or <14% of total lymphocyte in the presence of proven HIV infection, even in the absence of other infections.

Risk for HIV

HIV infection is usually acquired through sexual intercourse or exposure to infected blood or body fluids. This may occur

During sexual contact with a person with HIV, especially if you have unprotected vaginal or anal sex.
By sharing needles or syringes used by a person with HIV.
People who received a blood transfusion or other blood products before 1984.

Transmission from a pregnant woman to her baby may occur during pregnancy, birth or breastfeeding, although this is uncommon with the use of HIV medications during and after pregnancy.

Breast-feeding is not recommended as it is associated with risk of transmission up to 14% in those who are not virally suppressed. This risk reduces to 1% if the woman is virally suppressed.

NOTE: HIV infection is NOT spread by casual contact.

Treatment

Development of antiretroviral therapy (ART) have transformed HIV infection from an almost universally fatal illness to a chronic disease.

However, ART cannot eradicate HIV from the human body nor cure HIV infection.
Hence, it will be a life-long treatment.

Previous practice of ART initiation includes extensive patient preparation prior to starting ART. However, evidence from clinical trials have shown significant benefits of rapid ART initiation (within 7 days of diagnosis).

Rapid ART initiation or same day ART initiation should be offered to all patients with HIV infection, regardless of CD4 count.
Rapid ART initiation should be prioritised for individuals with

Advanced HIV disease (e.g. low CD4 count, symptomatic disease, or high risk of disease progression)
Pregnancy or breastfeeding
Acute HIV infection

Temporary delay of ART may be considered in the following circumstances.

Suspected or confirmed central nervous system opportunistic infections, particularly cryptococcal meningitis or tuberculosis meningitis, due to the risk of immune reconstitution inflammatory syndrome (IRIS).
Severe co-morbid conditions requiring stabilisation prior to ART initiation (e.g., uncontrolled renal or hepatic disease that may affect ART selection).
Significant psychosocial or structural barriers that may compromise adherence and require urgent intervention before treatment initiation.

The timing of ART initiation in HIV patients with opportunistic infections should balance the benefits of early viral suppression and immune recovery against the risk of immune reconstitution inflammatory syndrome (IRIS) and treatment-related complications.

Timing should therefore be individualised according to the type of opportunistic infection, clinical response to treatment and relevant monitoring parameters.
For most OIs, ART should be initiated early within 2 weeks, except in Cryptococcal meningitis and TB meningitis.

Once ART is started, it should be taken for the rest of the life.

An adherence to ART of 95% or more is believed to be the requirement to achieve optimal viral suppression.
Taking ART drugs inconsistently (e.g. missing doses) can sometimes lead to development of viral resistance.

First Line ART

An antiretroviral regimen for a treatment-naive patient generally consists of 2 NRTIs (e.g. tenofovir, emtricitabine, abacavir, lamivudine, zidovudine) in combination with a third agent:

Integrase inhibitor (e.g. dolutegravir, raltegravir)
NNRTI (e.g. efavirenz, nevirapine)
Protease inhibitor (e.g. lopinavir plus ritonavir, atazanavir plus ritonavir)

NOTE: Quadruple combination therapy has been found to be no more effective than triple combination therapy with currently available drugs.

At the end of year 2019, the Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV has updated its guidance to include a two-drug regimen (dolutegravir 50 mg plus lamivudine 300 mg OD) as an initial treatment option for most people with HIV infection, except for individuals with HIV RNA >500,000 copies/mL, hepatitis B coinfection, or in whom ART is to be started before the results of HIV genotypic resistance testing for reverse transcriptase or hepatitis B testing are available.

The recommendation is based on two large, randomised controlled trials that showed that dolutegravir plus lamivudine was not inferior to dolutegravir plus tenofovir plus emtricitabine.
This two-drug regimen avoids tenofovir-associated renal and bone toxicity and may be considered for selected treatment-naive HIV patient.

Therapy Goals

The primary goals of initial ART in treatment-naive HIV patients are to achieve sustained viral suppression, restore immune function, reduce HIV-associated morbidity and prevent onward sexual transmission (Undetectable = Untransmittable).

Undetectable=Untransmittable (U=U) concept: A person living with HIV who has undetectable viral load does not transmit their HIV to their partners.

Treatment outcome may be measured from three aspects:

Clinically by the reduction in the number and frequency of opportunistic infections (OIs) and improvement of general wellbeing
Immunologically by gradual and steady rise in CD4 T-cell counts
Virologically by a decrease in viral load (VL), ideally to undetectable level at six months after initiation of treatment (undetectable is defined as VL <20 copies/ml)

Treatment failure

HIV viral load is more accurate and reliable than CD4 cell counts to monitor treatment response and for early detection of treatment failure.

Effective therapy should generally result in a 10-fold (1.0 log10) decrease in HIV-1 RNA copies/ml in the first month and suppression to less than 200 copies/ml by 6 months.

Viral "Blips"

Defined as isolated transient rises in viral load to above detected level while on treatment after having achieved prior viral suppression and is followed by re-suppression.
The levels generally do not exceed 200 copies/ml.
It may reflect technical variations in laboratory assay performance, or biological events associated with viral replication.
Isolated "blips" are not associated with subsequent virologic failure.

Low Level Viremia

Defined as persistently low, but detectable viral load in the range of 50-1000 copies/ml.
Evidence shows that incomplete viral suppression leads to the accumulation of resistance, mutations with a concomitant increase in viral replication, reduction in CD4 cell counts, increased risk of virologic progression and clinical deterioration.
Patients experiencing LLV require reinforced adherence, close monitoring (e.g. with viral load testing) and treatment switch.

Virologic Failure

The optimal threshold for defining viral failure and for switching ART regimens has not been established.
WHO defines virologic failure by a persistently detectable viral load exceeding 1000 copies/ml (that is, two consecutive viral load measurements within 3-month interval with adherence support between measurements) after at least 6 months of starting a new ART regimen.

In the management of virologic failure, viral resistance testing is recommended.

Prevention of Mother-to-Child Transmission

Antenatal combination antiretroviral therapy (ART) is the recommended for prevention of mother-to-child transmission (PMTCT).

For women who are stable on ART before pregnancy, the existing ART is to be continued throughout pregnancy and after delivery, unless taking a regimen that is contraindicated in pregnancy.
Achieving HIV viral suppression by the third trimester reduces the risk of transmission to 0 to <0.5%.
Preferred choice for ART 1st line regimen is TDF/FTC + DTG or TDF/3TC/DTG.

Intrapartum intravenous zidovudine infusion (2 mg/kg for the 1st hour followed by 1 mg/kg/h subsequently until delivery) is recommended for women with a viral load of >50 copies/ml or unknown viral load, or positive rapid test during labour.

Give IV AZT infusion starting at labour onset or ≥3 hours before elective caesarean.
For HIV VL 50-1000 copies/ml, IV AZT may be considered (case-by-case; consider adherence, recent viral trends).

Vaginal delivery is acceptable for VL ≤50 copies/ml with continued ART.

In women who had not achieved maximal viral load suppression, pre-labour elective caesarean section (PLCS) has been proven to further reduce the risk of transmission.
For VL >50 copies/ml, elective caesarean is recommended at 38 weeks gestation.

Breastfeeding is associated with risk of transmission up to 14% in those who are not virally suppressed.

The risk reduces to 1% if the woman is virally suppressed.
Formula feeding remains the recommended option to eliminate HIV transmission risk.

Breastfeeding on ART may be considered under shared decision-making, particularly where safe formula feeding is not feasible, provided under these stringent circumstances:

Maternal viral suppression is sustained.
ART adherence is reliable.
Viral load is monitored regularly every 3 months.
Appropriate infant prophylaxis and testing are ensured.

Management of babies born to HIV infected mother

Children born to HIV positive mothers are usually asymptomatic at birth. However, all will have acquired maternal antibodies.
In uninfected children, antibody testing becomes negative by 10-18 months age.

Occupational Post-Exposure Prophylaxis (PEP)

The risk of HIV transmission is approximately 0.3% after a percutaneous exposure to HIV-infected blood and 0.09% after mucous membrane exposure.

PEP is recommended following a high-risk injury if the index case is known to be HIV-positive and is not on ART for >6 months with a suppressed viral load within the last 6 months.

PEP is most effective when initiated as soon as possible, ideally within 24 hours and no later than 72 hours after exposure.

Preferred regimen: TDF/FTC + DTG, or TDF/3TC/DTG
Alternative regimen: TDF/FTC + LPV/r, or AZT/3TC + LPV/r

The duration of PEP should be 28 days. PEP should be discontinued immediately if an HIV test on the source is found to be negative, unless the source is considered to be at higher risk of recent infection (i.e. within the HIV window period).
Occupational exposure to an unknown source (e.g. a needle in a sharps disposal container) creates challenges for post-exposure management because the HIV risk is not known. The decision to give PEP has to be individualised depending on the HIV epidemiology risk profile and nature of exposure.

During the 12 week follow up period, HIV-exposed healthcare workers should be advised to use condoms to prevent potential sexual transmission, avoid pregnancy and breast feeding in female HCWs and refrain from donating blood, plasma, organ, tissue or semen.

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