- HIV, za cause of AIDS is now za 4 th commonest cause of death world-wide.
- In 2000, 34.5 million were infected wz HIV, of whom 24.5 in Sub-Saharan Africa
- The human & economic costs are high because of high mortality & fall in life expectancy.
- Despite that HIV can be isolated from a wide
range of body fluids & tissue, the majority of
infections are transmitted via semen, cervical
secretions & blood.
1- Sexual transmission ( vaginal & anal):
Commonest route & coexistent STDs , sp
those causing genital ulceration, enhance
transmission. Transmission is more efficient
from men to women & to za passive partner
in anal intercourse.
2- Mother to Child (vertical): Commonest route in children. Transmission occur during pregnancy,
during delivery or after delivery through breast feeding. Most infections occur perinatally. Advanced dis. & high viral load in the mother, prolonged & premature rupture of membranes & chorioamnionitis increase za risk of transmission.
Interventions to reduce transmission include use antiretroviral agents, delivery by CS and avoidance of breast feeding.
3- Contaminated blood, blood products & organ
donations if not screened.
4- Contaminated needles & instruments . The risk
of acquiring HIV following a single needle-stick injury contaminated wz HIV is 0.3%.
*** No evidence of HIV transmission by social or household contact or by blood sucking insects.
- HIV belongs to retroviral family .
- 2 types: HIV-1 & HIV-2 ( West Africa. ? India).
HIV-2 is more indolent in nature.
- RNA virus & needs a living cell to multiply.
-The target cells for HIV are CD4 T-lymphocytes
1- HIV binds to za host CD4 via za envelope glycoprotein ( gp120 )
2- Reverse transcriptase converts viral RNA to ssDNA and host cell polymerase leads to formation of dsDNA which enters za nucleus of CD4 & inserted into its genome via integrase .
3- With za help of za protease enzyme new viral particles are assembled in za cytoplasm and are budded out of za cell ready to infect other CD4 cells.
- Virus production lasts 2 days & is limited by the death of za cell due to direct effect of za virus. The half life of za virus is only 6 hrs, but its
turnover is very high (10 to za power 9 each day) - Immunosuppression is due to progressive and severe depletion of CD4 T-lymphocytes causing both CM & humoral immune def.
- HIV also has a direct effect on za nervous tissue, lymphoid tissue & testes.
Diagnosis of HIV infection
1- Detection of virus specific Abs:
a/ Abs to gp 120 : - detects Abs against envelop glycoprotein gp 120
- Routine test for screening & based on ELIZA .
- Window period or serological latency is 3/12
- Abs have no protective fn & persist for life.
- Abs cross za placenta & not reliable indicator of active infection in za baby & in uninfected babies will be gradually lost over za 1 st 18/12 of life
- b/ Abs to p24 ( core protein): detected early
in infection & lost as dis progresses.
2- Ag assays by : a/ HIV DNA PCR assay : used in diagn of HIV in babies borne to infected mothers & in the
b/ HIV RNA PCR assay : superseded za above test.
It measures za amount of HIV RNA in za blood
( viral load ). Higher viral load is predictive of
faster dis progression. This test is also used to
assess za response to anti-viral therapy .
The viral load can also be measured by c/branched DNA tehneque .
3- Western blot :
- confirmatory test
- detects Abs against Ag coded by 3 diff viral
4- Isolation of virus in culture for research.
*** NACO guidelines for diagn HIV infection is based on 3 diff ELIZA/rapid tests using 3 diff Ags. AIDS is diagn by using 2 diff ELIZA/rapid
tests on diff Ags in za presence of AIDS-related
Clinical features of HIV infection
- It is za result of both direct HIV infection and associated immune dysfn .
- AIDS is defined as individuals wz CD4 < 200 with AIDS defining conditions in USA while in Europe it is defined without CD4 level. Both need positive HIV test .
- IP is 2-4Ws immediately following infection and is both clinically & serologically silent.
1- Primary HIV infection/ seroconversion
2- Asymptomatic infection/clinical latency
3- Symptomatic infection (ARC)
Acute pry infection CD4>500/microlit . Asymp infection CD4 200->500 Symp infection (ARC) CD4 200-500 AIDS CD4 <200 Acute seroconversion Illness in some pts. PGL in some pts. Oro/vulvovaginal candidiasis, ITP, P. neur Hairy leukopl, constitutional symp (fever, Diah > 1/12, mucocutaneous manifestation Constitutional symp ( Wt loss> 10%, Diah >1/12), neurological dis (dementia, myelopathy, P, neuropath), Kaposi's, NHL and Opportunistic infections .
** Seroconversion illness is a self-limiting non-sp
- Decrease za incidence of opportunistic infections.
- Reduce dis progression
- Prolong survival & improve quality of life.
- Possibly reduces za risk of transmission
** The goal of antiretroviral therapy is to bring down za viral load to <50 by triple drug therapy over Ws & Ms.
Classes of antiretrovirals
Antiretrovirals target two key enzymes, protease
and reverse transcriptase:
1- Reverse transcriptase inhibitors
a/ nucleoside reverse transcriptase
b/ non-nucleoside reverse transcriptase
inhibitors (NNRTs) 2- Protease inhibitors (PIs)
NRTIs NNRTIs PIs
Zidovudine Nevirapine Indinavir
Stavudine Efavirenz Nelfenavir
Lamivudine Delavirdine Ritonavir
When to initiate antiretrovirals?
1- Asym pts = CD4 goes below 350 or HIV RNA
above 30-55000 copies/ml
2- All sym pts irrespective of CD4 count or plasma viral load.
- 3 drugs should be used in combination to prevent drug resistance ( HAART).
- Initiate therapy using: a-2 NRTIs with either one PI or one NNRTIs e.g
Zidovudine + Lamivudine + Indinavir
Stavudine + Lamivudine + Nevirapine
b- 2 PIs + 2 NRTIs, but za following NRTIs
combinations should be avoided because of
antagonism or overlapping toxicity
Zidovudine + Stavudine
Zalcitabine + Stavudine or Didanosine
How long should za HIV-infected pt
continue taking antiretrovirals?
- Antiretrovirals should continue indefinitely
because they are only suppressive and not
- The pt should be committed to lifelong therapy.
- The virus remain latent in za long lived resting
memory CD4 cells & antiretrovirals are not
effective against these cells which are not
Follow up of HIV +ve patients using antiretroviral therapy
Follow up pts regularly every 3-6/12 by monitoring:
- CD4 counts
- Viral load using HIV RNA PCR test
- Clinically: look for Wt gain & reduction in the No of opportunistic infections.
- Adherence (drug combin)
- Drug interactions
- Drug side effects - Drug access.
Before initiating antiretroviral therapy discuss
following points wz za pts
- Therapy is only suppressive but za pt can lead
healthy productive life.
- Long life therapy
- Drugs free or at low cost
- Side effects & drug interactions
- The NO of pills taken is large, but can be reduced by combination therapy
- Avoid blood donation. Protected sex.
2- Treatment of common opportunistic infections
1- Tb = Anti-Tb drugs + ciprof in resist. cases
2- MAC = Azith + ETB +/- RIF
3-Oropharyngeal candidiasis= topical anti-fungal
4- Oesophageal or tracheal candidiasis= system
ketoconazole or fluconazole
5- Herpes simplex/Zoster= Acyclovir
6- CMV retinitis= Ganciclovir
7- Pneumocystic carinii= Co- trimoxazole
8- Toxoplasmosis= pyrimeth & sulfadiazine
9- Cryptococcal meningitis= Amph-B + flucytosin
OR Fluconazole + flucytosine & maintain on fluconazole
10- NHL= Chemotherapy
11- Kaposi's sarcoma= Chemotherapy depending on za extent of za dis.
12- Diarrhoea due to:
- Salmonella/ shigella= Ciprof, Co- trimoxazole
- Campylobacter= erythro/ Azith
- Clostridium difficile= metronidazole
- Amoeba & giardia= Metronidazole
- Isospora= Co- trimoxazole
- Stronyloides= Mebendazole
- CMV= Ganciclovir
- HSV= Acyclovir
- VL= SSG.
Pediatric HIV infection
- ELIZA testing is reliable only after za age of 18/12 since maternal Abs cross za placenta.
- HIV DNA PCR is recommended for diagn in children < 18/12 .
- Antiretroviral therapy is recommended in all children wz clinical symptoms or evidence of immune suppression regardless of age or viral
- In asym children <1 year start TR soon after diagn regardless of clinical or immune status or viral load.
- In asym children aged 1 year or above, start TR immediately or defer if immune status is normal wz regular follow up.
- triple therapy is recommended.
Maternal transmission of HIV
- It is za pry means for infants infection
- The risk is 7-40%. 50-70% of transmission occur in late pregnancy or during labour and delivery.
- Transmission occurs in utero, during labour and delivery or via breast feeding.
- Increased risk of maternal HIV transmission is associated with:
- high maternal viral load - low CD4 count
- advanced clinical dis - pry infection
- chorioamnionitis - mode of delivery - - >4 hr ruptured membr. - breast feeding
- Decrease risk of transmission by :
- Prophylactic antiretroviral therapy for mother and child to prevent maternal HIV transmission
- Use of formula feeding reduces risk of transmis
via breast milk as delivery by CS.
** Zidovudine & nevirapine are effective
Post-exposure prophylaxis for healthcare personal (PEP)
- Contact wz blood or bloody fluids or other potentially infectious fluids (CSF, synovial, pleural, pericardial and amniotic fluid) from HIV +ve pts is hazardous
- The risk of infection after percutaneous exposure is 0.3% & depends on za size & type of needle, depth & severity of exposure, volume of blood involved & viral load of pt. The risk after mucus membr exposure is 0.09%