HIV Infection - A brief note

This web-page is massively out of date, but we've retained it more or less out of historical interest.


The brilliant identification of the human immunodeficiency virus just three years after the clinical description of the Acquired Immune Deficiency Syndrome (AIDS) has unfortunately been marred by scruffy squabbles between the discoverers, and more recently by certain misguided scientists (with the help of the ignorant British lay press) questioning the causal association between HIV and AIDS. The fascinating biology of the virus has now been rather clearly elucidated, although some details still remain to be filled in. HIV is trophic for T lymphocytes, specifically those bearing the T4 receptor, although this receptor alone is not sufficient to allow the virus entry into T4-bearing cells. Because it is a retrovirus, HIV can integrate into the genome of the host (using the virus-supplied enzyme reverse transcriptase). This has tremendous implications for therapy, as one can never really be sure that, even if we appear to have eliminated the virus from the host, there is not a single copy lurking somewhere in some obscure cell, waiting to re-emerge and wreak havoc once more. The problem is compounded by the lack of proof-reading of viral transcripts. Normal cells check (proof-read) transcripts, eliminating mutant nucleic acids, but retroviral copies don't undergo this check, allowing HIV to mutate at a ferocious rate. This explains why, when an anti-retroviral drug is given in an attempt to control HIV, resistant mutants appear literally within days - some mutants are bound to arise that are resistant to the single drug. It also provides the rationale for combination therapy, which should hit the virus at several points, making emergence of resistant mutants less likely.

Unfortunately, in common with many of humanity's most vicious scourges, HIV is predominantly a disease of the poor and repressed. The majority of new cases are occurring in sub-Saharan Africa, where in some areas prevalence may be 30% of the population, but HIV is still spreading unchecked in other poor countries as well, especially in Asia. It is perhaps fortunate for researchers into the disease that the American (and indeed worldwide) homosexual community which initially seemed to be bearing the brunt of the illess has been so vocal in drawing attention to HIV, as vast amount of research funds have been poured into investigating HIV biology and finding therapeutic agents, but unfortunately all therapies, especially combination therapy is financially prohibitive for the vast majority of those afflicted with HIV.

Viral Properties

HIV-1 is a plus sense, single-stranded RNA virus, one of the lentiviruses, and vaguely related to other human retroviruses such as HTLV-1 (which is associated with adult T-cell leukaemias, and tropical spastic paraparesis). The viral core contains the vitally important reverse transcriptase which makes a DNA transcript of the RNA, as well as structural proteins, the most prominent of which are p24 (capsid) and p18 (matrix) proteins. Not content with hijacking the host genome, the virus also sneaks off with a lipid envelope derived from the host cell, but studded with two glycoproteins (gp120 and gp41) which are necessary for binding to T4 receptors and entry into host cells. The complex genome contains the three standard retroviral genes needed for replication (gag, pol and env), as well as at least six other regulatory genes. Of great significance is a viral protease, which is necessary to convert some key viral proteins to active forms.

Unfortunately for humans, T helper lymphocytes are not the only cells expressing T4 receptors - they are also found on monocytes, macrophages, and particularly, Langerhans cells in the skin. Even worse, certain central nervous system cells such as microglia express the receptor, giving the virus a tropism for the nervous system that practically ensures a long-term reservoir for the virus, even if it has been eliminated on the other side of the blood-brain barrier. Early infection of the central nervous system is thought to occur in many (perhaps most) infected individuals.

HIV progressively incapacitates the immune system by destroying T-helper cells. This affects every branch of immune system, resulting in opportunistic infection by a host of bacteria, parasites and viruses, as well as allowing tumours to proliferate in the affected person. Initial infection is commonly associated with an "acute viral syndrome" of fever, lymphadenopathy, pharyngitis and sometimes rash. There may be mild features of meningeal inflammation. It is at this time that individuals are perhaps most infective, with up to ten million virions per millilitre in their peripheral blood. Unfortunately, they initially show no evidence on antibody testing of HIV, so this highly infective stage might be missed were they unwise enough to, for example, donate blood after initial infection. There is a strong suggestion that those individuals who have the highest initial levels of virus infection progress more rapidly to immunodeficiency, which will develop within about a quarter to a third of infected individuals in the first seven years after infection. Even in asymptomatic individuals however, there is an ongoing and uneasy balance between the rampant proliferation of the virus and attempts by the body to maintain immune competence.


The first cases were reported from Los Angeles (and soon afterwards from New York) in 1981. Initially homosexual men and intravenous drug abusers appeared to be the target populations, but we now know that they represent a small subset of an enormous global population, most of whom are heterosexual.

Transmission is first and foremost sexual. Certain associations are common, notably other sexually transmissible diseases (especially Haemophilus ducreyi [chancroid] in African populations). In homosexual males, receptive anal intercourse is the major risk factor. Any exposure to HIV-infected semen or blood is a risk factor, and a vast number of haemophiliacs and other recipients of blood products worldwide have acquired the virus. Trans-placental and more importantly, perinatal infection is extremely common (the risk of infection of the infant being about 1 in 6, rising to 1 in 3 if the infant is breast fed post-natally).

Transmission to health-care workers is well documented, the overall risk being about 3 per 1000 needle-sticks, but substantially higher if viral titres are high in the source patient, if visible amounts of blood are found on the needle, with deep injuries, or if a hollow-core needle was involved. Rare infections have been reported with mucosal or even extensive skin exposure! Up to 40% of documented needlestick injuries were considered "preventable".

Prevention of HIV

The most important method for preventing HIV transmission is sexual abstinence or fidelity to one partner. Condoms help with prevention but failure of condoms to prevent pregnancy is common and similarly failure to prevent transmission of HIV is possible. The dangers of needle sharing by IV drug abusers are obvious. Transmission by blood transfusion should now be rare in developed countries where screening occurs. Health care workers should observe "universal precautions" to prevent transmission - any person should be regarded as a potential source of HIV infection. The following are important:

The development of an HIV vaccine seems years away, and will be technically extremely difficult to accomplish.

Organ Systems affected by HIV

Each and every organ system in the body may be affected by HIV, often directly, but even more frequently by opportunistic infections and/or malignancies. These include:

Pulmonary Problems

Commonest by far are Pneumocystic carinii pneumonia, and Mycobacterium tuberculosis infection.

Neurological Complications

Gastrointestinal HIV manifestations

AIDS is commonly accompanied by substantial GIT morbidity, including:

Haematological & Oncological problems

Renal Disease

Apart from the frequent electrolyte disorders encountered in advanced AIDS, a variety of renal diseases is seen, including the specific entity "HIV-associated nephropathy", which shows focal segmental glomerulosclerosis as its characteristic lesion. Nephrotic syndrome is common, followed by rapid progression to florid renal failure, responding poorly to therapy.

Cardiac Problems

These are common at autopsy but often missed clinically, and include myocarditis (possibly due to the virus itself), marantic endocarditis, and pericarditis (for example, tuberculous pericarditis).

Endocrine and Metabolic Disorders

Often clinically silent apart from hypogonadism, endocrine manifestations are not commonly identified antemortem. In contrast, electrolyte disturbances are common, and wasting is prevalent and has a major impact on morbidity and mortality.

Rheumatological Disease

A host of rheumatological disorders is seen, ranging from mild arthralgias and myopathies, to debilitating arthritis, the "painful articular syndrome" on starting zidovudine, polymyositis, and Reiter's syndrome in up to 10% of HIV-infected persons with arthritis. Vasculitides and Sjogren's syndrome also occur.

The skin and AIDS

Cutaneous involvement is common, including a transient roseola-like rash with initial infection, superficial infections with dermatophytes, candida and scabies, molluscum contagiosum, papilloma virus infections including condylomata acuminata, zoster, disseminated herpes simplex, a variety of cutaneous fungal and mycobacterial infections, bacillary angiomatosis (Rochalimaea henselae), and of course Kaposi's sarcoma. The above list is not comprehensive, and newer and more unusual skin problems continue to be identified.


There are two main components: diagnosis of HIV itself, and diagnosis of complicating disorders, especially opportunistic infections. We will here only consider diagnosis of HIV infection itself. This must always be seen in the clinical context: is there evidence of immune compromise, and/or opportunistic infection or malignancy? HIV infection is commonly diagnosed using antibody detection (ELISA or agglutination). False positives may occur, although currently licenced ELISAs have over 98% sensitivity and specificity, so confirmation is most desirable, using for example western blot (immunoblot) techniques, [Postgrad Med 1995 Nov;98(5):177-180 ], or further specific tests such as competitive ELISA. All of the above detect antibodies to HIV.

"Third-generation" ELISA assays that can detect anti-viral IgM and IgA have considerably narrowed the "immunological window".

Fairly recently, nucleic-acid-based assays have emerged: these allow for detection in the newborn (who may have maternal antibodies that confuse the issue), characterisation of strains, and monitoring of response to therapy. [See Gurtler L: Lancet 1996 348(9021) pp176-179 ] Polymerase chain reaction is commonly used.

p24 core antigen assay is also available, but is far less sensitive in detecting HIV infection than is nucleic-acid based amplification [e.g. Sitnik & Pinho: Mem Inst Oswaldo Cruz 1998 May;93(3):411-415 ] Newer ELISAs for antigen detection, for example the enzyme-linked amplified sorbent test (ELAST), can detect down to the equivalent of 330-1000 RNA copies/ml of blood. [Goldschmidt PL et al, Clin Diagn Lab Immunol : Jul 1998 5(4) pp513-518 ]

New "fourth-generation" ELISAs have also been developed that allow for simultaneous detection of HIV antigens and antibodies! [ Weber et al, J Clin Microbiol : Aug 1998 36(8) pp 2235-2239 ]

Note that EDTA blood is best suited for quantification of plasma viral load.

Prophylaxis after needle-stick injury

The risk of infection after percutaneous HIV exposure is about 0.3% (95% confidence interval 0.2 - 0.5%). Putting this in perspective, this is similar in magnitude to the risk after a single episode of receptive anal intercourse with an HIV positive male. Transmission to health-care workers has been documented even with undetectable levels of virus in the source patient, suggesting that one should give post-exposure prophylaxis (PEP) wherever risk of HIV transmission exists. Zidovudine monotherapy confers about 80% protection against infection; current recommendations are that at least two drugs be given (and possibly 'triple therapy' where the risk is extreme). [ See MMWR May 15 1998 47 RR-7 pp1-33 ]

Median time to seroconversion is 46 days, but median time to symptoms compatible with primary infection is only 25 days. Rarely, seroconversion may be delayed by up to 12 months or more, but it is usually in under six months, if it is going to occur.

In summary, the following regimen is probably acceptable:

  1. Wash the wound site; DO NOT apply caustics..

  2. Assess risk rapidly - when in doubt, start PEP.
  3. Start post-exposure prophylaxis as soon as possible, ideally within half an hour; A recent MMWR report suggests determining an "exposure code":
  4. Once have EC status, determine HIV status code ("SC"):

  5. THEN, if EC1 AND SC1, possibly don't give PEP
  6. IF EC1 + SC2, consider basic regimen
  7. IF EC2 and SC1, recommend basic regimen
  8. If EC2 and SC2, recommend expanded regimen
  9. If EC3, recommend expanded regimen.

  10. Basic Regimen: Use zidovudine (a nucleoside reverse transcriptase inhibitor=NRTI) 600mg/day (divided into 2 or 3 doses); AND another "NRTI": preferably lamivudine (3TC) 150mg BD OR possibly didanosine (ddI) or zalcitabine. The combination of ZDV + 3TC (Combivir) is available and given as 1 tablet BD (300mg ZDV + 150mg 3TC per tablet).
  11. Expanded regimen: With high-risk exposure, add a protease inhibitor(PI) such as indinavir 800mg 8 hourly OR nelfinavir 750mg 8 hourly. (If saquinavir is used, use the soft-gel formulation in the large dose of 1200mg TDS = 6 pills TDS).

  12. Compliance for four weeks is vital. This may be a problem as side-effects are common, especially GIT side effects.
  13. Be aware of drug interactions and side-effects, notably:
  14. ZVD + 3TC appears safe in pregnant women. We don't know about PIs.
  15. Counsel the health-care worker;
  16. Report the incident, including date, time, details of exposure, details of source, and of couselling, post-exposure management and follow-up. Follow-up testing should be done at least at 6 weeks, 12 weeks, and 6 months. Monitor for PEP toxicity.
  17. Also follow up & manage risk of other agents such as hepatitis B and C;
  18. Read the full MMWR report, and keep up to date with new developments in post-exposure prophylaxis.

Treatment of HIV infection

The mainstay of therapy is use of combinations of expensive agents. Three (or more) agents acting in different ways are combined to try and reduce serum viral load to undetectable levels (which means, using current technology, about 100 or fewer virions per millilitre of blood). Unfortunately, prior use of single agents predisposes to viral resistance. Current guidelines for treatment of early HIV infection recommend the use of three drugs (two nucleoside reverse transcriptase inhibitors and a protease inhibitor) [ MMWR 1997 46 RR-5 pp43-82 ]

Available agents include:

Prevention of opportunistic infection is extremely important.


This virus, originally found in West Africa and now spreading worldwide is only 40-50% similar (on a genomic basis) to HIV-1 but it causes similar clinical disease. HIV-2 appears to be less agressively pathogenic that HIV-1 causing immunosuppression over a longer period of time. Most of the registered tests for HIV-1 detect this virus with greater or lesser efficiency, but few seem to approach 100% sensitivity!