INTRODUCTION
AIDS (Acquired Immunodeficiency Syndrome) represents the late clinical stage of infection with HIV (Human Immunodeficiency Virus). The AIDS with all manifestations combined, it is called AIDS syndrome was first recognized in 1981, but probably it had existed at low endemic level in Central Africa before the epidemic spread to several areas of the World during 1980s.
The presence of a new type of viral infection that could progressively destroy the immune system was first suspected in 1981, in USA, when there was sharp increase in the number of reports of opportunistic illness Pneumocystis carinii pneumonia (PCP) and Kaposi's sarcoma in relatively young, previously healthy homosexual males and a comparable increase in the number of cases of PCP in young children of mothers who were injection drug users (IDUs). In 1983, hemophiliacs who had received transfusions of factor 8 were identified as a third group in whom incidence of immunodeficiency and PCP was increasing. Further investigations led to the discovery and isolation in 1983 of the pathogen responsible for AIDS, the human immunodeficiency virus (HIV). Since then, this retrovirus has been detected in more than 99 percent of patients diagnosed with AIDS.
CHARACTERISTICS OF HIV
HIV attacks the immune system as a lentivirus, a subfamily of the retroviruses. By definition, retroviruses are RNA viruses that contain the reverse transcriptase enzyme. Reverse transcriptase 2catalyzes the synthesis of DNA from an RNA template. As its name implies, reverse transcriptase causes the “reverse” of the usual transcription process, which involves the synthesis of RNA from a DNA template.
Following infection with the HIV virus, the viral reverse transcriptase produces a haploid double standard DNA provirus. This provirus gets inserted into the chromosomal DNA of the host cell. Once it is integrated, the provirus may remain latent, especially in resting lymphocytes. However, if the cells are activated, transcription and translation occur, allowing the assembly of viral proteins necessary for the production of virions that are released to infect other cells. HIV has a high replication and a high mutation rate, hence a patient may harbour a number of variants, which may pose problem for vaccine development and antiretroviral therapy.
Figure 1.1 shows the organization and structure of the HIV genome and virion. As with other retroviruses, HIV-1 contains the three key coding regions pol, gag and env. Pol encodes reverse transcriptase, integrase and protease, which are necessary for replication for HIV-1. gag encodes the capsid proteins. Env encodes for the external glycoprotein that attaches to cell receptors to initiate infection. Other proteins encoded for by HIV-1 regulate gene expression, promote propagation of the virus and increase the complexity of the virus.
Some of the major HIV-1 proteins include gp120, gp41, p16/p14, p19, p27/p25, and p24. The gp120 and gp41 proteins are external envelope proteins that bind to the receptors of CD4 cells. These proteins are found in the plasma membrane and envelope region of the virus. The p16/p14 “Tat” proteins, found mostly in the nucleus and nucleolus of infected cells function as an activator of viral transcription. The p19 rev protein is responsible for the transport and stability of viral RNA. This protein travels between the cytoplasm and the nucleolus of the infected cell. The p27/p25 nef proteins are active in the down-regulation of CD4 cells. They reside in the plasma membrane as well as the cytoplasm. The p24 gag protein functions in the core capsid and is found in the virion. Molecular epidemiologic data indicate that there are two subtypes: HIV type 1 (HIV-1) and type 2 (HIV-2). Both infections were zoonotic in origin.3
Fig. 1.1: (a) Schematic drawing of the HIV life cycle; (b) Antigenic structure of HIVSource 1: Guidelines, Govt. of India, Ministry of Health and Family Welfare
NATURAL HISTORY OF HIV
HIV infection is characterized by 3 phases as given in Figure 1.2: acute (primary) infection, latency, and chronic infection (including development of symptomatic disease and, eventually AIDS). Acute infection (acute seroconversion) occurs soon after a person has been affected with the virus. During this phase, HIV levels in plasma are high; immune response is active and usually sufficient to reduce the amount of virus in the circulation and shift it into the lymphatic system. Cytotoxic cells, complement, and neutralizing antibodies are activated in the acute infection phase, although neutralizing antibodies do not reach detectable levels for 2–3 months after infection. This period is known as “Window period” and persons tests negative by ELISA. Patients frequently (i.e., about 30 percent of the cases) present with a viral syndrome consisting of fever (97percent of cases), adenopathy (77 percent), pharyngitis(73 percent), rash (70 percent), and myalgia or arthralgia (58 percent).
Fig. 1.2: Typical course of HIV infection in persons who receive no treatment. Following primary infection, a chain of events occurs over the next decade of the person's life. Widespread dissemination of HIV in peripheral blood accompanied by an abrupt fall in CD4+ T lymphocytes; a clinical latency period lasting about 5 years; further declines in CD4 cells marked progressively by constitutional symptoms, opportunistic diseases and deathSource 1: Guidelines, Govt. of India, Ministry of Health and Family Welfare
During the clinical latency phase of HIV infection, outward clinical signs and symptoms are absent. Nevertheless, viral replication continues unabated within the lymphatic system. The patient's immune system responds to the virus, resulting in increased lymphocyte production. However, the immune system eventually begins to break down, and plasma virus levels rise as a consequence.
In the chronic infection phase, there is progressive, symptomatic clinical disease due to severe immune dysfunction, elevated plasma HIV levels, and decreased CD4 lymphocyte cell counts to below 200/cumm3.
HIV-1 compared to HIV-2 is associated with a higher mother-to-child transmission rate (20–35 percent vs 0–4 percent), attacks a younger age group (peak age 20–34 years vs. 45–55 years), and produces higher mortality (10-fold vs. twofold). The lower efficiency of heterosexual transmission of HIV-2 is also believed to be due to lower concentration of this virus type in cervicovaginal secretions.
MODES OF TRANSMISSION OF HIV
HIV infection is spread by sexual intercourse, injecting drug use, prenatal transmission, transfusion of blood and blood products, organ transplantation, and occupational exposure to HIV-contaminated blood or body fluids. The likelihood of infection after a single exposure by the various routes is given in Table 1.1 and the amount of virus isolated from various body fluids, inside the cells or as cell free virus particles are given in Table 1.2.
Sexual Transmission
Largest number of cases in the world have been observed to be via the sexual route. Unprotected receptive anal/vaginal intercourse is the most effective mode of the sexual transmission of HIV. Among MSM, the biggest HIV risk factor is a combination of receptive anal intercourse and a high number of male sexual partners. History of anogenital rectal gonorrhea or other ulcerative STDs like Hepes simplex, syphilis and rectal trauma enhance the chances of transmission.
Vaginal penile heterosexual intercourse is not a very efficient mode of HIV transmission especially from infected women to a man but the efficiency is higher from male to female by sexual mode.6
The chances are higher when other well defined risk factors are also present like multiple sex partners, presence of STD's e.g. genital ulcers (allowing direct exposure to HIV laden blood), engaging in receptive anal intercourse and sex with persons from areas of high HIV infections or high risk behaviors (e.g. IDU's). Non-ulcerative STD's like gonorrhea and chlamydia also facilitate transmission nearly 3 times compared to in a woman without these STD's. Other factors include genital trauma, an exposure to blood during intercourse (e.g. sex during the time of menses), lack of male circumcision and the use of IUD's. Sexual transmission is more likely when partner has clinical manifestation, i.e. AIDS, when there are high viral loads both in blood and genital fluids.
Behavioral factors such as use of alcohol or other addictive drugs impair judgment and may lead to risky sexual behavior, enhancing the probability of transmission. Table 1.3 shows the factors affecting HIV-1 shedding in the genital tract and Figure 1.2 depict the factors affecting transmission by sexual route.7
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Use of Condoms and Other Protective Agents
Latex condoms reduce/block the passage of HIV through it. Consistent and correct use of condoms can reduce the risk of HIV amongst heterosexual couples, MSM's and prostitutes. Uses of topical vaginal microbicides are under trial for preventing HIV transmission.
Transmission among Injecting Drug Users (IDUs)
Injecting drug use is a major risk factor and in many parts of the developed world it contributes more to the number of cases than heterosexual or homosexual acts. Drug injection practices, sexual behavior, presence of STD's, and increase of addictive drugs are all factors that contribute to HIV transmission amongst IDU's.8
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Fig. 1.3: Interplay of factors which determine the probability of transmission of HIV in sexual relationship.Source 2: Guidelines, Govt. of India, Ministry of Health and Family Welfare
IDU's frequently share needles and syringes among themselves as a routine practice leading to high rate of infection. Among IDU's HIV infections progresses more rapidly to AIDS with increasing age.
Perinatal (Vertical) Transmission
HIV can be transmitted from mother to fetus in utero, intrapartum, or during postpartum by breast-feeding to the infant. Although the timing of maternal fetal transmission is uncertain HIV has been isolated in fetal tissue during the early to late stages of pregnancy, from placental tissue during the first trimester, and from cord blood of infants at delivery. Usually 65–80 percent of transmission occurs during intrapartum period. Caesarean section appears to reduce the risk of HIV transmission significantly. The incidence of HIV infection among infants varies from 14 percent in Europe to 45 percent in Africa and other developing countries. In mothers who become infected during late pregnancy or lactation, the risk of HIV transmission through breast milk may be as high as 50 percent due to a very high viral load, which occurs at the early stage of infection. However, the rate of postnatal transmission of HIV-1 from mothers who have been HIIV positive throughout their pregnancy is lower (5–15 percent).
Transmission by Blood Transfusion, Blood Products and Organ Transplantation
The risk of HIV transmission from whole organ of an HIV infected donor is nearly 100 percent. Fresh frozen, unprocessed bone from an infected donor has a higher risk, if marrow elements or tissues are not removed. Vascular solid tissues pose a lower risk for HIV transmission if processed by techniques that might have inactivated the HIV. Persons may become infected by receipt of blood, organs and tissues from donors who are in the “window period” and hence have tested seronegative by ELISA during the period of donation, but would become positive later.
Transmission to Health Care Workers
HIV infection is a risk for health care workers and laboratory personnel who handle sharp instruments or body fluids from HIV 10infected patients. Needle-stick accidents pose a far greater risk than does intact skin on mucous membrane exposure to HIV contaminated blood or body fluids. A 0.4 percent HIV seroconversion rate has been reported in health care workers who have percutaneous injuries with HIV contaminated surgical instruments.
The risk of HIV infection is greatest when the health care worker has been exposed to a large quantity of blood from patients with advanced HIV disease who have very high viral loads. Single exposure of mucosal and intact skin to HIV contaminated body fluids accounts for a lower infection risk (less than 0.1 percent) than does penetrating exposures.
In hospitals in the developing worlds, inadequate infection control practices of contaminated syringes and needles have resulted in HIV transmission to patients.
Environmental and Casual Contact Transmission
No one has been infected with HIV due to contact with an environmental surface because HIV is unable to reproduce, spread or maintain infectivity outside its living host. There is no evidence to support the possibility of HIV transmission by insects.
Household transmission of HIV in absence of sexual or percutaneous exposure is rare. HIV has not been shown to be transmitted through the sharing of household items, such as towels, plates, sheets, glasses, toilet or bath or shower facilities that have been soiled by feces, saliva, urine or tears, as the quantity is very small or the virus may be absent as observed from Table 1.2.
An Overview of the HIV/AIDS Pandemic
The WHO/UNAIDS have given the following estimates which depict the problem worldwide and show that it is progres-sing (Table 1.4).
The countries in the African and the Asian region have the highest numbers because of the large population base where small percentages are translated into large number of infected individuals in the community. In Africa the number is highest because the prevalence amongst pregnant women is high, nearly 30–45 percent. As a result more number of children are also affected in the absence of an antiretroviral therapy to prevent transmission from mother to child. This phenomenon is observed whenever heterosexual transmission is the major mode of spread.11
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In countries where the spread is primarily through homosexuals and injecting drug users the number in the population rise slowly as observed in the other regions of the globe. The region wise description as follows.
Sub-Saharan Africa
Africa remains by far the worst affected region in the world: 3.5 million new infections occurred in Africa in 2001, bringing to 28.5 million the total number of people living with HIV/AIDS in the region (Fig. 1.4). Of the 14 million children orphaned by AIDS worldwide, 11 million live in sub-Saharan Africa. The highest HIV prevalence rate worldwide for pregnant women stands at 44.9 percent in Botswana. As the epidemic matures younger women are affected as observed in Botswana, where among 25–29-Year-Old women attending antenatal clinics in urban areas, 55.6 percent of pregnant women (one out of two) were living with HIV/AIDS. The prevalence in other African regions are also increasing except in Uganda where over the past eight years the seroprevalence has fallen from 29.5 to 11.2 percent among pregnant women in Kampala. The experience in Uganda and Senegal bring to light how a rampant HIV/AIDS epidemic can be brought under control with intensive prevention programs.
Asia and the Pacific
3Currently the estimate for this region stands at approximately 6.6 million. India alone has 3.97 million HIV cases in 2001 which is highest for any individual country after South Africa.12
Fig. 1.4: Adults and children estimated to be living with HIV/AIDS as of End 2001[From UNAIDS, Report on the Global HIV/AIDS Epidemic, XIV International Conference on AIDS, Barcelona, 7/102:http://www.unaids.org]
The epidemics in this region, which were initially localized and hence reported low prevalence figures for the country suddenly flared up and engulfed wide regions and large number of persons. This phenomenon has been observed in Indonesia, India and China due to high population density coupled with heterosexual mode of transmission. The low socioeconomic status of the region is the main impediment to prevention programmes. However Thailand has demonstrated success in prevention programmes and is combating the epidemic successfully, throwing a ray of hope for the region.
Eastern Europe and Central Asia Eastern Europe is experiencing the fastest growing epidemic in the world (Fig. 1.4). Within three to four years, the number of HIV infected people rapidly rose from less than 100,000 to over 1 million, a ten-fold increase. Unfortunately, fewer than 1,000 people (0.1 percent) are estimated to be receiving antiretroviral therapy.
Latin America and the Caribbean An estimated 1.9 million adults and children are living with HIV in this region (Fig. 1.4), and an estimated 170,000 (8–9 percent) people were receiving antiretroviral treatment. Brazil has a nationalized antiretroviral therapy campaign which provides drugs for all eligible HIV-infected individuals. By reducing HIV/AIDS related morbidity through treatment, 13Brazil's program is estimated to have avoided 234,000 hospitalizations in 1996 to 2000, thereby demonstrating a cost-effective approach to care. In the Caribbean region, adult HIV prevalence rates are the second highest in the world after sub-Saharan Africa, e.g. Haiti 6 percent prevalence.
High Income Countries Western Europe, North America, and Australia have benefited from broad access to treatment for the nearly 1.5 million people living in these regions (Fig. 1.1). Approximately 33 percent people are receiving antiretroviral therapy. A major concern is the high rate of sexually transmitted infections among men who have sex with men (MSM), signaling a rise in unsafe sex and highlighting the need for renewed prevention efforts, especially among young people.
Problem In India
The nationwide surveillance being done since 1998 till date to find out the HIV positive amongst various groups in the country, have generated data for the high risk groups like STD patients, IVDUS, MSM and low risk group as the ANC mothers. It is assumed that when the prevalence crosses 1 percent amongst the ANC women in a geographical area, then HIV is a problem for the community. Based on this prevalence data, the country has been divided into three regions as given in the map of India (Fig. 1.5).
High prevalence (>5 percent in STD, >1 percent ANC)—The states are Tamil Nadu, Maharastra, Karnataka, Manipur, Andhra Pradesh and Nagaland. The range of HIV positivity amongst STD patients is from 9.2–26.6 percent.
Moderate prevalence (>5 percent in STD patients and <1 percent in ANC”S) Gujarat and Goa fall in this category.
Low prevalence (<5 percent in STD patients and <1 percent in ANC's) Rest of the states and UTs.
The overall prevalence for the country is 0.7 percent(UN AIDS)
These figures do no reflect the intense epidemic in some regions/groups such as 55 percent HIV positive amongst CSW's in Goa and Mumbai. 56 percent HIV positive in IVDU's at Manipur, and more than 3 percent in pregnant women in Mumbai. The major mode of transmission is heterosexual which leads to infection in women and children.14
Evolution of HIV Epidemic in India
The first case of HIV positive was detected in 1986 amongst CSWs in Chennnai and the first AIDS case was detected in 1987 in Mumbai heralding the arrival of the infection in the country. The epidemic has spread in three waves. The first is of the “Core transmitters” consisting of groups with high risk behavior such as STD patients, CSWs, MSM and IVDUs (in the northeast region). Then the infection is carried to the general population through the “Bridge population” like the clients of CSWs and IVDUs, etc. The third wave is in the general population which involves the monogamous housewife and the transmission to the children. The shift from the first to the third wave usually occurs when the HIV prevalence amongst the high risk group crosses 5 percent. The interval for the shift is nearly 3–5 years. All the moderate and low prevalence state should use this opportunity to implement the programs for preventing further spread. The waves are depicted in Figure 1.6.
The various groups and factors determining the spread are given below.
STD Patients
The median prevalence of HIV infection amongst STD patients is 26.6 percent for AP, 17 percent for Mumbai, 15 percent for Goa and 13 percent for Tamil Nadu3. It is 6.6 percent for Kerala, a state also in south. Factors like number of sex partners, lack of condom use and previous or present STD/s were found to be important predictors of prevalent and incident HIV infection. Recent use of condoms reduced the risk of acquiring HIV infection by almost half. A high HIV prevalence of about 14 percent was found amongst women attending STD clinic who denied history of sex work.
Bridge’ Population
A high HIV point prevalence of 20–30 percent was found amongst truck drivers/helpers, in AP, Karnataka, Maharashtra3 provide epidemiological support to the findings that the bridge population plays the role of carrying over the infection to the low risk group.
Blood Donors and Recipients
HIV prevalence among voluntary/replacement blood donors in the cities of India during 2000–2001was 0.56 percent5. Mandatory testing of blood and blood products for HIV antibodies was initiated in July 1989. Under the Blood Safety Programme all blood and blood products should be tested before administration.
Pregnant Women
The HIV seroprevalence among the pregnant women primarily attending the public hospitals has been reported to be between 0.5–3.3 percent in various parts of the country3. The HIV sentinel surveillance data amongst pregnant women shows that six states in India; Maharashtra, Tamilnadu. Andhra Pradesh, Karnataka, Manipur, and Nagaland have a HIV prevalence of more than 1 percent. Majority of them are industrialized or have lot of migrant population or are on the drug route (like Manipur).16
Gender-related Issues
Presence of STDs/HIV infection in low risk women is indicative of “ being married” as a risk factor. High HIV prevalence and incidence was noted amongst women attending STD clinics in Pune who denied history of sex work. Apart from practices like male/female age differences in sexual relationship and anatomical peculiarities of genitalia of the females; the fact that a high proportion of STDs tend to remain asymptomatic in women, increases the risk of acquiring HIV infection.
Men Who have Sex with Men
In India, HIV transmission among men has been reported from Mumbai and Chennai, and the HIV prevalence is 23.6 percent and 4 percent respectively. In most of the developing countries including India, men who have sex with men are far more likely to do so secretly, and they are less likely to have access to prevention and information programmes.
Rural/urban differential It has been observed that rural STD patients and ANCs are testing HIV positive, indicating spread in the rural area.
Age The surveillance data 2001 indicate that more persons < 20 years getting affected compared to past data, both amongst ANC and STDs. A wave amongst adolescents has to be avoided with adequate awareness programmes.
Sex More men than women are affected early in the epidemic, e.g. the male:female ratio for AIDS patients is 1:4 at present in India. However as the epidemic progresses the ratio becomes equal, which has occurred in Africa.
Vulnerability of women to HIV Women are biologically more susceptible to HIV infection than men. Male to female transmission of HIV is 2–4 times more efficient than female. This is because women have a larger mucosal surface exposed during sexual intercourse. Another reason is that semen contains a much higher concentration of HIV than vaginal fluid. Women are also disproportionately represented among those who receive blood or blood products as a consequence of their childbearing role, which exposes them to 17the risk of yet another mode of transmission. The fact that it is the norm for young women to have sex with, or marry older men, also increases the risk of infection. Poverty, lack of education and limited income-earning opportunities often propel women to commercial sex which significantly increases their risk of infection. Social norms which accept extra-marital and pre-marital sexual relationships in men as normal, and women's inability to negotiate safe sex practices with their partners, are factors that make it difficult for women to protect themselves from HIV infection. Unwillingness to use condoms further accentuates women's risk.
Infant feeding dilemmas Women breastfeeding infants is the norm in India. When a woman does not breastfeed and accepts replacement feeding (to avoid transmission) her HIV positive identity may be disclosed.
Mother to child transmission Since large number of ANCs are infected and they can pass the infection to their children, mothers can avail of the NACO programme to prevent MTCT by accepting voluntary testing and taking a dose of 2 mg tab of Neverapine during labour and a dose of 2 mg/kg bw to the infant within 72 hours. This programme has been implemented in all Govt. hospitals of high prevalence states and medical colleges in low prevalence states.
At present, epidemiologists cannot predict with certainty the momentum of the epidemic, and when it will peak, although short-term predictions can be made on the basis of information on risk behavior and accessibility to health services. There is strong evidence indicating that the rate of new infections will ultimately reduce if effective preventive programmes are carried out, encouraging abstinence, fidelity, safer sex and empowerment of women.
BIBLIOGRAPHY
- Bhattacharya M. Annual Sentinel Surveillance for HIV Infection in India, Country Report, NIHFW 2001.
- Levy Jay A., HIV and the Pathogenesis of AIDS. ASM Press, Washington D.C. 1998.
- Nelson Kenrad E., Williams Carolyn Masters, Graham Neil M.H. Infectious Disease: Epidemiology, Theory and Practice, Published by Aspen Publishers, Inc., Maryland 2001.
- UNAIDS, Report on the Global HIV/AIDS Epidemic, XIV International Conference on AIDS, Barcelona, 7/02, http://www.unaids.org.