HIV in Bundelkhand Region Prof. P.K. Jain MD,MNAMS Professor & Head, DR Awadhesh kr sharma,SR Department of Medicine, M.L.B. Medical College, Jhansi, UP
HIV: GLOBAL PERSPECTIVE First diagnosed in United States in 1981. Isolation of HIV virus – 1983. ELISA technique developed to diagnose HIV-1985. HIV :Indian Perspective In 2007, UNAIDS and NACO estimated about 2 million to 3.6 million people living with HIV. About 0.36% of India’s population is living with HIV.
HIV in Bundelkhand Region Yr. / Duration No. of Counselling No. of Testing No. of Positive Cases 1/5/01 - 1/12/06 Male 1991 Female 527 Total 2518 Male 1991 Female 527 Total 2518 Male 140 Female 46 Total 186 1/01/07 – 31/08/07 352 144 496 319 118 437 22 17 39 1/09/07 – 30/09/07 66 25 91 47 16 63 01 02 03 01/04/08 – 01/04/09 500 242 742 408 192 600 42 24 66 Total 2909 938 3847 2765 853 3618 205 89 294
No. of Patients Counselled – 3847 Male – 2909 Female – 938 HIV Testing - 3618 Male – 2765 Female – 853 Positive Cases - 294 Male – 205 Female - 89
Education level of HIV Positive Patients Illiterete 46 1-5 th standard 32 6-8 th standard 46 8-10 th standard 50 11-12 th standard 36 Graduated 13 Post Graduated 5 Seven patients were below 3 yrs. of age.
Marital Status of HIV Positive Patients Unmarried 12 Married 170 Widow 9 Divorced / Seperated 12 Living together 140 Seven patients were below 3 yrs. of age.
Etiologic Agent Family : Retroviridae Subfamily : Lentivirus There are two types of HIV viruses. HIV-1 & HIV-2 HIV virus is RNA virus containing reverse transcriptase It contain two major envelop proteins. 1. gp 120 – external 2. gp 41 - transmembrane
HIV has been demonstrated in seminal fluid both within infected mononuclear cells and in the cell-free state.
The virus appears to concentrate in the seminal fluid, particularly in situations where there are increased numbers of lymphocytes and monocytes in the fluid, as in genital inflammatory states such as urethritis and epididymitis conditions closely associated with other STDs .
The virus has also been demonstrated in cervical smears and vaginal fluid.
It is likely that anal intercourse provides at least two modalities of infection:
(1) direct inoculation into blood in cases of traumatic tears in the mucosa; and
(2) infection of susceptible target cells, such as Langerhans cells, in the mucosal layer in the absence of trauma .
Although the vaginal mucosa is several layers thicker than the rectal mucosa and less likely to be traumatized during intercourse, it is clear that the virus can be transmitted to either partner through vaginal intercourse.
Heterosexual transmission of HIV, male-to-female transmission was approximately eight times more efficient than female-to-male transmission
TRANSMISSION BY BLOOD AND BLOOD PRODUCTS HIV can be transmitted to individuals who receive HIV-tainted blood transfusions, blood products, or transplanted tissue as well as to injection drug users who are exposed to HIV while sharing injection paraphernalia such as needles, syringes, the water in which drugs are mixed, or the cotton through which drugs are filtered. It is estimated that 90 to 100% of individuals who were exposed to such HIV contaminated products became infected. Transfusions of whole blood, packed red blood cells, platelets, leukocytes, and plasma are all capable of transmitting HIV infection. In contrast, hyperimmune globulin, hepatitis B immune globulin, plasma-derived hepatitis B vaccine, and Rho immune globulin have not been associated with transmission of HIV infection.
OCCUPATIONAL TRANSMISSION OF HIV: HEALTH CARE WORKERS AND LABORATORY WORKERS Risk of HIV transmission following skin puncture from a needle or a sharp object that was contaminated with blood from a person with documented HIV infection is 0.3% and after a mucous membrane exposure it is 0.09% Transmission of HIV through intact skin has not been documented. An increased risk for HIV infection following percutaneous exposures to HIV-infected blood is associated with exposures involving a relatively large quantity of blood, as a procedure that involves a needle placed directly in a vein or artery, or a deep injury. Factors that might be associated with mucocutaneous transmission of HIV include exposure to an unusually large volume of blood, prolonged contact, and a potential portal of entry.
MATERNAL-FETAL/INFANT TRANSMISSION HIV infection can be transmitted from an infected mother to her fetus during pregnancy, during delivery, or by breast-feeding. In the absence of prophylactic antiretroviral therapy to the mother during pregnancy, labor, and delivery, and to the fetus following birth , the probability of transmission of HIV from mother to infant/fetus ranges from 15 to 25% in industrialized countries and from 25 to 35% in developing countries. Studies have demonstrated that truncated regimens of zidovudine alone or in combination with lamivudine given to the mother during the last few weeks of pregnancy or even only during labor and delivery, and to the infant for a week or less, reduced transmission to the infant by 50% compared to placebo.
TRANSMISSION BY OTHER BODY FLUIDS Although HIV can be isolated typically in low titers from saliva of a small proportion of infected individuals, there is no convincing evidence that saliva can transmit HIV infection, either through kissing or through other exposures, such as occupationally to health care workers. Secretory leukocyte protease inhibitor (SLPI), blocks HIV infection in several cell culture systems, and it is found in saliva at levels that approximate those required for inhibition of HIV in vitro. In this regard, higher salivary levels of SLPI in breast-fed infants were associated with a decreased risk of HIV transmission through breast milk. It has also been suggested that submandibular saliva reduces HIV infectivity by stripping gp120 from the surface of virions, and that saliva-mediated disruption and lysis of HIV-infected cells occurs because of the hypotonicity of oral secretions.
Although virus can be identified, if not isolated, from virtually any body fluid, there is no evidence that HIV transmission can occur as a result of exposure to tears, sweat, and urine.
PATHOPHYSIOLOGY AND PATHOGENESIS The hallmark of HIV disease is a profound immunodeficiency resulting primarily from a progressive quantitative and qualitative deficiency of the subset of T lymphocytes referred to as helper T cells , or inducer T cells . This subset of T cells is defined phenotypically by the presence on its surface of the CD4 molecule which serves as the primary cellular receptor for HIV. The initial infection of susceptible cells may vary somewhat with the route of infection. Virus that enters directly into the bloodstream via infected blood or blood products (i.e., transfusions, use of contaminated needles for injecting drugs, sharp-object injuries, maternal-to-fetal transmission either intrapartum or perinatally, or sexual intercourse is likely to be cleared from the circulation to the spleen and other lymphoid organs, where it replicates to a critical level and then leads to a burst of viremia that disseminates virus throughout the body.
It is estimated that 50 to 70% of individuals with HIV infection experience an acute clinical syndrome approximately 3 to 6 weeks after primary infection.
Clinical Findings in the Acute HIV Syndrome General: Fever Pharyngitis Lymphadenopathy Headache/retroorbital pain Arthralgias / myalgias Lethargy/malaise Anorexia/weight loss Nausea/vomiting/diarrhea Neurologic: Meningitis Encephalitis Peripheral neuropathy Myelopathy Dermatologic Erythematous maculopapular rash Mucocutaneous ulceration
THE ASYMPTOMATIC STAGE — CLINICAL LATENCY Although the length of time from initial infection to the development of clinical disease varies greatly, the median time for untreated patients is 10 years. HIV disease with active virus replication is ongoing and progressive during this asymptomatic period. The rate of disease progression is directly correlated with HIV RNA levels. Patients with high levels of HIV RNA in plasma progress to symptomatic disease faster than do patients with low levels of HIV RNA .
Symptoms of HIV disease can appear at any time during the course of HIV infection. Generally speaking, the spectrum of illness that one observes changes as the CD4 T cell count declines. The more severe and life-threatening complications of HIV infection occur in patients with CD4 T cells counts 200/L.
A diagnosis of AIDS is made in anyone with HIV infection and a CD4 T cell count 200/L and in anyone with HIV infection who develops one of the HIV-associated diseases considered to be indicative of a severe defect in cell-mediated immunity.
The diagnosis of HIV infection depends upon the demonstration of antibodies to HIV and/or the direct detection of HIV or one of its components.
Antibodies to HIV generally appear in the circulation 2 to 12 weeks following infection. The standard screening test for HIV infection is the ELISA, also referred to as an enzyme immunoassay (EIA). This solid-phase assay is an extremely good screening test with a sensitivity of 99.5%.
EIA tests are generally scored as positive (highly reactive), negative (nonreactive), or indeterminate (partially reactive). While the EIA is an extremely sensitive test, it is not optimal with regard to specificity .
The most commonly used confirmatory test is the western blot . This assay takes advantage of the fact that multiple HIV antigens of different, well-characterized molecular weights elicit the production of specific antibodies. These antigens can be separated on the basis of molecular weight, and antibodies to each component can be detected as discrete bands on the western blot.
Criteria established by the U.S. Food & Drug Administration (FDA) in 1993 for a positive western blot state that a result is considered positive if antibodies exist to two of the three HIV proteins: p24, gp41, and gp120/160.
The FDA-approved reverse transcriptase inhibitors include
the nucleoside analogues zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir, and emtricitabine;
the nucleotide analogue tenofovir; and
the nonnucleoside reverse transcriptase inhibitors nevirapine, delavirdine, and efavirenz.
These were the first class of drugs that were licensed for the treatment of HIV infection. They are indicated for this use as part of combination regimens. It should be stressed that none of these drugs should be usedas monotherapy for HIV infection.
The two options for initial therapy most commonly in use are two different three-drug regimens.
The first regimen utilizes two nucleoside analogues (one of which is usually lamivudine) and a nonnucleoside reverse transcriptase inhibitor.
The second regimen utilizes two nucleoside analogues and a protease inhibitor.
Following the initiation of therapy one should expect a 1 log (tenfold) reduction in plasma HIV RNA levels within 1 to 2months and eventually a decline in plasma HIV RNA levels to 50copies per milliliter. During this same time there should be a rise in the CD4 T cell count of 100 to 150/L that is particularly brisk during the first month of therapy.
Several factors have been associated with an increased risk for occupational transmission of HIV infection including: deep injury, the presence of visible blood on the instrument causing the exposure, injury with a device that had been placed in the vein or artery of the source patient, terminal illness in the source patient, and lack of post exposure antiretroviral therapy in the exposed health care worker.
Regardless of the decision to use postexposure prophylaxis, the wound should be cleansed immediately and antiseptic applied. If a decision is made to offer postexposure prophylaxis, U.S. Public Health Service guidelines recommend
(1) a combination of two nucleoside analogue reverse transcriptase inhibitors given for 4 weeks for routine exposures, or
(2) a combination of two nucleoside analogue reverse transcriptase inhibitors plus a third drug given for 4 weeks for high-risk or otherwise complicated exposures
Education, counseling, and behavior modification are the cornerstones of an HIV prevention strategy.
Use of condoms can markedly decrease the chance of HIV transmission. It should be remembered that condoms are not 100% effective in preventing transmission of HIV infection, and there is an 10% failure rate of condoms used for contraceptive purposes. Most condom failures result from breakage or improper usage, such as not wearing the condom for the entire period of intercourse. Petroleum-based gels should never be used for lubrication of the condom, since they increase the likelihood of condom rupture.
Treatment of an HIV-infected mother with antiretroviral therapy during pregnancy and the infant during the first weeks following birth has proven very effective in dramatically decreasing mother to child transmission of HIV. In situations such as that seen in certain developing countries where pregnant women frequently present to a health care system during labor, administration of a short course (as little as a single dose of one drug) of antiretroviral therapy to the mother during labor and to the infant within 48 h of birth has also been successful in decreasing the incidence of mother to child transmission of HIV.
Principles of Therapy of HIV Infection 1. Ongoing HIV replication leads to immune system damage and progression to AIDS. 2. Plasma HIV RNA levels indicate the magnitude of HIV replication and the rate of CD4 T cell destruction. CD4 T cell counts indicate the current level of competence of the immune system. 3. Rates of disease progression differ among individuals, and treatment decisions should be individualized based upon plasma HIV RNA levels and CD4 T cell counts. 4. Maximal suppression of viral replication is a goal of therapy; the greater the suppression the less likely the appearance of drug-resistant species. 5. The most effective therapeutic strategies involve the simultaneous initiation of combinations of effective anti-HIV drugs with which the patient has not been previously treated and that are not cross-resistant with antiretroviral agents that the patient has already received.
6. The antiretroviral drugs used in combination regimens should be used according to optimum schedules and dosages. 7. The number of available drugs is limited. Any decisions on antiretroviral therapy have a long-term impact on future options for the patient. 8. Women should receive optimal antiretroviral therapy regardless of pregnancy status. 9. The same principles apply to children and adults. The treatment of HIV-infected children involves unique pharmacologic, virologic, and immunologic considerations. 10. Compliance is an important part of ensuring maximal effect from a given regimen. The simpler the regimen, the easier it is for the patient to be compliant.