The human immunodeficiency virus (HIV) is a retrovirus infection which causes the acquired immunodeficiency syndrome (AIDS) (Fig. 1.1). It attacks the body's immune system; particularly destroying the CD4 T lymphocytes. This damage to immunity results in opportunistic infections and malignancies.
The first case of HIV was diagnosed in India in 1986 in a female sex worker (FSW) in Chennai. At that time, more than 20,000 cases had already been reported worldwide. Such a delayed detection of the first case in India was probably due to a lack of laboratory facilities and scientific knowledge about this disease in this country. The HIV prevalence in India among adults is now about 0.26% (2015 data); of whom 0.30% are males and 0.22% are females. Among the states, Manipur has the highest occurrence, followed by Mizoram, Nagaland, Andhra Pradesh and Telangana, Karnataka, Gujarat, and Goa. The total burden of people living with HIV (PLHIV) is approximately 21.17 lacs (in 2015); of which 6.54% are children and 40.5% are women. India is still facing an epidemic of HIV.
In 2015, the HIV prevalence in India was an estimated 0.26%. However, of the 2.1 million patients with HIV in India, only 43% are on antiretroviral therapy (ART). The Government of India's new goal is to stop HIV spreading by testing and treating all patients by 2030.
The HIV/AIDS can affect all sectors of the population, both rich and poor, children and the old, males and females, homosexuals and heterosexuals but its prevalence is greater in certain individuals who belong to the high-risk groups. These include FSWs, men who have sex with men (MSM), transgenders (TGs)/Hijras and injecting drug users (IDUs). The people who transfer infection from the high-risk to the low-risk group are known as the bridging population, which includes migrants and long distance truckers. In India, this infection follows, the so-called type 4 pattern where first the virus enters into the high-risk groups, then involves the bridging population and finally infects the general public.
WHEN TO SUSPECT HIV/AIDS?
The following are the clinical scenarios for suspecting HIV infection:
- All persons who are being evaluated or being treated for sexually transmitted diseases (STDs)
- Voluntary testing after high-risk sexual activity
- Recurrent infections in a person
- Unexplained weight loss
- Chronic diarrhea
- More than three vaginal infections in 1 year (not related to the use of antibiotics)
- Recurrent pelvic inflammatory disease (PID)
- Abnormal Pap test or cervical cancer
- Confusion and difficulty concentrating
- Persisting dry cough
- Explained fever
- Recurrent oral ulcers
- Night sweats
- Unexplained lymph node swelling
- Repeated outbreaks of herpes simplex
- Thrush
- An opportunistic infection (with bacteria, viruses, fungi, or protozoa).
ACUTE HUMAN IMMUNODEFICIENCY VIRUS
The HIV infection represents a spectrum of disease that can begin like a flu-like illness after viral exposure. This may be absent in some people and can 5be easily missed in many cases as the symptoms are very nonspecific. The symptoms of early HIV include headaches, fever, tiredness, swollen lymph nodes, sore throat, muscle and joint pains, mouth ulcers, genital ulcers, night sweats and diarrhea. Early HIV symptoms generally arise after 1–2 months of infection, although they can arrive as early as 2 weeks after exposure. Later Chapters in the book deal with how to test for HIV in the acute setting.
OPPORTUNISTIC INFECTIONS AND MALIGNANCIES
The HIV/AIDS patients are prone to many opportunistic infection and malignancies (Fig. 1.2). Many of these infections will be discussed in detail later; the opportunistic infections are related to CD4 cell counts of patient (Fig. 1.3). However, some of the clinical conditions are discussed in this chapter. These include—Toxoplasmosis and Penicilliosis.
Toxoplasmosis
This is caused by the intracellular protozoan Toxoplasma gondii. It usually manifests when cell-mediated immunity falls with the level of the CD4 cell count being less than 100/mm3. Its mode of spread is through the consumption of undercooked meat and water contaminated with oocysts. Transplacental transfer has been reported in HIV-infected mothers resulting in congenital toxoplasmosis. The severity of the infection depends upon the trimester of pregnancy in which the mother has acquired the infection, being most severe if this has been in the first trimester.
Cerebral Toxoplasmosis: This is the most common and most fatal presentation of Toxoplasma infection. Usually the patient presents with altered mental status, headaches, fever, fits, unilateral limb weakness, difficulty in speech and vision, ataxia, cranial nerve palsies, and features of an increased intracranial pressure.
Extracerebral Toxoplasmosis: The eyes and lungs are the most affected sites, and may present without central nervous system (CNS) features. Very rarely, the infection may involve the liver, heart, bone marrow, gastrointestinal tract, musculoskeletal system, spinal cord, and testis.
Diagnosis
Serologic studies can be used for detection. A rising immunoglobulin G (IgG) level in a patient whose baseline titer is known indicates reactivation of the infection. A rise in the immunoglobulin G (IgM) titer may indicate acute infection. However, serology cannot be used as the sole modality for diagnosis. Contrast-enhanced computed tomography (CECT) or magnetic resonance imaging (MRI) brain scans show an asymmetrical target sign, which represent ring-enhancing lesions, which are usually multiple, and characteristically in the basal ganglia, brainstem, pituitary, and junction of the white and gray matter.
The differential diagnosis of cerebral toxoplasmosis includes tuberculoma, abscesses (fungal or bacterial), primary brain lymphoma, primary brain tumors, brain metastases, infarcts, arteriovenous (AV) malformations and demyelinating disease (Fig. 1.4).7
Treatment
Primary prophylaxis should start with TMP-SMX double strength daily in Toxoplasma IgG-positive individuals with CD4 cell counts less than 100. The acute infection should be treated with pyrimethamine (200 mg PO once daily followed by weight-based therapy with pyrimethamine and sulfadiazine) and leucovorin. After completion of acute treatment, all patients should be initiated onto maintenance therapy.
Penicilliosis
This is due to a dimorphic fungus Penicillium marneffei which causes systemic infections in patients with HIV/AIDS who have CD4 cell counts less than 100 cells/mm3. Southeast Asia is the endemic area for this fungus. In India, a new endemic zone has been recognized in Manipur.
The patient acquires the infection by inhalation of microconidia or from reactivation of a silent focus. Its clinical features are usually nonspecific (fever, anemia and weight loss). The patient usually presents with generalized skin lesions in the form of papules with central umbilication as seen in molluscum contagiosum, starting from the face and gradually spreading to involve the limbs and trunk. It may present with symptoms related to other organs such as the CNS, lymph nodes, liver, lung, intestine, and bone marrow. The definitive diagnosis is made by isolation or demonstration of the fungus in clinical specimens. An early diagnosis can be made by microscopic examination with Giemsa stain of a skin scraping, bone marrow or lymph node aspirate, which shows intracellular and extracellular yeast-like organisms with clear central septation.8
To prevent the first episode of acute infection prophylaxis should be given in the form of itraconazole 200 mg once daily to the patient whose CD4 cell counts are less than 100/mm3. Alternatively, fluconazole may be used (400 mg PO once weekly). Acute infection in severely ill patients should be managed with intravenous (IV) liposomal amphotericin B (3–5 mg/kg/day for 2 weeks) followed by itraconazole (200 mg PO BID for 10 weeks). Milder infections can be treated with itraconazole alone (200 mg PO BID for 8 weeks). The patient should then be continued on maintenance therapy with itraconazole (200 mg PO daily). Alternatively, an acute infection can be managed with voriconazole. ART should be started along with treatment of penicilliosis to improve the outcome.
HIV-RELATED MALIGNANCIES
Patients suffering from HIV are prone to develop malignancies. There are types which are—AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs). With the introduction of highly active antiretroviral therapy (HAART), the cases of ADCs have reduced significantly.
AIDS-defining cancers: They are Kaposi's sarcoma (KS), primary CNS lymphoma, non-Hodgkin's lymphoma (NHL), and cervical cancer. ADCs reflect the point at which HIV infection has progressed to AIDS. KS is a low-grade soft tissue tumor of vascular origin, and it is associated with human herpesvirus 8 (HHV-8) infection. Manifestations of KS range from asymptomatic skin lesions to symptom producing visceral (lung and intestine) or oral lesions. NHL is a malignancy of the lymphoid tissue. In HIV/AIDS patients, the important risk factors for the development of NHL are a low CD4 count, high viral load, increasing age, and male gender. The World Health Organization (WHO) has divided AIDS-related lymphomas (ARLs) into three groups:
- Those also found in immunocompetent patients like Burkitt's or diffuse large B-cell lymphoma.
- Those found more specifically in HIV-infected patients like primary effusion lymphoma, and plasmablastic lymphoma.
- Those also occurring in other immunodeficiency states such as post-transplant lymphoproliferative disorders.
Certain viruses also play important roles in NHL such as Epstein-Barr virus (EBV) and HHV-8. The incidence of invasive cervical carcinoma is increased in HIV/AIDS-infected females mainly due to infection by the human papillomavirus (HPV).
Non-AIDS-defining cancers: The incidence of NADCs has increased greater than three fold in the last 10 years. This increase is due to the longer survivals in the combination ART (cART) era and due to the direct effect of HIV itself. 9All of these malignancies may found in HIV patients but their occurrence does not imply progression to AIDS. These NADCs are bronchogenic carcinoma, colorectal carcinoma, anal carcinoma, prostate carcinoma, testicular carcinoma, melanomas, Hodgkin's disease and cutaneous malignancies.
SUGGESTED READING
- Buchacz K, Baker RK, Palella FJ, Jr., et al. AIDS-defining opportunistic illnesses in US patients, 1994-2007: a cohort study. AIDS. 2010;24(10):1549–59.
- http://naco.gov.in/about-us/policies-guidelines. Opportunistic Infections and Their Management National AIDS Control Organisation. Lasted accessed on 02.01.2018.
- https://aidsinfo.nih.gov/guidelines. Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents. Last accessed on 27.12.2017
- Jones JL, Kruszon-Moran D, Sanders-Lewis K, et al. Toxoplasma gondii infection in the United States, 1994-2004, decline from the prior decade. Am J Trop Med Hyg. 2007;77(3):405–10.
- Patel PK, Erlandsen JE, Kirkpatrick WR, et al. The changing epidemiology of oropharyngeal candidiasis in patients with HIV/AIDS in the era of antiretroviral therapy. AIDS Res Treat. doi: 10.1155/2012/262471.
- Rottingen JA, Cameron DW, Garnett GP. A systematic review of the epidemiologic interactions between classic sexually transmitted diseases and HIV: how much really is known? Sex Transm Dis. 2001;28(10):579–97.
- Wheat LJ, Connolly-Stringfield PA, Baker RL, et al. Disseminated histoplasmosis in the acquired immune deficiency syndrome: clinical findings, diagnosis and treatment, and review of the literature. Medicine (Baltimore). 1990;69(6):361–74.
- World Health Organization. Global Tuberculosis Report. Geneva: World Health Organization; 2015. Available at http://apps.who.int/iris/bitstream/10665/191102/1/9789241565059_eng.pdf.