Analysis of virologic and immunologic events in HIV infection

A number of pathogenic events occurring immediately after the transmission of HIV lead to the establishment of chronic infection. In fact, despite the detection of vigorous virus-specific immune responses during primary infection, HIV is able to establish chronic infection in most of the cases. This is the result of several virologic and immunologic mechanisms that HIV has evolved to escape and/or to weaken virus-specific immune responses. Lymphoid organs represent the primary anatomic site for the establishment of chronic infection, and if highly active antiretroviral therapy is not initiated in early stage disease, there is a progressive destruction of lymphoid tissue that ultimately leads to the profound immunosuppression typical of AIDS. Therefore, analysis of lymphoid organs is crucial for the correct evaluation of the effectiveness of antiretroviral therapy in HIV infection.     

Tuberculosis and HIV infection. Clinical characteristics and diagnosis

The in vitro radiosensitivity of dermal fibroblasts has been found to vary between individuals, and a number of studies have also shown that this parameter correlates with radiation-induced late injuries in clinical radiotherapy. In addition, certain genetic disorders are known to effect radiosensitivity, e.g. normal tissues of patients homozygous or heterozygous for the ataxia teleangiectasia gene show unusual sensitivity to radiation both in vivo and in vitro. Thus, it has been assumed that there is a genetically determined component resulting in a certain intrinsic cellular radiation response in an individual. To study this possible relationship between different cells of a specific patient, we established eight pairs of dermal and tumor fibroblast cultures. The donor patients had either adenocarcinoma of the uterus or squamous cell carcinoma (SCC) of the head and neck. The radiosensitivity of these strains was determined by a 96-well plate clonogenic assay, previously used by us for radiosensitivity testing of cancer cells. From a paired comparison, the values for the cell fraction surviving 2.0 Gy (SF2), of both fibroblast strains, were found to be on the same level in five out of eight cases. In patient 6, the SF2 of tumor fibroblasts was significantly higher than that of dermal fibroblasts (P=0.0014). In two additional cases the tendency was the same, but not statistically significant. As groups, the two types of fibroblasts did not differ from each other, mean SF2 values of 0.24+/-0.07 and 0.21+/-0.05, respectively. The SF2 of tumor fibroblasts from SCC patients proved to be significantly higher than that of the adenocarcinoma patients (P=0.030). These preliminary results indicate that the in vitro radiosensitivity of tumor fibroblasts correlates with normal cell sensitivity in many cases, but not in all. The radiosensitivity of tumor fibroblasts also seems to follow the level of in vitro radiosensitivity determined for the corresponding histological type of tumor cells. Further studies are needed to determine more closely the relationship between the radiosensitivities of tumor cells and tumor fibroblasts, thus evaluating the possibility of testing radiosensitivity from tumor fibroblasts in order to estimate tumor response.     

Pneumocystis carinii pneumonia in HIV primary infection]

We report a case of osteoid osteoma as a cause of hip pain in a young athlete. Excision of the lesion resulted in complete relief of the symptoms.     

Lymphocytic alveolitis after primary HIV infection with CMV coinfection

Herein is a report of an adult case of primary HIV infection with cytomegalovirus coinfection causing cough, fever, and lymphocytic alveolitis. Primary HIV infection has not been previously reported as a cause of lymphocytic alveolitis.     

Risk factors and clinical presentation of acute primary HIV infection in India

CONTEXT: Most previous studies of clinical presentation and risk factors in early human immunodeficiency virus (HIV) infection have relied on retrospective analyses and referred seroconverters, and thus were subject to possible bias. OBJECTIVES: To apply a method based on measurement of prevalent HIV-1 p24 antigenemia for identification of risk factors for newly acquired HIV infection and to describe the signs and symptoms of acute HIV infection. DESIGN AND SETTING: Nested case-control study in Pune, India. PARTICIPANTS: HIV antibody-negative persons attending 2 sexually transmitted disease (STD) clinics between May 1993 and June 1996. OUTCOME MEASURES: Prevalent p24 antigenemia, risk factors for HIV infection, and clinical symptoms of acute primary HIV infection. RESULTS: Of 3874 HIV antibody-negative persons tested, 58 (1.5%) were p24 antigen positive at initial presentation to the clinics. Unprotected sexual contact with a commercial sex worker (CSW) was reported by 39 (77%) of the 51 p24 antigenemic men, compared with 131 (51 %) of 255 control men (adjusted odds ratio [AOR], 3.4; 95% confidence interval [CI], 1.2-9.6; P=.02). The presence of an active genital ulcer at the time of screening was found in 46 (79%) of the 58 p24 antigenemic men and women, compared with 137 (47%) of the 290 control subjects (AOR, 4.2; 95% CI, 2.0-9.0; P<.001). Signs and symptoms independently associated with p24 antigenemia in HIV antibody-seronegative persons included fever, which was reported by 28 (48%) of the 58 p24 antigenemic subjects, but only 52 (18%) of the 290 control subjects (AOR, 4.7; 95% CI, 2.4-9.0; P<.001). Joint pain was reported by 10% of subjects recently HIV infected, compared with 2% of the control subjects (AOR, 6.5; 95% CI, 1.7-24.8; P=.006). Night sweats were reported by 9% of the p24 antigenemic, but only 1% of the control subjects (AOR, 9.1; 95% CI, 1.7-47.6; P=.009). Overall, fever, joint pain, and/or night sweats were reported in 27 (47%) of the 58 subjects with recent HIV infection. CONCLUSIONS: This systematic case-control study of p24 antigen screening in HIV-seronegative patients attending STD clinics in India identified unprotected sex with a CSW and a genital ulcer as independent risk factors associated with newly acquired HIV infection. In addition, p24 antigen positivity identified recent fever, night sweats, and arthralgias as symptoms that may be predictive of recent HIV infection. In a study of patients attending STD clinics in India, screening for p24 antigen in HIV antibody-negative persons was found to be a reliable and effective research method for determining recent risk behavior and identifying clinical signs of acute primary HIV infection.     

Pediatric HIV infection and the primary care physician. Meeting unique needs

The number of HIV-infected children and adolescents is expected to increase during the next decade. Most of these patients are likely to receive nearly all of their healthcare from primary care physicians. Management must be multifaceted and consist of medical care for acute illnesses, routine pediatric care that includes immunizations, and social service intervention.     

Meeting the challenge of early identification of HIV infection in primary care

The authors review the role of human immunodeficiency virus (HIV) testing in primary care, including an overview of epidemiologic trends of the HIV epidemic; avenues for HIV counseling and testing; HIV testing assays; guidelines for HIV test counseling in primary care; special situations involving testing of pregnant women, infants, and young children; post-exposure prophylaxis; and related resources available to Wisconsin primary care clinicians. HIV disease is a major cause of premature death and disability in the United States. Advances in the understanding of the pathogenesis of HIV and developments of newer antiretroviral therapies have resulted in dramatic changes in the management of HIV disease. Combination antiretroviral drug therapy has resulted in prolonged and near complete suppression of detectable HIV replication in many HIV-infected persons. These clinical developments underscore the importance of early identification and intervention in HIV disease. Intervention during primary HIV infection, the time when the viral burden "set point" is achieved, may present a special window of opportunity to effectively intervene in limiting viral replication in an infected individual. This earliest intervention may have major benefits for infected persons and society at large. Decreasing viral load during primary HIV infection may decrease an individual's infectiousness and thereby decrease the overall rate of transmission of infection to others. Primary care clinicians play a critical role in diagnosing, managing, and preventing HIV infection. Because of the ongoing relationship between patient and health care provider, the primary health care clinician is in the best position to provide HIV risk assessment, testing, related prevention education, and coordination of needed health care. This article presents guidelines for conducting HIV counseling and testing in primary care for purposes of furthering the public health objective of early identification of HIV infection. Clinicians can achieve this objective by including HIV risk assessment during the initial history and physical exam of every patient.     

HIV treatment strategies utilizing virologic and immunologic markers as criteria for changing treatments

Currently available antiviral drugs used in the treatment of AIDS patients are effective for a limited time. Therapy consisting of different drugs given in sequence thus has the potential to yield the greatest possible benefit to patients, yet it is not known in what order the drugs should be administered, or for how long. Can patient-specific information, such as viral load or determination of mutation status, be used to make these decisions on a patient by patient basis? We propose a general model for the relationship between treatment, virologic or immunologic markers, and clinical disease progression that can provide answers to these questions. We develop guidelines for optimizing progression under several settings. Optimal survival is derived for full, partial, or no interim information.     

HIV infection and AIDS

The entry of one HIV virion into a human being has the potential to cause death by the inexorable replication of the virus within the principal T lymphocyte, the CD4+ T cell. Although combination antiretroviral therapy, particularly therapy with protease inhibitors, decreases the viral burden to very low, even undetectable, levels, sequestration of the virus in privileged sites, including a long-lived CD4+ T cell, has frustrated efforts at eradication of HIV. Activation of the immune system, therefore, appears essential before this infection can be conquered. Powerful vaccines capable of preventing infection remain the hope of the world.     

Paediatric HIV infection

HIV infection in children is a family disease, with social, economic and medical aspects that make it one of the most challenging diseases of our time. Knowledge about the factors involved in mother-to-child transmission and the natural history of the disease is gradually increasing although there is still much to understand. As the majority of children become infected through mother-to-child transmission, perinatally acquired infection will parallel increases in heterosexual transmission and the numbers of infected women of childbearing age. Current estimates of the rate of vertical transmission range from 14% to 39% in different studies. The relative proportion of transmission occurring in utero, peripartum or postpartum may vary in different localities and remains unclear. A study recently carried out in the USA showed that zidovudine given late in pregnancy, peripartum and in the neonatal period decreases HIV transmission from 25% to 8%. The clinical presentation of HIV infection in children depends in part on exposure to different infections. In developing countries the children usually present with nonspecific signs and symptoms, such as failure to thrive, chronic diarrhoea, cough and recurrent bacterial infections. Other common presentations include generalized lymphadenopathy, oropharyngeal candidiasis, dermatitis, enlargement of parotid glands and neurological problems, including delayed development.     

Primary HIV infection

Up to 70% of individuals with primary HIV infection will develop symptoms of an acute illness. The most common symptoms reported are fever, generalized lymphadenopathy, arthralgia and myalgia, headache, pharyngitis, enanthema, skin rash, diarrhoea, and mucocutaneous ulcerations. More rarely, oesophageal candidiasis, meningoencephalitis, rhabdomyolysis and epiglottitis have been reported. The diagnosis of the acute HIV infection syndrome can be established by demonstrating antibodies to HIV or by demonstration of HIV antigen positivity. Detection of virus through culture or PCR may prove to be more sensitive, but are not yet used as routine methods. The course of the primary infection has prognostic importance for the subsequent course of HIV infection. This probably reflects the importance of both the viral phenotype and of the initial immune response to HIV. Primary HIV infection should be considered in any patient with possible exposure to HIV presenting with fever of unknown cause.     

New mechanisms of viral persistence in primary human immunodeficiency virus (HIV) infection

Viruses, including the Human Immunodeficiency Virus (HIV), have evolved multiple strategies to overcome host immune defenses, allowing them to persist in the host. Molecular and cellular approaches were simultaneously used to provide sensitive and unbiased delineation of the diversity and dynamics of the immune response, and to study the relative compartimentalization of HIV-specific CTL clones in patients undergoing primary HIV infection. This approach revealed that some HIV-specific CTL clones can be deleted in presence of high levels of antigen, a phenomenon analogous to high-dose tolerance or clonal exhaustion described in murine models of persistent viral infections. Also, HIV-specific CTL clones were found to accumulate preferentially in peripheral blood as compared to lymph nodes, even though the large majority of viral replication during primary HIV infection takes place within lymph nodes. These two mechanisms may decrease the effectiveness of the host cell-mediated immune responses, and favor the establishment of virus persistence during primary HIV infection.