Occurrence Of Opportunistic Infections Research Articles

Cytomegalovirus Infection Complicating Immunosuppressive Therapy for Dermatomyositis

The occurrence of opportunistic infections is not rare during the treatment of connective tissue diseases, including dermatomyositis because of the patient's immunosuppression. We describe here cytomegalovirus (CMV) infection that affected two of our patients with dermatomyositis. CMV infection has not been considered to be a frequent event in dermatomyositis, and its significance for disease progression has not been sufficiently recognized. Our case reports demonstrate the importance of close monitoring of such patients and prompt initiation of appropriate therapy to manage a suspected CMV infection.

P.419 Patients infected with HIV/HCV and the liver injury as a side effect of HAART

The effect of highly active antiretroviral therapy (HAART) in the treatment of HIV infection is usually measured by survival, CD4 lymphocyte counts, HIV-1 RNA viral load testing, and the occurrence of opportunistic infections. This pilot study sought to measure the impact of HAART treatments on a wide range of clinical outcomes and psychological variables in a sample of patients with advanced HIV infection. Seventy patients with advanced AIDS who were protease inhibitor naı̈ve were started on HAART regimens. Patients were admitted to an AIDS inpatient unit of a long-term care facility that provides treatment and palliative care. All patients were diagnosed with AIDS, had CD4 cell counts below 300/cc3, and had a projected survival of greater than one month. Patients were started on triple-drug HAART regimens with daily medical supervision and observation. In addition to standard clinical and laboratory markers, a series of observer-rated and self-report instruments were used to measure various physical and psychological factors (e.g., pain and symptom distress, psychological well-being, depression). Data were collected at baseline and after 1 and 3 months of HAART therapy. As expected, the CD4 count increased and viral load levels decreased significantly over the 3-month study period. In addition, patients improved significantly in body weight, and serum albumin and ferritin levels. The only psychosocial measure that improved significantly with treatment was depression. Ratings of pain intensity, physical and psychological symptom distress, and overall quality of life did not change. Of the 70 patients studied, 84.3% were still alive after the 3-month study period. Of these, 6 (8.6%) were discharged to community. However, 17 surviving patients (24.3%) had HAART regimens discontinued due to drug intolerance and 11 patients (15.7%) expired during the study period. While these data are preliminary, HAART regimens appear to have positive effects on CD4 count, HIV viral load, and several other measures of physical well-being in patients with advanced AIDS. Despite these improvements, the benefits of treatment on pain and symptom distress, and psychological well-being were less clear. In addition, treatment failure (mortality and intolerance) were not uncommon in this sample (40%). Further research is clearly necessary to better understand the benefits of HAART therapy in patients with advanced HIV infection.

Antiretrovirals: Need for an effective drug delivery

Human Immunodeficiency Virus (HIV) is a retrovirus that causes irreversible destruction of the immune system, leading to the occurrence of opportunistic infections and malignancies. During the last decade, even though attempts were being made to eradicate HIV, it was found that eradication of HIV is highly unlikely, and effective antiretroviral therapy is required on a long-term basis to maintain viral suppression and reduce disease progression. During this decade, effective therapies aimed at continued suppression of HIV replication and targeted at resting HIV reservoirs such as brain, lymphatic systems will be critical to prolong survival and renewing hopes for a cure. Currently available antiHIV drugs can be classified into three categories: nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors. Most of these drugs bear some significant drawbacks such as relatively short half-life, low bioavailability, poor permeability and undesirable side effects. Efforts have been made to design drug delivery systems for antiHIV agents to: a) reduce the dosing frequency, b) increase the bioavailability and decrease the degradation/metabolism in the gastrointestinal tract, c) improve the CNS penetration and inhibit the CNS efflux, and d) deliver them to the target cells selectively with minimal side effects. This article is an attempt to compile all major research work towards drug delivery for AIDS therapy and channel future attempts in the area of more effective controlled delivery of antiHIV agents.

A review of cardiovascular complications accompanying AIDS.

Manifestations of cardiovascular system involvement are not uncommon complications of HIV infection, especially in AIDS patients. However, the frequency of these manifestations is influenced by different variables including: survival prolongation in HIV-infected patients, because of advances in antiretroviral treatment; improvement of immunodepression and reduction in the occurrence of opportunistic infections; adverse effects of some drugs. At present, on the whole cardiovascular complications that are HIV correlated in the western world, including Italy, occur less frequently than in the past. However complications associated with alterations in lipometabolism prevail because they can be promoted by some protease inhibitors in predisposed subjects. The most frequently reported questions and a careful analysis of recent data in the medical literature regarding the most common HIV-correlated cardiovascular complications are discussed in this review.

Occurrence and Management of Opportunistic Infections Associated with HIV/AIDS in Asia

Illnesses, diseases and malignancies occur among HIV-infected individuals along a continuum. These are directly correlated with the degree of immune suppression and are caused by common patho gens and opportunistic infections. In decreasing order offrequency, frequent opportunistic infections and malignancies that occur in Asia are: Mycobacterium tuberculosis, Cryptococcus neoformans, Candida spp., Herpes simplex, Cryptosporidium parvum, Pneumocystis carinii, Toxoplasma gondii, non-Hodgkin's lymphoma and Kaposi's sarcoma. The association of morbidityand mortality due to co-infection with HIV and M.tuberculosis has become more evident in the region. Natural history studies conducted in Mumbai and Bangkok have reported incubation periods from infection to AIDS of eight and nine years respectively. Despite the advent of antiretroviral therapy (ART) and improved affordability of the generic drugs, only 30,000 (2 to 3 per cent) of the estimated 1.3 million eligible persons with AIDS in South Asia are presently on AR T. Apparently, the focus of the low-cost care in the region still continues to be of care and management of prevalent opportunistic infections. As care practices start to include ART over the next few years, there will be consequent change in the occurrence of opportunistic infections and need for their prophylaxis.

Natural alpha interferon-producing cells respond to human immunodeficiency virus type 1 with alpha interferon production and maturation into dendritic cells.

Natural alpha interferon (IFN-alpha)-producing cells (IPCs) are now recognized as identical to plasmacytoid dendritic cell (DC) precursors in human blood and are thought to play an important role in antiviral immunity. In the present study, we examined the susceptibility as well as the cellular responses of IPCs to human immunodeficiency virus type 1 (HIV-1) infection. HLA-DR(+) CD11c(-) lineage-negative cells (IPCs) were purified from peripheral blood mononuclear cells by magnetic-bead separation and cell sorting. We substantiated that IPCs expressing the major HIV-1 coreceptors, CXCR4 and CCR5, are susceptible to infection of both T-cell-line-tropic NL4-3 and macrophage-tropic JR-CSF HIV-1 by quantification of HIV-1 p24 in the culture supernatants and by provirus integration assay using human conserved Alu-HIV-1 long terminal repeat PCR. To evaluate the cellular response of IPCs to HIV-1, we examined IFN-alpha production and their differentiation into DCs. After incubation with either NL4-3 or JR-CSF, IPCs produced a large amount of IFN-alpha and at the same time underwent morphological differentiation into DCs with upregulation of CD80 and CD86. Heat inactivation of the supernatants containing HIV-1 did not affect the IFN-alpha production and maturation, whereas removal of virions by ultracentrifugation completely nullified both biological effects, indicating that these cellular responses do not require actual HIV-1 infection but are elicited by interaction with HIV-1 virions or certain viral components. In conclusion, these data strongly suggest that IPC can directly recognize and respond to HIV-1 with IFN-alpha production, which is crucial for preventing progress of HIV-1 infection and occurrence of opportunistic infection.

Evaluation of pediatric HIV care provided in Ryan White CARE Act Title IV Women, Infants, Children, and Youth Clinics.

This evaluation examines the changing practices and outcomes of pediatric HIV care provided by the Ryan White Comprehensive AIDS Resources and Emergency (CARE) Act, Title IV grantees from 1996 through 1998--a period of rapidly changing medical practice within the United States. Using medical chart abstraction, 26 Title IV grantees reported information from the records of 525 HIV positive clients between the ages of 2 and 12. The chart abstractions covered medical care and case management provided to these clients including the number of clinical visits, use of antiretroviral therapy, use of laboratory tests such as CD4+ cell count (cells/mm3) and HIV-1 RNA viral load (copies/mL), enrollment in clinical trials, and receipt of opportunistic infection prophylaxis. Information on disease progression and hospitalization as well as client socio-demographic characteristics also is analyzed. Study results indicate that use of HIV combination therapy increased, while the occurrence of opportunistic infections and hospitalizations decreased. The increasing use of new pharmaceuticals during the study period indicates the feasibility of transferring information learned about HIV treatments from clinical trials to clinical practices that treat primarily Medicaid and pediatric populations.

Correlation between breadth of memory HIV-specific cytotoxic T cells, viral load and disease progression in HIV infection.

Memory cytotoxic T lymphocytes (CTL) should play a key role in controlling HIV infection. The correlations between the breadth and specificities of memory CTL and virus production and disease progression are still unknown, but are of major importance for vaccine strategies. One-hundred and forty-eight chronically-infected patients, enrolled before the advent of highly active antiretroviral therapy, were followed-up prospectively over 5 years. Memory CTL were tested in vitro against autologous target cells expressing Env, Gag, Pol, Nef, Vif, Rev or Tat HIV-LAI sequences. At entry, an HIV-specific CTL response was detected against at least one viral protein in 77% cases, with Pol and Gag recognized in 57% each, Env and Nef in 36% and 30%, Vif, Rev and Tat in 14%, 10% and 5% of cases respectively. The same pattern was observed over time with some individual variations in responder status. Multivariate analysis of longitudinal data showed that the average number of recognized proteins of two at entry significantly decreased over time with the average loss of one protein per 7 years. The number of recognized proteins was negatively associated with viral load (P < 0.05), and with occurrence of opportunistic infection (P < 0.01), and significantly correlated with CD8 cell counts (P < 0.05) but not with CD4 cell counts. The breadth of HIV antigens recognized by memory CTL is a major correlate of immune control of HIV-replication and disease progression.

Containment of simian immunodeficiency virus infection in vaccinated macaques: correlation with the magnitude of virus-specific pre- and postchallenge CD4+ and CD8+ T cell responses.

Macaques infected with the SIV strain SIVmac251 develop a disease closely resembling human AIDS characterized by high viremia, progressive loss of CD4(+) T cells, occurrence of opportunistic infection, cachexia, and lymphomas. We report in this study that vaccination with the genetically attenuated poxvirus vector expressing the structural Ags of SIVmac (NYVAC-SIV-gag, pol, env) in combination with priming with DNA-SIV-gag, env resulted in significant suppression of viremia within 2 mo after mucosal exposure to the highly pathogenic SIVmac251 in the majority of vaccinated macaques. The control of viremia in these macaques was long lasting and inversely correlated to the level of both pre- and postchallenge Gag-specific lymphoproliferative responses, as well as to the level of total SIV-specific CD4(+) T lymphocyte responses at the peak of acute viremia as detected by intracellular cytokine-staining assay. Viremia containment also correlated with the frequency of the immunodominant Gag(181-189)CM9 epitope-specific CD8(+) T cells present before the challenge or expanded during acute infection. These data indicate, for the first time, the importance of vaccine-induced CD4(+) Th cell responses as an immune correlate of viremia containment. The results presented in this work also further demonstrate the potential of a DNA-prime/attenuated poxvirus-boost vaccine regimen in an animal model that well mirrors human AIDS.

Natural type 1 interferon producing cells in HIV infection

Natural type 1 interferon producing cells (IPCs) are in the first line of defense against infectious pathogens. Besides the known properties of type 1 interferons in inhibiting human immunodeficiency virus (HIV) replication, the recent characterization of human IPCs and the possibility to purify them for in vitro studies has greatly accelerated the study of their role in HIV infection. The blood IPC numbers and function are decreased in HIV primary infection and in advanced stages of HIV infection. Loss of circulating IPCs correlates with a high HIV viral load and the occurrence of opportunistic infections. Moreover, HIV can directly infect IPCs in vitro, providing a potential explanation for their in vivo depletion. Thus, the balance between IPCs and HIV replication might be critical in determining the control or progression of HIV infection.

HIV disease: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

HIV disease: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Persistence of intracellular HIV-1 mRNA correlates with HIV-1-specific immune responses in infected subjects on stable HAART.

To determine if low level, persistent, HIV-1 replication within specific immune cells contributes to HIV-1-specific immune responsiveness. We analyzed 59 HIV-1-infected subjects on stable highly active antiretroviral therapy (HAART) therapy (not including zidovudine) with suppressed plasma viremia (< 400 copies/ml) for phenotypic and lymphoproliferative correlates of immune function. Peripheral blood mononuclear cells were collected for immunophenotyping, lymphoproliferative assays, and simultaneous immunophenotyping/ultrasensitive in situ hybridization. Plasma was collected for plasma viral load as determined by the Ultra Sensitive Roche Amplicor RT-PCR. Descriptive statistics (mean and SD, median, first and third quartiles) were determined for all variables in two groups defined as having persistent viral replication present or absent. The two-sided Wilcoxon test (continuity correction, 0.5) was used to compare lymphocyte phenotypes, lymphoproliferative assay responses, intracellular gag-pol mRNA, lowest CD4 counts and CD4% of these two groups. HIV-1 replication in CD4, CD45RO memory T lymphocytes persists in spite of undetectable plasma viral load. Patients (n = 24) with persistent intracellular expression of HIV-1 mRNA (> 0.3%) showed significant in vitro proliferative responses to HIV-1 p24 (stimulation index > or = 10) compared to patients (n = 35) without persistent intracellular replication. The group with persistent HIV-1 replication in cells showed no significant response to the recall antigen tetanus toxoid but a trend toward higher responses to pathogen antigens. There were no differences between the groups in the prevalence of AIDS or occurrences of opportunistic infections; however, the high viral persistence group was more HAART experienced (P < 0.05). These results suggest that HIV-1-specific immune responses correlate with evidence of ongoing HIV-1 replication.

Modeling changes in CD4-positive T-lymphocyte counts after the start of highly active antiretroviral therapy and the relation with risk of opportunistic infections: the Aquitaine Cohort, 1996-1997.

After initiation of a treatment for human immunodeficiency virus type 1 infection containing a protease inhibitor, immune restoration associated with increases in CD4-positive (CD4+) T lymphocyte count may be delayed. In a sample of patients who had been prescribed protease inhibitors for the first time, the authors tested to see whether there was a minimal duration of CD4+ cell count increase before the increase had an impact on the occurrence of opportunistic infections. The evolution (difference between time t and baseline) of CD4+ cell count was modeled using a mixed effects linear model. Changes in CD4+ count estimated by this model were then included as time-dependent covariates in a proportional hazards model. Finally, the authors tested for the existence of a CD4+ change x time interaction. The authors used a sample of 553 French patients first prescribed protease inhibitors in 1996 and followed for a median of 16 months. During the first 120 days, there was no association between CD4+ change and the rate of opportunistic infections. After 120 days, each 50-cell/mm3 increase in CD4+ count was associated with a 60% (95% confidence interval: 45, 72) reduction in the incidence of opportunistic infections. These results, based on modeling of CD4+ cell response, at least indirectly reinforce the concept of a delayed but possible immune recovery with the use of protease inhibitors. The findings support the potential for interruption of certain types of prophylaxis against opportunistic infections under reasonable conditions of duration of antiretroviral therapy and sustained CD4+ cell response.

The Use of Highly Active Antiretroviral Therapy (HAART) in Patients With Advanced HIV Infection: Impact on Medical, Palliative Care, and Quality of Life Outcomes

The effect of highly active antiretroviral therapy (HAART) in the treatment of HIV infection is usually measured by survival, CD4 lymphocyte counts, HIV-1 RNA viral load testing, and the occurrence of opportunistic infections. This pilot study sought to measure the impact of HAART treatments on a wide range of clinical outcomes and psychological variables in a sample of patients with advanced HIV infection. Seventy patients with advanced AIDS who were protease inhibitor naı̈ve were started on HAART regimens. Patients were admitted to an AIDS inpatient unit of a long-term care facility that provides treatment and palliative care. All patients were diagnosed with AIDS, had CD4 cell counts below 300/cc 3, and had a projected survival of greater than one month. Patients were started on triple-drug HAART regimens with daily medical supervision and observation. In addition to standard clinical and laboratory markers, a series of observer-rated and self-report instruments were used to measure various physical and psychological factors (e.g., pain and symptom distress, psychological well-being, depression). Data were collected at baseline and after 1 and 3 months of HAART therapy. As expected, the CD4 count increased and viral load levels decreased significantly over the 3-month study period. In addition, patients improved significantly in body weight, and serum albumin and ferritin levels. The only psychosocial measure that improved significantly with treatment was depression. Ratings of pain intensity, physical and psychological symptom distress, and overall quality of life did not change. Of the 70 patients studied, 84.3% were still alive after the 3-month study period. Of these, 6 (8.6%) were discharged to community. However, 17 surviving patients (24.3%) had HAART regimens discontinued due to drug intolerance and 11 patients (15.7%) expired during the study period. While these data are preliminary, HAART regimens appear to have positive effects on CD4 count, HIV viral load, and several other measures of physical well-being in patients with advanced AIDS. Despite these improvements, the benefits of treatment on pain and symptom distress, and psychological well-being were less clear. In addition, treatment failure (mortality and intolerance) were not uncommon in this sample (40%). Further research is clearly necessary to better understand the benefits of HAART therapy in patients with advanced HIV infection.

Impacto de la terapia anti retroviral en la mortalidad de pacientes VIH (+) chilenos: estudio caso-control (MORTAR)

Combined antiretroviral therapy (AVR) has shown a protective effect (PE) on morbidity and survival in HIV (+) patients of industrialised countries where triple-drug therapy (ARV-3) is standard. In Chile the public health system began providing double-drug therapy in 1997 (ARV-2) with 2 reverse transcriptase inhibitors. To assess the impact of ARV in morbimortality of HIV (+) patients in Chile after a year of follow up. Retrospective case-control (1:1) study. Cases were 97 patients followed during 1997 for 6 or more months and dying during that period. Each case had a control of the same gender and CDC stage, similar age and CD4 count, but surviving a same period of follow up. A comparison of ARV before and during follow up (rate and type) was done. P carinii prophylaxis, pneumococcal immunization at baseline or follow up, frequency of hospital admissions and occurrence of opportunistic infections in both groups were assessed. Odds ratio (OR) for mortality, hospitalization and opportunistic infections in ARV user, as well as treatment PE were calculated. Twenty four (24.7%) cases and sixty six (68%) controls received ARV during follow up (p < 0.001), OR was 0.15 (CI 95% 0.08-0.3), p < 0.001, the PE was 6.6 for ARV users versus non users, among cases 19 patients received ARV-2 and five received ARV-3. Among controls, 41 patients received ARV-2 and 25 received ARV-3. These differences established an OR of 0.20 (CI 95% 0.09-0.04) and a PE of 5 for ARV-2 versus no ARV. For ARV-3 compared with no ARV the OR was 0.08 (CI 95% 0.003-0.26), and the PE 12.5. Fifty three (54.6%) cases and 13 (13.4%) controls required hospital admission, OR 0.49 (CI 95% 0.25-0.94), p = 0.03, and PE of 2.04 of ARV versus no ARV; 82 (85.3%) cases and 50 (51%) controls had opportunistic infections, OR 0.5 (CI 95% 0.26-0.96), p = 0.03 and PE of 2 for ARV versus no ARV. There were no significant differences in prior ARV, prophylaxis and immunisation between cases and controls. This study showed the high impact of ARV in short term morbimortality of HIV(+) patients and the need to implement antiretroviral therapy to all patients as an official health policy. This study did not answer the question of the role, if any, of weaker-than standard antiretroviral therapy.

Relevant prevalence of Mycoplasma hominis and Ureaplasma urealyticum serogroups in HIV-1 infected men without urethritis symptoms

M. hominis and U. urealyticum are the better-known mycoplasma species pathogenic to the human genitourinary tract, causing mainly urethritis, bacterial vaginosis and pregnancy complications. In HIV-infected patients, the prevalence and role of these species is still not well known. The aim of this work was to determinate the prevalence of these species in this group of male patients (HIV group), in comparison to a group of men with clinical symptoms of urethritis (STD group). M. hominis was isolated from 7.5% patients (8/106) and U. urealyticum from 18.9% patients (20/106) from the HIV group, being among these 62.5% and 85% in significant concentrations, respectively. In the STD group these rates were 0.9% (1/110) for M. hominis and 13.6% (15/110) for U. urealyticum, being 100% and 93.3% in significant concentrations, respectively. We could demonstrate infection rates by these mycoplasma species in the HIV group as high as the one found in the STD one, what may indicate the occurrence of opportunistic infections in our population. This fact is discussed here because in immunosuppressed patients, specially M. hominis has been reported causing severe infections, even systemically.

Mycophenolate mofetil (Cellcept)

Mycophenolate mofetil (MMF) is a new immunosuppressive drug designed to inhibit inosine monophosphate dehydrogenase (IMPDH). IMPDH is a key enzyme in the purine synthesis pathway of lymphocytes. IMPDH is crucially important for the proliferative responses of human T- and B-lymphocytes. Therefore, inhibition of IMPDH leads to selective lymphocyte suppression. Following successful testing in different in vitro and animal models, MMF entered clinical trials, where it has been used in combination with cyclosporin and steroids. MMF has rapid and complete absorption following oral administration. Pilot studies suggested a significant reduction in the incidence of rejection at doses of 1 - 3 g/day. These data led to the initiation of 3 pivotal trials, in which MMF was compared against different standard immunosuppressive protocols. Nearly 1500 patients were enrolled in these 3 randomised, double-blind, multicentre studies of the addition of MMF to standard immunosuppressive protocols for the prevention of acute renal allograft rejection. After six months, the rate of biopsy-proven rejection was significantly reduced. The adverse event profile resembles that of triple therapy with azathioprine: primarily involving the gastrointestinal (GI) tract, the haematopoietic system and the occurrence of opportunistic infections. MMF affords improved immunosuppressive therapy following renal, and probably other solid organ, transplantation. It is licensed for the prevention of acute renal allograft rejection in most countries around the world.

Effectiveness of Preventing Opportunistic Infections in HIV Patients

Multiple drugs varying in efficacy, toxicity, and cost are available to reduce the occurrence of opportunistic infections in HIV-infected people. These

Radiotherapy of epidemic Kaposi's sarcoma: the experience of the Henri-Mondor Hospital (643 patients)

Retrospective analysis of results of radiotherapy in epidemic Kaposi sarcoma at the Henri-Mondor hospital. From June 1986 to December 1996, 643 patients presenting with acquired immunodeficiency syndrome (AIDS)-related epidemic Kaposi's sarcoma were treated with irradiation at the Oncology Department of Henri Mondor University Hospital. Three-hundred eighty-seven patients (60%) had previously received a treatment with interferon (259 patients, 40.2%), vinblastine (225 patients, 34.5%), doxorubicin (22 patients, 3.4%), bleomycin (19 patients, 2.9%), and/or antiviral treatment (216, 33.5%). The radiotherapy was delivered by 4 MeV or 8 MeV electron beam for extended cutaneous fields and 45-100 kV x-ray for localized fields. The delivered dose was 20 Gy in 2 weeks (2.5 Gy/fraction, 4 fractions/week) followed by 2 weeks rest and second series of 10 Gy in 1 week. For oral cavity lesions, we used a series of 15.2 Gy was delivered (1.9 Gy/fraction, 4 fractions/week), followed for three patients by a 3 week rest and by a similar second series of 15.2 Gy. Six-hundred and twenty-one patients were evaluable and the objective response rate was 92%, with a complete regression of clinical and functional symptoms for all patients. The skin tolerance was good, with 7.3% grade I reactions, 69.3% of grade II reactions, and 23.4% grade III reactions. There was a correlation between recurrence rate and the occurrence of opportunistic infections. This analysis shows the efficacy of dose radiotherapy for treatment of epidemic Kaposi sarcoma.

Epidemiologic principles in studies of infectious disease outcomes: Pediatric HIV as a model

Epidemiologic principles have been employed in the investigation of AIDS since the early 1980s. Although such principles have demonstrated the difficulties in reporting the ever-changing rates of incidence and prevalence, in addition to distributions of children with HIV, they have also established specific pieces of a multifaceted puzzle. Professional interested in examining only a piece of the puzzle, such as a particular communication disorder, often are unable to see how it fits into the complete puzzle. This article presents several epidemiologic findings of pediatric HIV, including population distributions, a summary of modes of transmission, occurrence of opportunistic infections, and manifestations of the disease in child populations. It also discusses HIV-related speech, language, swallowing, and voice disorders, examining the complexities of quantification of risk for each piece within the pediatric HIV puzzle. The purpose is to broaden the perspective of professionals concerned with how these disorders fit within the overall puzzle of immunocompromised populations of children.