Asymptomatic Human Immunodeficiency Virus Infection Research Articles

High resting energy expenditure, less fat-free mass, and less muscle strength in HIV-infected children: a matched, cross-sectional study.

Many improvements have been made in the treatment of human immunodeficiency virus (HIV) in pediatric patients; however, challenges remain in terms of achieving normal growth, body composition, and metabolism during treatment, etc. Current nutritional recommendations are based on studies performed in adults, with limited data on the HIV-infected pediatric population. Therefore, this study aimed to compare the resting energy expenditure (REE) of asymptomatic HIV-infected pediatric patients with healthy counterparts and to compare body composition, dietary intake, and physical activity between the two groups. This was a cross-sectional study of asymptomatic HIV-infected children who were receiving antiretroviral therapy; the infected group was compared with the uninfected group, matched by age (± 6 months), sex, and body mass index (± 0.5 z-score). Participants were recruited between 2021 and 2022, as outpatients. In both groups, REE was determined by indirect calorimetry and body composition by bioelectrical impedance analysis and hand strength, measured using a hydraulic hand dynamometer. Seventy-eight participants were enrolled, where n = 39 HIV-infected children and n = 39 controls, with a mean age of 11.6 ± 3.4 years old. REE was significantly higher in the HIV group (1254.4 ± 334.7 kcal/day vs. 1124.7 ± 321 kcal/day, p = 0.013) than in the control group. Fat-free mass (FFM) was lower in the HIV group (28.2 ± 10.5 kg vs. 32 ± 11.2 kg, p = 0.001); this trend continued when the index skeletal muscle was evaluated (7.2 ± 1.2 vs. 7.6 ± 1.5, p = 0.04). The strength of the dominant hand was also lower in the HIV group (12 (8-18) kg vs. 20 (10.5-26) kg, p < 0.0001). Children with asymptomatic HIV infection have higher REE than their uninfected peers. They also present decreased FFM, skeletal muscle mass index, and muscle strength. These parameters should be considered during nutritional assessment in this population to have a favorable impact on nutritional status and growth.

DENSIDAD MINERAL ÓSEA BAJA EN VARONES JÓVENES CON INFECCIÓN ASINTOMÁTICA POR EL VIRUS DE LA INMUNODEFICIENCIA HUMANA EN TRATAMIENTO ANTIRRETROVIRAL

The aim of this study was determine the frequency of low bone mineral density (BMD) in young men with asymptomatic Human Immunodeficiency Virus (HIV) infection on antiretroviral therapy for less than 2 years, as well as to compare the frequency of low and normal BMD according to antiretroviral treatment (ART) scheme and level of physical activity. 39 young men with asymptomatic HIV infection and ART less than 2 years were included. A bone densitometry was performed, and the following areas were evaluated: lumbar spine, left femoral neck and total left hip. 12 patients (31%) with low BMD and 27 patients (69%) with normal BMD were found. No differences were found between patients with normal and low BMD according to type of ART and level of physical activity. The frequency of low BMD is high in young men with asymptomatic HIV infection under antiretroviral treatment for less than 2 years.

Symptomatic human immunodeficiency virus infection is associated with advanced presentation and perioperative mortality in patients undergoing surgery for peripheral arterial disease

ObjectivePrior studies have demonstrated an increased risk of developing cardiovascular and peripheral arterial disease (PAD) in patients with human immunodeficiency virus (HIV). However, the effect of chronic HIV infection in patients with preexisting PAD and requiring vascular intervention is unclear. In the present study, we assessed the differences in clinical presentation and perioperative outcomes for patients with PAD who had undergone revascularization or amputation with and without HIV infection. MethodsInternational Classification of Diseases, 9th and 10th Revisions, Clinical Modification, codes were used to identify patients with a prior diagnosis of PAD who had undergone lower extremity revascularization or amputation in the National Inpatient Sample (2003-2017). From this group, the patients were divided for analysis into those with and without HIV infection. Of the patients with HIV infection (PWHs), we identified additional subsets of patients: those with any prior or current diagnosis of an HIV-related illness, including acquired immunodeficiency syndrome, designated as symptomatic HIV, and those without such a diagnosis, designated as asymptomatic HIV infection. Propensity score matching was performed to create matched cohorts. Population-based comparative analyses were performed of the clinical characteristics of the HIV-infected and HIV-uninfected groups. Univariate and multivariate logistic regression analyses of the perioperative in-hospital outcomes were performed on the matched cohorts. ResultsA total of 224,912 patients aged 18 to 85 years were identified who had been admitted with an established diagnosis of PAD and had undergone a lower extremity procedure. Of these patients, 1264 (0.56%) also had a diagnosis of HIV infection. Symptomatic PWHs were more likely to present with critical limb ischemia than were the HIV-uninfected patients or asymptomatic PWHs (66.2% vs 46.3% and 43.6%; P < .01). However, both asymptomatic and symptomatic PWHs were more likely to have required minor (7.5% and 6.7% vs 2.6%; P < .01) and major (12.9% and 27.4% vs 7.0%; P < .01) amputations than were matched HIV-uninfected controls. Although adjusted multivariate logistic regression analysis demonstrated symptomatic HIV infection to be a significant, independent predictor of in-hospital mortality (odds ratio, 2.46; 95% confidence interval, 1.37-4.40; P = .003), the perioperative mortality for the asymptomatic PWH was comparable to that of matched HIV-uninfected controls. ConclusionsSymptomatic PWHs, including patients living with acquired immunodeficiency syndrome, who had required a PAD-related procedure had presented with more advanced vascular disease and were most at risk of early perioperative mortality. However, the presentation and mortality between asymptomatic PWHs with well-controlled disease and HIV-uninfected patients were comparable. All PWHs with PAD were more likely to undergo lower extremity amputations than were HIV-uninfected matched controls. Asymptomatic, well-controlled HIV infection should not be a contraindication to elective PAD-related procedures because the mortality was similar to that of HIV-uninfected controls. However, the limb salvage rates might be lower for all PWHs with PAD, regardless of HIV disease severity. Taken together, these findings can improve perioperative risk stratification and surgical management of PAD in this high-risk population.

MuSK Myasthenia Gravis in an HIV-infected Chinese old man successfully treated with pyridostigmine

MuSK Myasthenia Gravis in an HIV-infected Chinese old man successfully treated with pyridostigmine

Fulminant anaplastic large cell lymphoma (ALCL) concomitant with primary cytomegalovirus (CMV) infection, and human herpes virus 8 (HHV-8) infection together with Epstein-Barr-virus (EBV) reactivation in a patient with asymptomatic HIV-infection.

BackgroundMost malignant lymphomas in HIV-patients are caused by reactivation of EBV-infection. Some lymphomas have a very rapid fulminant course. HHV-8 has also been reported to be a cause of lymphoma. The role of CMV in the development of lymphoma is not clear, though both CMV and HHV-8 have been reported in tissues adjacent to the tumour in Burkitt lymphoma patients. Here we present a patient with asymptomatic HIV infection, that contracted a primary cytomegalovirus (CMV) infection and human herpes virus 8 (HHV-8) infection. Three weeks before onset of symptoms the patient had unprotected sex which could be possible source of his CMV and also HHV-8 infection He deteriorated rapidly and died with a generalized anaplastic large cell lymphoma (ALCL).MethodsA Caucasian homosexual male with asymptomatic human immunodeficiency virus (HIV) infection contracted a primary cytomegalovirus (CMV) infection and human herpes virus 8 (HHV-8) infection. He deteriorated rapidly and died with a generalized anaplastic large cell lymphoma (ALCL). Clinical and laboratory records were compiled. Immunohistochemistry was performed on lymphoid tissues, a liver biopsy, a bone marrow aspirate and the spleen during the illness and at autopsy. Serology and PCR for HIV, CMV, EBV, HHV-1–3 and 6–8 was performed on blood drawn during the course of disease.ResultsThe patient presented with an acute primary CMV infection. Biopsies taken 2 weeks before death showed a small focus of ALCL in one lymph node of the neck. Autopsy demonstrated a massive infiltration of ALCL in lymph nodes, liver, spleen and bone marrow. Blood samples confirmed primary CMV- infection, a HHV-8 infection together with reactivation of Epstein- Barr-virus (EBV).ConclusionPrimary CMV-infection and concomitant HHV-8 infection correlated with reactivation of EBV. We propose that these two viruses influenced the development and progression of the lymphoma. Quantitative PCR blood analysis for EBV, CMV and HHV-8 could be valuable in diagnosis and treatment of this type of very rapidly developing lymphoma. It is also a reminder of the importance of prevention and prophylaxis of several infections by having protected sex.

Impact of HIV infection on the haemostatic response during sepsis and malaria.

Patients positive for the human immunodeficiency virus (HIV) are more susceptible to sepsis and malaria, two conditions known to activate the coagulation system. As chronic HIV infection also influences haemostatic mechanisms, we determined the influence of HIV co-infection on coagulation, anticoagulation and the endothelium during sepsis or malaria. We performed a prospective observational study in 325 subjects with or without HIV infection (103 with sepsis, 127 with malaria and 95 asymptomatic controls) in an HIV endemic area in Central Africa. We measured plasma biomarkers indicative of activation of distinct haemostatic mechanisms. Sepsis and malaria had similar effects with elevated markers of coagulation, reduced anticoagulation markers and activation of endothelium. In particular, asymptomatic HIV infection reduced the plasma levels of the anticoagulant co-factor free protein S, and increased activation of the vascular endothelium, which were not normalized by combination antiretroviral therapy. HIV co-infection during sepsis and malaria caused more profound changes in free protein S and von Willebrand factor in sepsis and malaria, and ADAMTS13 in sepsis, while not influencing sepsis- or malaria-induced coagulation activation. These results show for the first time that HIV infection augments selective haemostatic changes during sepsis and malaria, which may contribute to the enhanced morbidity of these conditions in HIV patients.

Evaluating the use of procalcitonin in an asymptomatic, HIV-infected antiretroviral therapy-naïve, South African cohort.

The chronic stage of human immunodeficiency virus (HIV) infection, although clinically asymptomatic, is characterized by activation of the immune system and persistent inflammation. Procalcitonin (PCT) has been studied in HIV infection as a marker of bacterial infection. Our aim was to assess the effect of persistent immune activation on PCT levels in asymptomatic treatment naïve HIV infected subjects. This was a cross-sectional study of 68 asymptomatic antiretroviral therapy-naive HIV infected participants and 42 uninfected controls. Stored serum samples were used to measure: PCT, interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP), high sensitivity C-reactive protein (hsCRP), immunoglobulin G (IgG) and albumin. PCT was correlated with markers of: disease progression (CD4 count and viral load), immune activation (CD 38 on CD8+ T cells, IgG and LBP), inflammation (IL-6, hsCRP and albumin). IL-6, IgG and CD8/38 were all significantly increased while albumin and CD4 counts were significantly lower in the HIV infected group. PCT levels were not significantly different between the two groups. There was no significant difference in LBP and hsCRP; however, their levels were increased in both groups. PCT correlated only with LBP (p=0.0001). IL-6 and LBP correlated positively with hsCRP and IgG. Albumin correlated inversely with IL-6 and viral load. Only IgG and CD8/38 correlated inversely with CD4 counts. We demonstrated the activation of the innate (raised LBP), humoral (raised IgG) and cellular immune systems (increased CD8/38 T cells). Despite a state of persistent inflammation, PCT levels are not elevated in asymptomatic untreated HIV infection.

Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection

BackgroundData from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter.MethodsWe randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non–AIDS-related event, or death from any cause.ResultsA total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non–AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P=0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions.ConclusionsThe initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.)

HIV Coinfection Enhances Complement Activation During Sepsis.

Human immunodeficiency virus (HIV)-induced complement activation may play a role in chronic immune activation in patients with HIV infection and influence the complement system during acute illness. We determined the impact of HIV infection on the complement system in patients with asymptomatic HIV infection and HIV-infected patients with sepsis or malaria. We performed a prospective observational study of 268 subjects with or without HIV infection who were asymptomatic, were septic, or had malaria. We measured complement activation products (C3bc and C4bc) and native complement proteins (C3 and C4). levels of mannose-binding lectin and C1q-C4 were measured to examine activation of the lectin and classical pathways, respectively. Asymptomatic HIV infection was associated with increased C4 activation, especially in patients with high HIV loads, and was accompanied by elevated C1q-C4 levels. Similarly, sepsis and malaria resulted in increased C4 activation and elevated C1q-C4 concentrations. HIV coinfection enhanced C4 activation and consumption in patients with sepsis; this effect was not detected in patients with malaria. Mannose-binding lectin deficiency (defined as a mannose-binding lectin level of <500 ng/mL) did not influence complement activation in any group. HIV activates the complement system, predominantly via the classical pathway, and causes increased C4 activation and consumption during sepsis. HIV-induced complement activation may contribute to tissue injury during chronic infection and acute intercurrent bacterial infections.

術前検査を契機に発見された無症候期HIV感染症の1例

術前検査を契機に発見された無症候期HIV感染症の1例

Clinical and Epidemiological Characteristics of HIV Infection/AIDS in Hospitalized Patients.

Introduction:More than three decades after recognition of acquired immunodeficiency syndrome (AIDS) in the United States, the pandemic of human immunodeficiency virus (HIV) infection has dramatically changed the global burden of disease.Aim:The main goal of this research is retrospective analysis of epidemiological and clinical characteristics of 28 HIV infected patients, who were diagnosed and treated at the Clinic for Infectious Diseases in University Clinical Center Tuzla in the period from 1996 until the end of 2013.Subjects and Methods:Retrospective analysis was performed using the medical records of 28 HIV-infected persons. Two rapid tests were used for HIV testing: OraQuick Advance test, Vikia HIV1/2, Elisa combo test, HIV RNA test. AIDS disease was determined by using the criteria from WHO.Results:Among a total of 28 HIV-infected persons, 23 (82.14%) were males and 5 (17.86%) were females, with the male: female ratio of 4,6:1. In terms of the transmission route, a large proportion of cases were infected through heterosexual contact 19 (67.86%). At the time of the first visit, 16 (57.15%) patients showed asymptomatic HIV infection, 4 (14.28%) HIV infection with symptoms other than the AIDS defining diseases, and 8 (28.57) had AIDS. At the time of first hospital visit, the CD4 + cells count ranged from 40 to 1795/µl (conducted in 19 patients), and mean value of CD4 + cells was 365,31/µl, and mean HIV RNA titer was 287 118 copies/ml³. Of 28 HIV-infected persons 39 cases of opportunistic diseases developed in 12 patients (42.9%). In terms of the frequency of opportunistic diseases, tuberculosis (12 cases, 42.9%). Among a total of 28 HIV-infected patients, 6 (21.4%) of them died.Conclusion:This study characterizes the epidemiological and clinical patterns of HIV–infected patients in Tuzla region of Bosnia and Herzegovina to accurately understand HIV infection/AIDS in our region, in the hope to contribute in the establishment of effective HIV guidelines in the Tuzla region of B&H in the future.

Association of Hematological Profile of Human Immunodeficiency Virus-Positive Patients with Clinicoimmunologic Stages of the Disease

Aim:This work was carried out to study the hematologic profile of human immunodeficiency virus (HIV)-positive patients and its association with the clinicoimmunologic stage of the disease.Materials and Methods:A total of 187 patients with HIV, whether symptomatic or asymptomatic, diagnosed by enzyme-linked immunosorbent assay (ELISA) method according to the National AIDS Control Organization (NACO) guidelines were included in this study. Patients in the study population were divided into two groups: (1) Group A (antiretroviral therapy (ART) included patients receiving ART [ART-Y]) and (2) Group B included treatment naïve patients (ART-N). The patients were tested for hemoglobin (Hb), total red blood cells (RBC) count, RBC indices, reticulocyte count, packed cell volume (PCV), total lymphocyte counts(TLC), differential leukocyte counts (DLC), platelet count, and erythrocyte sedimentation rate (ESR). Cut-off values were determined as Hb < 10 g/dl, platelet count < 1.5 lakh/cumm, and TLC < 4,000/cumm. The group or categorical data were tested for statistical significance using Chi-square test and Z-test. The difference was reported as significant if P < 0.05.Results:(1) Anemia (predominantly normocytic normochromic) was prevalent in 40.1%, with slightly higher prevalence in those not receiving ART. It occurred with high frequency in patients with immunological (42.05%) and clinical acquired immunodeficiency disease syndrome (AIDS) (70.58%) compared with those who had an asymptomatic HIV infection with CD4 > 200/μl (28.57%). Patients on zidovudine (AZT) therapy had 34.6% anemia with increased mean corpuscular volume (MCV). (2) Thrombocytopenia was seen in 3.74% patients (higher percentage in untreated patients). (3) Leucopenia was observed in 5.88% in ART-Y (Group A) and 8.14% in ART-N (Group B) patients. (4) Pancytopenia was found in 1.6% patients.

An unusual case of peripheral ulcerative keratitis as a presenting feature in an otherwise healthy patient with undiagnosed human immunodeficiency virus infection and low CD4 counts

Sir, Peripheral ulcerative keratitis (PUK) as initial manifestation in a patient with asymptomatic human immunodeficiency virus (HIV) infection is rarely reported. Herein, we describe HIV vasculitis presenting as PUK in an otherwise healthy HIV-infected patient. A 40-year-old married female presented with right eye redness, blurring of vision and pain since 1 month with no history of trauma, discharge, watering or contact lens wear without any complaints in left eye and no significant systemic history. The best corrected visual acuity was 20/40 and 20/20 in the right and left eyes, respectively. On slit lamp examination, the right eye showed a crescentic lesion involving the nasal corneal margin from 1 to 5 o′clock in the clockwise direction with associated stromal thinning; conjunctival involvement in the form of nodular lesion with dilated tortuous vessels and underlying scleral thinning [Fig. 1]. Ocular adnexa, corneal sensations and dilated fundus examination of both eyes were normal. Figure 1 Right eye showing a crescentic lesion nasally with associated stromal thinning, conjunctival involvement and underlying scleral thinning With an impression of PUK, the patient was advised the following investigations: erythrocyte sedimentation rate (ESR), rheumatoid arthritis factor, antineutophil cytoplasmic antibody, Venereal Disease Research Laboratory test, counselled enzyme-linked immunoassay (ELISA) for HIV, X-ray chest, Mantoux test and rheumatologist opinion. Corneal scraping was subjected to Gram and Giemsa stains, KOH mount and culture and sensitivity, and was reported to be negative. Rheumatology opinion showed no clinical evidence of collagen vascular disorder. All blood investigations, Mantoux test (4 mm induration), ESR (15 mm) and X-ray chest were normal. ELISA for HIV was reported to be positive. The patient was started on lubricant drop and referred to the HIV clinic. CD4 counts (110 cells/cu mm) and viral load by polymerase chain reaction (PCR) (163,960 copies/mL) were done and the patient was started on anti-retroviral therapy (ART) – (zidovudine 300 mg BD, lamivudine 150 mg BD and efavirenz 600 mg OD). Impression cytology of the lesion showed inflammatory cells (neutrophils and lymphocytes) suggesting an active disease process. Scraping was repeated and PCR done for herpes simplex virus 1 and 2 and herpes zoster virus, and was negative. The lesion that initially showed worsening after starting ART (immune recovery response) showed almost complete resolution over the next 2 months, with minimal residual subconjunctival scarring [Fig. 2]. Figure 2 Right eye showing almost complete resolution of the lesion with minimal subconjunctival scarring at 8 weeks follow-up PUK with central retinal vein occlusion[1] and PUK secondary to ocular surface infection with herpes zoster virus[2] have been previously reported in the literature as presenting feature of HIV infection. Our patient had no history of chicken pox, no evidence of herpes zoster or any systemic condition known to be associated with PUK in HIV infection. Vasculities in HIV infection is an uncommon but important pathogenic factor that might manifest as organ-based disease process. HIV vasculopathy is an indirect effect of HIV infection via the immune complex-mediated mechanism or direct infection of vascular/perivascular tissue.[3] Negative serological and microbiological tests, simultaneous involvement of cornea, conjunctiva and sclera,[4] acute inflammatory cells on impression cytology, a high viral load with low CD4 counts and excellent resolution with ART led us to suspect HIV vasculopathy as a possible pathogenesis in our patient. Further research will help us determine the exact pathogenesis in these types of cases.

Prevalence of Undiagnosed HIV Infection in Patients With Ocular Surface Squamous Neoplasia in a Tertiary Center in Karnataka, South India

To evaluate the prevalence of undiagnosed and asymptomatic human immunodeficiency virus (HIV) infection in patients with ocular surface squamous neoplasia (OSSN) in a referral hospital in Karnataka, South India. A consecutive series of patients presenting with OSSN were evaluated in an academic center during January 2009 to June 2010. A detailed history was obtained and physical examination in 25 consecutive patients with OSSN was performed. Twenty-three patients (88%) agreed to undergo serological HIV testing. Of these, 2 were excluded from the current study because they had xeroderma pigmentosa, a known predisposing factor for OSSN. Of the 21 patients, 6 (29%) patients were HIV positive. None of the patients had previous HIV testing. The median age of presentation among HIV-positive patients was 36 years, whereas it was 54 years among HIV-negative patients. The mean CD4 count in HIV-positive patients was 133 cells per mm, and all patients were started on antiretroviral treatment. The conjunctival tumor may be the primary and the only apparent manifestation of HIV in patients presenting with OSSN, and the ophthalmologist needs to be aware of this association.

Considerations in the rationale, design and methods of the Strategic Timing of AntiRetroviral Treatment (START) study

Untreated human immunodeficiency virus (HIV) infection is characterized by progressive depletion of CD4+ T lymphocyte (CD4) count leading to the development of opportunistic diseases (acquired immunodeficiency syndrome (AIDS)), and more recent data suggest that HIV is also associated with an increased risk of serious non-AIDS (SNA) diseases including cardiovascular, renal, and liver diseases and non-AIDS-defining cancers. Although combination antiretroviral treatment (ART) has resulted in a substantial decrease in morbidity and mortality in persons with HIV infection, viral eradication is not feasible with currently available drugs. The optimal time to start ART for asymptomatic HIV infection is controversial and remains one of the key unanswered questions in the clinical management of HIV-infected individuals. In this article, we outline the rationale and methods of the Strategic Timing of AntiRetroviral Treatment (START) study, an ongoing multicenter international trial designed to assess the risks and benefits of initiating ART earlier than is currently practiced. We also describe some of the challenges encountered in the design and implementation of the study and how these challenges were addressed. A total of 4000 study participants who are HIV type 1 (HIV-1) infected, ART naïve with CD4 count > 500 cells/µL are to be randomly allocated in a 1:1 ratio to start ART immediately (early ART) or defer treatment until CD4 count is <350 cells/µL (deferred ART) and followed for a minimum of 3 years. The primary outcome is time to AIDS, SNA, or death. The study had a pilot phase to establish feasibility of accrual, which was set as the enrollment of at least 900 participants in the first year. Challenges encountered in the design and implementation of the study included the limited amount of data on the risk of a major component of the primary endpoint (SNA) in the study population, changes in treatment guidelines when the pilot phase was well underway, and the complexities of conducting the trial in a geographically wide population with diverse regulatory requirements. With the successful completion of the pilot phase, more than 1000 participants from 100 sites in 23 countries have been enrolled. The study will expand to include 237 sites in 36 countries to reach the target accrual of 4000 participants. START is addressing one of the most important questions in the clinical management of ART. The randomization provided a platform for the conduct of several substudies aimed at increasing our understanding of HIV disease and the effects of antiretroviral therapy beyond the primary question of the trial. The lessons learned from its design and implementation will hopefully be of use to future publicly funded international trials.

Asymptomatic Human Immunodeficiency Virus (HIV) Infection: Report of Two Cases Treated with Didanosine and Indinavir

Asymptomatic Human Immunodeficiency Virus (HIV) Infection: Report of Two Cases Treated with Didanosine and Indinavir

Increased dopaminergic neurotransmission in therapy-naïve asymptomatic HIV patients is not associated with adaptive changes at the dopaminergic synapses

Central dopaminergic (DA) systems are affected during human immunodeficiency virus (HIV) infection. So far, it is believed that they degenerate with progression of HIV disease because deterioration of DA systems is evident in advanced stages of infection. In this manuscript we found that (a) DA levels are increased and DA turnover is decreased in CSF of therapy-naïve HIV patients in asymptomatic infection, (b) DA increase does not modulate the availability of DA transporters and D2-receptors, (c) DA correlates inversely with CD4+ numbers in blood. These findings show activation of central DA systems without development of adaptive responses at DA synapses in asymptomatic HIV infection. It is probable that DA deterioration in advanced stages of HIV infection may derive from increased DA availability in early infection, resulting in DA neurotoxicity. Our findings provide a clue to the synergism between DA medication or drugs of abuse and HIV infection to exacerbate and accelerate HIV neuropsychiatric disease, a central issue in the neurobiology of HIV.

Evaluation of immunoglobulin classes (IgA, IgG and IgM) levels and complement fixation activity in HIV infected subjects

The study was designed to evaluate the immunoglobulin A, G and M levels and complement fixation activity in HIV infected participants, who were not administered antiretroviral therapy (ART). Eighty (80) HIV infected participants, aged between 15 – 55 years (38 ±10 years), were recruited for the study. Forty five (45) of the participants were classified as symptomatic HIV (stage ii), while the remaining 35 were classified asasymptomatic HIV (stage i). Similarly, 40 seronegative participants served as control. Blood samples were collected from the participants for the determination of HIV status by immunochromatography, HIV confirmation by Western blot, determination of immunoglobulin levels by immunoturbidimetry, and complement activity by complement fixation test. The IgG and IgA were significantly increased in symptomatic HIV infection compared with asymptomatic HIV infection (p0.05). The complement fixation activities decreased in HIV infected patients compared with the values in HIV seronegatives. The increase in IgA concentration with HIV infected participants may suggest existence of mucosal infections, while theincrease in IgG concentration in HIV infected participants may suggest evidence of increased opportunistic infection requiring IgG response. The low level of complement activity in HIV infected participants maypredispose individuals with HIV infection to disease commonly controlled through immunological activity of the complement. Keywords: Human Immunodeficiency Virus (HIV), immunoglobulins (IgA, IgG and IgM), complements.

Quality care: a link between clinical and public health approaches to HIV infection in developing countries

As the importance of quality in health care provision is increasingly recognised, it is opportune to consider quality care as a key link between clinical and public health approaches to human immunodeficiency virus (HIV) infection in developing countries, especially in sub-Saharan Africa. This region has the lion's share of the global epidemic and the least resources to respond. Looking at health problems using a 'quality lens' may help bridge the gaps between clinical care and public health, the current and desired standard of care, and prevention and treatment. Quality care, with prompt diagnosis and effective treatment, of people with HIV infection is crucial for good individual health outcomes, public health outcomes (in terms of decreased HIV transmission) and societal outcomes (increased productivity and decreased costs of health provision for HIV-related care). A spotlight on quality care can bring clinicians and public health practitioners together in working towards universal access to quality HIV care and prevention - one of the greatest health challenges faced in developing countries in Africa today.

Lumbar Puncture in HIV‐Infected Patients with Syphilis and No Neurologic Symptoms

The decision to perform lumbar puncture in patients with asymptomatic human immunodeficiency virus (HIV) infection and syphilis is controversial. The Centers for Disease Control and Prevention recommend certain criteria that warrant lumbar puncture. Here, we assess the performance of these criteria for detecting asymptomatic neurosyphilis (ANS). Eligible subjects consisted of all patients with concurrent HIV infection and syphilis in a prospective clinical cohort who had no neurologic symptoms at the time of lumbar puncture. We retrospectively applied different stratification criteria to calculate the performance of lumbar puncture in detecting ANS: (1) lumbar puncture in patients with late latent syphilis or syphilis of an unknown duration, regardless of the CD4 cell count or rapid plasma reagin titer; (2) lumbar puncture if the CD4 cell count was 350 cells/mL and/or the rapid plasma reagin titer was 1:32, regardless of the syphilis stage; and (3) lumbar puncture in the context of serologic nonresponse to syphilis therapy. Two hundred two of 231 patients with syphilis did not have neurologic symptoms. Immediate lumbar puncture was performed for 46 patients, and 10 cases (22%) of ANS were detected. With use of the first criterion, 2 (14%) of 10 cases of ANS in patients with early-stage syphilis would have been missed (sensitivity, 80% [95% confidence interval [CI], 44%-97%]; specificity, 23% (95% confidence interval [CI], 11.4%-40.2%) [corrected] Criterion 2 would not have missed any cases of ANS (sensitivity, 100% [95% CI, 70%-100%]; specificity, 13.2% (95% CI, 4.4%-29.1%) [corrected] but would have required that a lumbar puncture be performed for 88% of patients. Performance of lumbar puncture performed in 13 cases based on serologic nonresponse to syphilis therapy yielded 4 cases (31%) of ANS. In patients with concurrent HIV infection and syphilis, the use of criteria based on rapid plasma reagin titer and CD4 cell count, instead of stage-based criteria, improved the ability to identify ANS.