Decrease In CD4 Cell Count Research Articles

Prevalence of Intestinal Parasitic Infections in Relation to the HIV Status of Patients Attending the Care Units in Three Divisions in the Centre Region of Cameroon

Background: Depression of the immune system caused by the human immunodeficiency virus (HIV) promotes the onset of opportunistic infections including intestinal parasites. Objectives: In this study, we are comparing the prevalence of these parasitic infections among individuals infected with HIV (HIV+) and non-infected (HIV-) enrolled in four HIV care units in the Centre Region of Cameroon. Methods: A cross-sectional study was conducted and stool samples were collected from 283 HIV positive subjects and 245 seronegative subjects. These samples were processed using direct wet mount, formol-ether concentration, Kato-Katz procedure, modified Ziehl-Neelsen staining, and Baermann techniques to identify both common and opportunistic intestinal parasites. Logistic regression analyses were used to assess the association between HIV infection and socio-demographics factors as well as infection with intestinal parasites. Results: A total of 123 (23.4%) individuals were found infected with at least one protozoan parasite species, and nine (1.7%) with intestinal worms. Overall, infection rates were 27.9% and 22.4% among HIV+ and HIV- subjects, respectively. The frequencies of Cryptosporidium spp. and Entamoeba histolytica/dispar were significantly more important among HIV+ subjects (P < 0.0455). Pentatrichomonas hominis and Entamoeba coli were significantly more prevalent among HIV- subjects (P < 0.0210). Heterogeneity was observed in the distribution of intestinal parasites, according to socio-demographic parameters. In addition, Cryptosporidium spp. was significantly associated with the decrease in CD4 cell count (P = 0.0035). The frequencies of infections with Cryptosporidium spp., Isospora belli, and Iodamoeba buetschlii were significantly more important in HIV positive patients not taking antiretroviral (P < 0.0226). Conclusions: Cryptosporidium spp., Entamoeba histolytica/dispar, and Blastocystis spp. were the intestinal pathogens more often found among HIV infected individuals. HIV positive subjects were significantly more infected with intestinal parasites than seronegatives in intermediate and rural settings, among individuals aged more than 45 years and among unemployed individuals.

CD4 count and tuberculosis risk in HIV-positive adults not on ART: a systematic review and meta-analysis.

BackgroundCD4 cell count in adults with human immunodeficiency virus (HIV) infection (PLHIV) not receiving antiretroviral therapy (ART) influences tuberculosis (TB) risk. Despite widespread use in models informing resource allocation, this relationship has not been systematically reviewed.MethodsWe systematically searched MEDLINE, Aidsinfo, Cochrane review database and Google Scholar for reports in English describing TB incidence stratified by updated CD4 cell count in cohorts of HIV-positive adults (age ≥15 years) not on ART (PROSPERO protocol no: CRD42016048888). Among inclusion criteria were: reporting precision for TB incidence, repeated CD4 measurements, and TB incidence reported for those not on ART or monotherapy. Study quality was assessed via the Newcastle-Ottawa tool for cohort studies. A Bayesian hierarchical model was fitted to estimate the pooled factor increase in TB incidence with respect to CD4 cell count decrement.ResultsA total of 1,555 distinct records were identified from which 164 full text articles were obtained. Common reasons for exclusion of full texts were: no valid TB incidence, no repeat CD4 measurements, and not reporting TB incidence by ART status. The seven studies included reported on 1,206 TB cases among 41,271 individuals, with a typical median follow-up of four years. Studies were generally rated as moderate or high quality. Our meta-analysis estimated a 1.43 (95% credible interval: 1.16–1.88)-fold increase in TB incidence per 100 cells per mm3 decrease in CD4 cell count.DiscussionOur analysis confirms previous estimates of exponential increase in TB incidence with declining CD4 cell count in adults, emphasizing the importance of early ART initiation to reduce TB risk in PLHIV.

Causal effects of HIV on employment status in low-income settings

This paper estimates the causal impact of being HIV positive on individual employment status using a recursive bivariate probit with male circumcision as the instrument to overcome the endogeneity arising from simultaneity bias. The results show that being HIV positive reduces the probability of being employed by 5 percentage points among males in Uganda. The effect is greater for individuals employed in manual labor than non-manual labor. When limiting the sample to mainly individuals employed in subsistence agriculture, we find a 4 percentage point reduction in the likelihood of employment, suggesting that the effect occurs primarily through reductions in labor supply as opposed to demand. This is supported by additional analysis using univariate probit regressions to assess the association between different levels of HIV illness (as measured by CD4 cell count) and the likelihood of employment. The magnitude of the association increases as CD4 cell count decreases. Having a CD4 cell count of 200permm3 or below is associated with a 9 percentage point reduction in employment compared to individuals with CD4 cell counts above 200permm3.

The role of CD4 cell count as discriminatory measure to guide chemoprophylaxis against Pneumocystis jirovecii pneumonia in human immunodeficiency virus-negative immunocompromised patients: A systematic review.

In recent years, the incidence of Pneumocystis jirovecii pneumonia (PJP) has increased in immunocompromised patients without human immunodeficiency virus (HIV) infection. Chemoprophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) is highly effective in preventing PJP in both HIV-positive and -seronegative patients. In HIV-positive patients, the risk of PJP is strongly correlated with decreased CD4 cell count. The role of CD4 cell count in the pathogenesis of PJP in non-HIV immunocompromised patients is less well studied. For most immunosuppressive conditions, no clear guidelines indicate whether to start TMP-SMX. We conducted a systematic literature review with the aim to provide a comprehensive overview on the role of CD4 cell counts in managing the risk of PJP in HIV-seronegative patients. Of the 63 individual studies retrieved, 14 studies report on CD4 cell counts in a variety of immunosuppressive conditions. CD4 cell count were <200/μL in 73.1% of the patients. CD4 cell count <200/μL is a sensitive biomarker to identify non-HIV immunocompromised patients who are at risk for PJP. Measuring CD4 cell counts could help clinicians identify patients who may benefit from TMP-SMX prophylaxis.

Endometrial dysfunction caused by chronic endometritis: сlinical and morphological aspects

to determine the clinical and morphological aspects of endometrial dysfunction caused by chronic endometritis (CE). The study included 239 reproductive-aged patients: 93 were examined for abnormal uterine bleeding; 37 patients of them had a history of miscarriage and secondary infertility, 17 patients had primary infertility (Group 1). The remaining 105 patients with infertility were examined for future in vitro fertilization (Group 2). A comparison group consisted of 41 patients with normal menstrual cycles and reproductive function across the cycle, who had separate diagnostic curettage before forthcoming surgery for uterine myoma. All the women in Groups 1 and 2 underwent standard clinical and morphological investigations, histopathological examination of the material obtained during hysteroscopy with separate diagnostic curettage (Group 1), and aspiration biopsy (Group 2) with the sections being stained with hematoxylin and eosin and by Mallory's method. Immunohistochemical diagnosis was used to assess endometrial receptivity to steroid hormones and glycodelin. Antibodies against CD4, СD8, and CD20 were employed to study local immunity. In Group 1, 52 (55.9%) of the 93 patients admitted to hospital for abnormal uterine bleeding were found to have CE on the basis of a morphopathological examination of the material after separate diagnostic study. In Group 2, CE was established in 59 (56.9%) of the 105 patients after postmortem examination. The patients with CE had a history of reproductive significant infections, such as Chlamydia, Trichomonas, Ureaplasma Mycoplasma, cytomegalovirus, papillomavirus infections, genital herpes, genital candidiasis, and bacterial vaginosis. The CE groups showed functional disorders of the endometrial glandular and surface epithelium. In the middle stage of proliferation, the expression of glycodelin in the glandular epithelial cells was detected to be moderate to strong in 83.3%. During the periovulatory period, no secretion of glycodelin is of fundamental importance for the regulation of reproductive function because this protein has contraceptive activity, by blocking the binding of sperm to the zona pellucida. Accordingly, endometrial glycodelin production during the proliferative phase, which has been identified by the authors in patients with CE, may be one of the pathogenic mechanisms for the development of infertility. In addition, the patients in Groups 1 and 2 compared with those in the comparison group were noted to have a decrease in CD4 cell counts with a simultaneous increase in CD8 expression and a reduction in CD20 levels, especially in Group 2. The patients with SE were identified to have endometrial dysfunction characterized by lower reception to steroid hormones, impairment in glycodelin secretion, retardation in the development of pinopods and in the phase of the menstrual cycle, and local immunity disorders. The above endometrial changes should be taken into account in the pregravid preparation of patients with CE.

Some Clinical and Biochemical Effects Associated With Acute Malathion-Induced Immunotoxicity in Minia City, Egypt

Pesticides have been implicated in increasing the prevalence of diseases associated with alterations of the immune response. The purpose of this review was to demonstrate some clinical effects and to investigate some biochemical changes that occur with acute malathion pesticide intoxication regarding immune system. During a period of six months that started from 1st of November 2014 till 30th of April2015, 43 subjects were chosen to be involved in this study. They were divided into 2 groups: group A (control): 10 apparently healthy subjects and group B: consists of 33 patients acutely intoxicated by malathion. Pseudocholine estrase enzyme level, interleukin 2 (IL-2), and cluster of differentiation cells (CD4, CD8 and CD19) were investigated for all subjects. The results of the current study revealed significant increase in male intoxicated cases andingestion was the most common route of intoxication. The mean ages of patients was 30.1±8.5 years old. Suicidal intent was the common mode of toxicity.The mean of delay interval between intoxication and hospital admission was 8.3±5.8 hours. Significant statistical differences in all vital signs, local and some systemic manifestation of the patient. Pseudocholine esterase level was reduced in all cases. Significant decrease in CD4, CD8 and CD19 cell count, while significant increase in IL-2 levels in group 2 patients as compared to control subjects. Significant positive correlation was evident between IL-2 and CD4 count, while significant negative correlation between IL-2 and CD19 count appeared. Insignificant correlations between pseudocholine esterase level and (CD 19, CD8 & CD4) and between IL-2 and (CD8 & Pseudocholine esterase level) were noticed. Critical cases represent 27.3% of patients.Hospital stay duration mean was 8.6±4.8 days. The study concluded that acute malathion toxicity can carry the risk of immunotoxicity. There is demand to continue to improve immunotoxicological studies. A concerted effort is required to organize and standardize a study protocol.

A study of anemia in human immunodeficiency virus patients: Estimating the prevalence, analyzing the causative effect of nutritional deficiencies, and correlating the degree of severity with CD4 cell counts

Background: Anemia is a common complication of human immunodeficiency virus (HIV) infection. The role of iron, Vitamin B12, and folate deficiencies, which are otherwise most common causes of anemia, is not well-established in HIV patients. Several studies in India have shown that severe immunodeficiency is associated with higher grade of anemia, but correlation of CD4 cell counts with severity of anemia is not well-documented. Aims: The aims of the present study were: To estimate the point prevalence of anemia in HIV patients, to analyze the causative role of iron, Vitamin B12, and folate deficiencies in anemic HIV patients, and correlating the degree of severity of anemia with CD4 cell counts. Materials and Methods: This study was a cross-sectional study. The study group enrolled 103 consecutive HIV patients attending medical emergency, medical outpatient department, medical wards, and anti-retroviral therapy (ART) center at a tertiary care medical center in North India. Study participation consisted of a single visit during which relevant data, including medical history, current medications, CD4 T-lymphocyte count, complete hemogram with red blood cell indices, peripheral smear picture, iron studies, serum Vitamin B12, serum folate and bone marrow studies, were recorded on a case report form. Anemia was classified according to the World Health Organization criteria. Data analysis was carried out using Microsoft Excel and Statistical Package for the Social Sciences software. Results: 86.4% (89/103) patients were found to be anemic. There was no significant difference in prevalence of anemia in ART-naive patients from those who were on ART (P > 0.05). Pearson's correlation had shown a highly significant positive correlation of hemoglobin and CD4 cell counts in male patients (r = 0.418) as well as female patients (r = 0.565). Normocytic normochromic was the most common type of anemia in males (46%) as well as females (42%). Significant iron deficiency (P = 0.022) was observed in 42.85% of the patients having microcytic hypochromic anemia. Significant Vitamin B12 and folate deficiencies were observed in patients having macrocytic anemia (47.05%, P = 0.003 and 35.29%, P = 0.012, respectively). Conclusions: This study shows that anemia is highly prevalent in HIV patients and severity of anemia increases with decrease in CD4 cell counts. Nutritional deficiencies play a significant role in causing anemia in these patients.

Changes in HIV RNA and CD4 cell count after acute HCV infection in chronically HIV-infected individuals.

Little is known about the impact of acute hepatitis C virus (HCV) co-infection on HIV-1 disease progression. We investigated CD4 cell count and HIV RNA concentration changes after HCV infection in individuals chronically infected with HIV-1. We selected individuals that had the last negative and first positive HCV RNA test less than 1 year apart. Bivariate linear mixed-effects regression was used to model trends in HIV RNA level and CD4 cell count from 2 years before the last negative HCV RNA test until the first of the following dates: start of anti-HCV medication, change in combination antiretroviral therapy (cART) status, and end of follow-up. At the estimated time of HCV co-infection, of 89 individuals, 63 (71%) were cART-treated and 26 (29%) were not on cART. In persons on cART, median CD4 cell count declined from 587 to 508 cells per cubic millimeter (P < 0.0001) during the first 5 months after HCV infection and returned to 587 cells per cubic millimeter after 2.2 years. Also, the probability of an HIV RNA >50 copies per milliliter peaked to 18.6% at HCV co-infection, with lower probabilities 6 months before (3.5%, P = 0.006 compared with peak probability) and after (2.9%, P = 0.009). In persons not on cART, no significant impact of HCV co-infection on trends in the HIV RNA level or CD4 cell count was observed. Acute HCV infection in cART-treated, chronically HIV-infected patients was associated with a temporary decrease in CD4 cell counts and increased risk of HIV viremia >50 copies per milliliter. This may increase the risk of further HIV transmission.

Clinical study of lipid abnormalities in anti-retroviral treatment-naive HIV patients

Background: HIV infection has reached pandemic proportions ever since the first case was reported in 1981. Now, it continues to be the most important communicable disease in India with its associated high morbidity, mortality and treatment costs. With the introduction of highly active antiretroviral therapy, people with HIV infection now live longer. And the major contributors to morbidity and mortality are drug toxicities and metabolic derangements due to HAART, not the opportunistic infections. Dyslipidemia is one such metabolic derangement which occurs either as an adverse effect of ART drugs or due to HIV infection per se. This study was undertaken to address the second issue, as the data from India is limited. Methods: 80 newly detected HIV patients who were naive to antiretroviral drugs and who did not have exclusion criteria like prior diabetes mellitus, thyroid disease, hepatitis, pregnancy etc. were selected randomly and enrolled into the study over a year. A baseline complete hemogram with CD4 cell count and all necessary biochemical tests were done. The patients were grouped according to WHO staging. 80 age and sex matched healthy controls were also enrolled during the same period and they were also subjected to similar investigations. The various lipid parameters were analysed and compared between two groups as well as among patients with different WHO stages and CD4 lymphocyte counts. Results: 80 cases and 80 controls who were age and sex matched were enrolled. Mean BMI was significantly less in cases. Among cases, 72 patients (90%) had CD4 count <200 cells/mm 3 and 59 of them had an opportunistic infection. The mean triglyceride (TG) was significantly higher in the HIV-infected patients than in the controls, 176.125 mg/dL vs. 119.225 mg/dL with a P value = 0.02. The HIV-infected patients also had significantly lower mean HDL-C 33.58 mg/dL vs. 48.38 mg/dL with a P value = 0.04. On subgroup analysis in the HIV-infected patients, the mean serum triglyceride and VLDL levels were significantly higher in those with CD4+ cell count <200 cells/mm 3 compared to those with CD4+ cell count of 200 to ≥500 cells/mm 3 , with a P value of 0.04 & 0.003 respectively. Similarly, the same lipid parameters showed a rising trend in serum values as the stage of HIV infection advanced. Conclusions: It can be concluded from the study that dyslipidemia manifesting as significant hypertriglyceridemia and low HDL cholesterol is common among treatment naive HIV infected patients and it worsens with advanced stages of illness with decreasing CD4 cell count. Hence, a baseline lipid profile should be obtained in all HIV infected patients before initiating HAART.

FRI0467 Low CD4/Cd8 Ratio is Associated with Lower Immunoglobulin Levels in Granulomatosis with Polyangiitis Patients Receiving Rituximab

BackgroundRituximab (RTX) is an effective B depleting agent for inducing and maintaining remission in patients with Granulomatosis with polyangiitis (GPA). RTX induced late onset neutropenia and hypogammaglobulinemia potentiates the risk...

Protein intake is associated with HIV disease progression in HIV‐infected patients (810.9)

Background: This longitudinal study examines the effect of protein intake on markers of HIV disease progression.Methods: In a secondary analysis of data from 267 HIV+ patients on ART over a period of 6 months, we estimated protein intake from 24‐hour recalls and obtained CD4 cell counts and viral load from medical records. Multiple Linear Regressions and Mixed Models were used for over time analyses. Statistical significance was set at p&lt;0.05.Results: Participants mean age was 49±5 years, 62% were male and 71.3% were African Americans. Mean protein intake was 111±87 g/day (1.8 times the RDA for age and gender), mean CD4 cell count was 516.7±342 cells/μL and viral load 2.5±1.5 log10. Protein intake (g/day) was associated with decreased CD4 cell counts (β=‐0.68, p=0.05) and increased viral loads (β=51.27, p&lt;0.01) over time. This adverse relationship remained significant (β=44.4, p&lt;0.01), after adjusting for age and gender.Conclusion: The results suggest a detrimental relationship of excessive protein consumption with disease progression over time in HIV‐infected patients on ART.Grant Funding Source: NIDA

Depression severity is associated with increased risk behaviors and decreased CD4 cell counts

Depression is a common comorbidity among HIV-infected individuals. We studied the relationship between depressive symptoms, risk behaviors (risky-sexual behavior, tobacco, alcohol, and illicit drug use) and HIV outcomes. This cross-sectional study conducted in 2009 at the Washington University HIV Clinic included screening for depression with patient health questionnaire, survey of sexual behavior, illicit drug, alcohol, and tobacco use within 30 days. Sociodemographics, plasma HIV RNA levels, CD4 cell counts, and sexually transmitted disease test results were obtained from medical records. Multivariate logistic and linear regression models were used to assess the association between depressive symptoms severity and risk behaviors, HIV outcomes and combination antiretroviral therapy (cART) adherence. A total of 624 persons completed the assessment of whom 432 (69%) were male and 426 (68%) African-American. The median CD4 cell count was 410 cells/mm3 and 479 persons (77%) were on cART of whom 112 (23%) had HIV RNA level > 400 copies/mL. Overall, 96 (15%) had symptoms of major depressive disorder. Depressive symptom severity was associated with increased likelihood of high-risk drinking (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.1–5.1), current tobacco use (OR, 1.8; 95% CI, 1.1–2.9), illicit drug use (OR, 1.7; 95% CI, 1.0–2.8), and risky-sexual behavior (OR, 1.5; 95% CI, 0.8–2.7). Suboptimal cART adherence (visual analog scale < 95%) was also associated with depressive symptoms severity (p < 0.05). After adjustment for age, sex, race, receipt of cART, and cART adherence, depressive symptoms severity was independently associated with lower CD4 cell count (p < 0.05) but not with higher HIV RNA level (p = 0.39). Depression adversely affects HIV-infected individuals, requiring greater effort at utilizing multidisciplinary interventions.

French 2013 guidelines for antiretroviral therapy of HIV-1 infection in adults.

IntroductionThese guidelines are part of the French Experts’ recommendations for the management of people living with HIV/AIDS, which were made public and submitted to the French health authorities in September 2013. The objective was to provide updated recommendations for antiretroviral treatment (ART) of HIV-positive adults. Guidelines included the following topics: when to start, what to start, specific situations for the choice of the first session of antiretroviral therapy, optimization of antiretroviral therapy after virologic suppression, and management of virologic failure.MethodsTen members of the French HIV 2013 expert group were responsible for guidelines on ART. They systematically reviewed the most recent literature. The chairman of the subgroup was responsible for drafting the guidelines, which were subsequently discussed within, and finalized by the whole expert group to obtain a consensus. Recommendations were graded for strength and level of evidence using predefined criteria. Economic considerations were part of the decision-making process for selecting preferred first-line options. Potential conflicts of interest were actively managed throughout the whole process.ResultsART should be initiated in any HIV-positive person, whatever his/her CD4 T-cell count, even when >500/mm3. The level of evidence of the individual benefit of ART in terms of mortality or progression to AIDS increases with decreasing CD4 cell count. Preferred initial regimens include two nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) plus a non-nucleoside reverse transcriptase inhibitor (efavirenz or rilpivirine), or a ritonavir-boosted protease inhibitor (atazanavir or darunavir). Raltegravir, lopinavir/r, and nevirapine are recommended as alternative third agents, with specific indications and restrictions. Specific situations such as HIV infection in women, primary HIV infection, severe immune suppression with or without identified opportunistic infection, and person who injects drugs are addressed. Options for optimization of ART once virologic suppression is achieved are discussed. Evaluation and management of virologic failure are described, the aim of any intervention in such situation being to reduce plasma viral load to <50 copies/ml.ConclusionThese guidelines recommend that any HIV-positive individual should be treated with ART. This recommendation was issued both for the patient’s own sake and for promoting treatment as prevention.

Prevalence and related factors of anemia in HAART-naive HIV positive patients at Gondar University Hospital, Northwest Ethiopia

BackgroundAnaemia is a common complication of infection with the human immunodeficiency virus (HIV) and may have various causes. The aim of this study was to determine the prevalence and related factors of anemia in HAART-naive HIV positive Patients.MethodsA retrospective study was conducted on HAART naive HIV positive patients at the Gondar University Hospital between September 2011 and August 2012. Socio-demographic and immunohematological (hemoglobin and CD4+ T cells) data were collected carefully from the existing ART logbook and patient follow up cards. Anaemia was defined according to the WHO criteria.ResultsThe overall prevalence of anaemia was 138 (35%). Female HAART naive HIV positive patients had significantly (P < 0.05) higher prevalence of anaemia than males (62% Vs 38%). The prevalence of anaemia at different CD4 level was; 6 (4%) with CD4 count greater than 500 cells/μL, 18 (13%) with a CD4 count of 350–500 cells/μL, 37 (27%) with a CD4 count of 200–349 cells/μL, 44 (32%) with a CD4 count of 100–199 cells/μL, 14 (10%) with a CD4 count of 50–99 and 19 (14%) with CD4 count of less than 50 cells/μL.ConclusionsOur findings showed that one-third of HAART naïve HIV positive patients were anaemic and the increase in prevalence of anaemia with decreased CD4 cell count was statistically significant. Therefore, early diagnosis and treatment of anaemia in these patients are essential.

Inhaled corticosteroid use in HIV‐positive individuals taking protease inhibitors: a review of pharmacokinetics, case reports and clinical management

As a consequence of inhibition of the hepatic cytochrome P450 3A4 isozyme, treatment with HIV protease inhibitors can result in significant drug-drug interactions. One noteworthy interaction is between protease inhibitors and inhaled or intranasal corticosteroids. This interaction can result in adrenal insufficiency and iatrogenic Cushing's syndrome (with symptoms such as rapid weight gain, obesity, facial hirsutism and swelling), as well as hypertension, osteoporosis and decreased CD4 cell count. In this paper, we review and unite pharmacokinetic data, case reports and current research regarding this drug-drug interaction in order to suggest options for the clinical management of HIV-positive patients requiring treatment with protease inhibitors and inhaled or intranasal corticosteroids.

Prolonged Decrease of CD4+ T Lymphocytes in HIV-1–Infected Patients After Radiotherapy for a Solid Tumor

In HIV-negative patients, radiotherapy (RT) decreases CD4 T-cell counts. We studied the effects of RT in HIV-1 positive patients. HIV-1 positive patients with a subsequent diagnosis of a solid tumor were selected from the Dutch national observational HIV cohort, Aids Therapy Evaluation in the Netherlands (ATHENA). The patients were grouped according to whether they had received RT or not. Primary endpoint of the study was the time from baseline to reaching CD4 cell counts higher than those at baseline. Kaplan-Meier estimates of the percentage of patients reaching the endpoint were calculated. Ninety patients were included of whom 36 received RT and 54 did not. Median duration of RT was 46 [interquartile range (IQR) 30-63] days. Median first CD4 cell count after stopping RT was 150 (IQR 30-270) × 10/L lower compared with baseline. In 13 of the 36 patients receiving RT, CD4 cell counts recovered to baseline, after a median of 469 (IQR 345-595) days. In 35 of the 54 patients without RT, the CD4 cell count recovered to baseline or higher, after a median of 112 (IQR 42-182) days. After 3 years, in 39% of patients who had RT compared with 71% of patients without RT, CD4 cell counts recovered to baseline or higher (P < 0.0001). In a Cox regression adjusted for potential confounders, RT was associated with a longer (hazard ratio 0.29; 95% confidence interval 0.13 to 0.63) and combination antiretroviral therapy use with a shorter time to return to baseline [hazard ratio 2.46 (95% confidence interval 1.11 to 5.48)]. RT resulted in a significant and prolonged decrease in CD4 cell counts.

Etiology and Outcome of Patients with HIV Infection and Respiratory Failure Admitted to the Intensive Care Unit

Background. Although access to HAART has prolonged survival and improved quality of life, HIV-infected patients with severe immunosuppression or comorbidities may develop complications that require critical care support. Our objective is to evaluate the etiology of respiratory failure in patients with HIV infection admitted to the ICU, its relationship with the T-lymphocytes cell count as well as the use of HAART, and its impact on outcome. Methods. A single-center, prospective, and observational study among all patients with HIV-infection and respiratory failure admitted to the ICU from December 1, 2011, to February 28, 2013, was conducted. Results. A total of 42 patients were admitted during the study period. Their median CD4 cell count was 123 cells/μL (mean 205.7, range 2.0–694.0), with a median HIV viral load of 203.5 copies/mL (mean 58,676, range <20–367,649). At the time of admission, 23 patients (54.8%) were receiving HAART. Use of antiretroviral therapy at ICU admission was not associated with survival, but it was associated with higher CD4 cell counts and lower HIV viral loads. Twenty-five patients (59.5%) had respiratory failure secondary to non-HIV-related diseases. Mechanical ventilation was required in 36 patients (85.1%). Thirteen patients (31.0%) died. Conclusions. Noninfectious etiologies of respiratory failure account for majority of HIV-infected patients admitted to ICU. Increased mortality was observed among patients with sepsis as etiology of respiratory failure (HIV related and non-AIDS related), in those receiving mechanical ventilation, and in patients with decreased CD4 cell count. Survival was not associated with the use of HAART. Complementary studies are warranted to address the impact of HAART on outcomes of HIV-infected patients with respiratory failure admitted to ICU.

Neuropsychological test performance before and after HIV-1 seroconversion: the Multicenter AIDS Cohort Study

The objective of this study is to compare neuropsychological test performance before and after HIV-1 seroconversion in order to identify possible acute changes in psychomotor speed, memory, attention, and concentration secondary to seroconversion. The study utilized mixed effects models to examine longitudinal neuropsychological test data. We conducted a nested cohort study of 362 male HIV-1 seroconverters enrolled in the Multicenter AIDS Cohort Study. We used linear mixed models with random subject effects to compare repeated neuropsychological test outcomes from 5 years before seroconversion to 2 years after seroconversion on the Trail Making Test (parts A and B), Symbol-Digit Test, Grooved Pegboard (dominant and non-dominant hands), Stroop Color-Interference Test, Rey Auditory Verbal Learning Test, and the CalCAP Reaction Time Test. We found no significant changes in the time-dependent score after seroconversion for the majority of neuropsychological tests used in the Multicenter AIDS Cohort Study. There was a significant change in time trend after seroconversion on part B of the Trail Making Test (p=0.042), but the difference only represented a 2 % decrease in performance. We found the following characteristics to be associated with worse neuropsychological test performance: lower education levels, history of depression, older age, and no previous neurocognitive testing (p< .05). Our results suggest that despite a 50 % decrease in CD4 cell count immediately following infection, HIV-1 does not appear to have a measurable effect on psychomotor or complex cognitive processing for up to 2 years following infection, using this set of neurocognitive measures.

Commentary on the role of treatment-related HIV compensatory mutations on increasing virulence: new discoveries twenty years since the clinical testing of protease inhibitors to block HIV-1 replication

Approximately 20 years has passed since the first human trial with HIV-1 protease inhibitors. Protease inhibitors set the stage for combination therapy in the mid-1990s but are now rarely used in first-line combination therapy and reserved for salvage therapy. Initially, resistance to protease inhibitors was deemed unlikely due to the small enzymatic target with limited genetic diversity, the extended drug binding site in protease, and the need to cleave multiple sites in the HIV-1 precursor proteins. However, a highly protease inhibitor-resistant virus can emerge during treatment and is found to harbor a collection of primary drug-resistant mutations near the drug and/or substrate binding site as well as secondary mutations that compensate for fitness loss. For years, the research field has debated the impact of these secondary mutations on the emergence rates of high-level protease inhibitor resistance. A recent study poses a more pertinent question, related to disease progression in patients newly infected with a virus harboring secondary protease inhibitor-associated polymorphisms. The authors of that study show that increased rates of disease progression, inferred by increased viral loads and decreased CD4 cell counts, correlate with a fitness score of the infecting virus. The modeled fitness scores increased with an accumulation of these secondary protease inhibitors mutations, and not because of any one specific polymorphism.

Chronic immune activation and decreased CD4 cell counts associated with hepatitis C infection in HIV-1 natural viral suppressors

We have established a cohort of natural viral suppressors (NVS) who can suppress HIV-1 replication to less than 400 copies/ml in the absence of therapy (similar to Elite Controllers/Elite Suppressors). Of the 59 patients currently in the NVS cohort, 45.8% have chronic hepatitis C virus (HCV) infection, thereby presenting a unique opportunity to study immune activation and the interaction between HCV and HIV. NVS with chronic HCV infection had elevated levels of immune activation (CD38-positive HLA-DR-positive CD8 cells) compared to NVS without chronic HCV (P = 0.004). The increased levels of immune activation were not associated with sex, HLA B57 status, or injection drug use use. NVS patients with chronic HCV had lower mean CD4 cell counts, CD4 percentage, and CD4/CD8 ratios than NVS without chronic HCV infection (P = 0.038, P = 0.008, and P = 0.048, respectively). The difference in CD4 cell count appeared to occur early in HIV infection with no difference observed in CD4 slopes between groups. Among all NVS, there was a direct correlation between mean CD4 cell count, mean CD4 percentage, and mean CD4/CD8 ratio with percentage of CD38 HLA-DR CD8 cells (P = 0.0018; P = 0.0069; and P = 0.0014, respectively). This study suggests a relationship between HCV infection, immune activation, and CD4 cell counts in the NVS, with chronic HCV infection associated with lower CD4 cell counts and higher levels of immune activation. Further studies are needed to determine if successful HCV treatment lowers immune activation levels and/or increases CD4 cell counts in these patients.