Plasma Human Immunodeficiency Virus Load Research Articles

Can HIV Be Cured and Should We Try?

An estimated 35.0 million persons live with HIV; 2.1 million new infections occurred and 1.5 million persons died of HIV in 2013 (World Health Organization, http://www.who.int/hiv/data/epi_core_dec2014.png?ua=1). Despite effective combination antiretroviral therapy (cART), less than one-quarter of patients can access these life-prolonging medications; and despite its effectiveness, cART does not normalize life expectancy, as premature aging, metabolic complications and chronic inflammation complicate HIV therapy. HIV is incurable due to the presence of a latent viral reservoir. During the life cycle of the virus, HIV integrates into the host DNA. A subset of integrated HIV provirus remains transcriptionally silent, producing neither viral proteins nor viral progeny, until reactivation by various physiologic stimuli. This latency of HIV allows some infected cells to escape immune detection and elimination, and these latently infected cells constitute the viral reservoir. The latent viral reservoir allows viral rebound within weeks of interruption of cART, 1,2 where the magnitude of viral replication approaches that present pre-therapy. Although it was once thought that viral rebound occurred universally following therapy interruption, several recent reports challenge that paradigm. The “Berlin patient” successfully cleared HIV after two allogeneic transplants from a donor with homozygous CCR5Δ32 mutation,3 and he has not rebounded HIV after nearly seven years. This case likely represents a cure from HIV; yet other cases have been described where HIV rebound has been attenuated, or delayed. The “Mississippi” baby was a perinatally HIV-infected infant who initiated cART within hours of birth, and when interrupted eighteen months later, viremia remained undetectable for nearly two years.4 The Harvard BMT cases underwent allogeneic BMT, developed undetectable HIV DNA, yet rebounded viremia within only eight months after cART discontinuation.5 Together these cases demonstrate that control of viremia in the absence of cART is possible, if not durable.4 The VISCONTI cohort of 14 HIV-infected adults who initiated antiretroviral therapy during acute infection, and in whom high level rebound viremia had not occurred several years after cessation of therapy,6 similarly demonstrated that viral rebound following cART interruption can be attenuated. These cases have reinvigorated research toward finding a cure for HIV, which certainly will require an exceptional investment of time, talent and resources. Thus it is prudent to question whether such resources would be better devoted to more proximate needs with proven results (such as supplying cART to those without access to it, or supplying pre/post exposure prophylaxis to reduce the rate of new infections).

Case of newly onset type 1 diabetes after highly active antiretroviral therapy against HIV infection.

The survival of patients infected with human immunodeficiency virus (HIV) has been dramatically improved after the introduction of highly active antiretroviral therapy (HAART), the combination of multi-antiretroviral agents to decrease the replication of HIV type 1 (HIV-1). Although HIV-infected patients commonly show a low CD4-positive lymphocyte (CD4) count and a high CD8 count, HAART can effectively reduce the plasma HIV load, thus the CD4 count drastically increases, which is denoted as ‘immune reconstitution’. It was reported that several autoimmune diseases could occur after immune reconstitution during HAART1. Here, we report a case of newly-onset type 1 diabetes after HAART against HIV infection. A previously healthy 40-year-old Japanese man presented to Kawasaki Medical School (Kurashiki, Japan) in June 2009 for further examination of HIV-1 infection. HAART was started because of the low CD4 count and high titer of HIV ribonucleic acid. Then, the laboratory findings showed a total disappearance of HIV ribonucleic acid and increase of CD4 count with good clinical course (Figure​(Figure1).1). Around October 2011, however, the patient had nocturia and intense thirst with 6-kg weight loss. On admission, laboratory findings showed the elevation of glycated hemoglobin (12.5%) and glycoalbumin (30.8%) with mild ketosis. Endogenous insulin secretion was disturbed; serum C-peptide level was 0.6 ng/mL with plasma glucose level 242 mg/dL. Furthermore, anti-GAD antibody was positive (34.8 U/mL), but IA-2 antibody and anti-insulin antibody were negative. In addition, the patient had no obesity and/or diabetic family history, and human leukocyte antigen deoxyribonucleic acid typing of DRB1 and DQB1 was DRB1 *09:01-DQB1* 03:03, which is typical haplotype in Japanese type 1 diabetes. Thereby, we diagnosed the patient with newly-onset type 1 diabetes and introduced multiple daily injection, using insulin aspart and detemir. After that, his glycemic control was gradually improved, and he was discharged at day 19. It is likely that when the CD4 count is markedly increased, autoimmunity is stimulated by the CD4 dominant state. In the present case, the onset of type 1 diabetes and the marked increase of CD4 count around October 2011 were completely synchronized (Figure​(Figure1).1). To the best of our knowledge, there was only one report about the onset of type 1 diabetes after HAART2. According to the allele frequency net database (http://www.allelefrequencies.net)3, human leukocyte antigen DRB1*09:03 is very rare or absent in Caucasians, but this is common in Japan. In fact, the difference in haplotypes associated with type 1 diabetes between Japanese and Caucasian populations has been reported, and it can be explained by the frequency of haplotypes in each ethnicity4. Although the mechanism of the onset of type 1 diabetes is not clear, we assume that after HAART, type 1 diabetes can be induced in Japanese rather than in Caucasians. Therefore, we believe that the present case report would call for attention from the clinical point of view, and that we should consider the possibility of newly-onset type 1 diabetes when HAART is introduced against HIV infection, especially in Japanese patients. Figure 1 Time-course of CD4 cell count and human immunodeficiency virus (HIV)-ribonucleic acid (RNA) copies after highly active antiretroviral therapy in an HIV-infected patient.

Factors Associated with Symptomatic Vulvovaginal Candidiasis: A Study among Women Attending a Primary Healthcare Clinic in Kwazulu-Natal, South Africa.

Background:Symptomatic vulvovaginal candidiasis (VVC) is one of the most common problems leading women to seek advice in primary healthcare facilities.Aim:The aim of this study is to describe the associations between some hypothesized factors and the presence of symptomatic VVC.Subjects and Methods:An analytical cross-sectional study was conducted. A total of 90 women diagnosed with symptomatic VVC and 108 women without symptomatic VVC were recruited when attending Umlazi D clinic, a primary health clinic in KwaZulu-Natal, South Africa between June 2011 and December 2011. Confirmed symptomatic VVC was determined by Gram stain and microbiological culture of vaginal swabs. For human immunodeficiency virus (HIV)-infected women, HIV ribonucleic acid load in plasma and genital fluid was determined by real-time-polymerase chain reaction (BioMerieux, Lyon, France). CD4 counts were obtained from patients’ medical records. Data were analyzed using the statistical package for the social sciences (SPSS) version 21.0 (SPSS Inc.; Chicago, IL, USA). Multiple logistic regression models were used to exclude univariate confounders. All tests were two-sided and a P < 0.05 was considered to be significant.Results:A total of 90% (81/90) of patients with symptomatic VVC complained of vulval itching, soreness and vaginal discharge when compared to 75.9% (82/108) of patients without symptomatic VVC (P < 0.01). Whilst pregnancy was independently associated with symptomatic VVC (P < 0.01), the latter was inversely related to Nugent's scores (P < 0.01). When compared with HIV negative women, the odds for symptomatic VVC increased among women with HIV-associated immunocompromise (CD4 counts < 200 cells/mm3, P < 0.001), significantly shedding HIV in their genital tracts (P = 0.04), with plasma HIV load > 1000 copies/mL (P < 0.001). There was a significant negative association between the use of highly active anti-retroviral therapy and the presence of symptomatic VVC in HIV-infected women (P < 0.01).Conclusion:Although symptomatic VVC is not classified as acquired immunodeficiency syndrome-related condition, HIV-related immune compromised women and particularly those who are anti-retroviral therapy-naïve are likely to develop symptomatic VVC.

Recalcitrant Pseudotumoral Anogenital Herpes Simplex Virus Type 2 in HIV-Infected Patients: Evidence for Predominant B-Lymphoplasmocytic Infiltration and Immunomodulators as Effective Therapeutic Strategy

In patients with human immunodeficiency virus (HIV) infection, genital herpetic lesions may be extensive and tend to persist for longer periods; in addition, atypical hypertrophic, ulcerative, or pseudotumor forms have been reported, frequently showing resistance to acyclovir (ACV) treatment. Between 2003 and 2011, 10 HIV-1-infected patients presenting with chronic pseudotumoral anogenital herpes simplex type 2 (HSV-2) infections were studied. All patients developed chronic, hypertrophic HSV-2 anogenital lesions with multilesional presentation in 7 cases and involvement of 2 anatomical sites in 6 of them. At the time of diagnosis, the median CD3(+)CD4(+) absolute blood count was 480.5 cells/µL (range, 165-632 cells/µL), whereas the plasma HIV load was undetectable in all cases. Histopathologic analysis of lesion biopsies showed a moderately dense dermal polytypic plasma cell infiltrate. Detection of HSV-2 by culture and/or polymerase chain reaction was positive for all patients, with evidence for ACV-resistant strains in 6 of 8 cases. In addition, viral resistance to ACV was found only in HSV-2 isolated from ulcerative lesions, whereas purely pseudotumoral ones harbored sensitive strains. Durable control was observed with HSV DNA polymerase inhibitors in only 2 cases, and the immunomodulators imiquimod and thalidomide allowed 5 patients to reach sustained complete response. HSV-2-related pseudolymphoma in HIV-infected patients is characterized by a predominant polyclonal lymphoplasmacytic infiltration, and is frequently refractory to antiherpetic drugs. Immunomodulatory therapeutic strategies using thalidomide showed consistent efficacy, and should be considered early during the course of disease.

Changes in Blood B Cell Phenotypes and Epstein‐Barr Virus Load in Chronically Human Immunodeficiency Virus–Infected Patients before and after Antiretroviral Therapy

Switched and nonswitched memory B cells, which usually constitute the main reservoirs of Epstein‐Barr virus (EBV), are rapidly depleted in patients with chronic human immunodeficiency virus (HIV) infection. Because the EBV load is frequently increased in these patients, other B cell reservoirs might participate in EBV persistence. We examined the combined expression of CD27, SIgD/G/M, CD38, CD10, CD5, CXCR5, CD62L, CD44, and CXCR3 on B cells from healthy donors (n = 30) and from HIV type 1-infected patients (n = 23) at diagnosis and after highly active antiretroviral therapy. The plasma HIV load and the DNA EBV load in peripheral blood mononuclear cells were assessed. Increased frequencies of CD38+SIgD+CD10+ B cells were found in patients with an EBV load >10(3)copies per 10(6)peripheral blood mononuclear cells and a strong depletion of memory B cells. This phenotype resembles that of transitional B cell subsets. Elevated percentages of these B cells were still found in 2 patients showing no decrease in EBV load after highly active antiretroviral therapy. Because transitional-like B cells persist concomitantly with high EBV load after highly active antiretroviral therapy, we suggest that this population might be an alternative EBV reservoir in patients with chronic HIV infection who have strongly reduced numbers of memory B cells. The consequences of EBV infection of immature B cells are discussed with regard to B cell maturation and a higher prevalence of B cell lymphoma in HIV‐infected patients.

Associations between Breast Milk Viral Load, Mastitis, Exclusive Breast‐Feeding, and Postnatal Transmission of HIV

. Exclusive breast-feeding is protective against postnatal transmission of human immunodeficiency virus (HIV), compared with mixed breast-feeding. Accordingly, exclusive breast-feeding for 6 months is the World Health Organization's recommendation to HIV-infected mothers for whom exclusive replacement feeding is not acceptable, feasible, affordable, safe, or sustainable. The mechanism of exclusive breast-feeding protection is unknown but is hypothesized to be mediated through reduced mastitis. We compared breast milk and plasma specimens of exclusive breast-feeding and mixed breast-feeding HIV- positive mothers archived from the ZVITAMBO trial in which mixed breast-feeding was associated with a 2-fold increased risk of postnatal transmission at 18 months. Plasma HIV load, breast milk HIV load and sodium/potassium ratio were measured as a proxy for subclinical mastitis. Mixed breast-feeding was not associated with mastitis or breast milk HIV load. Mastitis was associated with breast milk HIV load, and this effect increased with increasing maternal plasma HIV load; mastitis was associated with postnatal transmission only when maternal plasma HIV load was high (>3.7 log(10) copies/mL). Initiation of breast-feeding within an hour of delivery was associated with exclusive breast-feeding (adjusted odds ratio, 1.62; 95% confidence interval, 1.02-2.58). Exclusive breast-feeding is associated with reduced postnatal transmission of HIV from mother to child, but this protection is not mediated by reduced mastitis or breast milk HIV load. The deleterious effect of mastitis increases as the mother's plasma HIV load increases.

Seroepidemiological study of human parvovirus B19 among human immunodeficiency virus-infected patients in a medium-sized city in Rio de Janeiro, Brazil

Parvovirus B19 (B-19) may cause chronic anaemia in immunosuppressed patients, including those infected with human immunodeficiency virus (HIV). We studied single serum samples from 261 consecutive HIV-infected patients using an enzyme immunoassay to detect IgG antibodies to B-19. The seroprevalence of B-19-IgG was 62.8%. The differences in seroprevalence across gender, age, educational categories, year of collection of the serum samples, clinical and antiretroviral therapy characteristics, CD4+ count, CD4+ and CD8+ percentage and CD4+/CD8+ ratios were neither substantial nor statistically significant. There was a non-significant, inverse association between B-19 seropositivity and plasma HIV load and haemoglobin level. Our results indicated that 37.1% of patients might be susceptible to B-19 infection and remained at risk for being infected, mainly during epidemic periods. As B-19 infection can be treated with immune globulin preparations, it may be included in the diagnostic approach toward chronic anaemia in HIV-infected patients.

Anticardiolipin Antibodies in HIV Infection Are Independently Associated with Antibodies to the Membrane Proximal External Region of gp41 and with Cell‐Associated HIV DNA and Immune Activation

The demonstration of in vitro cardiolipin reactivity with 2 human immunodeficiency virus (HIV)-specific, broadly neutralizing antibodies (2F5 and 4E10) has prompted reevaluation of autoimmune manifestations in HIV infection. We evaluated autoantibodies, particularly anticardiolipin (aCL), in 67 untreated, asymptomatic, HIV-infected individuals with slow progression of HIV disease and their correlation with 2F5-, 4E10-, b12-, and 2G12-like antibodies directed against epitopes involved in broad neutralization, as well as their correlation with immune activation and virological and clinical indicators. Fifty individuals with chronic HIV infection and standard disease progression were control patients. The majority of the study patients with slow progression of HIV disease were men (78%); their median age was 37 years, their median CD4+ cell count was 672 cells/mL, and their median plasma HIV load was 6200 copies/mL. The majority of the control patients were also men (76%), and most (62%) were receiving highly active antiretroviral therapy; their median age was 43 years, their median CD4+ cell count was 202 cells/mL, and their median plasma HIV load was 2265 copies/mL. aCL immunoglobulin G was detected at similar levels in 49% of patients with slow progression of HIV disease and in 58% of control patients. Viral load was positively associated with aCL in both groups (P < .001), independent of CD4+ cell counts. In patients with slow progression of HIV disease, aCL levels were also correlated with plasma HIV load and cell-associated DNA level (r = 0.486 and r = 0.516, respectively; P < .001), with the proportion of activated CD4+ cells, human leukocyte antigen-DR+ cells (r = 0.445; P = or < .001) but not activated CD8+ T cells, and with the level of B cell activation (quantified by soluble CD23; r = 0.354; P = .007). The level of aCL antibodies was associated with the level of antibodies to the membrane proximal region of gp41 (P = .003). aCL is frequently detected in HIV-infected patients, regardless of disease stage, and is strongly linked with the level of viral replication, the level of CD4+ T and B cell activation, and the level of antibodies to the membrane proximal external region of gp41, independent of CD4+ cell deficiency.

Mitochondrial DNA Haplogroups and Highly Active Antiretroviral Therapy–Related Lipodystrophy

The combination of different point mutations in mitochondrial DNA (mtDNA), which are defined as haplogroups, may cause modification in organelle function and may be involved in several pathologies. We analyzed the distribution of mtDNA polymorphisms in human immunodeficiency virus (HIV)-infected patients with lipodystrophy, a relevant adverse event caused by highly active antiretroviral therapy, and their correlation with metabolic and viroimmunologic parameters. The frequency of the 9 most common European haplogroups was investigated in 346 white, HIV-infected patients with lipodystrophy. Haplogroups were identified on the basis of classic methods. Statistical analysis was performed with use of 1-way analysis of variance, the chi(2) test, and principal-components analysis. The distribution of mtDNA haplogroups among patients with lipodystrophy was similar to that among the general European population. We found no differences between patients with different haplogroups with regard to viroimmunologic results (plasma HIV load, CD4(+) T cell count, and nadir CD4(+) T cell count), glucose data (glucose, insulin, C-peptide, and glycosylated hemoglobin concentrations and insulin resistance), lipid data (levels of triglycerides, total cholesterol, high- and low-density lipoproteins, and apolipoprotein A1 and B), acid-base balance parameters (lactate level and anion gap), or anthropometric measures (weight, body mass index, and waist-to-hip ratio). No differences were observed in trunk fat levels, leg-fat ratio (which was determined by dual-energy x-ray absorptiometry), or exposure to different drug classes. Principal-components analysis confirmed that the spatial distribution of patients belonging to a given haplogroup was not influenced by different clinical parameters. Our study indicates that, in HIV-infected patients with lipodystrophy, mtDNA haplogroups are not related to major metabolic changes or to particular viroimmunologic features.

Low plasma selenium concentrations, high plasma human immunodeficiency virus load and high interleukin-6 concentrations are risk factors associated with anemia in adults presenting with pulmonary tuberculosis in Zomba district, Malawi

Although anemia is common among adults with pulmonary tuberculosis and human immunodeficiency virus (HIV) infection in sub-Saharan Africa, the factors contributing to its pathogenesis have not been well characterized. To characterize the antioxidant micronutrient status, interleukin-6 (IL-6) concentrations, and HIV load in relationship with anemia in adults with pulmonary tuberculosis. Zomba district, Malawi. Erythropoietin, IL-6, plasma HIV load, and markers of micronutrient status (hemoglobin (Hb), plasma concentrations of retinol, alpha-tocopherol, carotenoids, ferritin, zinc, and selenium) were measured in 500 adults who presented with pulmonary tuberculosis in Zomba Central Hospital, Malawi. Among 370 HIV-positive and 130 HIV-negative adults, the prevalence of anemia was 88 and 77%, respectively (P = 0.002), and moderate to severe anemia (Hb < 80 g/l) occurred in 30 and 15%, respectively (P = 0.001). Geometric mean IL-6 concentration was 21.1 pg/ml, with no difference between HIV-positive and -negative adults. The erythropoietin response to anemia was not different between adults with elevated IL-6 and those with lower IL-6 concentrations. In a multivariate logistic regression model, HIV load, and lower plasma selenium concentrations were associated with moderate to severe anemia. In a final multivariate linear regression model, IL-6, plasma HIV load, and plasma selenium concentrations were associated with Hb concentrations. This study suggests that low selenium concentrations, high HIV load, and high IL-6 concentrations are associated with anemia in adults with pulmonary tuberculosis in sub-Saharan Africa.

Micronutrient malnutrition and wasting in adults with pulmonary tuberculosis with and without HIV co-infection in Malawi.

BackgroundWasting and micronutrient malnutrition have not been well characterized in adults with pulmonary tuberculosis. We hypothesized that micronutrient malnutrition is associated with wasting and higher plasma human immunodeficiency virus (HIV) load in adults with pulmonary tuberculosis.MethodsIn a cross-sectional study involving 579 HIV-positive and 222 HIV-negative adults with pulmonary tuberculosis in Zomba, Malawi, anthropometry, plasma HIV load and plasma micronutrient concentrations (retinol, α-tocopherol, carotenoids, zinc, and selenium) were measured. The risk of micronutrient deficiencies was examined at different severity levels of wasting.ResultsBody mass index (BMI), plasma retinol, carotenoid and selenium concentrations significantly decreased by increasing tertile of plasma HIV load. There were no significant differences in plasma micronutrient concentrations between HIV-negative individuals and HIV-positive individuals who were in the lowest tertile of plasma HIV load. Plasma vitamin A concentrations <0.70 μmol/L occurred in 61%, and zinc and selenium deficiency occurred in 85% and 87% respectively. Wasting, defined as BMI<18.5 was present in 59% of study participants and was independently associated with a higher risk of low carotenoids, and vitamin A and selenium deficiency. Severe wasting, defined as BMI<16.0 showed the strongest associations with deficiencies in vitamin A, selenium and plasma carotenoids.ConclusionsThese data demonstrate that wasting and higher HIV load in pulmonary tuberculosis are associated with micronutrient malnutrition.

Early Plasmacytoid Dendritic Cell Changes Predict Plasma HIV Load Rebound during Primary Infection

During human immunodeficiency virus (HIV) infection, interruption of highly active antiretroviral therapy (HAART) is usually followed by virus load rebound. Previous data have suggested a role for plasmacytoid dendritic cells (pDCs) in anti-HIV innate immunity. Here, the number of pDCs was measured by flow cytometry before, during, and after receipt of HAART in 7 patients with documented primary HIV-1 infection. A negative correlation was evidenced between pDC counts after 1 month of HAART and mean plasma virus load after interruption of HAART (r2=0.85; Spearman's partial rho =-0.92; P=.03). pDC counts during treatment might help predict immune replication control after interruption of HAART.

Sarcoidosis in HIV‐Infected Patients in the Era of Highly Active Antiretroviral Therapy

To analyze the impact of highly active antiretroviral therapy (HAART) on the characteristics and outcome of sarcoidosis in patients infected with human immunodeficiency virus (HIV), we identified HIV-infected patients in whom sarcoidosis was diagnosed between 1996 and 2000 from the admission registers of the pneumology departments of 12 hospitals in the Paris region (France). Sarcoidosis was diagnosed in 11 HIV-infected patients, of whom 8 were receiving HAART. HIV infection was diagnosed before sarcoidosis in 9 cases. At diagnosis of sarcoidosis, the mean CD4 cell count (+/-SD) was 390+/-213 cells/mm(3), and the mean plasma virus load was 4002+/-10,183 copies/mL. Sarcoidosis occurred several months after HAART introduction, when the CD4 cell count had increased and the plasma HIV load had decreased. Clinical and radiological characteristics, laboratory values for bronchoalveolar lavage fluid samples, and outcome after a long follow-up were similar for the patients receiving HAART and for HIV-uninfected patients.

Monitoring of human immunodeficiency virus infection in resource-constrained countries.

The reference standards used to monitor human immunodeficiency virus (HIV) infection are flow cytometric analysis of T lymphocyte subsets to provide the CD4+ T cell count and molecular assays to quantify plasma HIV load. Few laboratories in resource-constrained countries can afford to perform these tests. A number of lower-cost assays requiring less expensive equipment may be well-suited to such countries. These include manual CD4 cell assays (Dynal, Coulter, BioRad) and ultrasensitive reverse transcriptase (Cavidi) and p24 (Perkin Elmer Life Sciences) assays to monitor virus load. Quality control and access to quality assurance programs are essential. The total lymphocyte count, although readily available and inexpensive, generally does not correlate as closely with CD4+ T cell counts. Other surrogate markers, such as beta2-microglobulin, are not suitable for routine monitoring of HIV infection. This review discusses the above assays and their role in addition to clinical monitoring in resource-constrained countries.

Treatment with megestrol acetate improves human immunodeficiency virus-associated immune thrombocytopenia.

Splenic macrophage Fc gamma receptors participate in the pathophysiology of immune cytopenias, and in such disorders, the beneficial effects of glucocorticoids are in part mediated by decreased expression of macrophage Fc gamma receptors. In the animal model, progesterones, like glucocorticoids, inhibit expression of these receptors. Megestrol acetate (MA) is a progesterone frequently used for treating human immunodeficiency virus (HIV)-associated anorexia-cachexia. Twenty-eight patients with HIV-associated thrombocytopenia with shortened platelet survival and increased platelet-associated immunoglobulin G (IgG) who were being treated with MA for anorexia-cachexia were prospectively studied for a 6-month period to assess the potential role of progesterones in the treatment of immune thrombocytopenia. Treatment with MA for non-consecutive periods of 2 months and 1 month significantly increased platelet count and platelet survival without significant alteration of platelet-associated immunoglobulin levels. Of the 28 patients studied, 22 presented a complete response, 19 presented a complete response 1 month after finishing the MA treatment regimen, and 12 remained in complete response for a further month. Expression of Fc gamma receptors (Fc gamma RI and Fc gamma RII) by peripheral blood monocytes and the in vitro recognition of IgG-sensitized cells by monocytes were significantly decreased by the MA treatment. Decreased expression and functioning of these receptors significantly correlated with platelet counts and survival times, but no relationship was found with platelet-associated immunoglobulin, circulating immune complexes, body mass index, plasma HIV load, or CD4 lymphocyte levels. These results suggest that treatment with progesterones, like MA, may be an alternative therapy for immune cytopenias, with few side effects.

Equal plasma viral loads predict a similar rate of CD4+ T cell decline in human immunodeficiency virus (HIV) type 1- and HIV-2-infected individuals from Senegal, West Africa.

Human immunodeficiency virus (HIV) type 2 infection is characterized by slower disease progression to acquired immunodeficiency syndrome than results from HIV-1 infection. To better understand the biological factors underlying the different natural histories of infection with these 2 retroviruses, we examined the relationship between HIV RNA and DNA levels and the rate of CD4(+) T cell decline among 472 HIV-1- and 114 HIV-2-infected individuals from Senegal. The annual rate of CD4(+) T cell decline in the HIV-2 cohort was approximately one-fourth that seen in the HIV-1 cohort. However, when the analysis was adjusted for baseline plasma HIV RNA level, the rates of CD4(+) T cell decline per year for the HIV-1 and HIV-2 cohorts were similar (a rate increase of approximately 4% per year for each increase in viral load of 1 log(10) copies/mL). Therefore, plasma HIV load is predictive of the rate of CD4(+) T cell decline over time, and the correlation between viral load and the rate of decline appears to be similar among all HIV-infected individuals, regardless of whether they harbor HIV-1 or HIV-2.

Iron status and indicators of human immunodeficiency virus disease severity among pregnant women in Malawi.

The relationships among hemoglobin, ferritin, and transferrin receptor levels and 2 markers of human immunodeficiency virus (HIV) disease severity--HIV load and CD4(+) lymphocyte count--were characterized among 483 pregnant women in Malawi, Africa. The only significant correlation was an inverse correlation between hemoglobin level and plasma HIV load (r=-.104; P<.03). The prevalence of iron deficiency anemia was not significantly different across quartiles of HIV load or CD4(+) lymphocyte count. In contrast to previous studies, these data suggest that iron status is not related to markers of HIV disease severity in pregnant women in Africa.

Long-term clinical outcome of human immunodeficiency virus-infected patients with discordant immunologic and virologic responses to a protease inhibitor-containing regimen.

Within a prospective cohort of 150 human immunodeficiency virus (HIV)-infected patients who began first-line protease inhibitor therapy in 1996, the outcome of 42 patients with discrepant virologic and immunologic responses to antiretroviral treatment at 12 months was analyzed at 30 months of treatment. The incidence of AIDS-defining events and deaths (14%) in the group of patients with immunologic responses in the absence of a virologic response was higher than that in full-responder patients (2%); yet, the incidence in this group was lower than that in patients with no immunologic response, despite a virologic response (21%), and was lower than that in patients without an immunologic or virologic response (67%; P<.0001, log-rank test). Differences in outcome were significant (relative risk, 6.9; 95% confidence interval, 1.9-39.3) when factors for progression were compared with those of responder patients. The results support the relevance of the CD4 cell marker over plasma HIV load for predicting clinical outcome in patients who do not achieve full immunologic and virologic responses.

Stability of plasma human immunodeficiency virus load in VACUTAINER PPT plasma preparation tubes during overnight shipment.

VACUTAINER PPT plasma preparation tubes were evaluated to determine the effects of various handling and shipping conditions on plasma human immunodeficiency virus (HIV) load determinations. Plasmas obtained from PPT tubes stored and shipped under nine different conditions were compared to conventional EDTA tube plasmas stored at -70 degrees C within 2 h after phlebotomy. Compared to viral loads in frozen EDTA plasma, those in PPT tube plasma that was frozen immediately and either separated or shipped in situ were not significantly different. Viral loads in PPT tube plasma after storage for 6 h at either room temperature or 4 degrees C, followed by shipment at ambient temperature or on wet or dry ice, were not significantly different from baseline viral loads in EDTA or PPT plasma. The results of this study indicate that the HIV load in PPT tube plasma is equivalent to that in standard EDTA plasma. Plasma viral load is not affected by storage or shipment temperature when plasma is collected in PPT tubes. Furthermore, plasmas can be shipped in spun PPT tubes, and the tubes provide a safer and more convenient method for sample collection and transport than regular EDTA tubes.

The effect of acute infectious illnesses on plasma human immunodeficiency virus (HIV) type 1 load and the expression of serologic markers of immune activation among HIV-infected adults.

The effect of acute coinfections on plasma human immunodeficiency virus (HIV) load and immune activation markers was evaluated. Thirty-two HIV-infected persons were prospectively enrolled; 18 had pre-illness, acute, and follow-up specimens. Plasma HIV RNA levels were determined by reverse transcriptase-polymerase chain reaction, and serum levels of activation markers, including tumor necrosis factor (TNF)-alpha, soluble (s) TNF receptors (R)-I and -II, interleukin (IL)-2, IL-6, IL-10, sIL-2R, sCD4, and sCD8, were assessed by commercial ELISAs. Median plasma HIV load increased 7. 8-fold during illness (P=.001) and decreased 1.5-fold (P=.01) during convalescence (median, 15 days). Significant virus load reductions were limited to subjects with clinical recovery. By regression analysis, changes in plasma HIV RNA were significantly associated with changes in sTNFR-I, sTNFR-II, and sIL-2R. Increased HIV replication during acute coinfections is associated with in vivo immune activation, which underscores the need to prevent and promptly treat intercurrent illnesses.