Human Immunodeficiency Virus Progression Research Articles

Latinas and Deadly Sex: The Politics of HIV/AIDS Reporting

HIV and AIDSThe general public first acknowledgement of AIDS in the United States occurred in the early 1980s when Rock Hudson became infected and subsequently died. In the 1990s, largely due to categorization of the virus as Gay Related Immune Deficiency (GRID), and subsequent neglect by the nation's political system, the virus quickly spread to previously uninfected populations (Shilts, 1986). Human Immunodeficiency Virus (HIV) is caused by exposure to infected blood, semen, vaginal fluids, and breast milk. When an individual's CD-4 or T cell count falls below 200 and/or the individual begins to experience serious complications, the Acquired Immune Deficiency Syndrome (AIDS) is diagnosed as a disease. [http://hopkinsaids. edu/publications/ pocketguide/pocketgd0105.pdf]. As the science of treatment improved and public health surveillance and treatment systems were established, HIV infected individuals with knowledge of the risks of infection and access to health care progressed much more slowly to AIDS. New AIDS cases experienced a dramatically curbed escalation in 1996 with the introduction of Highly Active Antiretroviral Therapy (HAART). [http://www.cdc.gov/hiv/stats/2003SurveillanceReport.pdf]. Although cases of AIDS decreased markedly due to improvements in treatment, overall HIV infections did not.Although modes of infection have been clear for some time, reporting mechanisms within the country have been obscured by many issues including the requirement of the Centers for Disease Control and Prevention (CDC) to report all HIV infections using a confidential, albeit not anonymous, system of name-based reporting, to which some states, like California, have objected. Due to the extensive window period that can average 10 to 15 years wherein HIV infected individuals experience no symptoms, comprehensive data collection and reporting on HIV infection becomes imperative if the US is to accurately target HIV prevention and management efforts, particularly among underserved populations.The Reporting System: HIV versus AIDSPublic health in the US begins at the local level and involves both private and public health providers. Early work with other sexually transmitted diseases such as Gonorrhea and Syphilis at the local level initiated and improved the reporting process from the local level to the state. [http://www.cdc.gov/std/Syphilis2003/SyphSurvSupp2003.pdf]. Nationally, the Atlantabased CDC initiated the collection of AIDS case data from the states.As an understanding of HIV's progression to AIDS matured, terms such as ARC, (AIDS Related Complex), were eliminated and the staging became reduced to HIV and AIDS as measured by T cell or CD-4 cell counts and more recently viral load. [http://hopkinsaids. edu/publications/ pocketguide/pocketgd0105.pdf]. Although AIDS cases are reported by each state to the CDC, many states have been slower in their progression to HIV reporting. A major issue among and between the states and the CDC arose as to the classification system to be used for reporting of HIV and AIDS cases, one that has still not been fully resolved for 19 states and the District of Columbia. Exposure categories for adults are further broken down into the two categories of HIV and AIDS. This paper analyzes the categories of exposure for adults, with emphasis placed on the emergence of HIV and AIDS in the Latino population, particularly among women.Due to HIV underreporting or reporting practices that do not meet the CDC requirements of name-based case identification, the most recent edition of the CDC's HIV/AIDS Surveillance Report includes HIV data from only 31 states. [http://www.cdc.gov/hiv/stats/2004SurveillanceReport.pdf]. The underreporting of HIV to the CDC is problematic for a number of reasons, as it fails to provide the nation with the information needed for an effective HIV/AIDS prevention and management strategy. This is particularly true among underserved populations such as Latinos, who are often uninsured or underinsured and may lack access to culturally and linguistically appropriate health care and HIV prevention information. …

Impact of Hepatitis C on HIV Progression in Adults With Alcohol Problems

Coinfection of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is a substantial medical and public health concern due to its increasing prevalence and complex patient management. Alcohol use may worsen HCV-related liver disease and interfere with adherence to antiretroviral therapy (ART) and medical care. We therefore studied the association between HCV infection and markers of HIV disease progression in adults with alcohol problems. This is a longitudinal study of 396 HIV-infected persons with alcohol problems, 199 (50%) of whom were coinfected with HCV (positive HCV RNA test). CD4 cell counts and HIV RNA levels were assessed at baseline and then every 6 months for up to 42 months. Hepatitis C virus RNA status was determined at study enrollment. We examined the relationship between HCV infection and laboratory markers of HIV progression (CD4 cell count and log10 HIV RNA) by fitting multivariable longitudinal regression models for each outcome. Among subjects who were adherent to ART, the presence of HCV infection was associated with a lower CD4 cell count (adjusted mean difference -46.0 cells/microL, p=0.03). There was no association observed between HCV infection and CD4 cell count among those not adherent to ART or those not taking ART. No significant association was observed between HCV infection and HIV RNA regardless of ART status. Hepatitis C virus infection has an adverse effect on CD4 cell count in patients with alcohol problems who are adherent to ART. Addressing HCV coinfection among these patients may confer additional immunologic benefit for this patient population.

Influence of Human T Cell Lymphotropic Virus Type 2 Coinfection on Virological and Immunological Parameters in HIV Type 1–Infected Patients

Human T cell lymphotropic virus type 2 (HTLV-2) infection is not rare among injection drug users with human immunodeficiency virus (HIV) infection and may exert a protective role in the progression of HIV disease. Immunological and virological parameters were compared in HIV-HTLV-2-coinfected patients and a control group of HIV-monoinfected subjects. All individuals were antiretroviral therapy naive. HIV-specific CD8+ T cell levels were measured using an interferon-gamma assay in response to 125 optimally defined HIV peptides divided into 5 pools. Immune activation was evaluated by measuring levels of CD38 in different CD4+ and CD8+ T cell subsets. In a subgroup of patients, the production of CCL4 in parallel with interferon-gamma was assessed in response to Gag peptides. Lower plasma HIV-RNA levels were found in HIV-HTLV-2-coinfected patients than in HIV-monoinfected patients, despite the 2 groups having similar CD4+ T cell counts. Coinfected patients also had significantly lower levels of CD38 expression in total CD8+ T cells and in its naive subset. CD8+ T cell levels specific for each pool of peptides were similar in both groups, but cells mainly contributing to HIV Gag-specific responses in coinfected patients were CCL4 positive and interferon-gamma negative, whereas for HIV-monoinfected subjects, the response was dominated by CCL4-positive and interferon-gamma-positive cells. HTLV-2 coinfection may exert a protective role on HIV disease progression by lowering HIV replication and immune activation. A predominance of CCL4 single positive HIV-specific CD8+ T cells in HIV-HTLV-2-coinfected patients could explain this effect.

679. Gene Transfer to Hematopoietic Stem/ Progenitor Cells Using SV40-Derived Vectors

Stem cell-based gene therapy of human immunodeficiency virus (HIV) infection aims at inhibiting HIV replication and progression of infection to acquired immunodeficiency syndrome (AIDS) by introducing antiviral genes in primitive hematopoietic stem cells (HSC). Ideally, after differentiation into mature blood cells, these antiviral genes should create a host-cell population that is resistant to HIV infection.

Valproic acid does not affect markers of human immunodeficiency virus disease progression

Valproic acid (VPA) reduces latent human immunodeficiency virus (HIV) reservoirs by activating resting CD4+ cells. This retrospective case-control study (n = 30) examined effects of VPA on markers of HIV progression. VPA was not associated with changes in cerebrospinal fluid viral loads (VL), plasma VL, or neuropsychological performance. VPA patients had a trend towards lower CD4+ cells (P = .08) at follow-up. Concurrent antiretrovirals did not alter these relationships. VPA does not induce viremia or promote disease progression and may be safe for clinical intervention.

Human herpesvirus 8 enhances human immunodeficiency virus replication in acutely infected cells and induces reactivation in latently infected cells

AbstractHuman herpesvirus 8 (HHV-8) is etiologically associated with Kaposi sarcoma (KS), the most common AIDS-associated malignancy. Previous results indicate that the HHV-8 viral transactivator ORF50 interacts synergistically with Tat protein in the transactivation of human immunodeficiency virus (HIV) long terminal repeat (LTR), leading to increased cell susceptibility to HIV infection. Here, we analyze the effect of HHV-8 infection on HIV replication in monocyte-macrophage and endothelial cells, as potential targets of coinfection. Primary or transformed monocytic and endothelial cells were infected with a cell-free HHV-8 inoculum and subsequently infected with lymphotropic or monocytotropic strains of HIV. The results show that HHV-8 coinfection markedly increases HIV replication in both cell types. HHV-8 infection induces also HIV reactivation in chronically infected cell lines and in peripheral blood mononuclear cells (PBMCs) from patients with asymptomatic HIV, suggesting the possibility that similar interactions might take place also in vivo. Furthermore, coinfection is not an essential condition, since contiguity of differently infected cells is sufficient for HIV reactivation. The results suggest that HHV-8 might be a cofactor for HIV progression and that HHV-8-infected endothelial cells might play a relevant role in transendothelial HIV spread. (Blood. 2005;106:2790-2797)

Changes in Lipids and Routine Haematological Parameters as Human Immunodeficiency Virus (HIV) Infection Progresses to Acquired Immunodeficiency Syndrome (AIDS)

This study was conducted to determine the changes in some lipids and routine haematological parameters that take place as immunodeficiency virus (HIV) infection progresses to Acquired Immunodeficiency Syndrome (AIDS). Fifty HIV positive asymptomatic adults were recruited for the study, out of whom 30 developed clinical AIDS. Statistically significant decreases were observed for packed cell volume (PCV), haemaglobin (Hb), total white blood cell count (WCC), absolute neutrophil count, absolute lymphocyte count, LDL-cholesterol (P < 0.001) total cholesterol (P < 0.002) and triglyceride (P < 0.005) in HIV infections when compared with age and sex-matched control subjects. However, erythrocyte sedimentation rate (ESR) increased significantly (P < 0.001) in HIV infection. During AIDS episodes, a further decrease was observed for PCV, Hb, LDL-cholesterol (P < 0.001), and HDL cholesterol (P < 0.02). Increased levels were observed for WCC, ESR and triglyceride (P < 0.001). Whereas there was hypocholesterolaemia in HIV infection, hypertriglyceridaemia was observed in AIDS. The understanding of these various modifications will be of importance in AIDS management, intervention, and patients\' education in order to minimize the effects of associated complications. Key words: HIV progression, AIDS, lipids, haematological profiles Journal of Medical Laboratory Science Vol.13(1) 2004: 23 - 29

Temporal Trends in Early Clinical Manifestations of Perinatal HIV Infection in a Population-Based Cohort

The effect of early antiretroviral therapy (ART) on the early progression of perinatal human immunodeficiency virus (HIV) infection is not well defined. To examine early disease progression and survival in a population-based cohort with perinatal HIV infection in relation to year of birth and use of ART. Retrospective study of temporal trends in early progression of perinatal HIV infection among 205 HIV-infected children in Northern California born between January 1, 1988, and December 31, 2001, and followed up through age 3 years. Prevalence of and age at progression to a first US Centers for Disease Control and Prevention category C diagnosis relative to year of birth, type of ART, and age at initiation of therapy. Of 205 children, 134 (65%) received ART and/or Pneumocystis jiroveci pneumonia prophylaxis. By age 3 years, 81 (40%) progressed to a category C diagnosis, 41 (51%) of whom died. Untreated children were significantly more likely to progress to a category C diagnosis (62% [44/71] untreated vs 28% [37/134] treated children, P<.001); none of 23 infants who received triple ART progressed to category C. However, even without triple ART, very early mono/dual ART (by age 2 months vs 3-4 months) was associated with delayed and decreased progression to category C (P = .02). Of 33 children born between January 1, 1996, and December 31, 2001, only 7 (21%) progressed to category C (P = .02 compared with 1988-1995), 6 of 7 of whom received no therapy. More recent year of birth and more advanced therapy were associated with improved survival. This population-based cohort demonstrated decreased early HIV progression and improved survival at age 3 years, associated with more advanced therapy. Although limited by small sample size, the findings suggest that very early treatment, even without triple ART, was associated with improved outcome.

Cortical NAA Deficits in HIV Infection without Dementia: Influence of Alcoholism Comorbidity

Alcoholism comorbidity is highly prevalent in individuals infected with human immunodeficiency virus (HIV). Each condition is known to affect brain structure, function, and metabolism, but the combined effects on the brain have only recently been considered. Single-voxel, proton MR spectroscopy (MRS) has yielded sensitive measures of early brain deterioration in the progression of HIV, but has limited coverage of neocortex, whereas MRS imaging (MRSI) can simultaneously interrogate large regions of cortex. Included were 15 men with HIV+alcoholism, nine men with HIV alone, eight men with alcoholism alone (abstinent for 3-17 months), and 23 controls. The two HIV groups were matched in T-cell count and were not demented; the two alcoholism groups were relatively matched in lifetime alcohol consumption. We used MRSI with a variable-density spiral sequence to quantify major proton metabolites--N-acetylaspartate (NAA), creatine (Cr), and choline (Cho)-in the superior parietal-occipital cortex. Metabolites were expressed in absolute units and as the NAA/Cr ratio. Significant group effects were present for NAA and Cr. Only the HIV+alcoholism group was significantly affected, exhibiting a 0.8 SD deficit in NAA and a 1.0 SD deficit in Cr. The deficits were not related to highly active antiretroviral therapy (HAART) status. Neither HIV infection nor alcoholism independently resulted in parietal-occipital cortical metabolite abnormalities, yet each disease carried a liability that put affected individuals at a heightened risk of neuronal compromise when the diseases were compounded. Further, the use of absolute measures revealed deficits in NAA and Cr that would have gone undetected if these metabolites were expressed as a ratio.

Distribution of HIV/AIDS protective SDF1, CCR5 and CCR2 gene variants within Cretan population

An interesting finding in the epidemiology of human immunodeficiency virus (HIV) infection is that certain mutations in genes coding for chemokine receptors and their ligands may confer resistance to HIV-1 infection and/or AIDS progression. The mutations most frequently studied are the CCR5-delta32, CCR2-64I and SDF1-3′A. We examined the frequency of the above polymorphisms within the Cretan population, evaluating their contribution to a protective genetic background against HIV infection and progression. Two hundred blood samples were recruited at random among prospective blood donors from Crete. Genotyping was initially performed by polymerase chain reaction (PCR) analysis. CCR2 and SDF-1 PCR-amplified genomic regions were further subjected to restriction fragment length polymorphism (RFLP) analysis for genotype determination. The CCR5-delta32 allele frequency among our study group was 3.25%, although no respective homozygous samples were detected. The screening for the CCR2-64I polymorphism yielded 39 heterozygous (19.5%) and 4 homozygous (2%) subjects, revealing a CCR2-64I allele frequency of 11.75%. Among our 200 PCR-RFLP analysed samples, 73 (36.5%) were found heterozygous and 23 (11.5%) homozygous for the SDF1-3′A mutant variant. The allele frequency of the above polymorphism reached 29.75%. The frequency of the CCR5-delta32 allele among our study population seems to be remarkably lower compared to previously reported frequencies in other Caucasian groups. However, the SDF1-3′A allele frequency shows significantly higher distribution profiles within our study group compared to those observed in other Caucasian–European populations. The indicated difference could be attributed to the increased homogeneity of our population, which is well balanced and dispersed over a small geographical area. Since this polymorphism is related with delayed progression from HIV infection to AIDS, it could be used for prognostic genotyping in HIV infected Cretan individuals.

Measurable Predictive Factors for Progression to AIDS among HIV-infected Patients in Singapore

Introduction: This study identifies measurable factors at the time of diagnosis that predict the progression to Acquired Immunodeficiency Syndrome (AIDS) among Human Immunodeficiency Virus (HIV)-infected patients in Singapore. Materials and Methods: We carried out a retrospective study of 790 HIV-infected patients from 16 May 1985 to 31 December 2001. The end-point was the onset of AIDS-defining illness listed in the 1987 and 1991 revised Centers for Disease Control and Prevention criteria, but excluded CD4 cell counts as a criterion. Using the Kaplan-Meier method, AIDS-free survival curves were plotted for age groups at diagnosis, baseline CD4 counts and periods for utilisation of antiretroviral treatment. A Cox regression model was constructed to determine independent predictors of disease progression. Results: Univariate analysis showed that patients of older age at diagnosis had a significantly higher risk of progression compared to younger patients, and patients with higher baseline CD4 cell counts had a lower risk of progression to AIDS. Adjusting for the simultaneous influence of several covariates on the rate of HIV progression to AIDS, multivariate analysis using the Cox model showed a significantly higher risk of progression for older patients at diagnosis, and the progressive lowering of risk with increasing baseline CD4 cell counts. Conclusions: This study found older age at diagnosis and baseline CD4 cell counts to be measurable predictors for HIV progression to AIDS at time of diagnosis. Identification of these risk factors enables physicians to provide counselling and advice, and to start appropriate treatment early. This could lower the risk of progression and improve survival.

Early versus Deferred Antiretroviral Multidrug Therapy in Infants Infected with HIV Type 1

The clinical impact of early antiretroviral multidrug therapy on the risk of early-onset severe human immunodeficiency virus (HIV) disease has not been evaluated on a large scale. We evaluated the risk of early-onset events associated with acquired immunodeficiency syndrome (AIDS), particularly the risk of encephalopathy, among infants in the French Perinatal Cohort, according to whether antiretroviral multidrug therapy was initiated before or after the age of 6 months. Of 83 HIV-infected infants born in 1996 (when HAART became available) or later, 40 received early treatment on or before the age of 6 months, and 43 received deferred multidrug therapy after the age of 6 months. In the group that received early multidrug therapy, no child developed an opportunistic infection or an encephalopathy during the first 24 months of life. In the deferred multidrug therapy group, 6 infants presented with a total of 7 AIDS-associated events (P=.01), 3 of which were encephalopathies (P=.08). The small number of events prevented the identification of clinical and biological markers that accurately predict progression of early-onset severe HIV disease. In this observational study, infants who received multidrug therapy before 6 months of age did not have the early-onset severe form of childhood HIV disease. Further studies are needed to find accurate early markers of disease progression in this age group.

Helminth Infection Is Not Associated with Faster Progression of HIV Disease in Coinfected Adults in Uganda

We studied a cohort of human immunodeficiency virus (HIV)-infected adults in Uganda who were not receiving antiretroviral therapy, to explore the impact of helminths on HIV progression in areas where antiretrovirals are not available. A total of 663 patients were screened for helminths, treated presumptively with albendazole and selectively with praziquantel, and monitored for 6 months. Blood samples were analyzed for CD4+ cell count and HIV-1 RNA. Schistosoma mansoni, hookworm, Strongyloides stercoralis, and Mansonella perstans were the most prevalent helminths. Helminth infection was not associated with higher viral load, lower CD4+ cell count, or faster decrease in CD4+ cell count preceding antihelminthic therapy. The effect of coinfection on HIV disease progression varied with species. CD4+ cell counts were highest in subjects with hookworm and Mansonella perstans infection. For most helminths, effective treatment was associated with greater decrease in CD4+ cell count than in those in whom infection was still present at follow-up. A highly significant decrease in viral load at 6 months was seen in patients with persistent Mansonella perstans infection at follow-up. Mortality was lower in subjects with hookworm infection at enrollment. Helminth infection was not associated with more-advanced HIV disease or faster disease progression. Antihelminthic therapy may not be beneficial in slowing HIV progression in coinfected adults.

US youths in the early stages of HIV disease have low intakes of some micronutrients important for optimal immune function

Objective We examined the association between micronutrient intakes and human immunodeficiency virus (HIV) infection in youths who were at increased nutritional risk because of the demands of growth and disease as well as poor dietary habits. Design This was a cross-sectional study to collect dietary intake data using the Block Food Frequency Questionnaire (98.2). Anthropometric, biochemical, clinical, and sociodemographic data were available. Subjects/Setting Participants included 264 HIV-infected and 127 HIV-uninfected adolescents and young adults from the Reaching for Excellence in Adolescent Care and Health network, a multisite observational study on HIV progression. Statistical analyses CD4 + T cells were stratified for HIV-infected youths: ≥500, 200 to 499, and <200 cells/μL. Micronutrient intakes were compared by presence of HIV infection, using two-sample Student’s t tests. Categoric analyses used χ 2 test. Generalized linear regression determined predictors of vitamins A, C, and E; iron; and zinc intakes. Results Almost half (49.0%) of the HIV-infected participants had CD4 + T cells ≥500 cells/μL. After controlling for other factors, HIV-infected participants with CD4 + T cells ≥500 had decreased iron intake ( P<.05) and tended to be associated with lower intakes of vitamins C and E ( P<.10) compared with those with more advanced disease and HIV-uninfected youths. Among those youths with CD4 + T cells between 200 and 499 cells/μL, a high anxiety score was associated with a sixfold increase in vitamin A intake as compared with those with a low score. Applications/conclusions Given the increased micronutrient requirements, nutrition counseling with HIV-infected youths should focus on early increase of intake of foods rich in micronutrients to improve growth, slow disease progression, and increase survival.

HAART and the HCV-infected liver: friend or foe?

HAART and the HCV-infected liver: friend or foe?

Liver transplantation in patients with HIV infection.

1. Liver transplantation for human immunodeficiency virus (HIV)-positive patients with end-stage liver disease in the era of highly active retroviral therapy has proven to be an effective treatment. The concerns of HIV progression have not been borne out by the growing worldwide experience. 2. CD4 counts are stable and HIV viral load is controllable with medication following liver transplantation. 3. Hepatitis C virus (HCV) coinfection in HIV-positive recipients is universal, but the severity of recurrence does not appear to be different from that in HIV-negative patients with HCV liver disease. 4. Complex pharmacokinetic interactions between the calcineurin inhibitors used for immunosuppression along with protease inhibitors are present, but management directed at recognizing the need for monitoring levels does not appear to increase the risk of toxicity. 5. The degree of immunosuppression from iatrogenic drug therapy and HIV does not lead to increased risk of infectious complications.

Overweight and human immunodeficiency virus (HIV) progression in women: associations HIV disease progression and changes in body mass index in women in the HIV epidemiology research study cohort.

An association of increased weight with a slower progression of human immunodeficiency virus (HIV) disease has been reported in studies that have not included large numbers of women. We evaluated the association of HIV disease progression with body mass index (BMI) in 871 women and present cross-sectional, survival, and longitudinal analyses. A higher baseline BMI was associated with a lower rate of occurrence of the first CD4 cell count <200 cells/mm(3). In analyses that incorporated time-varying BMI, underweight and normal women had an increased risk of clinical acquired immune deficiency syndrome, and underweight women had increased risk of HIV-related death, compared with obese women. The association between change in BMI and CD4 cell count was estimated; increases in BMI were associated with slight increases in CD4 cell counts, even after controlling for prior values of CD4 cell count, viral load, and treatment. Higher BMI and increases in BMI are associated with a decreased risk of HIV progression.

Polymorphism of human and primate RANTES, CX3CR1, CCR2 and CXCR4 genes with regard to HIV/SIV infection.

Among genes that influence human susceptibility to HIV (human immunodeficiency virus) infection or AIDS (acquired immunodeficiency syndrome) progression, chemokine-receptor and chemokine genes were extensively studied because of their role as HIV co-receptors or co-receptor competitors, respectively. We have studied in non-human primates (chimpanzee, gorilla, gibbon, orang-utan, crab-eating and rhesus macaque, baboon and marmoset) the RANTES, CCR2 and CX3CR1 gene sequences in regions surrounding human mutations that were associated with susceptibility to HIV or AIDS progression: RANTES G-403A and C-28G, CCR2 V64I, CX3CR1 V249I and CX3CR1 T280M. Among these five dimorphisms, only RANTES G-403A is observed in one of the eight primate species studied here (gibbon). This suggests that these mutations appeared recently in humans and probably do not account for variable HIV/SIV disease progression in primates. It is noteworthy that chimpanzees, which are naturally resistant to HIV-1- and HIV-2-induced AIDS, do not have the human mutations associated with delayed disease progression. Inter-species and intra-species polymorphic positions are observed in primates and we discuss the potential impact of these mutations on HIV/SIV disease progression. Particularly, we identified polymorphisms in old-world monkey (OWM) genes, and it could be of great importance to analyse the possible association between these polymorphisms and disease progression in OWM species that are currently used in research for HIV vaccine and therapy.

What constitutes efficacy for a human immunodeficiency virus vaccine that ameliorates viremia: issues involving surrogate end points in phase 3 trials.

Initial human immunodeficiency virus (HIV) vaccines are unlikely to prevent acquisition of HIV in all recipients. Moreover, several HIV vaccines are under evaluation that are designed to reduce viremia after acquisition of infection. Such vaccines could provide important benefits to delay HIV progression and to reduce transmission. The decision to license a vaccine on the basis of observed effects on virus load and other postinfection surrogate end points in an efficacy trial is complicated by uncertainty about whether the vaccine effects will persist and reliably predict clinical effects, and by the challenge in interpreting the data posed by treatment of some seroconverters with antiretroviral drugs. Here, we evaluate how analyses of certain surrogate end points can be used for inferring clinically significant vaccine effects and propose end points that could be evaluated in efficacy trials to support licensure. The assessment suggests that a vaccine demonstrating moderately durable effects to delay therapy and to ameliorate viremia merits consideration for licensure.

A low level of CD4+CD28+ T cells is an independent predictor of high mortality in human immunodeficiency virus type 1-infected patients.

This study investigated coexpression of CD28, CD45RA, and CD45RO on CD4(+) and CD8(+) cells in 107 human immunodeficiency virus (HIV) type 1-infected patients, who were followed-up prospectively and were not treated with highly active antiretroviral therapy, and 65 control subjects. The most important novel finding was that a 50% reduction in CD4(+)CD28(+) cells predicted increased mortality (relative hazards [HR], 1.6; 95% confidence interval [CI], 1.0-2.6; P=.04), even after adjusting for the CD4(+) cell counts, virus load, beta(2)-microglobulin and hemoglobin levels, and HIV disease stage. Patients with progressed HIV infection had decreased concentrations of all studied cell subsets. Concerning the proportions of cells, only CD4(+)CD28(+), CD4(+)CD45RA(+), and CD8(+)CD45RO(+) cells decreased with HIV progression. Low proportions of CD4(+)CD45RA(+), CD8(+)CD45RA(+), and CD8(+)CD45RO(+) cells predicted mortality only in univariate but not in multivariate Cox analyses. If our results are confirmed in other studies, coexpression of CD28 on CD4(+) cells may be a useful marker to evaluate HIV progression.