Risk Of HIV Disease Progression Research Articles

Cholecalciferol Supplementation Does Not Affect the Risk of HIV Progression, Viral Suppression, Comorbidities, Weight Loss, and Depression among Tanzanian Adults Initiating Antiretroviral Therapy: Secondary Outcomes of a Randomized Trial

BackgroundObservational studies suggest that blood concentrations of 25-hydroxyvitamin D [25(OH)D] are associated with morbidity, viral suppression, and mortality among adults living with HIV. ObjectivesWe evaluated the effect of cholecalciferol (vitamin D3) supplementation on the risk of HIV disease progression, HIV-1 viral suppression, comorbidities, weight change, and depression among HIV-infected individuals that were initiating antiretroviral therapy (ART) in Dar es Salaam, Tanzania. MethodsWe conducted a randomized, double-blind, placebo-controlled trial of vitamin D3 supplementation among 4000 HIV-infected adult men and nonpregnant women initiating ART with insufficient serum 25(OH)D concentrations (<30 ng/mL). Participants were randomly assigned to receive either weekly 50,000-IU doses for 4 wk followed by daily 2000 IU vitamin D3 until 1 y or a matching placebo regimen given in weekly followed by daily doses until 1 y. Participants were followed up at weekly visits for the first month followed by monthly visits thereafter. We conducted intent-to-treat analyses to assess the effect of vitamin D3 supplementation on the secondary trial outcomes of HIV progression or death, viral suppression, comorbidities, change in BMI, >10% weight loss, incident wasting, and depression. ResultsDuring follow-up, 345 participants (17.2%) in the vitamin D3 group and 371 participants (18.6%) in the placebo group experienced HIV disease progression or death and there was no difference in risk between groups (RR: 0.91; 95% CI: 0.79, 1.06). Vitamin D3 supplementation did not affect the risk of an unsuppressed HIV-1 viral load (>1000 copies/mL) after 6 mo (RR: 1.10; 95% CI: 0.87, 1.41) and there was also no effect on change in BMI, risk of >10% weight loss, wasting, comorbidities, and depression (P values >0.05). ConclusionsVitamin D supplementation did not affect the risk of HIV progression, viral suppression, common morbidities, weight-related indicators, or depression among adults initiating ART in Tanzania.This trial was registered at clinicaltrials.gov as NCT01798680.

Relationship Between Anemia and Systemic Inflammation in People Living With HIV and Tuberculosis: A Sub-Analysis of the CADIRIS Clinical Trial.

People with HIV (PWH) are at increased risk of developing active tuberculosis (TB), and anemia is a common complication in both conditions. Anemia in TB patients has been linked to immune activation, levels of inflammatory biomarkers in blood, and risk for HIV disease progression and death. In this study we show that anemia was associated with a more pronounced inflammatory profile in HIV-TB coinfected persons in a cohort of 159 individuals with advanced HIV disease (CD4 count < 100 cells/µL) recruited as part of a randomized clinical trial (NCT00988780). A panel of plasma biomarkers was assessed on plasma obtained prior to combination antiretroviral therapy (cART) initiation. We performed a series of multidimensional analyses including clinical variables and concentrations of inflammatory biomarkers to profile systemic inflammation of PWH with and without anemia. We observed that TB participants presented with moderately lower levels of hemoglobin than non-TB participants. These participants also presented a higher Degree of Inflammatory Perturbation (DIP) score, related to increased levels of IFN-γ and TNF. The DIP was associated with TB coinfection and anemia before cART initiation. Future mechanistic studies are warranted to assess the determinants of such associations and the implications on treatment outcomes.

Impact of cellular restriction gene (TRIM5α, BST-2) polymorphisms on the acquisition of HIV-1 and disease progression.

TRIM5α and BST-2 are cellular restriction factors affecting the HIV-1 infection and its progression. Genetic variability in these genes alters the expression pattern. Hence, we aimed to examine the impact of the TRIM5α (rs10838525, rs7127617 and rs904375) and BST2 (rs3217318 and rs71694748) polymorphisms on the acquisition of HIV-1 and its progression. Genotyping of TRIM5α and BST-2 polymorphisms was performed in a total of 153 HIV-infected patients and 158 unrelated healthy individuals using a polymerase chain reaction-restriction fragment length polymorphism method. No significant differences were found in the genotype frequencies of TRIM5α polymorphisms between HIV patients and healthy controls. BST-2 Δ19/i19 and i19/i19+ Δ19/i19 genotypes appeared more frequently in HIV patients compared to healthy controls (10.4% versus 7.0%, p = 0.20; 11.10% versus 7.6%, p = 0.16). The BST-2 i19 allele was associated with the acquisition of HIV-1 [odds ratio (OR) = 2.76, p = 0.030)]. TRIM5α haplotypes ATG and ACA elevated the risk, whereas haplotype ATA reduced the risk for the acquisition of HIV-1 (OR = 1.92, p = 0.026; OR = 4.88, p = 0.016; OR = 0.31, p = 0.014). BST-2 Δ19/i19 and i19/i19+ Δ19/i19 genotypes were more prevalent in patients with early HIV disease stage compared to healthy controls (15.9% versus 7.0%, p = 0.096; 15.9% versus 7.6%, p = 0.12). The prevalence of TRIM5α rs7127617 CC and BST-2 Δ19/i19 genotypes was observed to be higher in alcohol-using HIV patients compared to non-users (27.8% versus 20.0%, p = 0.35, 22.2% versus 10.0%, p = 0.24). TRIM5α haplotypes and the BST-2 i19 allele may significantly affect the modulation of HIV-1 acquisition and its progression. TRIM5α rs7127617 CC and BST-2 Δ19/i19 genotypes in alcohol-using HIV patients elevated the risk of HIV disease progression.

Alcohol Types and HIV Disease Progression Among HIV-Infected Drinkers Not Yet on Antiretroviral Therapy in Russia and Uganda.

In HIV-infected drinkers, alcohol types more likely to cause inflammation could plausibly increase the risk of HIV disease progression. We therefore assessed the association between alcohol type and plasma HIV RNA level (HIV viral load) among HIV-infected drinkers not on antiretroviral therapy (ART) in Russia and Uganda. We analyzed the data of participants from cohorts in Russia and Uganda and assessed their HIV viral load at enrollment by the alcohol type predominantly consumed. We defined predominant alcohol type as the alcohol type contributing>50% of total alcohol consumption in the 1month (Russia) or 3months (Uganda) prior to enrollment. Using multiple linear regression, we compared log10 HIV viral load by predominant alcohol type, controlling for age, gender, socioeconomic status, total number of standard drinks, frequency of drinking≥6 drinks/occasion, and in Russia, history of injection drug use. Most participants (99.2% of 261 in Russia and 98.9% of 352 in Uganda) predominantly drank one alcohol type. In Russia, we did not find evidence for differences in viral load levels between drinkers of fortified wine (n=5) or hard liquor (n=49), compared to drinkers of beer/low-ethanol-content cocktails (n=163); however, wine/high-ethanol-content cocktail drinkers (n=42) had higher mean log10 viral load than beer/low-ethanol-content cocktail drinkers (β=0.38, 95% CI 0.07-0.69; p=0.02). In Uganda, we did not find evidence for differences in viral load levels between drinkers of locally-brewed beer (n=41), commercially-distilled spirits (n=38), or locally-distilled spirits (n=43), compared to drinkers of commercially-made beer (n=218); however, wine drinkers (n=8) had lower mean log10 HIV viral load (β=-0.65, 95% CI -1.36 to 0.07, p=0.08), although this did not reach statistical significance. Among HIV-infected drinkers not yet on ART in Russia and Uganda, we observed an association between the alcohol type predominantly consumed and the HIV viral load level in the Russia sample. These exploratory results suggest that, in addition to total number of drinks and drinking patterns, alcohol type might be a dimension of alcohol use that merits examination in studies of HIV and alcohol related outcomes.

Hormonal Contraception, Pregnancy, Breastfeeding, and Risk of HIV Disease Progression Among Zambian Women

Background:Some studies suggest that hormonal contraception, pregnancy, and/or breastfeeding may influence rates of HIV disease progression.Methods:From 1994 to 2012, HIV discordant couples recruited at couples' voluntary HIV counseling and testing centers in Lusaka were followed 3-monthly. Multivariate survival analyses explored associations between time-varying contraception, pregnancy, and breastfeeding and 2 outcomes among HIV-positive women: (1) time to death and (2) time to antiretroviral treatment (ART) initiation.Results:Among 1656 female seropositive, male seronegative couples followed for 3359 person-years (PY), 224 women died [6.7/100 PY; 95% confidence interval (CI): 5.8 to 7.6]. After 2003, 290 women initiated ART (14.5/100 PY; 95% CI: 12.9 to 16.2). In a multivariate model of time to death, hormonal implant [adjusted hazard ratio (aHR) = 0.30; 95% CI: 0.10 to 0.98] and injectable (aHR = 0.59; 95% CI: 0.36 to 0.97) were significantly protective relative to nonhormonal method use, whereas oral contraceptive pill (OCP) use was not (aHR = 1.08; 95% CI: 0.74 to 1.57) controlling for baseline HIV disease stage, time-varying pregnancy, time-varying breastfeeding, and year of enrollment. In a multivariate model of time-to-ART initiation, implant was significantly protective (aHR = 0.54; 95% CI: 0.31 to 0.95), whereas OCP (aHR = 0.70; 95% CI: 0.44 to 1.10) and injectable (aHR = 0.85; 95% CI: 0.55 to 1.32) were not relative to nonhormonal method use controlling for variables above, woman's age, and literacy. Pregnancy was not significantly associated with death (aHR = 1.07; 95% CI: 0.68 to 1.66) or ART initiation (aHR = 1.24; 95% CI: 0.83 to 1.86), whereas breastfeeding was protective for death (aHR = 0.34; 95% CI: 0.19 to 0.62) and ART initiation (aHR = 0.49; 95% CI: 0.29 to 0.85).Conclusions:Hormonal implants and injectables significantly predicted lower mortality; implants were protective for ART initiation. OCPs and pregnancy were not associated with death or ART initiation, whereas breastfeeding was protective for both. Findings from this 18-year cohort study suggest that (1) HIV-positive women desiring pregnancy can be counseled to do so and breastfeed and (2) all effective contraceptive methods, including injectables and implants, should be promoted to prevent unintended pregnancy.

Immune activation despite suppressive highly active antiretroviral therapy is associated with higher risk of viral blips in HIV-1-infected individuals

Viral blips are thought to represent random biological variations around a steady state of residual HIV viraemia and to lack clinical significance. We aimed to assess the association of immune activation and the occurrence of blips. HIV-infected patients from our out-patient cohort who developed a blip after having been on fully suppressive highly active antiretroviral therapy (HAART) for at least 180 days were matched with patients without blips according to duration of complete viral suppression (CVS), age, sex and Centers for Disease Control and Prevention (CDC) stage. Frequencies of CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(+) HLA-DR(+), CD4(+) CD45RA(+), CD16(+) CD56(+) CD3(-) and CD19(+) cells, as well as C-reactive protein (CRP) levels and clinical parameters, were included in conditional logistic regression models. Adherence to HAART was assessed by measuring prescribed nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) plasma levels in a sample of 57 patients. Eighty-two patients with viral blip were matched with 82 controls from the same cohort. The mean age was 47.2 years [standard deviation (SD) 12.1 years], 80.5% of patients were male and 42.7% had CDC stage C disease. Viral blips occurred after a median of 14 months [interquartile range (IQR) 8-34 months] of CVS. In the logistic regression, activated CD3(+) HLA-DR(+) lymphocytes [odds ratio (OR) 1.25 per 100 cells/μL; 95% confidence interval (CI) 1.02-1.54; P = 0.03] were significantly associated with blips and there was a trend for an association of longer time on HAART with blips (OR 1.31 per year; 95% CI 0.96-1.78; P = 0.09). No between-group difference regarding subtherapeutic drug levels was found (P = 0.46). The occurrence of viral blips after suppressive HAART was associated with elevated markers of T-cell activation. Blips may identify a subset of patients with higher immune activation and increased risk for HIV disease progression.

Suboptimal plasma HIV-1 RNA suppression and adherence among sex workers who use illicit drugs in a Canadian setting: an observational cohort study

ObjectiveStudies have demonstrated the central function of plasma HIV-1 RNA viral load (pVL) levels on determining the risk of HIV disease progression and transmission. However, there is limited empirical research...

Vitamin D–related Host Genetic Variants Alter HIV Disease Progression in Children

Vitamin D deficiency is common in HIV infection and has been associated with advanced disease. This study investigated whether vitamin D-related genetic variants were associated with disease progression in HIV-infected children. The Fok-I (C/T), Bsm-I (G/A), GC (A/C), DHCR7 (G/T) and CYP2R1 (G/A) genetic variants were detected by real-time polymerase chain reaction in HIV-infected children who participated in the Pediatric AIDS Clinical Trials Group P152 and P300 protocols, which predated the availability of effective combination antiretroviral therapy. The primary endpoints included time to progression to the first HIV-related disease endpoint (≥2 opportunistic infection, weight growth failure) or death, which constituted the progression-free survival. Analyses were performed for age>2 years and ≤2 years separately adjusting for race and treatment effect. Of the 998 children evaluated, 139 experienced HIV disease progression. For children>2 years, rapid disease progression was associated with the DHCR7 G allele compared with the T allele (G/G vs. T/T: hazard ratio [HR]=5.0, P = 0.035; G/T vs. T/T: HR=4.5, P=0.042; G/G+G/T vs. T/T: HR=4.8, P=0.036) and the Bsm-I A allele compared with the G allele (A/G vs. G/G: HR=2.2, P=0.014 and A/G+A/A vs. G/G: HR=2.0, P=0.026). In children≤2 years, the Bsm-I A allele increased the risk of disease progression in Hispanics (A/A vs. G/A+G/G: HR=2.8, P=0.03 and A/A vs. G/G: HR=2.8, P=0.046) and whites (A/A vs. G/G: HR=6.6, P=0.025 and A/A vs. G/A+G/G: HR=3.6, P=0.038). Vitamin D-related host genetic variants that alter the availability and activity of vitamin D are associated with risk of HIV disease progression in children and may vary by age and race.

Rate and Predictors of Carotid Artery Intima Media Thickness Progression in Antiretroviral-Naive HIV-Infected and Uninfected Adults: A 48-Week Matched Prospective Cohort Study

Carotid intima media thickness (CIMT) progresses faster in HIV-infected adults on antiretroviral therapy (ART) than the general population. It is unclear if the rate of progression is similarly faster in ART-naive, HIV-infected adults. This was a 48-week prospective cohort study to compare change in CIMT and inflammation markers in ART-naive, HIV-infected adults in no immediate need of ART (HIV-positive/ART-naive) and age/sex/body mass index (BMI)-matched controls (HIV-negative). A total of 85 HIV-positive/ART-naive and 45 HIV-negative participants were enrolled. In the HIV-positive/ART-naive group, median baseline CD4+ T-cell count and HIV-1 RNA were 535 cells/mm3 and 6,916 copies/ml. Baseline common carotid artery (CCA) and bulb CIMTs were similar between groups. Changes in CIMT to 48 weeks at both sites were not different within- or between-groups (median [IQR] change in HIV-positive/ART-naive versus HIV-negative CCA CIMT -0.0071 mm [-0.0267-0.0233] versus 0.0113 mm [-0.0117-0.0306]; P = 0.19 between-groups; and bulb CIMT 0.0017 mm [-0.0367-0.06167] versus 0.01 mm [-0.0383-0.0625]; P = 0.54). After adjustment for cardiovascular disease (CVD) risk factors, change in CCA CIMT was greater in HIV-negative participants (-0.0046 versus 0.0177 mm for HIV-positive/ART-naive versus HIV-negative; P = 0.01). In HIV-positive/ART-naive, interleukin (IL)-6, soluble tumour necrosis factor-α receptor (sTNFR)-II, vascular cell adhesion molecule-1 and intercellular adhesion molecule (ICAM)-1 were higher at both time points and D-dimer was higher at week 48 (P < 0.01 for all). IL-6, sTNFR-I and D-dimer increased over 48 weeks in HIV-positive/ART-naive participants (P < 0.01 for all). In HIV-positive/ART-naive participants, independent predictors of greater change in CCA CIMT were higher BMI (P = 0.05) and family history of CVD (P < 0.01) and of greater change in bulb CIMT were higher sTNFR-I (P = 0.03) and higher diastolic blood pressure (P < 0.01). In ART-naive HIV-infected adults at low risk of HIV disease progression and low cardiovascular risk, CIMT progression rate was similar to matched controls. In addition to traditional CVD risk factors, higher levels of sTNFR-I predicted greater bulb CIMT changes.

Self-reported sleep disturbance is associated with lower CD4 count and 24-h urinary dopamine levels in ethnic minority women living with HIV

Sleep disturbance is associated with dopamine dysregulation, which can negatively impact immune status. Individuals living with HIV experience more sleep difficulties, and poor sleep may compound immune decrements associated with HIV infection. Little research has examined associations between sleep, dopamine, and immune status (CD4 count) in individuals with HIV. As ethnic minority women living with HIV (WLWH) are at heightened risk for HIV disease progression, we related sleep reports to both CD4 count and dopamine levels in a cohort of ethnic minority WLWH. Participants were 139 low-income WLWH (ages 20-62; 78.3% African-American or Caribbean) who reported both overall sleep quality and sleep disturbance on the Pittsburgh sleep quality index (PSQI). CD4 count and HIV viral load were measured via morning peripheral venous blood samples, and concentrations of dopamine were measured via 24-h urine collection. Covariates included HIV viral load, length of time since HIV diagnosis, HAART adherence, perceived stress and depression. After controlling for all covariates, greater sleep disturbance was associated with significantly lower CD4 count (β=-.20, p=.03) and lower levels of dopamine (β=-.25, p=.04). Poorer overall sleep quality was marginally associated with lower CD4 count (β=-.16, p=.08), and was not associated with dopamine. Our analyses suggest that sleep disturbance is independently related with immune status and dopamine levels in WLWH. Lower levels of dopamine may indicate neuroendocrine dysregulation and may impact immune and health status. Results highlight sleep disturbance rather than overall sleep quality as potentially salient to neuroendocrine and immune status in ethnic minority WLWH.

Effect of hormonal contraceptive methods on HIV disease progression

Systematically assess from the literature whether women living with HIV who use hormonal contraception are at increased risk of HIV-disease progression compared with those who do not use hormonal contraception. We searched PUBMED and EMBASE for articles published in peer-reviewed journals through December 15, 2011 for evidence relevant to all hormonal contraceptive methods and HIV-disease progression. Twelve reports of 11 studies met inclusion criteria. One randomized controlled trial (RCT) found increased risk for the composite outcome of a reduced CD4 cell count or death among hormonal contraceptive users when compared with copper intrauterine device (IUD) users. Ten cohort studies reported no increased risk for HIV disease progression (as measured by mortality, time to a CD4 cell count below 200, time to initiation of antiretroviral therapy, an increase in HIV-RNA viral load, or a decrease in CD4 count) among women who used hormonal contraception compared with those who did not. The preponderance of evidence indicates that HIV-positive women can use hormonal contraceptive methods without concerns related to HIV-disease progression. Cohort studies consistently found no association between hormonal contraceptive use and HIV-disease progression compared with nonuse of hormonal contraceptives. One RCT found that hormonal contraceptive use was associated with increased risk of HIV-disease progression when compared with IUD use, but this study had important methodological shortcomings. Prevention of unintended pregnancy among women living with HIV remains a public health priority to safeguard women's and infants' health and to prevent vertical transmission of HIV.

HIV and malaria interactions: where do we stand?

Reversing the spread of HIV infection and the incidence of malaria constitute two of the Millenium Development Goals. However, despite recent achievements, both diseases still entail global heath problems. Furthermore, their overlapping geographical distribution raises concerns and challenges for potential immunological, clinical and therapeutic interactions. It has been reported that HIV infection increases malaria susceptibility and reduces the efficacy of antimalarial drugs. On the other hand, the effect of malaria on HIV-infected individuals has also been explored, with the parasitic infection increasing the risk of HIV disease progression and mother-to-child transmission of HIV. The spread of malaria and parasite resistance to antimalarials could also be accelerated by HIV-associated immunosuppresion. Current knowledge of the epidemiological, clinical, immunological and therapeutic interactions of the two diseases is reviewed in this article. We focus on the latest available data, pointing out key future research areas and challenges of the field.

Effect of Combined Antiretroviral Therapy on Selected Trace Elements and CD4+T-cell Count in HIV-Positive Persons in an African Setting

In HIV-infected persons, low serum concentrations of trace elements have been associated with an increased risk of HIV disease progression and mortality. Few data are available to determine whether HAART ameliorates micronutrient deficiencies in HIV-positive persons. In the current study, we investigated the effects of HAART on selected trace elements such as selenium, zinc and copper and on CD4+T-cell count in HIV-positive persons. Fifty HIV-positive individuals with 25 on HAART and 25 who were not on HAART were recruited for the study. Twenty five apparently health persons who were HIV-negative serve as a control group. Serum concentrations of selenium, zinc and copper were estimated by atomic absorption spectrophometric method while CD4+T-cell count was determined by flow cytometric method. Persons on HAART showed significantly (P<0.05) high Zn and CD4+Tcell count compared to PRE-HAART. There was no significant difference in the serum selenium and copper levels between HAART and PRE-HAART persons. In conclusion, HAART significantly improved the immunological status as evidenced by increased CD4+T-cell count and also significantly increased the zinc level in the same group. A large randomized placebo-controlled trial is recommended for future study.

Educational level and HIV disease progression before and after the introduction of HAART: a cohort study in 989 HIV seroconverters in Spain

ObjectivesTo analyse the effect of educational level on the progression from HIV seroconversion to highly active antiretroviral therapy (HAART) requirement, HAART initiation, AIDS and death from any cause at different...

Pregnancy Outcomes in Women with Advanced HIV Infection in Italy

Pregnancy has been associated with a low risk of HIV disease progression. Most pregnancies with HIV currently involve women who have not experienced AIDS-defining events, and are clinically classified as Centers for Disease Control and Prevention (CDC) groups A or B. We evaluated the main maternal outcomes among pregnant women with more advanced HIV disease, defined by CDC-C disease stage. Data from the Italian National Program on Surveillance on Antiretroviral Treatment in Pregnancy were used. A total of 566 HIV-infected mothers, 515 in stage A or B (CDC-AB group) and 51 in stage C (CDC-C group) were evaluated. The two groups had similar baseline characteristics. No differences were found in the main maternal and neonatal outcomes. Most of the women achieved viral suppression at end of pregnancy (>1000 copies per milliliter: CDC-C: 17.2%; CDC-AB: 13.7%). One year after delivery, HIV replication (HIV-RNA >1000 copies per milliliter) was present in 11.5% of CDC-AB women and 30.0% CDC-C women. Despite lower initial CD4 counts (300 versus 481 cells per microliter), CDC-C women maintained stable CD4 levels during pregnancy, and 1 year after delivery, a significant increase in CD4 count from preconception values was observed in both groups (CDC-C: +72 cells per microliter, p=0.031; CDC-AB: +43 cells per microliter, p<0.001). Only one AIDS event occurred in a woman with a previous diagnosis of AIDS. In CDC-C women, pregnancy is not associated with an increased rate of adverse maternal or neonatal outcomes, and a good immunovirologic response can be expected. During postpartum care, women with more advanced HIV infection should receive particular care to prevent loss of virologic suppression.

Pharmacoeconomics of darunavir

Darunavir boosted with ritonavir (DRV/r) in combination with other antiretrovirals (ARVs) was initially approved in 2006 for the treatment of HIV infection in ARV treatment-experienced adults and has subsequently been approved for use in treatment-naive adults in 2008. Clinical studies have shown that DRV/r in combination with other ARVs achieves superior levels of undetectable plasma HIV RNA and generates significant CD4 increases, which reduce the risk of HIV disease progression. Economic evaluations, based on data from controlled clinical trials, found DRV/r combination therapy to generate savings in hospital costs and other non-ARV costs of care in treatment-experienced patients, to maximize the number of patients reaching undetectable plasma HIV RNA, to improve health-related quality of life and quality-adjusted life expectancy, and to be cost effective across different patient populations.

Dissociation of CD154 and Cytokine Expression Patterns in CD38+ CD4+ Memory T Cells in Chronic HIV-1 Infection

Expression of the activation antigen CD38 on T cells is a strong predictor of the risk of HIV disease progression, but it is not known whether CD38 is a marker or mediator of dysfunction. We examined the relationship between CD38 expression and responses to T-cell receptor stimulation in central memory and effector memory CD4 T cells in HIV-infected persons and in healthy controls. Basal CD38 expression was preserved by blocking golgi transport with brefeldin A. Intracellular expression of interleukin 2, interferon γ, and CD154 was measured after stimulating peripheral blood mononuclear cells with the superantigen staphylococcal enterotoxin B with or without anti-CD28 costimulation. Interferon-γ responses were comparable or increased in stimulated CD38 memory cells, and the interleukin 2 responses of costimulated CD38 central memory cells were decreased in HIV infection. In CD38 cells and especially in CD38 cells of HIV-infected persons, stimulated memory cells more often failed to express CD154 (CD40 ligand) when induced to express cytokine. A dissociated cytokine and CD154 expression by memory CD4 T cells may impair interactions between T cells and antigen-presenting cells, contribute to impaired immunity and help explain the relationship between CD38 expression and disease progression in chronic HIV infection.

Short-Term Risk of HIV Disease Progression and Death in Ugandan Children Not Eligible for Antiretroviral Therapy

Increasing numbers of HIV-infected children not yet eligible for antiretroviral therapy (ART) are entering health care in Africa. We sought to characterize the risk of short-term disease progression in this population. In a cohort of HIV-infected ART-naive and -ineligible Ugandan children older than 1 year, the rates of clinical/immunologic progression within 2 years were assessed using Kaplan-Meier survival analysis and multivariate Cox proportional-hazards modeling. Among 192 children (mean age: 6.4 years, CD4%:25), 19% progressed within 2 years by World Health Organization stage 3/4 event (n = 22), death (n = 3), or World Health Organization-defined CD4 threshold for ART initiation (n = 12). Significant univariate predictors were CD4% [hazard ratio (HR) = 2.0 per 10% decrease, P = 0.005], HIV RNA level (HR = 2.4 per log10 increase, P = 0.002), male gender (HR = 2.0, P = 0.04), age < 3 years (HR = 3.7, P = 0.001), CD4 activation (%CD4+ CD38+ HLADR+) (HR = 1.6 per 10% increase, P = 0.05), and CD8 activation (%CD8+ CD38+ HLADR+) (HR = 1.3 per 10% increase, P = 0.05] (HR = 1.3, P = 0.5). In multivariate analysis, CD4% (HR = 2.0, P = 0.034), HIV RNA level (HR = 1.8, P = 0.013), and age < 3 years (HR = 3.0, P = 0.008) were independently predictive. Children with HIV RNA >10 copies per milliliter and CD4% <25 had progression rates of 29% (1 year) and 34% (2 years). Even with frequent CD4 monitoring, HIV-infected Ugandan children experienced significant clinical events while ineligible for ART per WHO 2006 guidelines.

Safety of hormonal and intrauterine methods of contraception for women with HIV/AIDS: a systematic review

To determine from the literature whether HIV-infected women who use hormonal or intrauterine contraception are at increased risk of HIV disease progression, other adverse health outcomes, or HIV transmission to uninfected sexual partners. A systematic review. We searched PubMed for articles published in peer-reviewed journals through August 2009 for evidence relevant to all hormonal and intrauterine contraceptive methods and HIV/AIDS. Eight observational studies reported no increased risk of HIV disease progression with hormonal or intrauterine contraceptive use, whereas one randomized controlled trial found increased risks of declining CD4 cell count and death for hormonal contraceptive users compared with intrauterine device users. Women with HIV who used hormonal contraception had increased risks of acquiring sexually transmitted infections compared with women not using hormonal contraception, similar to the risks reported among uninfected women. One study found no association between hormonal or intrauterine contraceptive use and increased risk of HIV transmission to uninfected partners, whereas findings from nine studies examining contraceptive use and viral shedding from the genital tract were inconsistent. Evidence regarding the safety of hormonal and intrauterine contraceptive use among women with HIV remains limited, but generally reassuring regarding adverse health effects, disease transmission to uninfected partners, and disease progression; however, one randomized trial raised concerns about enhanced disease progression among women using hormonal contraception. Preventing unintended pregnancy among women with HIV remains a high priority in public health, both for the health of the woman as well as for the prevention of mother-to-child transmission of HIV.

Antiretroviral Therapy Initiation Before, During, or After Pregnancy in HIV-1-Infected Women: Maternal Virologic, Immunologic, and Clinical Response

BackgroundPregnancy has been associated with a decreased risk of HIV disease progression in the highly active antiretroviral therapy (HAART) era. The effect of timing of HAART initiation relative to pregnancy on maternal virologic, immunologic and clinical outcomes has not been assessed.MethodsWe conducted a retrospective cohort study from 1997–2005 among 112 pregnant HIV-infected women who started HAART before (N = 12), during (N = 70) or after pregnancy (N = 30).ResultsWomen initiating HAART before pregnancy had lower CD4+ nadir and higher baseline HIV-1 RNA. Women initiating HAART after pregnancy were more likely to receive triple-nucleoside reverse transcriptase inhibitors. Multivariable analyses adjusted for baseline CD4+ lymphocytes, baseline HIV-1 RNA, age, race, CD4+ lymphocyte count nadir, history of ADE, prior use of non-HAART ART, type of HAART regimen, prior pregnancies, and date of HAART start. In these models, women initiating HAART during pregnancy had better 6-month HIV-1 RNA and CD4+ changes than those initiating HAART after pregnancy (−0.35 vs. 0.10 log10 copies/mL, P = 0.03 and 183.8 vs. −70.8 cells/mm3, P = 0.03, respectively) but similar to those initiating HAART before pregnancy (−0.32 log10 copies/mL, P = 0.96 and 155.8 cells/mm3, P = 0.81, respectively). There were 3 (25%) AIDS-defining events or deaths in women initiating HAART before pregnancy, 3 (4%) in those initiating HAART during pregnancy, and 5 (17%) in those initiating after pregnancy (P = 0.01). There were no statistical differences in rates of HIV disease progression between groups.ConclusionsHAART initiation during pregnancy was associated with better immunologic and virologic responses than initiation after pregnancy.