The Spectrum projection package: improvements in estimating mortality, ART needs, PMTCT impact and uncertainty bounds

BACKGROUND: The approach to national and global estimates of HIV/AIDS used by UNAIDS starts with estimates of adult HIV prevalence prepared from surveillance data using either the Estimation and Projection Package (EPP) or the Workbook. Time trends of prevalence are transferred to Spectrum to estimate the consequences of the HIV/AIDS epidemic, including the number of people living with HIV, new infections, AIDS deaths, AIDS orphans, treatment needs and the impact of treatment on survival. METHODS: The UNAIDS Reference Group on Estimates, Modelling and Projections regularly reviews new data and information needs and recommends updates to the methodology and assumptions used in Spectrum. The latest update to Spectrum was used in the 2007 round of global estimates. RESULTS: Several new features have been added to Spectrum in the past two years. The structure of the population was reorganised to track populations by HIV status and treatment status. Mortality estimates were improved by the adoption of new approaches to estimating non-AIDS mortality by single age, and the use of new information on survival with HIV in non-treated cohorts and on the survival of patients on antiretroviral treatment (ART). A more detailed treatment of mother-to-child transmission of HIV now provides more prophylaxis and infant feeding options. New procedures were implemented to estimate the uncertainty around each of the key outputs. CONCLUSIONS: The latest update to the Spectrum program is intended to incorporate the latest research findings and provide new outputs needed by national and international planners

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

Pregnancy 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.We 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).0.01). There were no statistical differences in rates of HIV disease progression between groups.HAART initiation during pregnancy was associated with better immunologic and virologic responses than initiation after pregnancy

Emergence of Minor Drug-Resistant HIV-1 Variants after Triple Antiretroviral Prophylaxis for Prevention of Vertical HIV-1 Transmission

Background: WHO-guidelines for prevention of mother-to-child transmission of HIV-1 in resource-limited settings recommend complex maternal antiretroviral prophylaxis comprising antenatal zidovudine (AZT), nevirapine single-dose (NVP-SD) at labor onset and AZT/lamivudine (3TC) during labor and one week postpartum. Data on resistance development selected by this regimen is not available. We therefore analyzed the emergence of minor drug-resistant HIV-1 variants in Tanzanian women following complex prophylaxis. Method: 1395 pregnant women were tested for HIV-1 at Kyela District Hospital, Tanzania. 87/202 HIV-positive women started complex prophylaxis. Blood samples were collected before start of prophylaxis, at birth and 1–2, 4–6 and 12–16 weeks postpartum. Allele-specific real-time PCR assays specific for HIV-1 subtypes A, C and D were developed and applied on samples of mothers and their vertically infected infants to quantify key resistance mutations of AZT (K70R/T215Y/T215F), NVP (K103N/Y181C) and 3TC (M184V) at detection limits of,1%. Results: 50/87 HIV-infected women having started complex prophylaxis were eligible for the study. All women took AZT with a median duration of 53 days (IQR 39–64); all women ingested NVP-SD, 86 % took 3TC. HIV-1 resistance mutations were detected in 20/50 (40%) women, of which 70 % displayed minority species. Variants with AZT-resistance mutations were found in 11/50 (22%), NVP-resistant variants in 9/50 (18%) and 3TC-resistant variants in 4/50 women (8%). Three wome

Lack of effect of chemokine receptor CCR2b gene polymorphism on HIV-1 plasma RNA viral load and immune activation among HIV-1 seropositive female sex workers in Abidjan, Côte d'Ivoire

The prevalence of the CCR2b-V64I mutation among human immunodeficiency virus (HIV)-seropositive and -seronegative female workers and the potential effect of heterozygosity of this mutation on HIV-1 plasma RNA viral load and markers of immune activation were assessed. CCR2b-V64I was detected by polymerase chain reaction, followed by restriction enzymes analysis; plasma viral load was measured by the Amplicor HIV-1 monitor assay and CD4(+) T-cell counts and markers of immune activation by standard three-color FACscan flow cytometry. Of the 260 female workers, 56 (21.5%) were heterozygous for CCR2b-V64I, and 8 (3%) were homozygous. Of the 99 HIV-seronegative female workers, 19 (19.2%) were heterozygous for the CCR2b-V64I mutation compared with 37 (23%) of the 161 HIV-seropositive FSW (P = 0.47). In a univariate analysis of viral load among HIV-seropositive FSW, no difference was noted between those heterozygous for or without the mutation; both groups had plasma viral loads of 5.0 log(10) copies/ml. After controlling for the effects of CD4(+) T-cell counts in a multivariate analysis, no significant difference was observed between the groups in viral load or in markers of immune activation. The data suggest that the presence of the CCR2b mutation has no effect on HIV-1 plasma viral load and markers of immune activation in our study population. The finding that the frequency of this mutation is similar in HIV-seropositive and -seronegative female workers suggests that its presence is not associated with increased risk of HIV infection

Changes in level of immune activation and reconstitution among HIV-1-infected Africans receiving antiretroviral therapy

Not the final published versionOBJECTIVE: To describe changes in immune activation and reconstitution markers among HIV-1-infected patients receiving antiretroviral therapy (ART) in Abidjan, Côte d'Ivoire. METHODS: Between November 1998 and February 2001, we analyzed changes in immune activation and reconstitution markers among 52 patients. Good virologic responders (n = 26) were defined as those who had suppressed and maintained plasma viral load (VL) below the detection limit of the assay for at least 12 months. Poor virologic responders (n = 26) were defined as those with a detectable VL at 6 and 12 months after beginning ART. RESULTS: Of the 26 good virologic responders, 20 (77%) were on highly active antiretroviral therapy (HAART) compared with one (4%) of the poor responders. Among the 26 good responders, baseline median levels of CD38+CD8+ T cells were elevated, but had decreased significantly at 6 months (P < 0.001) and at 12 months of therapy (P < 0.001). Median levels of HLA-DR+CD8+ T cells also decreased from baseline at 6 months (P < 0.001) and at 12 months of therapy (P < 0.001). Levels of CD62L+CD4+ T cells increased steadily during the 6 and 12 months of therapy and reached levels observed among HIV-negative blood donors (P = 0.07). Among the 26 poor responders, median levels of CD38+CD8+ T cells decreased significantly at 12 months of therapy (P = 0.006), but were higher than levels in blood donors (P = 0.005). Levels of HLA-DR+CD8+ T cells decreased significantly at 12 months of therapy (P < 0.001). Levels of CD62L+CD4+ decreased over time. CONCLUSION: Our results suggest that HAART can be successfully used in African populations with elevated baseline immune activation markers

A human milk factor susceptible to cathepsin D inhibitors enhances human immunodeficiency virus type 1 infectivity and allows virus entry into a mammary epithelial cell line

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Guidelines for the Management of HIV Infection in Pregnant Women and the Prevention of Mother-to-Child Transmission of HIV

The prevalence of HIV infection amongst women giving birth in England and Wales has increased every year since 1990. Results from the Unlinked Anonymous Surveys of infection in pregnancy, show that in 2003, the prevalence reached one in 180 (0.56%) in inner London, one in 271 in outer London (0.37%) and one in 1,282 (0.08%) in the rest of England [1]. The majority of these women are from sub-Saharan Africa. The Department of Health policy of recommending an HIV test to every pregnant woman [2] has resulted in an increase in the proportion of these women who are aware of their diagnosis prior to delivery (more than 80% in London in 2001) and a decrease in the absolute number of infants infected in the UK [3]