The WHO public-health approach to antiretroviral treatment against HIV in resource-limited settings.

WHO has proposed a public-health approach to antiretroviral therapy (ART) to enable scaling-up access to treatment for HIV-positive people in developing countries, recognising that the western model of specialist physician management and advanced laboratory monitoring is not feasible in resource-poor settings. In this approach, standardised simplified treatment protocols and decentralised service delivery enable treatment to be delivered to large numbers of HIV-positive adults and children through the public and private sector. Simplified tools and approaches to clinical decision-making, centred on the "four Ss"--when to: start drug treatment; substitute for toxicity; switch after treatment failure; and stop--enable lower level health-care workers to deliver care. Simple limited formularies have driven large-scale production of fixed-dose combinations for first-line treatment for adults and lowered prices, but to ensure access to ART in the poorest countries, the care and drugs should be given free at point of service delivery. Population-based surveillance for acquired and transmitted resistance is needed to address concerns that switching regimens on the basis of clinical criteria for failure alone could lead to widespread emergence of drug-resistant virus strains. The integrated management of adult or childhood illness (IMAI/IMCI) facilitates decentralised implementation that is integrated within existing health systems. Simplified operational guidelines, tools, and training materials enable clinical teams in primary-care and second-level facilities to deliver HIV prevention, HIV care, and ART, and to use a standardised patient-tracking system

Transmission of HIV-1 infection in sub-Saharan Africa and effect of elimination of unsafe injections

During the past year, a group has argued that unsafe injections are a major if not the main mode of HIV-1 transmission\ud in sub-Saharan Africa. We review the main arguments used to question the epidemiological interpretations on the lead\ud role of unsafe sex in HIV-1 transmission, and conclude there is no compelling evidence that unsafe injections are a\ud predominant mode of HIV-1 transmission in sub-Saharan Africa. Conversely, though there is a clear need to eliminate\ud all unsafe injections, epidemiological evidence indicates that sexual transmission continues to be by far the major\ud mode of spread of HIV-1 in the region. Increased efforts are needed to reduce sexual transmission of HIV-1

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

Implementing services for Early Infant Diagnosis (EID) of HIV: a comparative descriptive analysis of national programs in four countries

<p>Abstract</p> <p>Background</p> <p>There is a significant increase in survival for HIV-infected children who have early access to diagnosis and treatment. The goal of this multi-country review was to examine when and where HIV-exposed infants and children are being diagnosed, and whether the EID service is being maximally utilized to improve health outcomes for HIV-exposed children.</p> <p>Methods</p> <p>In four countries across Africa and Asia existing documents and data were reviewed and key informant interviews were conducted. EID testing data was gathered from the central testing laboratories and was then complemented by health facility level data extraction which took place using a standardized and validated questionnaire</p> <p>Results</p> <p>In the four countries reviewed from 2006 to 2009 EID sample volumes rose dramatically to an average of >100 samples per quarter in Cambodia and Senegal, >7,000 samples per quarter in Uganda, and >2,000 samples per quarter in Namibia. Geographic coverage of sites also rapidly expanded to 525 sites in Uganda, 205 in Namibia, 48 in Senegal, and 26 in Cambodia in 2009. However, only a small proportion of testing was done at lower-level health facilities: in Uganda Health Center IIs and IIIs comprised 47% of the EID collection sites, but only 11% of the total tests, and in Namibia 15% of EID sites collected >93% of all samples. In all countries except for Namibia, more than 50% of the EID testing was done after 2 months of age. Few sites had robust referral mechanisms between EID and ART. In a sub-sample of children, we noted significant attrition of infants along the continuum of care post testing. Only 22% (Senegal), 37% (Uganda), and 38% (Cambodia) of infants testing positive by PCR were subsequently initiated onto treatment. In Namibia, which had almost universal EID coverage, more than 70% of PCR-positive infants initiated ART in 2008.</p> <p>Conclusions</p> <p>While EID testing has expanded dramatically, a large proportion of PCR- positive infants are initiated on treatment. As EID services continue to scale-up, more programmatic attention and support is needed to retain HIV-exposed infants in care and ensure that those testing positive initiate treatment in a timely manner. Namibia's experience demonstrates that it is feasible for a rural, low-income country to achieve high national coverage of infant testing and treatment.</p

High Uptake of Exclusive Breastfeeding and Reduced Early Post-Natal HIV Transmission

BACKGROUND. Empirical data showing the clear benefits of exclusive breastfeeding (EBF) for HIV prevention are needed to encourage implementation of lactation support programs for HIV-infected women in low resource settings among whom replacement feeding is unsafe. We conducted a prospective, observational study in Lusaka, Zambia, to test the hypothesis that EBF is associated with a lower risk of postnatal HIV transmission than non-EBF. METHODS AND RESULTS. As part of a randomized trial of early weaning, 958 HIV-infected women and their infants were recruited and all were encouraged to breastfeed exclusively to 4 months. Single-dose nevirapine was provided to prevent transmission. Regular samples were collected from infants to 24 months of age and tested by PCR. Detailed measurements of actual feeding behaviors were collected to examine, in an observational analysis, associations between feeding practices and postnatal HIV transmission. Uptake of EBF was high with 84% of women reporting only EBF cumulatively to 4 months. Post-natal HIV transmission before 4 months was significantly lower (p = 0.004) among EBF (0.040 95% CI: 0.024–0.055) than non-EBF infants (0.102 95% CI: 0.047–0.157); time-dependent Relative Hazard (RH) of transmission due to non-EBF = 3.48 (95% CI: 1.71–7.08). There were no significant differences in the severity of disease between EBF and non-EBF mothers and the association remained significant (RH = 2.68 95% CI: 1.28–5.62) after adjusting for maternal CD4 count, plasma viral load, syphilis screening results and low birth weight. CONCLUSIONS. Non-EBF more than doubles the risk of early postnatal HIV transmission. Programs to support EBF should be expanded universally in low resource settings. EBF is an affordable, feasible, acceptable, safe and sustainable practice that also reduces HIV transmission providing HIV-infected women with a means to protect their children's lives. TRIAL REGISTRATION. ClinicalTrials.gov NCT00310726National Institute of Child Health and Human Development; National Institutes of Health (R01 HD 39611, R01 HD 40777); Centers for Disease Control and Prevention; Global AIDS Program; Glaser Pediatric AIDS Foundation; USAID Country Research (GHS-A-00-00020-00

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