Wednesday, October 31, 2012

programme to prevent mother-to-child HIV transmission in South Africa.

Challenges for routine health system data management in a large public programme to prevent mother-to-child HIV transmission in South Africa.

Recent changes to South Africa’s prevention of mother-to-child transmission of HIV (PMTCT) guidelines have raised hope that the national goal of reducing perinatal HIV transmission rates to less than 5% can be attained. While programmatic efforts to reach this target are underway, obtaining complete and accurate data from clinical sites to track progress presents a major challenge. Mate and colleagues assessed the completeness and accuracy of routine PMTCT data submitted to the District Health Information System in three districts of Kwazulu-Natal province, South Africa. They surveyed the completeness and accuracy of data reported for six key PMTCT data elements between January and December 2007 from all 316 clinics and hospitals in three districts. Through visits to randomly selected sites, they reconstructed reports for the same six PMTCT data elements from clinic registers and assessed accuracy of the monthly reports previously submitted to the District Health Information System. Data elements were reported only 50.3% of the time and were “accurate” (i.e. within 10% of reconstructed values) 12.8% of the time. The data element “Antenatal Clients Tested for HIV” was the most accurate data element (i.e. consistent with the reconstructed value) 19.8% of the time, while “HIV PCR testing of baby born to HIV positive mother” was the least accurate with only 5.3% of clinics meeting the definition of accuracy. Data collected and reported in the public health system across three large, high HIV-prevalence districts was neither complete nor accurate enough to track process performance or outcomes for PMTCT care. Systematic data evaluation can determine the magnitude of the data reporting failure and guide site-specific improvements in data management. Solutions are currently being developed and tested to improve data quality.

the finding of data missing at source, the weakest link in this data chain is the actual data collation at the clinic level, followed by lack of submission of data to the district level. Unless health workers are supported and supervised in the execution of data management tasks and unless data collection is designed in the first instance to be used locally to improve patient care, front line staff will not have the capacities nor perceive the value of data collection. Effective health information systems are simple, acceptable, timely, accurate, flexible, and useful. Only then do staff, who can improve clinical practice locally through analysis of performance and outcomes data, truly value them. This foundation stone is key to a health information system that helps national health systems assess progress towards established goals and plan future resource allocations.

HIV transmission in a state prison system,

HIV transmission in a state prison system,

HIV prevalence among state prison inmates in the United States is more than five times higher than among non-incarcerated persons, but HIV transmission within U.S. prisons is sparsely documented. Jafa and colleagues investigated 88 HIV seroconversions reported from 1988-2005 among male Georgia prison inmates. They analyzed medical and administrative data to describe seroconverters’ HIV testing histories and performed a case-crossover analysis of their risks before and after HIV diagnosis. The authors sequenced the gag, env, and pol genes of seroconverters’ HIV strains to identify genetically-related HIV transmission clusters and antiretroviral resistance. They combined risk, genetic, and administrative data to describe prison HIV transmission networks. Forty-one (47%) seroconverters were diagnosed with HIV from July 2003-June 2005 when voluntary annual testing was offered. Seroconverters were less likely to report sex (OR [odds ratio] = 0.02, 95% CI [confidence interval]: 0-0.10) and tattooing (OR = 0.03, 95% CI: <0.01-0.20) style="text-decoration: underline;">Of 67 seroconverters’ specimens tested, 33 (49%) fell into one of 10 genetically-related clusters; of these, 25 (76%) reported sex in prison before their HIV diagnosis. The HIV strains of 8 (61%) of 13 antiretroviral-naïve and 21 (40%) of 52 antiretroviral-treated seroconverters were antiretroviral-resistant. Half of all HIV seroconversions were identified when routine voluntary testing was offered, and seroconverters reduced their risks following their diagnosis. Most genetically-related seroconverters reported sex in prison, suggesting HIV transmission through sexual networks. Resistance testing before initiating antiretroviral therapy is important for newly-diagnosed inmates.

Although HIV testing is mandatory at prison entry since 1988 in Georgia, USA and voluntary annual testing was introduced in 2003, HIV testing and counselling is not offered to inmates at the time of release from prison. HIV prevention programming to reduce risk of HIV exposure while incarcerated, an offer of pre-release HIV testing, and referral to ensure uninterrupted medial care on release are custodial corrections responsibilities. Drug resistance testing before and during antiretroviral treatment is particularly important in closed settings such as this where resistant virus clearly is being transmitted.

Is HIV becoming more virulent? Initial CD4 cell counts among HIV

Is HIV becoming more virulent? Initial CD4 cell counts among HIV seroconverters during the course of the HIV epidemic: .

Whether human immunodeficiency virus (HIV) seroconverters have been presenting with progressively lower CD4 cell counts over the course of the HIV epidemic is controversial. Additional data on whether HIV might have become more virulent on a population level (measured by post-seroconversion CD4 cell counts) may provide important insights regarding HIV pathogenesis. To determine whether post-seroconversion CD4 cell counts have changed over time, Crum-Cianflone and colleagues evaluated 2174 HIV seroconverters as part of a large cohort study during the period 1985-2007. Participants were documented antiretroviral-naive HIV seroconverters who had a CD4 cell count measured within 6 months after receiving a diagnosis of HIV infection. Multiple linear regression models were used to assess trends in initial CD4 cell counts. The mean initial CD4 cell count decreased during the study period from 632 cells/mm(3) in 1985-1990 to 553 cells/mm(3) in 1991-1995, 493 cells/mm(3) in 1996-2001, and 514 cells/mm(3) in 2002-2007. During those periods, the percentages of seroconverters with an initial CD4 cell count <350> were 12%, 21%, 26%, and 25%, respectively. In the multiple linear model, the mean decrease in CD4 cell count from 1985-1990 was 65 cells/mm(3) in 1991-1995 (P < .001), 107 cells/mm(3) in 1996-2001 (P < .001), and 102 cells/mm(3) in 2002-2007 (P < .001). Similar trends occurred with regard to CD4 cell percentage and total lymphocyte count. Similar decreases in initial CD4 cell counts were observed among African American and white persons during the epidemic. A significant decrease in initial CD4 cell counts among HIV seroconverters in the United States has occurred during the HIV epidemic. These data provide an important clinical correlate to suggestions that HIV may have adapted to the host, resulting in a more virulent infection.

findings for this large incident cohort (i.e. with a known date of seroconversion), in which 93% had a CD4 cell count measured within 3 months of seroconversion, suggest that initial CD4 counts among seroconverting military men (96% of the cohort were men) declined early in the HIV epidemic in the USA. Possible explanations include changes in the host, virus, or environment over time. Because the decline stabilized after introduction of potent antiretroviral therapy in 1996, it is plausible that treatment has stimulated a loss of viral fitness and diversity. The findings in the literature are conflicting and there are insufficient data to warrant a change in the assumptions about disease progression used in epidemiological modelling. Therefore further studies of the complexities of HIV virulence and host susceptibility are clearly warranted.

treatment-naive patients of the Swiss HIV Cohort Study. AIDS.

African descent is associated with slower CD4 cell count decline in treatment-naive patients of the Swiss HIV Cohort Study. AIDS.

Miller and colleagues investigated the effect of descent (African versus European) on the progression of untreated HIV infections in a prospective cohort study of HIV-1-infected individuals. They estimated the linear rate of decline of the CD4 cell count and the setpoint viral load in patients with sufficient data points. The effect of descent was assessed by multivariate regression models including descent, sex, viral subtype, the earliest date of confirmed infection, age, and the baseline CD4 cell count; the rate of CD4 cell count decline was also analyzed with mixed-effect models and with matched comparisons between patients of African and European descent based on the baseline CD4 cell count. The authors found that the decline slope of the CD4 cell count was significantly less steep , patients of African descent (n = 123) compared with patients of European descent (n = 463), and this effect was independent of differences in the infecting viral subtypes. Matched comparisons confirmed the effect of African descent (P < style="text-decoration: underline;">Slower disease progression in patients of African descent might be related to host factors allowing better tolerance of high virus levels in patients of African descent compared with patients of European descent.

Editors’ note: Faster rates of HIV disease progression have been associated with immune activation. Even HIV-negative Africans have evidence of increased immune activation, likely due to prevalent co-infections. Comparing HIV–infected individuals of African and European descent who are exposed to the same low-antigen environment of Switzerland can narrow down differences in disease progression to viral and host factors. This study found no effect of viral sub-type suggesting that host factors must be key in the slower CD4 count decline observed in people of African origin living with HIV in Switzerland. Perhaps it is the lack of Duffy antigen receptors for chemokines (DARC-negative status) on the red blood cells in patients of African descent (see Weijing et al in HIV This Week issue 56).

Uptake of HIV testing and counselling

Uptake of HIV testing and counselling is lower among members of the poorest households in sub-Saharan countries, thereby creating significant inequalities in access to HIV testing and counselling and possibly antiretroviral treatment. Helleringer and colleagues set out to measure uptake of home-based HIV testing and counselling and estimate HIV prevalence among members of the poorest households in a sub-Saharan population. Residents of 6 villages of Likoma Island ( Malawi) aged 18-35 and their spouses were offered home-based HIV testing and counselling services. Socioeconomic status, HIV testing history, and HIV risk factors were assessed. Differences in uptake of HIV testing and counselling and in HIV infection prevalence between members of households in the lowest income quartile and the rest of the population were estimated using logistic regression. Members of households in the lowest income quartile were significantly less likely to have ever used facility-based HIV testing and counselling services than the rest of the population (odds ratio = 0.60, 95% confidence interval (CI): 0.36 to 0.97). In contrast, they were significantly more likely to use home-based HIV testing and counselling services provided during the study (adjusted odds ratio = 1.70, 95% CI: 1.04 to 2.79). Socioeconomic differences in uptake of home-based HIV testing and counselling were not due to underlying differences in socioeconomic characteristics or HIV risk factors. The prevalence of HIV was significantly lower among members of the poorest households tested during home-based HIV testing and counselling than among the rest of the population (adjusted odds ratio = 0.37, 95% CI: 0.14 to 0.96). HIV testing and counselling uptake was high during a home-based HIV testing and counselling campaign on Likoma Island, particularly among the poorest. Home-based HIV testing and counselling has the potential to significantly reduce existing socioeconomic gradients in HIV testing and counselling uptake and help mitigate the impact of AIDS on the most vulnerable households.

Editors’ note: Less than a quarter of this study population had participated in facility-based HIV testing and counselling but more than 75% accepted to be tested and immediately retrieved their test results at home. HIV prevalence overall was 8%. This is the first study to document the impact that a home-based approach can have in increasing uptake of HIV testing and counselling among young adults in the poorest households. Young women from these households were the least likely to have used facility-based testing and were the second most likely to participate in home-based HIV testing and counselling after their male counterparts. Reaching out to poorer people in their homes can help ensure that access to HIV prevention and treatment services is more equitable.

The cost and impact of male circumcision on HIV/AIDS in Botswana. J Int AIDS

The cost and impact of male circumcision on HIV/AIDS in Botswana. J Int AIDS .

The HIV epidemic continues to be a major issue facing Botswana, with overall adult HIV prevalence estimated to be 25.7 percent in 2007. This paper estimates the cost and impact of the draft Ministry of Health male circumcision strategy using the Decision-Makers' Programme Planning Tool (DMPPT). Demographic data and HIV prevalence estimates from the recent National AIDS Coordinating Agency estimations are used as input to the DMPPT to estimate the impact of scaling-up male circumcision on the HIV epidemic. These data are supplemented by programmatic information from the draft Botswana National Strategy for Safe Male Circumcision, including information on unit cost and program goals. Alternative scenarios were developed in consultation with stakeholders. Results suggest that scaling-up adult and neonatal circumcision to reach 80% coverage by 2012 would result in averting almost 70,000 new HIV infections through 2025, at a total net cost of US$47 million across that same period. This results in an average cost per HIV infection averted of US$689. Changing the target year to 2015 and the scale-up pattern to a linear pattern results in a more evenly-distributed number of male circumcisions required, and averts approximately 60,000 new HIV infections through 2025. Other scenarios explored include the effect of risk compensation and the impact of increasing coverage of general prevention interventions. Scaling-up safe male circumcision has the potential to reduce the impact of HIV in Botswana significantly; program design elements such as feasible patterns of scale-up and inclusion of counselling are important in evaluating the overall success of the program.

development and programme planning processes for the scale-up of safe male circumcision services for heterosexual men in high HIV prevalence settings are enhanced by the use of this decision-makers’ programme planning tool developed by the Futures Institute in collaboration with UNAIDS. Both Botswana and Namibia have used the tool and several other countries have already or are currently conducting the costing studies that provide key inputs to determine future costs and the impact of male circumcision service scale-up on their HIV epidemics.

Kumaranayake L. The global strategy to eliminate HIV infection

Kumaranayake L. The global strategy to eliminate HIV infection in infants and young children: a seven-country assessment of costs and feasibility.

The objective of this study was to model the feasibility and affordability of the 2001 United Nations General Assembly Special Session on AIDS (UNGASS) goals to reduce mother-to-child transmission of HIV (MTCT) by 50% by 2010 and achieve 80% coverage of interventions to reduce it among women presenting for antenatal care. The cost and human resource needs of prevention of MTCT (PMTCT) and paediatric treatment were modelled for 2007-2015 and compared with the AIDS budgets and available health workforce in Burkina Faso, Cameroon, Cote d’Ivoire, Malawi, Rwanda, United Republic of Tanzania, and Zambia. Interventions used were promotion of family planning to people living with HIV, HIV testing and counselling, antiretroviral treatment to prevent MTCT and for HIV-infected children, and cotrimoxazole prophylaxis for mothers with advanced HIV infection and HIV-exposed children. The cumulative cost from 2007 to 2015 of the intervention in the seven countries combined amounted to US$587 688 291, 86% for PMTCT and 14% for paediatric treatment. Three out of the seven countries - Rwanda, Zambia, and Burkina Faso (almost) - were predicted to have sufficient AIDS funding, but only one - Zambia - was predicted to have also sufficient human resources to scale up the interventions by 2010 and sustain them up to 2015. The cost-effectiveness would be less than US$1150 per infection prevented in fully scaled-up programmes. Scaling up PMTCT will require more funds than currently available in many countries, but human resources appear to be a greater bottleneck than funding. The authors suggest that human resource capacity be assessed when increased funds for PMTCT are requested.

these projections do not include primary prevention of HIV transmission to women of childbearing age, they do include the cost of addressing unmet family planning need among women with HIV who are of reproductive age and living in union. The model also estimated funding requirements to prevent mother-to-child transmission with antiretroviral prophylaxis, treat mothers in need of antiretroviral treatment for 9 months after the birth during breastfeeding, and treat infected children for 2 years. Although commodities (drugs, diagnostics, and supply chain management) represent 81% of the funds required and human resources represent 14%, it is the lack of sufficient numbers of health workers to implement the programme that is a major impediment in 6 of these countries striving to achieve the UNGASS goals of a 50% reduction in the incidence of HIV infection in infants by 2010.

HIV This Week Issue #70A

HIV This Week Issue #70

Welcome to the 70th issue of HIV This Week ! In this issue, we cover HIV testing (why pregnant women need extra protection in pregnancy; home-based HIV testing and counselling on Likoma Island, Malawi increases access to prevention and treatment for the poorest households), pathogenesis and prognosis (African descent predicts slower CD4 cell count decline in Switzerland; did the advent of combination antiretroviral treatment in 1996 abort increasing HIV virulence?), structural determinants: prison (88 seroconversions in prisons in Georgia, USA provoke reflection), cost-effectiveness (a 7-country study shows that human resources are the major impediment to reducing incidence of HIV infection in infants by 50% by 2010; the decision-makers’ programme planning tool determines costs and the potential impact of male circumcision on Botswana’s HIV epidemic), health information systems (why PMTCT programme data collection has to improve clinical practice locally first in order for national data to be valid ), monitoring and evaluation (how well PEPFAR did in Africa from 2004 to 2007), national responses: policy (policy analysis shows a way forward in Pakistan), sexual behaviour (heterosexual anal intercourse in Cape Town, South Africa), epidemiology (how mortality in people living with HIV compares to that of the general population in sub-Saharan Africa), cardiovascular morbidity and HIV (atherosclerosis and HIV infection: the carotid reveals a link; HIV infection increases plasma proteins that are associated with risk of heart attack), trial conduct (people who inject drugs in Sydney, Australia reveal challenges for vaccine trial recruitment), and girls and sexual violence (one-third of Swazi girls experience sexual violence before they turn 18 years old).

eglected disease research and developmentA

Neglected disease research and development: how much are we really spending? .

The need for new pharmaceutical tools to prevent and treat neglected diseases is widely accepted. However, funders wishing to invest in this vitally important area currently face an information gap. In order to address these information deficits, the Bill & Melinda Gates Foundation commissioned the George Institute for International Health to conduct five sequential annual surveys of global investment into research and development (R&D) of new pharmaceutical products to prevent, manage, or cure diseases of the developing world. This article summarises key data from the first G-FINDER report. G-FINDER was designed to include all neglected diseases and products of significance to developing countries, seeking to capture 2007 data from more than 500 funders and countries. Just over US$2.5 billion was invested into R&D of new neglected disease products in 2007. Funding was highly concentrated, with AIDS, TB, and malaria receiving nearly 80% of the total. Overall, product R&D investment was heavily focused on drugs and vaccines. Investment in new diagnostics was patchy, while platform technologies applicable to many diseases, for instance vaccine adjuvants, diagnostic platforms, and delivery technologies, received less than 0.4% of total R&D investment. Neglected disease funding remains primarily the realm of public and philanthropic donors, who collectively invested US$2.3 billion or 90% of the total funding in 2007. Several major OECD ( Organisation for Economic Co-operation and Development) governments were missing in action from the top 10, top 20, or even the top 50 funders of R&D for neglected diseases . It is also remarkable that investment by some private firms is now rivalling or exceeding spending by many public organizations. While the authors commend these companies and philanthropists, their efforts are meant to support, not replace, those of wealthy governments around the world. A broadening of funding efforts so that all who are able to contribute do so, and all diseases receive the attention they deserve, would lead to a dramatic positive impact on the health of developing country patients afflicted with these diseases.

Neglected diseases were defined in this survey research as diseases that disproportionately affect people in developing countries for which there is a need for new products and for which there is market failure, i.e. there is no commercial market to attract research and development by private industry. This survey, which included a wide range of funders and countries, found little correlation between research funding and burden of disease, as measure by disability-adjusted life years (DALYs). This suggests that beyond scientific and epidemiological considerations, investment decisions may be influenced by donor perceptions and preferences, the presence of policy frameworks and funding mechanisms that prioritise specific diseases, the possibility of product development partnerships, and the influence of civil society advocacy. However, the overall pie is too small for the task and it is clearly time for those who can contribute to step forward now.

Tuesday, October 30, 2012

Despite different levels of HIV prevalence

comparison of data from four African longitudinal studies. Sex Transm Infect.

Todd et al set out to compare reported numbers of sexual partners in Eastern and Southern Africa. Sexual partnership data from four longitudinal population-based surveys (1998-2007) in Zimbabwe, Uganda and South Africa were aggregated and overall proportions reporting more than one lifetime sexual partner calculated. A lexis-style table was used to illustrate the average lifetime sexual partners by site, sex, age group and birth cohort. The male-to-female ratio of mean number of partnerships in the last 12 months was calculated by site and survey. For each single year of age, the proportion sexually active in the past year, the mean number of partners in the past year and the proportion with more than one partner in the past year were calculated. Over 90% of men and women between 25 and 45 years of age reported being sexually active during the past 12 months, with most reporting at least one sexual partner. Overall, men reported higher numbers of lifetime sexual partners and partners in the last year than women. The male-to-female ratio of mean partnerships in the last year ranged from 1.41 to 1.86. In southern African cohorts, individuals in later birth cohorts reported fewer sexual partners and a lower proportion reported multiple partnerships compared with earlier birth cohorts, whereas these behavioural changes were not observed in the Ugandan cohorts. Across the four sites, reports of sexual partnerships followed a similar pattern for each sex. The longitudinal results show that reductions in the number of partnerships were more evident in southern Africa than in Uganda.

Editors’ note: This interesting analysis compares sexual behaviour trends over time in four sites in East and Southern Africa, finding decreased numbers of lifetime sexual partners reported by later birth cohorts. The exception is Uganda, where this change has been described as occurring in the 1990s before the period considered in this paper. Despite different levels of HIV prevalence, the reported number of sexual partners is similar across these four sites. Qualitative research would help interpret these findings and explore the suggestion that differences in partner types and partnership duration may help explain the observed discrepancies in HIV prevalence.

Drug resistance mutations for surveillance of transmitted HIV-1 drug-resistance: 2009 update.

Drug resistance mutations for surveillance of transmitted HIV-1 drug-resistance: 2009 update.

Programs that monitor local, national, and regional levels of transmitted HIV-1 drug resistance inform treatment guidelines and provide feedback on the success of HIV-1 treatment and prevention programs. To accurately compare transmitted drug resistance rates across geographic regions and times, the World Health Organization has recommended the adoption of a consensus genotypic definition of transmitted HIV-1 drug resistance. In January 2007, Bennet and colleagues outlined criteria for developing a list of mutations for drug-resistance surveillance and compiled a list of 80 reverse transcriptor and protease mutations meeting these criteria (surveillance drug resistance mutations). Since January 2007, several new drugs have been approved and several new drug-resistance mutations have been identified. In this paper, the authors follow the same procedures described previously to develop an updated list of surveillance drug resistance mutations that are likely to be useful for ongoing and future studies of transmitted drug resistance. The updated surveillance drug resistance mutation list has 93 mutations including 34 non-nucleoside reverse transcriptase protease inhibitor-resistance mutations at 15 reverse transcriptor positions, 19 non-nucleoside reverse transcriptase protease inhibitor-resistance mutations at 10 reverse transcriptor positions, and 40 protease inhibitor-resistance mutations at 18 protease positions.

Editors’ note: Population-based surveillance of transmitted drug resistance in recently infected individuals is a cornerstone of optimal treatment programmes. This WHO updated list of surveillance drug mutations is not designed to be used for individual patient management. Rather, its value lies in the fact that it permits accurate estimation of transmitted resistance as well as comparison of estimates of transmitted resistance from different regions and times.

Elite suppressor-derived HIV-1 envelope glycoproteins

Elite suppressor-derived HIV-1 envelope glycoproteins exhibit reduced entry efficiency and kinetics.

Elite suppressors are a rare subset of HIV-1-infected individuals who are able to maintain HIV-1 viral loads below the limit of detection by ultra-sensitive clinical assays in the absence of antiretroviral therapy. Mechanism(s) responsible for this elite control are poorly understood but likely involve both host and viral factors. This study assesses elite suppressors plasma-derived envelope glycoprotein (env) fitness as a function of entry efficiency as a possible contributor to viral suppression. Fitness of virus entry was first evaluated using a novel inducible cell line with controlled surface expression levels of CD4 (receptor) and CCR5 (co-receptor). In the context of physiologic CCR5 and CD4 surface densities, elite supressors envs exhibited significantly decreased entry efficiency relative to chronically infected viremic progressors. Elite suppressors envs also demonstrated slow entry kinetics indicating the presence of virus with reduced entry fitness. Overall, elite suppressors env clones were less efficient at mediating entry than chronic progressor envs. Interestingly, acute infection envs exhibited an intermediate phenotypic pattern not distinctly different from elite suppressors or chronic progressor envs. These results imply that lower env fitness may be established early and may directly contribute to viral suppression in elite suppressors individuals.

Editors’ note: This study is the first to provide direct evidence that the envelope glycoprotein, the coat protein of HIV, in elite suppressors is less efficient in supporting HIV entry into host cells that that of HIV found in people with disease progression. In acute infection, there are HIV variants with a wide range of efficiencies, suggesting that elite suppressors may be selecting relatively lower fitness env variants right at the start. How they would do this remains a mystery, as no data exist on the natural history of acute infection in elite suppressors.C

the Netherlands. Circulating HIV type

the Netherlands. Circulating HIV type 1 drug resistance will have limited impact on the effectiveness of preexposure prophylaxis among young women in Zimbabwe.

Preexposure prophylaxis (PrEP) with antiretroviral drugs may prevent transmission of human immunodeficiency virus (HIV). The objective of van de Vijver and colleagues was to predict whether PrEP, in the presence of circulating drug resistance, will reduce the risk of infection with HIV. They used risk equations to calculate the monthly risk of infection with HIV before and after the introduction of PrEP. Uncertainty and sensitivity analyses were performed for 2 ranges of PrEP effectiveness (40%-60% and 60%-80%). Circulating drug resistance was assumed to reduce the effectiveness of PrEP by 50%-90% and the transmissibility of HIV by 0%-30%. Parameter ranges were chosen for women 17-29 years of age from publications on HIV in Manicaland in Zimbabwe. PrEP would decrease the median risk of HIV transmission by 21%-33% (effectiveness of PrEP, 40%-60% and 60%-80%). If 50% of HIV strains are drug resistant, then the median risk reduction would be 19%-26% if drug-resistant strains were less transmissible than wild-type HIV and 12%-19% if they were equally transmissible. The risk would increase if condoms were frequently replaced with PrEP. Use of PrEP for sexual acts for which no protection is currently used would be beneficial. The public health impact of PrEP will depend on its effectiveness and on risk behaviour. Circulating drug resistance will have only a small impact on the effectiveness of PrEP.

Editors’ note: As this mathematical modelling shows, the precise impact of PrEP will depend on many factors such as its effectiveness (which remains to be determined by clinical trials in humans), the prevalence of condom use, the frequency with which condom use is replaced by PrEP when it becomes available, the number of sex acts performed, and the level of PrEP use among individuals currently not using condoms. Most discussion of drug resistance in relation to PrEP has focused on the extent to which PrEP use might create drug resistance. Interestingly, this model looked at the impact on PrEP of various levels of circulating M184V, the mutation resistant to emtricitabine or FTC. The model predicts limited impact of population-level drug resistance on PrEP’s contribution to HIV prevention, assuming that resistant virus is less fit.

Elite suppressor-derived HIV-1 envelope glycoproteins

Elite suppressor-derived HIV-1 envelope glycoproteins exhibit reduced entry efficiency and kinetics.

Elite suppressors are a rare subset of HIV-1-infected individuals who are able to maintain HIV-1 viral loads below the limit of detection by ultra-sensitive clinical assays in the absence of antiretroviral therapy. Mechanism(s) responsible for this elite control are poorly understood but likely involve both host and viral factors. This study assesses elite suppressors plasma-derived envelope glycoprotein (env) fitness as a function of entry efficiency as a possible contributor to viral suppression. Fitness of virus entry was first evaluated using a novel inducible cell line with controlled surface expression levels of CD4 (receptor) and CCR5 (co-receptor). In the context of physiologic CCR5 and CD4 surface densities, elite supressors envs exhibited significantly decreased entry efficiency relative to chronically infected viremic progressors. Elite suppressors envs also demonstrated slow entry kinetics indicating the presence of virus with reduced entry fitness. Overall, elite suppressors env clones were less efficient at mediating entry than chronic progressor envs. Interestingly, acute infection envs exhibited an intermediate phenotypic pattern not distinctly different from elite suppressors or chronic progressor envs. These results imply that lower env fitness may be established early and may directly contribute to viral suppression in elite suppressors individuals.

Editors’ note: This study is the first to provide direct evidence that the envelope glycoprotein, the coat protein of HIV, in elite suppressors is less efficient in supporting HIV entry into host cells that that of HIV found in people with disease progression. In acute infection, there are HIV variants with a wide range of efficiencies, suggesting that elite suppressors may be selecting relatively lower fitness env variants right at the start. How they would do this remains a mystery, as no data exist on the natural history of acute infection in elite suppressors.C

Defined by virologic parameters, they are called the HIV controllers,

With the advent of viral load assays in clinical care, new groups of patients with slow disease progression joined the patients known as long-term nonprogressors. Defined by virologic parameters, they are called the HIV controllers, some of whom are elite controllers. Although the definitions of these various groups vary in the literature and there is some overlap, they are of intense interest because the mechanisms by which they have some natural protection against HIV may provide insights for the development of preventive and therapeutic vaccines. Both viral factors and host genetic factors, such as HLA-B27 and HLA-B57, may play a role. This study of more than 110,000 patients confirms the very low prevalence (less than 0.5%) of these valuable patients. Some are viraemic with high CD4 counts while others control viraemia but have CD4 depletion and yet others appear to have both viral control and stable CD4 cell counts.

long-term nonprogressors and HIV controller patients in the French Hospital Database on HIV. AIDS.

long-term nonprogressors and HIV controller patients in the French Hospital Database on HIV. AIDS.

Grabar and colleagues set out to estimate the prevalence and characteristics of long-term nonprogressor and HIV controller patients in a very large French cohort of HIV 1-infected patients. In the French Hospital Database on HIV [FHDH, Agence Nationale de Recherches sur le SIDA et les hépatites virales (ANRS) CO4], they selected patients who had been seen in 2005, who had been infected for more than 8 years, who were treatment-naive, and who remained asymptomatic. Patients with these characteristics then categorized as follows: long-term nonprogressor (> or =8 years of HIV infection and CD4 cell nadir > or =500/microl), elite long-term nonprogressor (> or =8 years of HIV infection, CD4 cell nadir > or =600/microl, and a positive CD4 slope), HIV controllers (>10 years of HIV infection with 90% of plasma viral load values < or ="500" style="text-decoration: underline;">elite controllers (same as HIV controllers, but with last plasma viral load value < or ="50" style="text-decoration: underline;">46 880 HIV-1-infected patients followed in 2005 in the French Hospital Database on HIV, 0.4% (N = 202) were long-term nonprogressor, 0.05% (N = 25) were elite long-term nonprogressor, 0.22% (N = 101) were HIV controllers, and 0.15% (N = 69) were elite controllers. Ten elite long-term nonprogressor patients (40% of 25) were also HIV controllers, eight (32%) were elite controllers, and 60% had detectable plasma viral load (>50 copies/ml). Among the elite controllers, 32 (46%) were long-term nonprogressor, eight (12%) were elite long-term nonprogressor, and one-quarter had a last CD4 cell count less than 500/microl. Long-term nonprogressor, elite LTNP, HIV controller, and elite controller patients are rare phenotypes. Elite long-term nonprogressor patients are less frequent than HIV controllers. There is little overlap among the four subgroups of patients.

HIV disease progression by hormonal contraceptive method

HIV disease progression by hormonal contraceptive method: secondary analysis of a randomized trial.

HIV-infected women need access to safe contraception. Stringer and colleagues hypothesized that women using depomedroxyprogesterone acetate (DMPA) contraception would have faster HIV disease progression than women using oral contraceptive pills and nonhormonal methods. In a previously reported trial, the authors randomized 599 HIV-infected women to the intrauterine device (IUD) or hormonal contraception. Women randomized to hormonal contraception chose between oral contraceptive pills and DMPA. This analysis investigates the relationship between exposure to hormonal contraception and HIV disease progression [ defined as death, becoming eligible for antiretroviral therapy, or both]. Of the 595 women not on antiretroviral therapy at the time of randomization, 302 were allocated to hormonal contraception, of whom 190 (63%) initiated DMPA and 112 (37%) initiated oral contraceptive pills. Women starting IUD, oral contraceptive pills, or DMPA were similar at baseline. Compared with women using the IUD, the adjusted hazard of death was not significantly increased among women using oral contraceptive pills [1.24; 95% confidence interval (CI) 0.42-3.63] or DMPA (1.83; 95% CI 0.82-4.08). However, women using oral contraceptive pills (adjusted hazard ratio (AHR) 1.69; 95% CI 1.09-2.64) or DMPA (AHR 1.56; 95% CI 1.08-2.26) trended toward an increased likelihood of becoming eligible for antiretroviral therapy. Women exposed to oral contraceptive pills (AHR 1.67; 95% CI 1.10-2.51) and DMPA (AHR 1.62; 95% CI 1.16-2.28) also had an increased hazard of meeting this study’s composite disease progression outcome (death or becoming antiretroviral therapy eligible) than women using the IUD. In this secondary analysis, exposure to oral contraceptive pills or DMPA was associated with HIV disease progression among women not yet on antiretroviral therapy. This finding, if confirmed elsewhere, would have global implications and requires urgent further investigation.

The relationship between hormonal contraception and disease progression was not an a priori hypothesis of this trial and 47% of the participants switched contraceptive methods, withdrew from the study, or were lost to follow-up. The researchers addressed the switching by treating contraceptive method as a time-varying exposure but the fact that women assigned to the contraceptive arm could choose either DMPA or oral contraceptives could have introduced confounding. Given that the risk of maternal mortality increases with each subsequent pregnancy, with a women’s lifetime risk of dying in pregnancy as high as one in 22 in sub-Saharan Africa, women need safe and effective contraception when they want it. These results are by no mean definitive but they support the urgent call for a trial evaluating the potential relationship between HIV disease progression and hormonal contraception.

Monday, October 29, 2012

Whether therapeutic drug monitoring of protease inhibitors improves outcomes in HIV

A randomized trial of therapeutic drug monitoring of protease inhibitors in antiretroviral-experienced, HIV-1-infected patients.

Whether therapeutic drug monitoring of protease inhibitors improves outcomes in HIV-infected patients is controversial. Demeter and colleagues evaluated this strategy in a randomized, open-label clinical trial, using a normalized inhibitory quotient (NIQ), which incorporates drug exposure and viral drug resistance. NIQs /=1000 copies/ml on a failing regimen, and began a new protease inhibitor containing regimen at entry. All FDA-approved protease inhibitors available during the study recruitment (June 2002-May 2006) were allowed. One hundred and eighty-three participants with NIQ , were randomized at week 4 to standard of care (SOC) or protease inhibitor dose escalation (therapeutic drug monitoring). The primary endpoint was change in log10 plasma HIV-1 RNA concentration from randomization to 20 weeks later. Ninety-one patients were randomized to standard of care and 92 to therapeutic drug monitoring. NIQs increased more in the therapeutic drug monitoring arm compared to standard of care (+69 versus +25%, P = 0.01). Despite this, therapeutic drug monitoring and standard of care arms showed no difference in outcome (+0.09 versus +0.02 log10, P = 0.17). In retrospective subgroup analyses, patients with less HIV resistance to their protease inhibitors benefited from therapeutic drug monitoring (P = 0.002), as did black and Hispanic patients (P = 0.035 and 0.05, respectively). Differences between black and white patients persisted when accounting for protease inhibitor susceptibility. There was no overall benefit of therapeutic drug monitoring. In post hoc subgroup analyses, therapeutic drug monitoring appeared beneficial in black and Hispanic patients, and in patients whose virus retained some susceptibility to the protease inhibitors in their regimen.

Editors’ note: Although the authors state that they compared differences between the therapeutic drug monitoring group and the standard of care group with respect to the primary endpoint (change in viral load after 20 weeks) in specific sub-groups of patients according to sex, race and ethnicity, number of protease inhibitors in the study regimen, and whether fos-amprenavir was used) no data are provided for women who constituted 13% of the study participants. This is another example of the ‘fugitive data issue’ that the Women and Trials movement has identified as problematic. Authors need to make an extra effort to publish these data, as not enough is known about sex differences in pharmacokinetics and pharmacodynamics

Early antiretroviral therapy reduces AIDS progression

Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial. PLoS

Optimal timing of antiretroviral therapy initiation for individuals presenting with AIDS-related opportunistic infections has not been defined. A5164 was a randomized strategy trial of “ early antiretroviral therapy”—given within 14 days of starting treatment for acute opportunistic infection versus “deferred antiretroviral therapy”—given after treatment for acute opportunistic infection is completed. Randomization was stratified by presenting opportunistic infections and entry CD4 count. The primary week 48 endpoint was 3-level ordered categorical variable: 1. Death/AIDS progression; 2. No progression with incomplete viral suppression (ie HIV viral load (VL) >or=50 copies/ml); 3. No progression with optimal viral suppression (ie HIV VL <50 style="text-decoration: underline;">The early and deferred arms started antiretroviral therapy a median of 12 and 45 days after the start of treatment for opportunistic infections, respectively. AIDS progression/death was seen in 20 (14%) vs. 34 (24%); whereas no progression but with incomplete viral suppression was seen in 54 (38%) vs. 44 (31%); and no progression with optimal viral suppression in 67 (48%) vs 63 (45%) in the early vs. deferred arm, respectively (p = 0.22). However, the early antiretroviral therapy arm had fewer AIDS progression/deaths (OR = 0.51; 95% CI = 0.27-0.94) and a longer time to AIDS progression/death (stratified HR = 0.53; 95% CI = 0.30-0.92). The early antiretroviral therapy had shorter time to achieving a CD4 count above 50 cells/mL (p<0.001) and no increase in adverse events. Early antiretroviral therapy resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred antiretroviral therapy. These results support the early initiation of antiretroviral therapy in patients presenting with acute AIDS-related opportunistic infections, absent major contraindications.

Editors’ note: Waiting to complete treatment for an opportunistic infection before initiating antiretroviral treatment in this USA/South Africa study was associated with a higher risk of HIV disease progression and/or death, with no safety or virological advantage. Concerns about toxicity, drug-drug interactions, immune reconstitution inflammatory syndrome, and adherence have made clinicians cautious about initiating antiretroviral treatment during treatment for opportunistic infections. However, as this study demonstrates, earlier antiretroviral treatment brings earlier improvement in immune responsiveness, which narrows the ‘window of vulnerability’ to additional HIV-related complications, preventing clinical progression.

Early antiretroviral therapy reduces AIDS progression

Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial. PLoS

Optimal timing of antiretroviral therapy initiation for individuals presenting with AIDS-related opportunistic infections has not been defined. A5164 was a randomized strategy trial of “ early antiretroviral therapy”—given within 14 days of starting treatment for acute opportunistic infection versus “deferred antiretroviral therapy”—given after treatment for acute opportunistic infection is completed. Randomization was stratified by presenting opportunistic infections and entry CD4 count. The primary week 48 endpoint was 3-level ordered categorical variable: 1. Death/AIDS progression; 2. No progression with incomplete viral suppression (ie HIV viral load (VL) >or=50 copies/ml); 3. No progression with optimal viral suppression (ie HIV VL <50 style="text-decoration: underline;">The early and deferred arms started antiretroviral therapy a median of 12 and 45 days after the start of treatment for opportunistic infections, respectively. AIDS progression/death was seen in 20 (14%) vs. 34 (24%); whereas no progression but with incomplete viral suppression was seen in 54 (38%) vs. 44 (31%); and no progression with optimal viral suppression in 67 (48%) vs 63 (45%) in the early vs. deferred arm, respectively (p = 0.22). However, the early antiretroviral therapy arm had fewer AIDS progression/deaths (OR = 0.51; 95% CI = 0.27-0.94) and a longer time to AIDS progression/death (stratified HR = 0.53; 95% CI = 0.30-0.92). The early antiretroviral therapy had shorter time to achieving a CD4 count above 50 cells/mL (p<0.001) and no increase in adverse events. Early antiretroviral therapy resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred antiretroviral therapy. These results support the early initiation of antiretroviral therapy in patients presenting with acute AIDS-related opportunistic infections, absent major contraindications.

Editors’ note: Waiting to complete treatment for an opportunistic infection before initiating antiretroviral treatment in this USA/South Africa study was associated with a higher risk of HIV disease progression and/or death, with no safety or virological advantage. Concerns about toxicity, drug-drug interactions, immune reconstitution inflammatory syndrome, and adherence have made clinicians cautious about initiating antiretroviral treatment during treatment for opportunistic infections. However, as this study demonstrates, earlier antiretroviral treatment brings earlier improvement in immune responsiveness, which narrows the ‘window of vulnerability’ to additional HIV-related complications, preventing clinical progression.

People living with HIV

People living with HIV

Kimbrough and colleagues evaluated the use of social networks to reach persons with undiagnosed HIV infection in ethnic minority communities and link them to medical care and HIV prevention services. Nine community-based organizations in 7 cities received funding from the United States Centers for Disease Control and Prevention to enlist HIV-positive persons to refer others from their social, sexual, or drug-using networks for HIV testing; to provide HIV counselling, testing, and referral services; and to link HIV-positive and high-risk HIV-negative persons to appropriate medical care and prevention services. From October 1, 2003, to December 31, 2005, 422 recruiters referred 3172 of their peers for HIV services, of whom 177 were determined to be HIV positive; 63% of those who were HIV-positive were successfully linked to medical care and prevention services. The HIV prevalence of 5.6% among those recruited in this project was significantly higher than the approximately 1% identified in other counselling, testing, and referral sites funded by the Centers for Disease Control and Prevention. This peer-driven approach is highly effective and can help programs identify persons with undiagnosed HIV infection in high-risk networks.

Editors’ note: HIV takes advantages of networks so why can’t HIV prevention and treatment take advantage of social networks? This peer-driven strategy though community-based organisations proved to be an efficient high-yield approach to accessing and providing HIV counselling, testing, and referral services to key populations at higher risk of HIV exposure that are difficult to reach with other more conventional strategies.

development assistance for AIDS has increasingly been provided through

development assistance for AIDS has increasingly been provided through Global Health Initiatives (GHI), specifically the United States Presidential Emergency Plan for AIDS Relief, the Global Fund to Fight HIV, TB and Malaria and the World Bank Multi-country AIDS Programme. Zambia, like many of the countries heavily affected by HIV in southern Africa, also faces a shortage of human resources for health. The country receives significant amounts of funding from GHIs for the large-scale provision of antiretroviral treatment through the public and private sector. This paper examines the impact of GHIs on human resources for antiretroviral treatment roll-out in Zambia, at national level, in one province and two districts. Hanefeld and Musheke undertook a qualitative policy analysis relying on in-depth interviews with more than 90 policy-makers and implementers at all levels. Findings show that while GHIs do not provide significant funding for additional human resources, their interventions have significant impact on human resources for health at all levels. While GHIs successfully retrain a large number of health workers, evidence suggests that GHIs actively deplete the pool of skilled human resources for health by recruiting public sector staff to work for GHI-funded nongovernmental implementing agencies. The secondment of GHI staff into public sector facilities may help alleviate immediate staff shortages, but this practice risks undermining sustainability of programmes. GHI-supported programmes and initiatives add significantly to the workload of existing public sector staff at all levels, while incentives including salary top-ups and overtime payments mean that antiretroviral treatment programmes are more popular among staff than services for non-focal diseases. Research findings suggest that GHIs need to actively mediate against the potentially negative consequences of their funding on human resources for health. Evidence presented highlights the need for new strategies that integrate retraining of existing staff with longer-term staff development to ensure staff retention. The study results show that GHIs must provide significant new and longer-term funding for additional human resources to avoid negative consequences on the overall provision of health care services and to ensure sustainability and quality of programmes they support.
Editors’ note: Zambia faces a severe shortage in human resources for health with the greatest need being for laboratory technicians, followed by pharmacists, doctors, nurses, and data monitors. There is rapid turnover of staff, high staff absenteeism, and unequal urban-rural distribution. At the time this research was conducted, the only targeted human resource intervention receiving any donor support was the rural retention scheme. Countries should require Global Health Initiatives to conduct human resource impact assessments. It is time to think seriously about the wisdom of addressing public sector human resources needs, in the interest of the long-term sustainability of antiretroviral treatment programmes.

Integrating HIV clinical services into primary health care in Rwanda

Integrating HIV clinical services into primary health care in Rwanda: a measure of quantitative effects.

With the intensive scale-up of care and treatment for HIV in developing countries, some fear that intensified attention to HIV programmes may overwhelm health care systems and lead to declines in delivery of other primary health care. Few data exist that confirm negative or positive synergies on health care provision generally resulting from HIV-dedicated programs. Using a retrospective observational design Price and colleagues compare aggregate service data in Rwandan health facilities before and after the introduction of HIV care on selected measures of primary health care. The study tests the hypothesis that non-HIV care does not decrease after the introduction of basic HIV care. Overall, no declines were observed in reproductive health services, services for children, laboratory tests, and curative care. Statistically significant increases were found in utilization and provision of some preventive services. Multivariate regression, including introduction of HIV care and two important health care financing initiatives in Rwanda, revealed positive associations of all with observed increases. Introduction of HIV services was especially associated with increases in reproductive health. While hospitalization rates increased for the whole sample, declines were observed at health facilities that offered basic HIV care plus highly active antiretroviral therapy. The authors indicate that their results partially counter fears that HIV programs are producing adverse effects in non-HIV service delivery. Rather than leading to declines in other primary health care delivery, they say their findings suggest that the integration of HIV clinical services may contribute to increases.

Editors’ note: This study of 30 primary health centres that had at least 6 months experience offering basic HIV care, defined as voluntary counselling and testing, prevention of mother-to-child transmission services, and preventive therapy with cotrimoxasole, found positive synergies between HIV care and the delivery of other primary care services, particularly antenatal care. This study would be strengthened by consideration of outcome indicators, such as maternal mortality and incidence of congenital syphilis, rather than solely service utilisation indicators. The changes documented here occurred against a backdrop of two important nationally coordinated health care financing programmes that the researchers did try to take into account– the mutuelle de santé, Rwanda’s nationwide primary health insurance system, and performance based financing of health centres. Both of these programmes would be expected to increase uptake and improve outcomes.

Godfrey-Faussettg P. Disseminated bacille Calmette–Guérin disease in HIV

Godfrey-Faussettg P. Disseminated bacille Calmette–Guérin disease in HIV-infected South African infants. Bull World Health Organ. .

The authors set out to determine the population-based incidence of disseminated bacille Calmette–Guérin (BCG) disease in HIV-infected infants (aged less than 1 year) in a setting with a high burden of tuberculosis and HIV infection coupled with a well-functioning programme for the prevention of HIV infection in infants. The numerator, or number of new cases of disseminated BCG disease, was derived from multicentre surveillance data collected prospectively on infants with a confirmed HIV infection during 2004–2006. The denominator, or total number of HIV-infected infants who were BCG-vaccinated, was derived from population-based estimates of the number of live infants and from reported maternal HIV infection prevalence, vertical HIV transmission rates and BCG vaccination rates. The estimated incidences of disseminated BCG disease per 100 000 BCG-vaccinated, HIV-infected infants were as follows: 778 (95% confidence interval, CI: 361–1319) in 2004 (vertical HIV transmission rate: 10.4%); 1300 (95% CI: 587–2290) in 2005 (transmission rate: 6.1%); and 1013 (95% CI: 377–1895) in 2006 (transmission rate: 5.4%). The pooled incidence over the study period was 992 (95% CI: 567–1495) per 100 000. Multicentre surveillance data showed that the risk of disseminated BCG disease in HIV-infected infants is considerably higher than previously estimated, although likely to be under-estimated. There is an urgent need for data on the risk–benefit ratio of BCG vaccination in HIV-infected infants to inform decision-making in settings where HIV infection and tuberculosis burdens are high. Safe and effective tuberculosis prevention strategies are needed for HIV-infected infants.

light of the results of this three-year multicentre surveillance study in South Africa, WHO now recommends that BCG vaccination be delayed for all babies born to mothers with HIV infection until they are determined to not have HIV infection, even in high TB burden settings. This gives added impetus to UNAIDS’ call at the 2009 World Health Assembly for the elimination of mother-to-child transmission by 2015. Strengthened antenatal services, increased HIV testing uptake, contraceptive services for women living with HIV who are not planning a pregnancy, timely provision of antiretroviral prophylaxis, and infant feeding counselling are among the building blocks to achieve this goal.

Immune reconstitution inflammatory syndrome among HIV

Immune reconstitution inflammatory syndrome among HIV-infected South African infants initiating antiretroviral therapy.

Smith and colleagues set out to determine the incidence, clinical manifestations, and risk factors for immune reconstitution inflammatory syndrome (IRIS) in young children initiating highly active antiretroviral therapy. Using data from a prospective cohort of antiretroviral-naïve HIV-infected children less than 24 months of age enrolled in a treatment strategies trial in Johannesburg, South Africa. Among 169 HIV-infected children initiating antiretroviral therapy, April 2005 to November 2006, the records of 83 children suspected to have IRIS within 6 months of starting treatment were reviewed to determine whether they met criteria for IRIS. Seven were excluded due to incomplete follow-up. Pretreatment and post-treatment characteristics of children with and without IRIS were compared. Overall, 34/162 (21%) children developed IRIS at a median of 16 days (range 7-115 days) post-antiretroviral therapy initiation. Bacille Calmette-Guérin reaction was most common occurring in 24/34 (71%) children, primarily injection site lesions and/or ipsilateral axillary lymphadenitis with abscess. Other IRIS conditions (not mutually exclusive) included Mycobacterium tuberculosis (n = 12), cytomegalovirus pneumonia (n = 1), Streptococcus pneumonia sepsis (n = 1), and severe seborrheic dermatitis (n = 1). Children with IRIS were younger (median age 7 vs. 10 months, P = 0.007) with a lower CD4 cell percentage (median 13.9 vs. 19.2, P = 0.009) at antiretroviral treatment initiation than controls. After 24 weeks on antiretroviral treatment, 62% of IRIS cases vs. 28% of controls had HIV RNA more than 400 copies/ml (P = 0.001), odds ratio = 2.88 (95% confidence interval = 1.14-7.29) after adjusting for baseline factors. Infants and young children with advanced HIV disease initiating antiretroviral treatment are at high risk for developing IRIS, leading to additional morbidity and possibly impairing virologic response to antiretroviral treatment.

Editors’ note: All the children in this study had advanced HIV disease at the time of antiretroviral treatment initiation so it is possible that the incidence of immune reconstitution inflammatory syndrome (IRIS) would be much lower when infants are started on treatment as soon as they are diagnosed, as is currently recommended. The fact that the most common IRIS manifestation in this study (71% of children) was reaction to the tuberculosis vaccine BCG lends support to the WHO guidelines discouraging BCG for HIV-infected infants.

Sunday, October 28, 2012

prevent mother-to-child HIV transmission in developed countries

The use of highly active antiretroviral treatment during pregnancy is now standard care to prevent mother-to-child HIV transmission in developed countries. There is controversy about its impact on low birth weight. Briand and colleagues set out to evaluate the impact of antiretroviral therapy during the pregnancy on birth weight, length, and head circumference. The study was performed in uninfected infants born to HIV-1-infected mothers, enrolled from 1990 to 2006 in the Agence Nationale de Recherches sur le SIDA French Perinatal Cohort CO1. The authors excluded mothers who used illicit drugs during pregnancy or had no prenatal care before the third trimester, twins and stillbirths. They used Z-scores adjusted for gestational age and sex. In 8192 mother-infant pairs, the mean birth weight Z-scores increased between 1990 and 1997 and then remained stable until 2006. There was no significant relation between the type of antiretroviral therapy and the proportion of small for gestational age (birth weight Z-score