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For full PDF access to this issue: HIV This Week Issue #78

Kamarulzaman A, Saifuddeen SM. Int J Drug Policy.2009.Dec [Epub ahead of print].

Although drugs are haram and therefore prohibited in Islam, illicit drug use is widespread in many Islamic countries throughout the world. In the last several years increased prevalence of this problem has been observed in many of these countries which has in turn led to increasing injecting drug use driven HIV epidemics across the Islamic world. Whilst some countries have recently responded to the threat through the implementation of harm reduction programmes, many others have been slow to respond. In Islam, The Quran and the Prophetic traditions or the Sunnah are the central sources of references for the laws and principles that guide the Muslims’ way of life and by which policies and guidelines for responses including that of contemporary social and health problems can be derived. The preservation and protection of the dignity of man, and steering mankind away from harm and destruction are central to the teachings of Islam. When viewed through the Islamic principles of the preservation and protection of the faith, life, intellect, progeny and wealth, harm reduction programmes are permissible and in fact provide a practical solution to a problem that could result in far greater damage to the society at large if left unaddressed.

For abstract access click here: 1 

Editors’ note: Following an in-depth tour of the epidemiology of illicit drug consumption, injecting drug use, and the HIV epidemic in Islamic countries, this paper presents the basic guidelines provided in the Quran and the Sunnah (Prophetic traditions) that support needle exchange programmes and opioid substitution therapy. The pragmatic evidence-informed public health approach of harm reduction programmes in the Islamic Republic of Iran, Malaysia and Indonesia contrasts starkly with the rejection of harm reduction in Libya, Tunisia, Syria, and Jordan. Despite the tenets of Islam, resistance in the latter countries appears ideological with roots in a criminal justice perspective. As the authors underscore, harm reduction is a public health issue that not only does not violate shariah law, it follows Islamic principles.

Wirtz VJ, Forsythe S, Valencia-Mendoza A, Bautista-Arredondo S. BMC Public Health. 2009. 9 Suppl 1:S6.

Antiretroviral medicines are one of the most costly parts of HIV treatment. Many countries are struggling to provide universal access to antiretroviral medicines for all people living with HIV. Although substantial price reductions of antiretroviral medicines have occurred, especially between 2002 and 2008, achieving sustainable access for the next several decades remains a major challenge for most low- and middle-income countries. The objectives of the present study were twofold: first, to analyze global antiretroviral prices between 2005 and 2008 and associated factors, particularly procurement methods and key donor policies on antiretroviral procurement efficiency; second, to discuss the options of procurement processes and policies that should be considered when implementing or reforming access to antiretroviral treatment programs. An antiretroviral medicines price-analysis was carried out using the Global Price Reporting Mechanism from the World Health Organization. For a selection of 12 antiretrovirals, global median prices and price variation were calculated. Linear regression models for each antiretroviral were used to identify factors that were associated with lower procurement prices. Logistic regression models were used to identify the characteristics of those countries which procure below the highest and lowest direct manufactured costs. Three key factors appear to have an influence on a country’s antiretroviral prices: (a) whether the product is generic or not; (b) the socioeconomic status of the country; (c) whether the country is a member of the Clinton HIV/AIDS Initiative. Factors which did not influence procurement below the highest direct manufactured costs were HIV prevalence, procurement volume, whether the country belongs to the least developed countries or a focus country of the United States President’s Emergency Plan for AIDS Relief. One of the principal mechanisms that can help to lower prices for antiretroviral medicines over the next several decades is increasing procurement efficiency. Benchmarking prices could be one useful tool to achieve this.

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Editors’ note: There has been an unprecedented global effort to increase antiretroviral drug price transparency, including through the requirements of the Global Fund, the Clinton Initiative, and others for countries to report their pricing data. The Global Price Reporting Mechanism (GPRM) provides information on the prices that countries actually paid for antiretroviral medications through its publicly accessible database http://www.who.int/hiv/amds/gprm/en/. Analysis of the GPRM data debunks the assumptions that procuring larger volumes will reduce prices (that was true for only 2 of the 12 drugs studied) and that generic competition leads to equivalent innovator prices (only the second line innovator product lopinavir/ritonavir was associated with lower prices than generic products). Since there is tiered pricing or discounts for most antiretroviral drugs bought by low- and low-middle-income countries, with the exception of the entry inhibitor maraviroc, continued expansion of the GPRM to include data from all countries will increase long-term efficiency (best value for money) in antiretroviral drug procurement.

Galárraga O, Colchero MA, Wamai RG, Bertozzi SM. BMC Public Health. 2009. 9 Suppl 1:S5.

After more than 25 years, public health programs have not been able to sufficiently reduce the number of new HIV infections. Over 7,000 people become infected with HIV every day. Lack of convincing evidence of cost-effectiveness may be one of the reasons why implementation of effective programs is not occurring at sufficient scale. This paper identifies, summarizes and critiques the cost-effectiveness literature related to HIV-prevention interventions in low- and middle-income countries during 2005-2008. Systematic identification of publications was conducted through several methods: electronic databases, internet search of international organizations and major funding/implementing agencies, and journal browsing. Inclusion criteria included: HIV prevention intervention, year for publication (2005-2008), setting (low- and middle-income countries), and cost-effectiveness estimation (empirical or modeling) using outcomes in terms of cost per HIV infection averted and/or cost per disability-adjusted life year(DALY) or quality-adjusted life year (QALY). The authors found 21 distinct studies analyzing the cost-effectiveness of HIV-prevention interventions published in the past four years (2005-2008). Seventeen cost-effectiveness studies analyzed biomedical interventions; only a few dealt with behavioural and environmental/structural interventions. Sixteen studies focused on sub-Saharan Africa, and only a handful on Asia, Latin America and Eastern Europe. Many HIV-prevention interventions are very cost effective in absolute terms (using costs per DALY averted), and also in country-specific relative terms (in cost per DALY measured as percentage of GDP per capita). There are several types of interventions for which cost-effectiveness studies are still not available or are insufficient, including surveillance, abstinence, school-based education, universal precautions, prevention for positives and most structural interventions. The sparse cost-effectiveness evidence available is not easily comparable; thus, not very useful for decision making. More than 25 years into the HIV epidemic and billions of dollars of spending later, there is still much work to be done both on costs and effectiveness to adequately inform HIV prevention planning.

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Editors’ note: Cost-effectiveness analyses in HIV prevention can provide part of the information that decision-makers use to decide on the optimal mix of interventions to tailor to their epidemic context. Although available cost-effectiveness data show that many HIV prevention interventions are cost-effective, there are huge gaps in our knowledge. For example, there are no cost-effectiveness studies on prevention for and with positive people, for key populations at higher risk of HIV exposure in concentrated epidemics around the world, and for inmates or other captive populations. We lack cost-effectiveness data by epidemic type and scale-up scenario, as well as for a number of HIV prevention interventions that are considered standard components of national strategies. Cost-effectiveness analysis has several limitations and is not the ‘be all, end all’ in decision-making but it can usefully inform difficult choices.

Smith R, Okano J, Kahn J, Bodine E, Blower S. Science. 2010. Jan. [Epub ahead of print]

Over the past two decades, HIV resistance to antiretrovirals has risen to high levels in the wealthier countries of the world able to afford widespread treatment. The authors have gained insights into the evolution and transmission dynamics of ARV resistance by designing a biologically complex multistrain network model. Using this model, they traced the evolutionary history of antiretroviral resistance in San Francisco and predict the future dynamics. Using classification and regression trees, Smith and colleagues have identified the key immunologic, virologic, and treatment factors that increase antiretroviral resistance. Their modelling shows that 60% of the currently circulating antiretroviral-resistant strains in San Francisco are capable of causing self-sustaining epidemics, as each individual infected with one of these strains can cause on average more than one new resistant infection. It is possible that a new wave of antiretroviral-resistant strains that pose a significant threat to global public health is emerging.

For abstract access click here: 1

Editors’ note: These modellers predict that a wave of NNRTI- (non-nucleoside reverse transcriptase inhibitor) resistant strains will emerge over the next 5 years in San Francisco due to HIV transmission from untreated individuals. They also claim that if the reproduction number (the number of infections that one person transmits) of wild-type strains is reduced below one in resource-constrained settings (which would normally see an epidemic decline), self-sustaining epidemics of NNRTI-resistant strains could arise. Whether their model’s predictions are accurate or not remains to be seen but clearly increased investment in resistance monitoring around the world is warranted as we scale up to universal access to antiretroviral treatment for all.

Improved Virological Outcomes in British Columbia Concomitant with Decreasing Incidence of HIV Type 1 Drug Resistance Detection.

Gill V, Lima V, Wen Zhang, Wynhoven B, Yip B, Hogg R, Montaner J, and Harrigan R . Clinical Infectious Diseases. 2010. 50:98–105.

There have been limited studies evaluating temporal changes in the incidence of detection of drug resistance among human immunodeficiency virus type 1 (HIV-1) isolates and concomitant changes in plasma HIV load for treated individuals in a population-wide setting. Longitudinal plasma viral load and genotypic resistance data were obtained from patients receiving antiretroviral therapy from the British Columbia Drug Treatment Program from July 1996 through December 2008. A total of 24,652 resistance tests were available from 5422 individuals. The incidence of successful plasma viral load suppression and of resistance to each of 3 antiretroviral categories (nucleoside/nucleotide reversetranscriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and protease inhibitors) was calculated for the population receiving therapy. There has been a drastic decrease in the incidence of new cases of HIV-1 drug resistance in individuals followed during 1996–2008. In 1997, the incidence rate of any newly detected resistance was 1.73 cases per 100 person-months of therapy, and by 2008, the incidence rate had decreased 112-fold, to 0.13 cases per 100 person-months of therapy. This decrease in the incidence of resistance has occurred at an exponential rate, with halftimes on the order of 2–3 years. Concomitantly, the proportion of individuals with plasma viral load suppression has increased linearly over time (from 64.7% with HIV RNA levels !50 copies/mL in 2000 to 87.0% in 2008; R2p0.97; P ! .001). The authors’ results suggest an increasing effectiveness of antiretroviral therapy at the populational level. The vast majority of treated patients in British Columbia now have either suppressed plasma viral load or drug-susceptible HIV-1, according to their most recent test results.

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Editors’ note: Rather than investigating the prevalence of transmitted drug resistance in the population or the prevalence of acquired drug resistance among people on treatment, these investigators, who were uniquely placed to do so, assessed the incidence of drug resistance over a 12-year period. They found exponential decreases in the incidence rate of drug resistance, including NNRTI (non-nucleoside reverse transcriptase inhibitor) resistance (40-fold decrease), despite increases in annual and cumulative exposure to antiretroviral drugs. These authors conclude that efforts to improve accessibility to antiretroviral treatment have the potential to greatly reduce HIV-1 levels in a population without increasing the risk of drug resistance.

Baeten JM, Donnell D, Kapiga SH, Ronald A, John-Stewart G, Inambao M, Manongi R, Vwalika B, Celum C; for the Partners in Prevention HSV/HIV Transmission Study Team. AIDS. 2009. Dec [Epub ahead of print].

Male circumcision reduces female-to-male HIV-1 transmission risk by approximately 60%. Data assessing the effect of circumcision on male-to-female HIV-1 transmission are conflicting, with one observational study among HIV-1-serodiscordant couples showing reduced transmission but a randomized trial suggesting no short-term benefit of circumcision. Data were collected as part of a prospective study among African HIV-1-serodiscordant couples were analyzed for the relationship between circumcision status of HIV-1-seropositive men and risk of HIV-1 acquisition among their female partners. Circumcision status was determined by physical examination. Cox proportional hazards analysis was used. A total of 1096 HIV-1-serodiscordant couples in which the male partner was HIV-1-infected were followed for a median of 18 months; 374 (34%) male partners were circumcised. Sixty-four female partners seroconverted to HIV-1 (incidence 3.8 per 100 person-years). Circumcision of the male partner was associated with a nonstatistically significant approximately 40% lower risk of HIV-1 acquisition by the female partner (hazard ratio 0.62, 95% confidence interval 0.35-1.10, P = 0.10). The magnitude of this effect was similar when restricted to the subset of HIV-1 transmission events confirmed by viral sequencing to have occurred within the partnership (n = 50, hazard ratio 0.57, P = 0.11), after adjustment for male partner plasma HIV-1 concentrations (hazard ratio 0.60, P = 0.13), and when excluding follow-up time for male partners who initiated antiretroviral therapy (hazard ratio 0.53, P = 0.07). Among HIV-1-serodiscordant couples in which the HIV-1-seropositive partner was male, the authors observed no increased risk and potentially decreased risk from circumcision on male-to-female transmission of HIV-1.

For access to abstract click here: 1 

Editors’ note: The trend seen here among 1096 couples toward a protective effect of male circumcision for HIV-negative women in discordant partnerships is intriguing. Sexual behaviours of couples with circumcised men were similar to those in which the man was not circumcised, only genetically-linked transmissions (i.e. transmissions within the couple) were considered (incidence 3.0 per 100 person years), and follow-up time after initiation of antiretroviral treatment (when viral loads presumably fell) was excluded. The result was a borderline statistically significant 47 per cent reduced risk of HIV-1 acquisition in women. Possible mechanisms that might explain lower risk for women are reduced risk of sexually transmitted infections in circumcised men or reduced likelihood of direct HIV transmission that would have otherwise occurred as a result of microtrauma or inflammation of the foreskin.

Price LB, Liu CM, Johnson KE, Aziz M, Lau MK, Bowers J, Ravel J, Keim PS, Serwadda D, Wawer MJ, Gray RH., PLoS One. 2010. 5:e8422.

Circumcision is associated with significant reductions in HIV, HSV-2, and HPV infections among men and significant reductions in bacterial vaginosis among their female partners. The authors assessed the penile (coronal sulci) microbiota in 12 HIV-negative Ugandan men before and after circumcision. Microbiota were characterized using sequence-tagged 16S rRNA gene pyrosequencing targeting the V3-V4 hypervariable regions. Taxonomic classification was performed using the RDP Naïve Bayesian Classifier. Among the 42 unique bacterial families identified, Pseudomonadaceae and Oxalobactericeae were the most abundant irrespective of circumcision status. Circumcision was associated with a significant change in the overall microbiota (PerMANOVA p = 0.007) and with a significantdecrease in putative anaerobic bacterial families (Wilcoxon Signed-Rank test p = 0.014). Specifically, two families-Clostridiales Family XI (p = 0.006) and Prevotellaceae (p = 0.006)-were uniquely abundant before circumcision. Within these families they identified a number of anaerobic genera previously associated with bacterial vaginosis including: Anaerococcus spp., Finegoldia spp., Peptoniphilus spp., and Prevotella spp. The anoxic microenvironment of the subpreputial space may support pro-inflammatory anaerobes that can activate Langerhans cells to present HIV to CD4 cells in draining lymph nodes. Thus, the reduction in putative anaerobic bacteria after circumcision may play a role in protection from HIV and other sexually transmitted diseases.

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Editors’ note: Although molecular analyses have been used to characterise the microbiota or microbial community in the vagina, this is the first molecular assessment of the bacterial diversity found in the male genital mucosa. This pre-post circumcision study of 12 men shows that removing the foreskin removes the oxygen-poor environment of the mucosa under the foreskin that provides a warm, moist home for bacteria, many of which are anaerobic and are associated with bacterial vaginosis in women. This helps explain why the female partners of circumcised men have fewer sexually transmitted infections and less bacterial vaginosis. Getting rid of these bacteria through circumcision reduces mucosal inflammation and may provide part of the explanation for the reduced risk of HIV, herpes simplex-2, and human papilloma virus (HPV) infections in circumcised men.

Paediatric European Network for Treatment of AIDS . AIDS. 2010. 24:231-41.

The aim of this study was to evaluate clinical, immunological, and virological consequences of CD4-guided antiretroviral therapy planned treatment interruptions compared with continuous therapy in children with chronic HIV infection in the Paediatric European Network for Treatment of AIDS 11 trial. This was a multicentre, 72-week, open, randomized, phase II trial. One hundred and nine children with HIV-RNA below 50 copies/ml and CD4% of at least 30% (2-6 years) or at least 25% and CD4 cell count of at least 500 cells/microl (7-15 years) were randomized to continuous therapy (53) or planned treatment interruptions (56). In planned treatment interruptions, antiretroviral therapy was restarted if confirmed CD4% was less than 20% or more than 48 weeks had been spent off antiretroviral therapy. The primary outcome was Centers for Disease Control and Prevention (CDC) stage C event, death, or CD4% less than 15% (and CD4 cell count less than 200 cells/microl for children aged 7-15 years). At baseline, median (interquartile range) age was 9 (6-12) years, CD4% 37% (33-41), CD4 cell count 966 (793-1258) cells/microl, nadir CD4% before combination antiretroviral therapy 18% (10-27), time on antiretroviral therapy 6 (3-6) years, and 26% were CDC stage C. After median (range) 130 (33-180) weeks of follow-up, 4 versus 48% of time was spent off antiretroviral therapy in continuous therapy and planned treatment interruptions, respectively. No child died or had a new CDC stage C event; one (2%) continuous therapy versus four (7%) planned treatment interruptions children had a primary outcome based on CD4%/cell count (P = 0.2). Lower nadir CD4% predicted faster CD4% decline after stopping antiretroviral therapy. Younger age and higher nadir CD4% predicted being off ART for at least 48 weeks and better CD4% recovery following planned treatment interruptions. In this first paediatric trial of planned treatment interruption, there were no serious clinical outcomes. Younger children had better CD4% recovery after planned treatment interruptions. Immunology substudies and long-term follow-up in Paediatric European Network for Treatment of AIDS 11 trial are ongoing. Further research into the role of treatment interruption in children is required, particularly, as guidelines now recommend early antiretroviral therapy for all infected infants.

For abstract access click here: 1 

Editors’ note: After starting antiretroviral treatment, children have a greater potential for immune regeneration than do adults because the thymus is more active in childhood. Furthermore, the risk-benefit balance of lifelong continuous treatment versus planned treatment interruptions in vertically HIV-infected children may be different than for adults, considering the risks of long-term drug toxicity and viral resistance. The encouraging results of this PENTA II pilot study, the first planned treatment interruption trial to take place in children, support continuation of two large treatment interruption trials ongoing in Africa. These are the CHER trial in South Africa studying 400 infants starting antiretroviral treatment before 12 weeks of age and stopping at first or second birthday, and the Bana trial in Botswana of 600 children which has a similar design to PENTA II with different CD4% thresholds for stopping and restarting. Given that it is recommended that all infants start antiretroviral treatment as soon as HIV infection is diagnosed, learning whether planned treatment interruptions are a good idea in children is an important clinical research question.

Mills L, Kagaayi J, Nakigozi G, Galiwango R, Ouma J, Shott J, Ssempijja V, Gray R, Wawer M, Serwadda D, Quinn T, and Reynolds S. Am. J. Trop. Med. Hyg. 2010. 82:145-147.

Mills and colleagues compared results of a malaria rapid diagnostic test (Binax Now ® Malaria, Binax-M, Inverness Medical Innovations, Inc., Waltham, MA) performed at rural mobile clinics in Uganda by clinicians evaluating febrile adult HIV patients to thick smear evaluated at a central laboratory by trained microscopists. Two hundred forty-six samples were analyzed, including 14 (5.7%) which were thick-smear positive for falciparum malaria. Sensitivity of Binax-M compared with thick smear was 85.7% (95% CI: 57.2–98.2), specificity 97.8% (95% CI: 94.9–99.3), positive and negative predictive values were 70.6% (95% CI: 44.0–89.7) and 99.1% (95% CI: 96.8–99.9), respectively. The rapid diagnostic test accurately ruled malaria “in or out” at the point-of-care, facilitating appropriate clinical management and averting unnecessary anti-malarial therapy.

For abstract access click here: 1 

Editors’ note: Through a PEPFAR-funded mobile HIV clinic programme, most participants in this study in a falciparum malaria endemic district in Uganda had received insecticide treated bed nets, cotrimoxasole prophylaxis regardless of CD4 count, and antiretroviral treatment if their CD4 counts fell below 250 cells/ µ l. With malaria suspected in 41.5% of general out-patient visits in this district, use of this point-of-care test in people living with HIV who presented with fever allowed health care providers to focus on other urgent causes of fever. The test had a high negative predictive value, meaning that a negative test was highly likely to mean that the person did not have malaria.

Keiser O, Spoerri A, Brinkhof MW, Hasse B, Gayet-Ageron A, Tissot F, Christen A, Battegay M, Schmid P, Bernasconi E, Egger M; for the Swiss HIV Cohort Study and the Swiss National Cohort. Am J Psychiatry. 2010. 167:143-150.

High rates of suicide have been described in HIV-infected patients, but it is unclear to what extent the introduction of antiretroviral therapy has affected suicide rates. The authors examined time trends and predictors of suicide in the pre-antiretroviral treatment (1988-1995) and antiretroviral treatment (1996-2008) eras in HIV-infected patients and the general population in Switzerland. The authors analyzed data from the Swiss HIV Cohort Study and the Swiss National Cohort, a longitudinal study of mortality in the Swiss general population. They calculated standardized mortality ratios comparing HIV-infected patients with the general population and used Poisson regression to identify risk factors for suicide. From 1988 to 2008, 15,275 patients were followed in the Swiss HIV Cohort Study for a median duration of 4.7 years. Of these, 150 died by suicide (rate 158.4 per 100,000 person-years). In men, standardized mortality ratios declined from 13.7 (95% CI=11.0-17.0) in the pre-antiretroviral treatment era to 3.5 (95% CI=2.5-4.8) in the late antiretroviral treatment era. In women, ratios declined from 11.6 (95% CI=6.4-20.9) to 5.7 (95% CI=3.2-10.3). In both periods, suicide rates tended to be higher in older patients, in men, in injection drug users, and in patients with advanced clinical stage of HIV illness. An increase in CD4 cell counts was associated with a reduced risk of suicide. Suicide rates decreased significantly with the introduction of antiretroviral treatment, but they remain above the rate observed in the general population, and risk factors for suicide remain similar.

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Editors’ note: The results of this study, revealing encouraging declines in the suicide rate among people living with HIV in Switzerland since the advent of antiretroviral treatment, need to be seen in context. Swiss suicide rates are in the top-third in Europe and the top quintile, i.e the top 20%, in the world. Declines in the suicide rate have occurred in the general population too but not to the extent seen in surrounding countries. Switzerland has no national suicide prevention programme to address this important public health problem and the suicide rate among people living with HIV, despite the important declines documented here, may be higher than in other European countries. They are certainly higher than in the general Swiss population and are higher than those in other patients with life-threatening conditions. Although 75% of people with HIV who committed suicide had a diagnosis of mental illness, it is unclear to what extent stigma, discrimination, social isolation, drug toxicity, and other factors are playing roles. Understanding what is influencing decisions to commit suicide is the first step to preventing such unnecessary deaths among people living with HIV.

Weigel R, Kamthunzi P, Mwansambo C, Phiri S, Kazembe PN. BMC Pediatr. 2009. 9(1):80.

The HIV prevalence in Malawi is 12 % and Kamuzu Central Hospital, in the capital Lilongwe, is the main provider of adult and paediatric HIV services in the central region. The Lighthouse at Kamuzu Central Hospital offers voluntary HIV testing and counselling for adults and children. In June 2004, Lighthouse was the first clinic to provide free antiretroviral treatment in the public sector, but few children accessed the services. In response, provider-initiated HIV testing and counselling and an antiretroviral treatment clinic were introduced at the paediatric department at Kamuzu Central Hospital in Quarter 4 (Q4) 2004. The authors analysed prospectively collected, aggregated data of quarterly reports from Q1 2003 to Q4 2006 from opt-in HIV testing and counselling centre registers, antiretroviral treatment registers and clinic registrations at the antiretroviral treatment clinics of both Lighthouse and the paediatric department. By comparing data of both facilities before (Q1 2003 to Q3 2004), and after the introduction of the services at the paediatric department (Q4 2004 to Q4 2006), they assessed the effect of this intervention on the uptake of HIV services for children at Kamuzu Central Hospital. Overall, 3971 children were tested for HIV, 2428 HIV-infected children were registered for care and 1218 started antiretroviral treatment. Between the two periods, the median (IQR) number of children being tested, registered and starting antiretroviral treatment per quarter rose from 101 (53-109) to 358 (318-440), 56 (50-82) to 226 (192-234) and 18 (8-23) to 139 (115-150), respectively. The median proportion of tested clients per quarter that were children rose from 3.8% (2.7-4.3) to 9.6% (8.8 to 10.0) (p=0.0009) and the proportion of antiretroviral treatment starters that were children rose from 6.9% (4.9-9.3) to 21.1% (19.2-24.2) (p=0.0036). The proportion of registered children and adults starting antiretroviral treatment each quarter increased similarly, from 26% to 53%, and 20% to 52%, respectively. Implementation of provider-initiated HIV testing and counselling and integration of antiretroviral treatment services within the paediatric ward are likely to be the main reasons for improved access to HIV testing and counselling and antiretroviral treatment for children at Kamuzu Central Hospital, and can be recommended to other hospitals with paediatric inpatients in resource limited settings with high HIV prevalence.

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Editors’ note: Even though providers initiated an offer of HIV testing and counselling with the caregivers of only 10% of admitted children at the Kamazu Central Hospital, there was a marked increase in the absolute numbers and proportions of children tested for HIV and started on antiretroviral treatment at this facility, compared to the era of parent/caregiver-initiated voluntary testing and counselling. It is unclear whether this modest increase in provider-initiated testing and counselling made the difference or whether it was the advent of free antiretroviral treatment that changed both client and health worker attitudes towards HIV counselling and testing. In any case, 41% of all children tested at the hospital were tested through the paediatric ward and the yield there was high, providing an additional entry point to antiretroviral treatment for children in Lilongwe.

“It’s better not to know”: perceived barriers to HIV voluntary counseling and testing among sub-Saharan African migrants in Belgium.

Manirankunda L, Loos J, Alou TA, Colebunders R, Nöstlinger C. AIDS Educ Prev. 2009. 21:582-93.

This study explored perceptions, needs, and barriers of sub-Saharan African migrants in relation to HIV voluntary counselling and testing. Using an inductive qualitative methodological approach, data were obtained from focus group discussions. Results showed that participants were in principle in favour of voluntary counselling and testing. However, they indicated that barriers outweighed advantages. Such barriers included fear of positive test results and its related personal and social consequences, lack of information, lack of preventive health behaviour, denial of HIV risk, and missed opportunities. Limited financial resources were only a concern for some subgroups like young people, asylum seekers, and recent migrants. This study identified multiple and intertwined barriers to voluntary counselling and testing from a community perspective. In order to promote voluntary counselling and testing, interventions such as raising awareness through culturally sensitive education should be adopted at community level. At level of service provision, provider initiated HIV testing including target group tailored counselling should be promoted.

For abstract access click here: 1 

Editors’ note: This first qualitative community-based study of the barriers to uptake of voluntary counselling and testing among sub-Saharan migrants in Belgium found that previously acquired experiences in their countries of origin negatively influenced testing uptake. The images of relatives or friends, who had been ill and died of AIDS, shaped attitudes toward knowledge of serostatus, as did the considerable responsibilities that many recent migrants have toward family and community members back home. Focus group participants indicated that provider-initiated discussions of HIV testing, combined with the testimonies of people living with HIV and in good health on how to live with HIV, would help reduce fears of HIV testing and counselling. Efforts to reduce stigma, increase social support, and increase testing uptake in a culturally sensitive manner will increase the proportion of migrants wanting to learn their HIV status.

Crampin AC, Mwaungulu JN, Mwaungulu FD, Mwafulirwa DT, Munthali K, Floyd S, Fine PE, Glynn JR. AIDS. 2010 Jan 28;24(3):417-26

The aim of the study was to estimate rates of recurrent tuberculosis due to reinfection and relapse, by HIV status, in a general population. A long-term cohort study was conducted in Karonga district, rural Malawi. All tuberculosis patients with culture-proven disease in Karonga district were followed up after treatment. HIV testing was offered and all Mycobacterium tuberculosis isolates were fingerprinted using IS6110 RFLP. Fingerprints from initial and recurrent disease episodes were compared to distinguish relapse and reinfection: a second episode was considered a relapse if the fingerprint was identical or differed by only 1-4 bands and was the first occurrence of that pattern in the population. Rates of and risk factors for recurrence, reinfection disease, and relapse were estimated using survival analysis and Poisson regression. Five hundred and eighty-four culture-positive episodes of tuberculosis were diagnosed and treatment was completed during 1995-2003 in patients with known HIV status; 53 culture-positive recurrences occurred by May 2005. Paired fingerprints were available for 39 of these. Reinfections accounted for 1/16 recurrences in HIV-negative and 12/23 in HIV-positive individuals. Rates of relapse were similar in HIV-positive and HIV-negative individuals. Using multiple imputation to allow for missing fingerprint information, the rate of reinfection disease in HIV-positive individuals was 2.2/100 person-years, and in HIV-negative individuals 0.4/100 person-years. HIV increases the rate of recurrent tuberculosis in this setting by increasing the rate of reinfection disease, not relapse.

For abstract access click here: 1 

Editors’ note: It appears from this and other studies that a second bout of tuberculosis (TB) in an HIV-negative person in most settings is most likely to be due to relapse and may reflect overall programme effectiveness in treating TB. Relapse rates following successful completion of treatment are highest in the first 6 months off treatment. Although numbers were small, relapse rates in this study were encouragingly similar for HIV-negative and HIV-positive people. The story was much different for re-infection with a rate ratio of 6.3 (1.3-31.5, p=0.02) comparing HIV-positive and HIV-negative individuals. That re-infection occurs at all among HIV-negative people begs the question: if natural infection does not always prevent re-infection, is there still hope for a TB vaccine, at least for some people? The higher risk of re-infection in HIV-positive people, none of them on antiretroviral treatment, suggests that HIV may directly influence the risk of re-infection, increase the risk of development of disease, and/or increase the risk of exposure to other TB strains in health care settings. It is important to untangle the contribution of each of these and to see if antiretroviral treatment scale-up to all HIV-positive patients with TB, along with environmental controls in TB and HIV clinics, can reduce the risk of re-infection and associated high mortality for people living with HIV.

Beck Z, Brown BK, Wieczorek L, Peachman KK, Matyas GR, Polonis VR, Rao M, Alving CR. PLoS One.2009.4:e8297.

Although CD4(+) cells represent the major target for HIV infection in blood, claims of complement-independent binding of HIV-1 to erythrocytes and the possible role of Duffy blood group antigen, have generated controversy . To examine the question of binding to erythrocytes, HIV-1 was incubated in vitro with erythrocytes from 30 healthy leukapheresis donors, and binding was determined by p24 analysis and adsorption of HIV-1 with reduction of infectivity for CD4(+) target cells. All of the cells, regardless of blood group type, bound HIV-1 p24. A typical preparation of erythrocytes bound <2.4% of the added p24, but erythrocytes selectively removed essentially all of the viral infectivity as determined by decreased infection of CD4(+) target cells; however, cell-associated HIV-1 was approximately 100-fold more efficient, via trans infection, than unadsorbed virus for infection of CD4(+) cells. All of the bound HIV-1 p24 was released by treatment of the cells with EDTA, and binding was optimized by adding Ca(2+) and Mg(2+) during the washing of erythrocytes containing bound HIV-1. Although the small number of contaminating leukocytes in the erythrocyte preparation also bound HIV-1 p24, there was no significant binding to CD4, and it thus appears that the binding occurred on leukocytes at non-CD4 sites. Furthermore, binding occurred to erythrocyte ghosts from which contaminating leukocytes had been previously removed. The results demonstrate that erythrocytes incubated in vitro with HIV-1 differentially adsorb all of the infectious HIV-1 virions (as opposed to non-infectious or degraded virions) in the absence of complement and independent of blood group, and binding is dependent on divalent cations. By analogy with HIV-1 bound to DC-SIGN on dendritic cells, erythrocyte-bound HIV-1 might comprise an important surface reservoir for trans-infection of permissive cells.

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Editors’ note : Although the exact mechanism of binding of HIV-1 to erythrocytes remains unknown, there is likely more than one mechanism. This study demonstrates that in the absence of complement which HIV-1 usually activates so that it can bind to complement receptors on cells, HIV-1 binds to erythrocytes, regardless of whether they display Duffy blood group antigen or not. The binding occurs only on the cell surface, permitting erythrocytes with HIV-1 on their surface to present it to CD4+ cells which are not in plentiful supply compared to other cell types. Thus, erythrocytes in the blood may be acting like dendritic cells in tissue to carry and offer HIV-1 to the very target cells that HIV-1 uses for replication, in a process called trans infection. This appears likely to be a far more frequent infecting mechanism than direct infection of CD4+ cells by circulating free virus.

García-Lerma G, Cong M, Mitchell J, Youngpairoj A, Zheng Q, Masciotra S, Martin A, Kuklenyik Z, Holder A, Lipscomb J, Pau C, Barr J, Hanson D, Otten R, Paxton L, Folks T and Heneine W. Sci Transl Med. 2010. 2: 14ra4.

Antiretroviral drugs have transformed the lives of HIV-infected people by preventing progression to full-blown AIDS. These drugs also dramatically reduce HIV transmission from mothers to infants during pregnancy and breastfeeding, and work in monkeys suggests that daily doses can also reduce transmission from unprotected sex. But prophylactic treatment with antiretroviral drugs is costly and impractical—even if confined to a high-risk population. García-Lerma et al. now show that in monkeys a more realistic medication schedule may work just as well as daily doses. To simulate how people are likely to be infected with HIV, the authors exposed macaque monkeys rectally to 14 weekly doses of simian-human immunodeficiency virus (SHIV) engineered to resemble the human virus. Control macaques treated in this way became infected within the first five exposures to SHIV. Researchers then assessed whether oral, human-equivalent doses of antiretroviral agents could prevent infection in monkeys. The best protection—equivalent to that provided by daily antivirals—occurred when the drug Truvada was given 1, 3, or 7 days before virus exposure followed by a second dose 2 hours after exposure. Less effective, but still better than no treatment at all, was a schedule in which the drug was given 2 hours before or after exposure and then again 24 hours later. Drugs given only 24 or 48 hours after exposure did not safeguard against infection. The results of this study are preliminary, largely because each of the groups had only six macaques, but they are nevertheless promising. If ongoing clinical trials in healthy people show that daily antiretroviral therapy can diminish the chances of acquiring HIV after exposure, a reasonable next step would be to evaluate more practical, less costly drug schedules in humans. For example, a weekly dose followed by a second dose after a possible exposure could prove both effective and tractable. It will also be important to evaluate treatments based solely on exposure, as these would not require ongoing prophylactic drug treatment and would minimize any drug toxicity. If one or more of these therapeutic regimens is successful, antiretroviral drugs may expand the transformation they have already engendered by preventing many more new infections as well as controlling existing ones.

For abstract access click here: 1

Editors’ note: Despite several limitations of these non-human primate trials, they nonetheless provide food for thought and for human trial design. All the current oral Pre-Exposure Prophylaxis (PrEP) phase IIb and III trials in humans are studying daily administration of either tenofovir (TDF) or a combination of TDF and emtricitabine (FTC). Good complements to each other, FTC appears to have more rapid absorption and tissue distribution while TDF has a long intracellular persistence. Based on these findings of good protection from rectal challenge in macaques given intermittent oral TDF/FTC treatment (varying times before but topping up 2 hours after exposure in active arms), the results of human trials of intermittent PrEP are needed. Intermittent PrEP regimens would likely be easier to adhere to, while decreasing drug costs and probably reducing drug toxicities. Those animals that did become infected appeared to have lower peak levels of virus in the blood. If lower viral set points are confirmed, this may reduce CD4+ cell count depletion and slow disease progression but may also mean less onward transmission. There are many questions to be answered about PrEP before it can be considered as a candidate to join the biomedical component of combination prevention (biomedical, behavioural, structural) strategies. The first question is whether daily administration will prove effective in the current trials of men who have sex with men, people who inject drugs, and heterosexuals at increased risk. If it does, there will be heightened interest in rapidly testing the safety and efficacy of intermittent PrEP in humans to inform policy and programme design decision-making.

Gordon R, Björklund NK, Smith RJ, Blyden ER. BMC Public Health. 2009;9 Suppl 1:S13.

A major deficit of all approaches to epidemic modelling to date has been the need to approximate or guess at human behaviour in disease-transmission-related contexts. Avatars are generally human-like figures in virtual computer worlds controlled by human individuals. The authors introduce the concept of a “havatar”, which is a (human, avatar) pairing. Evidence is mounting that this pairing behaves in virtual contexts much like the human in the pairing might behave in analogous real-world contexts. Gordon et al. propose that studies of havatars, in a virtual world, may give a realistic approximation of human behaviour in real-world contexts. If the virtual world approximates the real world in relevant details (geography, transportation, etc.), virtual epidemics in that world could accurately simulate real-world epidemics. Havatar modelling of epidemics therefore offers a complementary tool for tackling how best to halt epidemics, including perhaps HIV, since sexual behaviour is a significant component of some virtual worlds, such as Second Life. Havatars place the control parameters of an epidemic in the hands of each individual. By providing tools that everyone can understand and use, we could democratise epidemiology.

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Editors’ note: Reviewing current modelling approaches (continuous or deterministic, discrete or individual, and stochastic process modelling), these authors point out that all epidemic modelling second-guesses human behaviour. Their proposition that epidemiological modellers monitor the social networks of havatars (“h” stands for human) to obtain a better representation of real-world disease transmission raises several questions. Although the 13 million people who joined the virtual world Second Life signed waivers that would allow tracking of all transactions, there may be ethical issues to consider when modellers intervene in people’s virtual worlds with HIV epidemic simulations to study the behaviour of the avatars under a person’s control and make extrapolations to human behaviour. Unleashing invisible, simulated viruses that infect havatars and can be transmitted could cause problems, even if the viruses themselves have no effects such as simulated weight loss or changes in colour. The possibility of virtual world stigma might become real. As well, the people currently part of this virtual world are unlikely to represent populations at higher risk of HIV exposure around the world so the validity of the extrapolations to the HIV epidemic we face today could well be in question.

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For full PDF access to this issue: HIV This Week Issue# 77

Logie C, Gadalla TM. AIDS Care. 2009 2:742-53.

HIV-related stigma may negatively impact the health, quality of life, social support and well-being of people living with HIV (PLHIV). Previous studies have used diverse samples and a multitude of measurement instruments to examine demographic and health correlates of HIV-related stigma, highlighting the importance of synthesizing findings across different studies to gain a better understanding of these associations. This study examined the relationships between HIV-related stigma and a range of demographic, social, physical and health characteristics. A meta-analysis was conducted to assess the overall strength and direction of these relationships. Twenty-four studies of PLHIV, conducted in North America and published in peer-reviewed journals between January of 2000 and November of 2007, were examined and their findings integrated. The heterogeneity of reported results was also assessed and examined. Logie etal’s review revealed substantial variability in the ways researchers measure participants’ HIV-related stigma as well as their physical, emotional and mental health. In spite of this variability, high stigma level was consistently and significantly associated with low social support (r = -0.369, p<0.0005), poor physical health (r = -0.324, p<0.0005), poor mental health (r = -0.402, p<0.0005), age (-0.066, p<0.05) and income (-0.172, p<0.005). These correlations were of a medium size, which would be recognized by the individual in daily life. Health and mental health professionals working with individuals and families affected by HIV could benefit from an enhanced understanding of correlates of HIV-related stigma, which will inform assessments, interventions, and treatment plans. The association between HIV-related stigma and physical health has potential implications for treatment, care and support for people at different stages of HIV infection. AIDS Service Organizations are also encouraged to integrate findings into HIV stigma interventions and social support programs. Additionally, HIV-related stigma scales should be developed and validated, so that future studies using them are able to report findings that are operationally and conceptually consistent.

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Editors’ note: Drawing on data from 5600 individuals in 24 studies, this literature synthesis is the first to quantify the associations between HIV-related stigma and characteristics of people living with HIV. Five key variables were found to be significantly associated with high stigma levels: lack of social support, poor physical health, poor mental health, low income, and younger age. Effective interventions to address stigma operate on multiple levels and engage populations as diverse as policy makers, practitioners, communities, and people living with HIV. On a parallel track, it is high time to measure and better understand individual and collective strengths such as the resilience, resistance, solidarity, and empowerment that both help cope with stigma and reduce its prevalence.  

Li L, Liang LJ, Lin C, Wu Z, Rotheram-Borus MJ; the NIMH Collaborative HIV/STD Prevention Trial Group. AIDS. 2010 24:115-122.

The National Institute of Mental Health Collaborative HIV/Sexually Transmitted Disease Prevention Trial provided a unique opportunity to test whether, with the community-based diffusion of HIV/sexually transmitted disease prevention information and an elevated understanding of HIV, the level of stigmatizing attitudes toward people living with HIV in the community would be reduced. A total of 4510 market workers in Fuzhou, China, participated in the study, and longitudinal analyses included study samples of 3785 participants in the 12-month follow-up and 3716 participants in the 24-month follow-up. The authors graphically examined the change in HIV-related stigma indicators over time between control and intervention groups using boxplot and kernel density estimation. A logistic regression analysis with proportional odds model was further used to examine the intervention effect on HIV-related stigmatizing attitudes. Compared with no change over time for the control group, the intervention successfully reduced the level of HIV-related stigmatizing attitudes among the target population at the 12-month follow-up, and the effect increased by two-fold (with respect to odds ratios) at the 24-month follow-up. The intervention demonstrated positive attitude changes associated with HIV-related stigma. These results show the importance of social norms, rather than simply individual behaviours, in developing and implementing stigma reduction campaigns.

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Editors’ note: This trial was designed to identify, recruit, train, and engage community popular opinion leaders to convey HIV-risk reduction messages to food vendors in the markets that were randomised to the intervention arm. The ‘unintended’ finding of stigma reduction in a trial designed to reduce HIV/STD incidence and risk behaviour is puzzling. It may be due to community mobilisation and the use of social networks to convey information. It does suggest that HIV prevention and stigma reduction initiatives should be integrated for maximum benefit.

DART Trial Team. The Lancet, Early Online Publication, 9 December 2009 [Epub ahead of print]

HIV antiretroviral therapy (ART) is often managed without routine laboratory monitoring in Africa; however, the effect of this approach is unknown. This trial investigated whether routine toxicity and efficacy monitoring of HIV-infected patients receiving antiretroviral therapy had an important long-term effect on clinical outcomes in Africa. In this open, non-inferiority trial in three centres in Uganda and one in Zimbabwe, 3321 symptomatic, antiretroviral therapy-naive, HIV-infected adults with CD4 counts less than 200 cells per muL starting antiretroviral therapy were randomly assigned to laboratory and clinical monitoring (LCM; n=1659) or clinically driven monitoring (CDM; n=1662) by a computer-generated list. Haematology, biochemistry, and CD4-cell counts were done every 12 weeks. In the laboratory and clinical monitoring group, results were available to clinicians; in the clinically driven monitoring group, results (apart from CD4-cell count) could be requested if clinically indicated and grade 4 toxicities were available. Participants switched to second-line antiretroviral therapy after new or recurrent WHO stage 4 events in both groups, or CD4 count less than 100 cells per muL (laboratory and clinical monitoring only). Co-primary endpoints were new WHO stage 4 HIV events or death, and serious adverse events. Non-inferiority was defined as the upper 95% confidence limit for the hazard ratio (HR) for new WHO stage 4 events or death being no greater than 1.18. Analyses were by intention to treat. This study is registered, number ISRCTN13968779. Two participants assigned to clinically driven monitoring and three to laboratory and clinical monitoring were excluded from analyses. 5-year survival was 87% (95% CI 85-88) in the CDM group and 90% (88-91) in the LCM group, and 122 (7%) and 112 (7%) participants, respectively, were lost to follow-up over median 4.9 years’ follow-up. 459 (28%) participants receiving clinically driven monitoring versus 356 (21%) laboratory and clinical monitoring had a new WHO stage 4 event or died (6.94 [95% CI 6.33-7.60] vs 5.24 [4.72-5.81] per 100 person-years; absolute difference 1.70 per 100 person-years [0.87-2.54]; HR 1.31 [1.14-1.51]; p=0.0001). Differences in disease progression occurred from the third year on antiretroviral therapy, whereas higher rates of switch to second-line treatment occurred in LCM from the second year. 283 (17%) participants receiving clinically driven monitoring versus 260 (16%) LCM had a new serious adverse event (HR 1.12 [0.94-1.32]; p=0.19), with anaemia the most common (76 vs 61 cases). Antiretroviral therapy can be delivered safely without routine laboratory monitoring for toxic effects, but differences in disease progression suggest a role for monitoring of CD4-cell count from the second year of antiretroviral therapy to guide the switch to second-line treatment.

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Editors’ note: These findings, presented at the International AIDS Society conference in Cape Town in July 2009 are fully described here, complementing the excellent film produced by Tom Gibb (http://www.youtube.com/MRCcomms#p/u/1/MSyFmbiR-Hc). The results of this trial, designed to determine whether clinician monitoring of signs and symptoms without knowledge of CD4 count was not inferior to similar monitoring with knowledge of CD4 test results, suggest that once eligibility for antiretroviral treatment is determined, clinically driven monitoring holds the fort well for the first 2 years of treatment, freeing up resources and allowing extension of treatment access to more remote areas with no laboratory infrastructure.

McCarthy K, Chersich MF, Vearey J, Meyer-Rath G, Jaffer A, Simpwalo S, Venter WD. Int J STD AIDS. 2009 20:858-62.

Foreigners, including displaced persons, often have limited health-care access, especially to HIV services. Outcomes of antiretroviral therapy (ART) in South Africans and foreigners were compared at a Johannesburg non-governmental clinic. Records were reviewed of 1297 adults enrolled between April 2004 and March 2007 (568 self-identified foreigners, 431 South Africans citizens and 298 with unknown origin). Compared with citizens, foreigners had fewer hospital admissions (39%, 90/303 versus 51%, 126/244; P < 0.001), less missed appointments for antiretroviral therapy initiation (20%, 39/200 versus 25%, 51/206; P < 0.001), faster median time to antiretroviral therapy initiation (14 versus 21 days, P = 0.008), better retention in care (88%, 325/369 versus 69%, 155/226; P < 0.001) and lower mortality (2.5%, 14/568 versus 10%, 44/431; P < 0.001) after 426 person-years. In logistic regression, after controlling for baseline CD4 count and tuberculosis status, foreigners were 55% less likely to fail antiretroviral therapy than citizens (95% CI = 0.23-0.87). These findings support United Nations High Commissioner for Refugees recommendations that antiretroviral therapy should not be withheld from displaced persons.

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Editors’ note: South Africa at the end of 2007 had the world’s largest number of pending asylum applications and was second only to the United States of America in annual new asylum claims. The level of undocumented migrants is much higher. The findings from this study demonstrate that foreigners were about half as likely to fail antiretroviral treatment as citizens, despite having lower baseline median CD4 cell counts and being subject to significant hurdles in accessing and staying in care. This strongly supports the argument that foreigners should be included in the ‘right to access antiretroviral treatment for all.  

Guy R, Gold J, Calleja JM, Kim AA, Parekh B, Busch M, Rehle T, Hargrove J, Remis RS, Kaldor JM; WHO Working Group on HIV Incidence Assays. Lancet Infect Dis. 2009 9:747-59.

The authors systematically reviewed the accuracy of serological tests for recent infections with HIV that have become widely used for measuring population patterns incidence of HIV. Across 13 different assays, sensitivity to detect recent infections ranged from 42-100% (median 89%). Specificity for detecting established infections was between 49.5% and 100% (median 86.8%) and was higher for infections of durations longer than 1 year (median 98%, range 31.5-100.0). For four different assays, comparisons were made between assay-derived population incidence estimates and a reference incidence estimate. The median percentage difference between the assay-derived incidence and reference incidence was 26.0%. Serological assays have reasonable sensitivity for the detection of recent infection with HIV, but are vulnerable to misclassifying established infections as recent-potentially leading to biases in incidence estimates. This conclusion is highly qualified by the apparent absence of a standardised approach to assay evaluation. There is an urgent need for an internationally agreed framework for evaluating and comparing these tests.

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Editors’ note: Determining HIV incidence directly by measuring seroconversion and thereby monitoring HIV transmission is key to both assessing the need for and establishing the effectiveness of HIV prevention programmes. This extensive review confirms that the development of reliable and valid tests to detect recent infection is a public health priority. To date virtually all the assays that have been developed involve subtype B virus (clade C is the most common worldwide) and have been plagued by false positive results due to longstanding infections or an increasing duration of antiretroviral treatment. Given that HIV incidence reduction is a foundation of both national and international HIV commitments, it is urgent that a standardised approach to assay validation be developed and implemented.  

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Estimates of HIV incidence from household-based prevalence surveys.

Hallett TB, Stover J, Mishra V, Ghys PD, Gregson S, Boerma T. AIDS. 2010 ;24:147-52.

This study set out to estimate HIV incidence in the general population in countries where there have been two recent household-based HIV prevalence surveys (the Dominican Republic, Mali, Niger, Tanzania, and Zambia). Hallett et al applied a validated method to estimate HIV incidence using HIV prevalence measurement in two surveys. The authors estimate incidence among men and women aged 15-44 years to be: 0.5/1000 person-years at risk in the Dominican Republic 2002-2007, 1.1/1000 in Mali 2001-2006, 0.6/1000 in Niger 2002-2006, 3.4/1000 in Tanzania 2004-2008, and 11.2/1000 in Zambia 2002-2007. The groups most at risk in these epidemics are typically 15-24-year-old women and 25-39-year-old men. Incidence appears to have declined in recent years in all countries, but only significantly among men in the Dominican Republic and Tanzania and women in Zambia. Using prevalence measurements to estimate incidence reveals the current level and age distribution of new infections and the trajectory of the HIV epidemic. This information is more useful than prevalence data alone and should be used to help determine priorities for interventions.

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Editors’ note: Why have we not been estimating HIV incidence from household surveys? This straightforward method of comparing current age cohorts with their representation in a previous survey includes adjustments for deaths and the numbers of people on treatment by age group. The gold standard, a cohort incidence study, is too expensive and the cohorts in question may not represent the national population anyway. Just as trends in HIV prevalence among pregnant women aged 15 to 24 years have been a proxy for HIV incidence, so too can this approach detect changes in HIV incidence, but at a variety of ages .  

Ganguli I, Bassett IV, Dong KL, Walensky RP. Curr HIV/AIDS Rep. 2009;6:217-23.

Among an estimated 33 million individuals who are infected with HIV worldwide, only 10% are aware of their status. HIV testing is the cornerstone to preventing further transmission and to caring for those infected, particularly as access to treatment improves in resource-limited settings. However, efforts to expand testing through facilities-based testing have not achieved adequate testing coverage, prompting efforts to reach more individuals through strategies such as home-based HIV testing. Home testing is showing promising early results in some high-prevalence, resource-limited settings. This article reviews the mechanisms and literature to date of this door-to-door approach.

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Editors’ note: This review contrasts the literature on self-specimen collection and self-testing at home in the United States of America with ‘counsellor-initiated home-based testing’ in high HIV prevalence resource-limited settings. Those most likely to benefit from the latter may be the poor who have the lowest uptake of traditional, facility-based testing and counselling. Home-based testing in low- and middle-income settings may reach couples and families more efficiently than other strategies but individuals and the public will only benefit if there are strong links to effective HIV prevention, medical care, and psychosocial support for those who learn their test result.

Aghokeng AF, Mpoudi-Ngole E, Dimodi H, Atem-Tambe A, Tongo M, Butel C, Delaporte E, Peeters M. PLoS One. 2009 ;4:e7702.

Increased access to HIV testing is essential in working towards universal access to HIV prevention and treatment in resource-limited countries. The authors evaluated currently used HIV diagnostic tests and algorithms in Cameroon for their ability to correctly identify HIV infections. They estimated sensitivity, specificity, and positive and negative predictive values of 5 rapid/simple tests, of which 3 were used by the national program, and 2 fourth generation ELISAs. The reference panel included 500 locally collected samples; 187 HIV -1 M, 10 HIV-1 O, 259 HIV negative and 44 HIV indeterminate plasmas. None of the 5 rapid assays and only 1 ELISA reached the current WHO/UNAIDS recommendations on performance of HIV tests of at least 99% sensitivity and 98% specificity. Overall, sensitivities ranged between 94.1% and 100%, while specificities were 88.0% to 98.8%. The combination of all assays generated up to 9% of samples with indeterminate HIV status, because they reacted discordantly with at least one of the different tests. Including HIV indeterminate samples in test efficiency calculations significantly decreased specificities to a range from 77.9% to 98.0%. Finally, two rapid assays failed to detect all HIV-1 group O variants tested, with one rapid test detecting only 2 out of 10 group O specimens. In the era of antiretroviral therapy scaling-up in Africa, significant proportions of false positive but also false negative results are still observed with HIV screening tests commonly used in Africa, resulting in inadequate treatment and prevention strategies. Depending on tests or algorithms used, up to 6% of HIV-1 M and 80% of HIV-1 O infected patients in Cameroon do not receive antiretroviral therapy and adequate counselling to prevent further transmission due to low sensitivities. Also, the use of tests with low specificities could imply inclusion of up to 12% HIV negative people in antiretroviral therapy programs and increase budgets in addition to inconveniences caused to patients.

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Editors’ note: False-positive and false-negative HIV test results have negative implications for both individuals and programmes – all efforts must be made to minimise them. The first step is to evaluate assay performance using a serum panel from patients infected with subtypes that are circulating locally and the second step is instituting ongoing quality control. Inadequate sensitivity (ability to correctly identify presence of infection) and specificity (ability to correctly identify lack of infection) mean that infections are missed which can delay treatment or, on the other hand, that people who are not infected believe that they are, with personal and programmatic costs. When test kits are chosen by officials on the basis of lower price rather than performance efficacy, the results can be dire. This article should be essential reading for all national laboratory directors .

Ciaranello AL, Chang Y, Margulis AV, Bernstein A, Bassett IV, Losina E, Walensky RP. Clin Infect Dis. 2009;49:1915-27.

Responses to antiretroviral therapy (ART) among human immunodeficiency virus (HIV)-infected children in resource-limited settings have recently been reported, but outcomes vary. The authors sought to derive pooled estimates of the 12-month rate of virologic suppression (HIV RNA, <400 copies/mL) and gain in CD4 cell percentage (DeltaCD4%) for children initiating antiretroviral therapy in resource-limited settings. Ciaranello et al conducted a systematic review and meta-analysis of published reports of HIV RNA and CD4 outcomes for treatment-naive children aged 0-17 years old by means of the Medline, EMBASE (Excerpta Medica Database), and LILACS (Latin American and Caribbean Health Sciences Literature) electronic databases and the Cochrane Clinical Trials Register. Pooled estimates of the reported proportion with HIV RNA <400 copies/mL and DeltaCD4% after 12 months of antiretroviral therapy were derived using patient-level estimates and fixed- and random-effects models. To approximate intention-to-treat analyses, in sensitivity analyses children with missing 12-month data were assumed to have HIV RNA>400 copies/mL or DeltaCD4% of zero. In patient-level estimates after 12 months of antiretroviral therapy, the pooled proportion with virologic suppression was 70% (95% confidence interval [CI], 67%-73%); the pooled DeltaCD4% was 13.7% (95% CI, 11.8%-15.7%). Results from the fixed- and random-effects models were similar. In approximated intention-to-treat analyses, the pooled estimates decreased to 53% with virologic suppression (95% CI, 50%-55%) and to a DeltaCD4% of 8.5% (95% CI, 5.5%-11.4%). Pooled estimates of reported virologic and immunologic benefits after 12 months of antiretroviral therapy among HIV-infected children in resource-limited settings are comparable with those observed among children in developed settings. Consistency in reporting on reasons for missing data will aid in the evaluation of antiretroviral therapy outcomes in resource-limited settings.

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Editors’ note: Treatment outcomes for treatment-naïve children after 1 year are similar in resource-poor settings as they are in the United States of America and Europe, despite advanced stages of HIV disease at initiation of antiretroviral treatment, substantial barriers to service delivery, and predominantly non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. This is great news from this first study to provide pooled estimates of the virological suppression rate and change in CD4 percentage in children in countries with emerging or developing economies. These findings have particular importance for the estimated 90% of children living with HIV who reside in resource-limited settings and should spur on the movement to treat all children living with HIV.

Six-month gain in weight, height, and CD4 predict subsequent antiretroviral treatment responses in HIV-infected South African children.

Yotebieng M, Van Rie A, Moultrie H, Meyers T. AIDS. 2010 24:139-46.

The aim of the study was to construct percentile curves for 6-month gain in weight, height, CD4 cell count, and CD4 percentage (CD4%) in children initiating antiretroviral therapy, and to assess the association between lower percentiles and subsequent antiretroviral therapy responses. A cohort of 1394 HIV-infected children initiating antiretroviral therapy between April 2004 and March 2008, Johannesburg, South Africa were enrolled. The generalized additive model for location, scale, and shape was used to construct percentile curves for 6-month gain in weight, height, CD4 cell count, and CD4%. Cox proportional models were used to assess the association between lower percentiles of each distribution and death, virological suppression, and treatment failure between 6 to 36 months post-antiretroviral therapy initiation. Lower percentiles for gain in weight, CD4, and CD4% count after 6 months of antiretroviral therapy, but not height, were associated with poor subsequent treatment outcomes independent of baseline characteristics, with increasing strength of association as percentiles decreased. Age-specific 6-month post-antiretroviral therapy weight gain in this cohort was substantially higher compared with 6-month weight gain in non-HIV-infected American children of the Fels Institute cohort and the attained weight-for-age at 6 months post- antiretroviral therapy plotted on WHO weight-for-age growth charts were not associated with subsequent treatment outcomes. Gain in CD4% in the first 6 months of antiretroviral therapy was the best predictor of poor subsequent antiretroviral therapy outcomes. In areas with limited access to CD4%, weight gain post- antiretroviral therapy using these newly developed reference distributions for HIV-infected children on antiretroviral therapy is a good alternative to CD4%, and clearly superior to the commonly used ‘Road-to-Health’ weight-for-age charts.

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Editors’ note: A third of children vertically infected do not survive to their first birthday and more than half die before age 2. When children start antiretroviral treatment, it is important to monitor their clinical improvement to assess whether they are benefitting. This innovative study developed HIV-specific weight gain reference curves that can be used by health workers in settings without CD4 percentage laboratory tests to identify which children on treatment are likely to be virologically suppressed and which ones are at higher risk for treatment failure and subsequent death. These reference curves should be tested in other settings and adjusted as necessary to develop international weight gain reference curves for children starting antiretroviral treatment. 

Amon JJ, Kasambala T. Glob Public Health. 2009;4:528-45.

There has long been recognition that individual risk factors can only partially explain vulnerability to HIV infection, and that a broader range of socioeconomic, cultural and political factors must be taken into account. More recently this understanding has been applied to addressing obstacles to accessing HIV treatment. Yet, while structural interventions aimed at contextual factors related to HIV prevention and treatment have been shown to be effective, they have not been widely implemented. Using the situation of Zimbabwe as an example, Amon et al present an illustration of how contextual barriers can be understood in human rights terms, and how using a human rights analysis can specifically help define ’structural-rights’ interventions and compel their implementation.

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Editor’s note: In linking human rights obligations and structural-rights interventions, this paper considers four categories of global human rights concerns: the right to earn a livelihood and own property; the right to freedom of expression, assembly, and information; the right to freedom from gender-based and sexual violence; and the right to the progressive realisation of health. Using the situation of Zimbabwe as an illustration, the paper presents a list of structural-rights interventions linked to goals addressing each of these human rights concerns. This analytic framework explicitly links interventions to redress societal inequities, reduce vulnerability to HIV, and expand access to treatment with state obligations under national and international law. It reinforces the role of governments to address structural barriers and human rights abuses as part of their broader mission of public health.