Unaids Csa-Ro Hiv This Week 87 101223

HIV This Week: what scientific journals said
Welcome to the 87th issue of HIV This Week ! In this holiday issue, we cover the following topics:
1. HIV Prevention 10. National responses

• Taking a drug to prevent taking a drug: Proof of • Essential reading if you work in HIV in Asia
concept that antiretroviral chemoprophylaxis reduces
11. Supervised injecting facilities
the risk of HIV in men who have sex with men
• Medically supervised injecting services: what do
2. Female condoms people who inject drugs think?
• Pre-marketing research among sex professionals in
12. Stigma
Central America: time for female condoms to move to
centre stage • Casual conversations sparked by popular community
opinion leaders reduce stigma in Lima, Chiclayo, and
3. Blood transfusion risk Trujillo, Peru
• What is the residual risk of transfusion-transmitted HIV
13. Care and support
in Burkina Faso, Congo, Ivory Coast, Mali, and
Senegal? • Improving general health and mental health through a
cognitive Buddhist-inspired programme for people
4. Food insecurity living with HIV in Thailand
• "All I eat is ARVs": antiretroviral therapy and hunger in
14. Epidemiology
central Mozambique
• Adapting to a changing epidemic: what is new about
• How food insecurity and self-efficacy for exclusive
the 2009 UNAIDS estimation and projection package?
breastfeeding are linked among women in urban
Kenya 15. Treatment
5. Civil Society • Reducing the latent reservoir with antiretroviral therapy
during acute infection – can it be done?
• What role are more than 400 civil society organizations
playing now in China and what could make it bigger? 16. Financing
6. Tuberculosis • What will the HIV world look like in 2031: policy options
and their consequences for low- and middle-income
• Finding infectious tuberculosis among 124, 000 people
countries and their external partners
in Harare, Zimbabwe: the value of active approaches
17. Vaccines
7. Genetics
• A new regional network sets the course for Asia
• Phylogenetics: does the virus itself set the viral
setpoint? 18. Comorbidity
8. Basic science: HIV research • Striking findings on anal human papillomavirus
infection in women with HIV infection in the era of
• Mitochondria and HIV progression: early days
antiretroviral therapy
9. Universal access: paediatric formulations
19. Sexual transmission and concurrency
• Challenges revealed by an analysis of the global
• What role does primary HIV infection play?
paediatric antiretroviral drug market
Sylvia Béké-
Cate Hankins Precious Lunga Derek Christie Tania Lemay
Wilson
Chief Scientific Adviser to
UNAIDS Research officer Adviser Research consultant Assistant
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UNAIDS_CSA-RO_HIVthisweek_87_101223
Preexposure chemoprophylaxis for HIV prevention in men who have sex with men
Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, Goicochea P, Casapía M, Guanira-Carranza
JV, Ramirez-Cardich ME, Montoya-Herrera O, Fernández T, Veloso VG, Buchbinder SP, Chariyalertsak S,
Schechter M, Bekker LG, Mayer KH, Kallás EG, Amico KR, Mulligan K, Bushman LR, Hance RJ, Ganoza C,
Defechereux P, Postle B, Wang F, McConnell JJ, Zheng JH, Lee J, Rooney JF, Jaffe HS, Martinez AI, Burns DN,
Glidden DV; the iPrEx Study Team. N Engl J Med. 2010 Nov 23. [Epub ahead of print] PubMed PMID: 21091279.
Antiretroviral chemoprophylaxis before exposure is a promising approach for the prevention of human
immunodeficiency virus (HIV) acquisition. Grant and colleagues randomly assigned 2499 HIV-seronegative
men or transgender women who have sex with men to receive a combination of two oral antiretroviral
drugs, emtricitabine and tenofovir disoproxil fumarate (FTC–TDF), or placebo once daily. All subjects
received HIV testing, risk-reduction counselling, condoms, and management of sexually transmitted
infections. The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8
years). Of these subjects, 10 were found to have been infected with HIV at enrolment, and 100 became
infected during follow-up (36 in the FTC–TDF group and 64 in the placebo group), indicating a 44%
reduction in the incidence of HIV (95% confidence interval, 15 to 63; P = 0.005). In the FTC–TDF group, the
study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects
(9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC–TDF group than
in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P = 0.57).
Oral FTC–TDF provided protection against the acquisition of HIV infection among the subjects. Detectable
blood levels strongly correlated with the prophylactic effect.
For abstract access click here:
Editors’ note: The iPrEx trial results from 11 sites in six countries (Peru, Ecuador, Brasil, USA,
Thailand, and South Africa) provide proof of concept of the safety and partial effectiveness of oral
antiretroviral drugs in preventing HIV acquisition in men who have sex with men. This study shows
the potential effects of combination prevention approaches—combining consistent condom use,
frequent HIV testing, counselling, and treatment of sexually transmitted infections with pre-exposure
prophylaxis (PrEP) for maximum prevention gains. Drug levels confirmed that excellent pill-taking
behaviour was clearly critical to protection. The trial was built on genuine, transparent, meaningful
participatory processes with study participants and communities during the entire life-cycle of the
trial, in line with published good participatory practice guidelines and ethical standards for
biomedical HIV prevention trials. [UNAIDS/AVAC Good participatory practice guidelines for
biomedical HIV prevention trials and UNAIDS/WHO Ethical considerations in biomedical HIV
prevention trials]. In a rollover study that will commence soon, all study participants, including
those in the placebo group, will now have access to the drug combination while researchers gather
information, including about factors influencing pill-taking behaviour and how to improve it. Four
other trials currently underway with people who inject drugs, women at higher risk of HIV exposure,
and serodiscordant couples (where one partner is HIV-positive and the other is HIV-negative) will
yield their results between 2011 and 2013. Many questions remain unanswered about the role that
pre-exposure prophylaxis, whether in oral tablet from as in iPrEx or for topical application as in the
1% tenofovir gel tested in CAPRISA 004, could play in HIV prevention programming. UNAIDS and
WHO are convening modelling groups, supporting 8 country consultations and, in partnership with
Georgetown University and Imperial College, organising 5 regional consultations to explore the
potential impact and acceptability of these new prevention technologies.
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2. Female condoms
Introducing female condoms to female sex workers in Central America
Mack N, Grey TG, Amsterdam A, Williamson N, Matta CI. Int Perspect Sex Reprod Health. 2010 Sep;36(3):149-
55.
Female condoms have a potential role in reducing HIV infection among female sex workers in Central
America. Research on how to introduce female condoms to this population is warranted. Two rounds of
focus groups with sex workers (115 in round one and 81 in round two) were conducted in El Salvador and
Nicaragua in 2007-2008. In addition, Mack and colleagues conducted structured interviews with 95 sex
workers and direct observations of six health educators. Women reported that the design of the female
condom made insertion and removal difficult to learn. About one-third of participants reported inserting it for
the first time alone. Most women reported practicing 2-10 times before feeling skilled enough to use it with
partners. Positive perceptions included lubrication, size, comfort and strength. Negative perceptions
included the large package, initial physical discomfort and the possibility that the device would
scare clients away. The participants preferred to learn to use female condoms from an instructional
brochure plus instructor-led training in their workplace. They cited lack of exposure to female condoms
among men and women as a barrier to female condom use and recommended education for both men
and women; they also recommended distribution of female condoms at places where male condoms
are available. If provisions are made for instructing women on female condom use in places where women
will not feel stigmatized, and if supplies are easily and consistently available, uptake of the female
condom among female sex workers in Central America seems likely. Health educators' use of promotional
tools such as checklists and standardized messages is strongly recommended.
Editors’ note: With a new generation of female condoms on the horizon soon to break the monopoly
position of FC2, including a tampon-shaped one for easier insertion, it is time to get serious about marketing
strategies to bring this orphan product into the mainstream of HIV prevention options. This mixed methods
study (using qualitative and quantitative methodologies) among sex professionals in El Salvador and
Nicaragua is an excellent example of pre-market research. It reveals the communication channels,
messages, and materials that would best complement skills-building to achieve excellent uptake and
increase the number of protected sex acts among sex workers. Similar pre-marketing studies are needed
with specific populations of women in this and other settings, including adolescents, young sexually active
women, women in serodiscordant couples, university and college students, factory workers, and many
others. With prices anticipated to drop with the advent of competition, it is high time for female condoms to
be taken seriously by international and national policy makers, donors and other development partners, as
well as women’s organisations, so that they enter centre stage to become a serious option for women
worldwide.
3. Blood transfusion risk
Estimate of the residual risk of transfusion-transmitted human immunodeficiency virus infection in

sub-Saharan Africa: a multinational collaborative study
Lefrère JJ, Dahourouh H, Dokekias AE, Kouao MD, Diarra A, Diop S, Tapko JB, Murphy EL, Laperche S, Pillonel
J. Transfusion. 2010 Sep 28. doi: 10.1111/j.1537-2995.2010.02886.x. [Epub ahead of print]
Sub-Saharan Africa remains the epicenter of the human immunodeficiency virus (HIV) pandemic. However,
there is a lack of multicentre data on the risk of transfusion-transmitted HIV from blood centres in sub-
Saharan Africa. The incidence of HIV infections in blood donations collected in the main blood banks of
five countries (Burkina Faso, Congo, Ivory Coast, Mali, and Senegal) was determined to estimate the
current transfusion risk of HIV infection using the incidence rate/window period model. The risk of
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transfusion-transmitted HIV infections associated with the window period varied from 1 in 90,200 donations
(Senegal) to 1 in 25,600 (Congo). Considering the five participating blood centres as a whole, the incidence
rate of HIV-positive donors per 100,000 person-years was 56.6 (95% confidence interval [CI], 47.1-67.9);
the residual risk was 34.1 (95% CI, 7.8-70.7) per 1 million donations, which represents 1 in 29,000
donations (95% CI, 1/128,000-1/14,000). Residual risk estimates varied according to the country. This is
potentially due to a lower incidence of HIV infection in the general population or to a more efficient selection
of blood donors in the countries with the lowest risk. The estimates of the transfusion risk of HIV infection in
each country are important, both to assess the impact of current preventative strategies and to contribute
data to policy decisions to reinforce transfusion safety.
Editors’ note: This is this first published study estimating the residual risk of transfusion-related HIV
transmission after standard blood screening using HIV incidence among repeat donors in five sub-Saharan
African countries. The result – 1 in 29,000 donations in Burkina Faso, Congo, Ivory Coast, Mali, and
Senegal – contrasts markedly with the estimate for South Africa of 1 in 479,000. South Africa uses nucleic
acid testing (NAT), the more expensive but efficacious option employed for blood donation screening in
industrialised countries. NAT identifies donors with HIV infection who are in the pre-seroconversion window
period, after infection and before HIV antibodies appear. WHO estimated in 2005 that up to 5% of HIV
transmissions in sub-Saharan Africa were transfusion-related. NAT would improve transfusion safety
significantly in this highest prevalence region in the world, with a cheaper interim option being some form of
combination antigen/antibody testing. Regardless, it is important to strengthen donor selection by restricting
donation to volunteer, unpaid, regular donors at low risk of blood-borne infections and sexually transmitted
infections. Upstream prevention of blood transfusion-related HIV transmission entails avoiding unnecessary
transfusions, along with prevention and timely management of anaemia caused by obstetrical haemorrhage,
nutritional deficiencies, and malaria and other infections.
4. Food insecurity
"All I eat is ARVs": the paradox of AIDS treatment interventions in central Mozambique
Kalofonos IA. Med Anthropol Q. 2010 Sep;24(3):363-80
The number of people on antiretroviral treatment in Mozambique has increased by over 1,500 percent since
it first became free and publicly available in 2004. The rising count of "lives saved" seems to portray a
success story of high-tech treatment being provided in one of the poorest contexts in the world, as people
with HIV-related disease experience dramatic recoveries and live longer. The "scale-up" has had significant
social effects, however, as it unfolds in a region with a complicated history and persistent problems related
to poverty. Hunger is the principal complaint of people on antiretroviral treatment. The inability of
current interventions to adequately address this issue leads to intense competition among people living
with HIV/AIDS for the scarce resources available, undermining social solidarity and the potential for
further community action around HIV issues. Discourses of hunger serve as a critique of these
shortcomings, and of the wider political economy underlying the HIV epidemic.
Editors’ note: This ethnographic study took place in central Mozambique during 6 weeks in 2003 before
public-sector antiretroviral therapy was available, 8 weeks in 2004 when it was first offered, and 12 months
in 2005-2006. It describes the early days of attempts to address food insecurity in the context of scale-up of
antiretroviral therapy through food aid provided by the World Food Programme and distributed through
associations of people living with HIV. This period pre-dates the skills building and agricultural input models
described in earlier issues of HIV This Week. There is no doubt that nutritional supplementation improves
4
treatment adherence and health outcomes. However, when it is provided as food aid against a context of
population-wide chronic malnutrition (46% of the general population in 2006 according to the Mozambique
Technical Secretariat on Food Security and Malnutrition), it can undermine social support for people living
with HIV and create competition and mistrust among them. Food insufficiency and HIV was the theme of a
day-long thematic session of the UNAIDS Programme Coordinating Board meeting held December 6-8,
2010. For an update on current progress and ongoing challenges go to www.unaids.org.
Food insecurity is associated with attitudes towards exclusive breastfeeding among women in
urban Kenya
Webb-Girard A, Cherobon A, Mbugua S, Kamau-Mbuthia E, Amin A, Sellen DW. Matern Child Nutr. 2010 Sep
28. doi: 10.1111/j.1740-8709.2010.00272.x. [Epub ahead of print]
This study aimed to document whether food insecurity was associated with beliefs and attitudes towards
exclusive breastfeeding among urban Kenyan women. Webb-Girard and colleagues conducted structured
interviews with 75 HIV-affected and 75 HIV-status unknown, low-income women who were either
pregnant or with a child ≤ 24 months and residing in Nakuru, Kenya to generate categorical and open-
ended responses on knowledge, attitudes and beliefs towards exclusive breastfeeding and food insecurity.
The authors facilitated six focus group discussions with HIV-affected and HIV-status unknown mothers (n
= 50 women) to assess barriers and facilitators to exclusive breastfeeding. Of 148 women with complete
interview data, 77% were moderately or severely food insecure. Women in households affected by food
insecurity had significantly greater odds of believing that breast milk would be insufficient for 6 months [odds
ratio (OR), 2.6; 95% confidence interval (95% CI), 1.0, 6.8], that women who exclusive breastfed for 6
months would experience health or social problems (OR, 2.7; 95% CI, 1.0, 7.3), that women need adequate
food to support exclusive breastfeeding for 6months (OR, 2.6; 95% CI, 1.0, 6.7) and that they themselves
would be unable to follow a counsellor's advice to exclusive breastfeed for 6 months (OR, 3.2; 95% CI, 1.3,
8.3). Qualitative analysis of interview and focus group discussion transcripts indicated that the maternal
experience of hunger contributes to perceived milk insufficiency, anxiety about infant hunger and a
perception that access to adequate food is necessary for successful breastfeeding. The lived
experience of food insecurity among a sample of low-income, commonly food insecure, urban Kenyan
women reduces their capacity to implement at least one key recommended infant feeding practices, that of
exclusive breastfeeding for 6 months.
Editors’ note: To reduce the risk of mother-to-child transmission of HIV, WHO recommends exclusive
breastfeeding for the first 6 months if exclusive replacement feeding is not affordable, feasible, acceptable,
safe, and sustainable. The gap between recommendations for exclusive breastfeeding and actual practice in
real life is often framed as cultural in nature, including, for example, potential problems with family and
neighbours if the mother does not mix feed her infant. This framework tends to ignore the underlying
material and political economic basis of mixed feeding. This study in Kenya where exclusive breastfeeding
rates are low (13% at 6 months) used quantitative and qualitative methods to better understand the
relationship between food insecurity and hunger, on the one hand, and negative attitudes and beliefs
towards exclusive breastfeeding, on the other. Its cross-sectional nature precludes drawing conclusions
about causality but the findings fit with the general literature on breastfeeding. Breastfeeding self-efficacy,
i.e. your confidence in your ability to breastfeed successfully, is influenced by factors such as psychological
depression and distress, employment outside the home, and belief that you will not produce enough breast
milk. Women who lived in moderately to severely food insecure households, regardless of HIV status,
understandably doubted that they would have enough milk for 6 months of breast-feeding. Alleviating food
insecurity is clearly an essential part of breastfeeding behaviour change.
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5. Civil Society
From spectators to implementers: civil society organizations involved in AIDS programmes in China
Li H, Kuo NT, Liu H, Korhonen C, Pond E, Guo H, Smith L, Xue H, Sun J. Intl J Epidemiology 2010;39:ii65–ii71
Over the past 20 years, civil society organizations in China have significantly increased their involvement in
the AIDS response. This article aims to review the extent of civil society participation in China AIDS
programmes over the past two decades. A desk review was conducted to collect Chinese government
policies, project documents, and published articles on civil society participation on HIV programmes in China
over the past two decades. Assessment focused on five aspects: (i) the political environment; (ii) access
to financial resources; (iii) the number of civil society organizations working on HIV; (iv) the scope of
work; and (v) the impact of civil society organizations involvement on programmes. The number of civil
society organizations specifically working on HIV increased from 0 before 1988 to over 400 in 2009.
Among a sample of 368 civil society organizations, 135 (36.7%) were registered. Civil society organizations
were primarily supported by international programmes. Government financial support to civil society
organizations has increased from USD 248 000 in 2002 to USD 1.46 million in 2008. Initially, civil society
played a minimal role. It is now widely involved in nearly all aspects of HIV-related prevention,
treatment, and care efforts, and has had a positive impact; for example, increased adherence to
antiretroviral treatment and HIV testing among hard-to-reach groups. The main challenges faced by
civil society organizations include registration, capacity and long-term financial support. Civil society
organizations have significantly increased their participation and contribution to AIDS programmes in China.
Policies for registration and financial support to civil society organizations need to be developed to enable
them to play an even greater role in AIDS programmes.
Editors’ note: This article is chosen from a December 2010 supplement, focused entirely on the response
to AIDS in China, which provides evidence and perspectives on China’s progress towards the Millennium
Development Goals, policy implementation, the scale-up and impact of HIV prevention services, and efforts
to strengthen epidemiological estimates and improve monitoring and evaluation. This one underscores the
increasingly valuable role that civil society organisations (CSOs) are playing in the HIV response and the
barriers to and facilitators of their involvement. Since the 2003 outbreak of severe acute respiratory distress
syndrome (SARS), the political environment for the AIDS response has expanded, with strong public
statements by senior government officials and supportive AIDS-specific polices and regulations. However,
the legal framework is provisional and restrictive for CSOs, with very stringent criteria for registration as a
CSO and a limit of only one CSO permitted to work on an issue per administrative level. Groups working on
the same issue in different places are prohibited from forming a regional, provincial, or national organisation.
Further, funds from international sources such as the Global Fund and foundations can only be used for
activities and not for operational costs. To strengthen and sustain its AIDS response for the critical years
ahead, China can foster further the important contributions of its CSOs by creating a supportive legal and
regulatory environment to facilitate their work.
6. Tuberculosis
Comparison of two active case-finding strategies for community-based diagnosis of symptomatic
smear-positive tuberculosis and control of infectious tuberculosis in Harare, Zimbabwe (DETECTB):
a cluster-randomised trial
Corbett EL, Bandason T, Duong T, Dauya E, Makamure B, Churchyard GJ, Williams BG, Munyati SS,
Butterworth AE, Mason PR, Mungofa S, Hayes RJ. Lancet. 2010 Oct 9;376(9748):1244-53.
Control of tuberculosis in settings with high HIV prevalence is a pressing public health priority. Corbett and
colleagues tested two active case-finding strategies to target long periods of infectiousness before
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diagnosis, which is typical of HIV-negative tuberculosis and is a key driver of transmission. Clusters of
neighbourhoods in the high-density residential suburbs of Harare, Zimbabwe, were randomised to receive
six rounds of active case finding at 6-monthly intervals by either mobile van or door-to-door visits.
Randomisation was done by selection of discs of two colours from an opaque bag, with one disc to
represent every cluster, and one colour allocated to each intervention group before selection began. In both
groups, adult (≥ 16 years) residents volunteering chronic cough (≥ 2 weeks) had two sputum
specimens collected for fluorescence microscopy. Community health workers and cluster residents
were not masked to intervention allocation, but investigators and laboratory staff were masked to allocation
until final analysis. The primary outcome was the cumulative yield of smear-positive tuberculosis per
1000 adult residents, compared between intervention groups; analysis was by intention to treat. The
secondary outcome was change in prevalence of culture-positive tuberculosis from before intervention to
before round six of intervention in 12% of randomly selected households from the two intervention groups
combined; analysis was based on participants who provided sputum in the two prevalence surveys. Forty-
six study clusters were identified and randomly allocated equally between intervention groups, with 55 741
adults in the mobile van group and 54,691 in the door-to-door group at baseline. HIV prevalence was
21% (1916/9060) and in the 6 months before intervention the smear-positive case notification rate was
2·8 per 1000 adults per year. The trial was completed as planned with no adverse events. The mobile van
detected 255 smear-positive patients from 5466 participants submitting sputum compared with 137 of 4711
participants identified through door-to-door visits (adjusted risk ratio 1·48, 95% CI 1·11-1·96, p=0·0087). The
overall prevalence of culture-positive tuberculosis declined from 6·5 per 1000 adults (95% CI 5·1-8·3)
to 3·7 per 1000 adults (2·6-5·0; adjusted risk ratio 0·59, 95% CI 0·40-0·89, p=0·0112). Wide implementation
of active case finding, particularly with a mobile van approach, could have rapid effects on tuberculosis
transmission and disease.
Editors’ note: People living with HIV are more susceptible to tuberculosis and the time period from infection
to diagnosis or death is shorter than in HIV-negative people, whose tuberculosis is often not diagnosed for a
year or more during which time they are infectious to others. In high HIV prevalence areas, early
identification of people with active tuberculosis through active case finding can benefit those with and
without HIV infection and provoke drops in community incidence. Recently transmitted tuberculosis is the
most common source of infections in endemic areas where the bulk of transmission is from casual rather
from close household contacts. This study compared two strategies for active case finding – a mobile van
that stayed in a study cluster for 5 days announcing free sputum tests for anyone with chronic cough
through a loudspeaker versus door-to-door visits asking for those with chronic cough and providing
specimen containers along with leaflets stressing the benefits of early diagnosis and the important role of
HIV-negative tuberculosis in transmission. Overall, active case finding provided the first investigation for
77% of smear-positive patients despite the fact that they were all symptomatic and lived within 2 km of a
primary clinic. A random sample of 12% of households in all 46 clusters was surveyed before the
intervention and before the 6th six-monthly intervention. This revealed that the mobile van approach
produced more smear-positive tuberculosis cases despite the finding that HIV prevalence was similar (72%
of cases in the mobile van group versus 67% of cases in the door-to-door group). Overall 41% of new TB
cases diagnosed in the study area over the 3-year period were identified through these two active case
finding approaches and infectious TB in the community fell by more than 40%. Active case finding played a
major role in bringing TB under control in industrialised countries so why not now, particularly in high HIV
prevalence countries?
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7. Genetics
Phylogenetic approach reveals that virus genotype largely determines HIV set-point viral load
Alizon S, von Wyl V, Stadler T, Kouyos RD, Yerly S, Hirschel B, Böni J, Shah C, Klimkait T, Furrer H, Rauch A,
Vernazza PL, Bernasconi E, Battegay M, Bürgisser, P, Telenti A, Günthard HF, Bonhoeffer S; Swiss HIV Cohort
Study. PLoS Pathog. 2010 Sep 30;6(9). pii: e1001123.
HIV virulence, i.e. the time of progression to AIDS, varies greatly among patients. As for other rapidly
evolving pathogens of humans, it is difficult to know if this variance is controlled by the genotype of the host
or that of the virus because the transmission chain is usually unknown. Alizon and colleagues apply the
phylogenetic comparative approach to estimate the heritability of a trait from one infection to the
next, which indicates the control of the virus genotype over this trait. The idea is to use viral RNA
sequences obtained from patients infected by HIV-1 subtype B to build a phylogeny, which approximately
reflects the transmission chain. Heritability is measured statistically as the propensity for patients
close in the phylogeny to exhibit similar infection trait values. The approach reveals that up to half of
the variance in set-point viral load, a trait associated with virulence, can be heritable. This estimate is
significant and robust to noise in the phylogeny. The authors also check for the consistency of their
approach by showing that a trait related to drug resistance is almost entirely heritable. Finally, they
show the importance of taking into account the transmission chain when estimating correlations between
infection traits. The fact that HIV virulence is, at least partially, heritable from one infection to the next
has clinical and epidemiological implications. The authors claim that the difference between earlier
studies and theirs comes from the quality of their dataset and from the power of the phylogenetic
comparative approach, which can be applied to large datasets and accounts for within-host evolution.
The phylogenetic comparative approach opens new perspectives for approaches linking clinical data and
evolutionary biology because it can be extended to study other traits or other infectious diseases.
Editors’ note: Why is it that some untreated people with HIV infection survive more than 25 years while
others die within a year of infection? How much of this difference is due to host factors and how much is due
to properties of the infecting virus? A lot of focus has been placed on host factors, including HLA (human
leucocyte antigen) alleles (HLA-B*57, HLA-B*27; HLA-B*51) associated with slower disease progression
and the CCR5delta32 mutation which protects against HIV infection when both gene alleles are affected and
slows progression if one allele is affected. The phylogenetic approach described in this paper focuses on
characteristics of the transmitted virus. It is well known that viral set point, i.e. the level at which viral load
settles during the asymptomatic phase of HIV infection, is associated with the time to AIDS. Previous
studies with small sample sizes have suggested that between 21% and 55% of the variance in viral setpoint
can be explained by virus genotype but the idea that the virus genome can influence virulence remains
controversial. These findings from this study of untreated patients in the large Swiss Cohort suggest that,
within subtype B, HIV virulence as defined by viral setpoint can indeed be inherited from one infection to the
next.
8. Basic science: HIV research

Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression
Hendrickson SL, Lautenberger JA, Chinn LW, Malasky M, Sezgin E, Kingsley LA, Goedert JJ, Kirk GD, Gomperts
ED, Buchbinder SP, Troyer JL, O'Brien SJ. PLoS One. 2010 Sep 21;5(9):e12862.
The human mitochondrial genome includes only 13 coding genes while nuclear-encoded genes
account for 99% of proteins responsible for mitochondrial morphology, redox regulation, and energetics.
Mitochondrial pathogenesis occurs in HIV patients and genetically, mitochondrial DNA haplogroups with
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presumed functional differences have been associated with differential AIDS progression. Here Hendrickson
and colleagues explore whether single nucleotide polymorphisms (SNPs) within 904 of the estimated 1,500
genes that specify nuclear-encoded mitochondrial proteins influence AIDS progression among HIV-1
infected patients. They examined nuclear-encoded mitochondrial proteins for association with the rate of
AIDS progression using genotypes generated by an Affymetrix 6.0 genotyping array of 1,455 European-
American patients from five US AIDS cohorts. Successfully genotyped SNPs gave 50% or better
haplotype coverage for 679 of known nuclear-encoded mitochondrial proteins genes. With a Bonferroni
adjustment for the number of genes and tests examined, multiple SNPs within two nuclear-encoded
mitochondrial protein genes showed significant association with AIDS progression: acyl-CoA
synthetase medium-chain family member 4 (ACSM4) on chromosome 12 and peroxisomal D3,D2-enoyl-
CoA isomerase (PECI) on chromosome 6. The authors’ previous studies on mitochondrial DNA showed that
European haplogroups with presumed functional differences were associated with AIDS progression and
antiretroviral therapy mediated adverse events. The modest influences of nuclear-encoded mitochondrial
genes found in the current study add support to the idea that mitochondrial function plays a role in AIDS
pathogenesis.
Editors’ note: Mitochondria perform several tasks that are crucial to cell functioning including producing
energy, regulating cell death, producing essential products such as cholesterol and hormones. HIV disrupts
a number of mitochondrial pathways and the proteins it encodes. This initially stops cell death causing
proliferation of infected cells and then causes cell death leading to immunodeficiency. It is believed that
mitochondria originally may have been bacteria that we accommodated eons ago because they proved
useful to us. In any case, they have only 13 genes themselves and rely on 1500 genes in the cell nucleus to
support the remaining protein machinery that keeps them functioning. This study attempted to find out
whether any of these nuclear-encoded mitochondrial proteins might be associated with HIV disease
progression because mutations in the mitochondria’s own genes have been reported to affect the rate. Two
of them may be associated with disease progression but validation by other studies is needed before any
conclusions can be drawn. Figuring out how to keep mitochondria ship-shape may eventually inform
strategies to improve symptom-free survival in people living with HIV.
9. Universal access: paediatric formulations

The global pediatric antiretroviral market: analyses of product availability and utilization reveal
challenges for development of pediatric formulations and HIV/AIDS treatment in children
Waning B, Diedrichsen E, Jambert E, Barnighausen T, Li Y, Pouw M, Moon S. BMC Pediatr. 2010 Oct
17;10(1):74. [Epub ahead of print]
Important advances in the development and production of quality-certified paediatric antiretroviral
drug formulations have recently been made despite significant market disincentives for
manufacturers. This progress resulted from lobbying and innovative interventions from HIV activists,
civil society organizations, and international organizations. Research on uptake and dispersion of these
improved products across countries and international organizations has not been conducted but is needed
to inform next steps towards improving child health. Waning and colleagues used information from the
World Health Organization Prequalification Programme and the United States Food and Drug Administration
to describe trends in quality-certification of paediatric formulations and used 7,989 donor-funded,
paediatric antiretroviral drugs purchase transactions from 2002-2009 to measure uptake and dispersion of
new paediatric antiretroviral drug formulations across countries and programs. Prices for new paediatric
antiretroviral drug formulations were compared to alternative dosage forms. Fewer antiretroviral drug
options exist for HIV treatment in children than adults. Before 2005, most paediatric antiretroviral drugs
were produced by innovator companies in single-component solid and liquid forms. Five 2-in-1 and four 3-
in-1 generic paediatric fixed-dose combinations in solid and dispersible forms have been quality-
9
certified since 2005. Most (67%) of these were produced by one quality-certified manufacturer. Uptake of
new paediatric fixed-dose combinations outside of UNITAID is low. UNITAID accounted for 97-100% of
2008-2009 market volume. In total, 33 and 34 countries reported solid or dispersible fixed-dose
combination purchases in 2008 and 2009, respectively, but most purchases were made through UNITAID.
Only three Global Fund country recipients reported purchase of these fixed-dose combinations in 2008.
Prices for paediatric fixed-dose combinations were considerably lower than liquids but higher than
half of an adult fixed-dose combination. Paediatric antiretroviral drug markets are more fragile than adult
markets. Ensuring a long-term supply of quality, well-adapted antiretroviral drugs for children requires
ongoing monitoring and improved understanding of global paediatric markets, including country-
based research to explain low uptake of new, improved formulations outside of UNITAID and what
can be done to accelerate children's access to HIV care. A close dialogue is needed between clinicians
making selection and prescribing decisions, supply chain staff dealing with logistics, donors,
international organizations, and pharmaceutical manufacturers to better match country-based
demand with global supply and donor policies.
Editors’ note: This article is essential reading for everyone committed to Millennium Development Goal 4, a
two-thirds reduction in mortality for children under five by 2015 – that has to be all of us. Clearly
documented here is the history and current status of paediatric antiretroviral therapy – an estimated 38% of
children in need were on antiretroviral therapy in 2008. Roll out started in industrialised countries but new
paediatric infections in these countries have dwindled dramatically with the advent of effective prevention of
mother-to-child transmission and safe supplies of blood and blood products. Many challenges face this field
in low- and middle-income countries where the vast majority of children living with HIV reside – demand,
logistics, funding, attitudes, formulation hurdles – all the factors underpinning low product utilization.
UNITAID; the Global Fund to fight AIDS, Tuberculosis and Malaria; PEPFAR; the WHO pre-qualification
programme; the USA Food and Drug Administration; Médecins sans Frontières; innovator pharmaceutical
companies; generic companies – these are some of key players shaping the global paediatric antiretroviral
market. Price negotiations need to ensure affordability along with sufficient profit to sustain prices and
stabilize the market. Research is urgently needed at country level to understand how to facilitate uptake of
new, improved formulations such as dispersible tablets which dissolve in a small amount of water – they are
lighter to carry than syrups and suspensions, and as heat stable as solid formulations.
10. National responses

AIDS in Asia amid competing priorities: a review of national responses to HIV
Rao PJ, Mboi N, Phoolcharoen W, Sarkar S, Carael M. AIDS. 2010 Sep;24 Suppl 3:S41-8.
The paper reviews progress in addressing the HIV epidemic and questions whether at the midway mark to
the conclusion of the Millennium Development Goal set for 2015, the goal number 6 of halting and reversing
the HIV epidemic will be reached. Fourteen 2008 United Nations General Assembly Special Session on
HIV/AIDS country progress reports and 18 country reports on Universal Access 2009 were analyzed. Data
on national HIV strategic plans were also provided by 18 countries that participated in a regional training on
costed national strategic plans held 15-16 September, in Bangkok in 2008. Four countries with
substantial populations in Asia are on track to achieve Millennium Development Goal 6. Elsewhere,
elements of a potentially effective response are being introduced, but the degree of urgency and scale
needed to curb the epidemics are not yet evident. Most national programmes still lack key planning
components for the operation and financing of the response. Only 13 national strategic plans explicitly
address three key populations at higher risk for HIV. One third of the countries that have designed plans
for effective interventions have not costed them. Early successes in controlling HIV epidemics in Asia may
not be sustainable in the future. There is an urgent need to make prevention scale-up as robust as
treatment scale-up and to focus programmes on high impact prevention, which directly contributes to
10
reduction of new HIV infection. A necessary objective is to convince policy makers that the emergency
posed by HIV continues.
Editors’ note: This article on national responses to HIV in Asia is one of a series included in an AIDS
supplement on HIV in Asia that covers costing, men who have sex with men, people who inject drugs, and
other topics. The HIV epidemic in this region, home to 60% of the world’s population, is diverse and
responses to it vary markedly. Where political commitment has been evident, great strides have been made.
Although it is difficult to generalise, the authors do point to the need for increased domestic resources for
HIV across the region - the proportion has increased at a far slower rate than in other regions. They single
out China and India as having made progress, now contributing 80% and 65% of total AIDS expenditure in
their countries, respectively. Structural barriers to effective HIV prevention programming include
criminalisation of same sex relations in 15 countries (India has decriminalised such relationships), sex work
being illegal in 18 countries (the Philippines now licenses sex work and has a focused programme), and
poor progress on harm reduction for people who inject drugs (promising in countries such as Malaysia;
Nepal, Bangladesh, and China). If you work in HIV in Asia, this would be a good overview article to orient
you to the challenges of planning, appropriately costing, and efficiently implementing effective HIV
programming across the region before you delve into others in this supplement.
11. Supervised injecting facilities

IDU perspectives on the design and operation of North America's first medically supervised
injection facility
Small W, Ainsworth L, Wood E, Kerr T. Subst Use Misuse. 2010 Sep 27. [Epub ahead of print]
While the public health benefits of supervised injection facilities (SIFs) have been well documented, there is
lack of research examining the views of people who inject drugs regarding the operation of these facilities.
This study used 50 semistructured qualitative interviews to explore the perspectives of people who inject
drugs on the design and operation of a supervised injection facility in Vancouver, Canada. Although the
environment and operation of the supervised injection facility are well accepted, long wait times and limited
operating hours, as well as regulations that prohibit sharing drugs and assisted injections, pose barriers to
using the supervised injection facility. Modifying operating procedures and expanding the capacity of the
current facility could address these barriers.
Editors’ note: The first officially sanctioned supervised injecting facility (SIF) opened in Switzerland in 1986.
Until 2000, only Germany and the Netherlands had joined Switzerland in offering such services in major
cities but, since 2000, SIFs have begun operating in Spain, Australia, Canada, Norway, and Luxembourg.
They vary in hours, staffing, operating models, etc. but all include professional supervision of hygienic
consumption of pre-obtained drugs with the goals of preventing overdose, reducing injecting-related
transmission of HIV and other blood borne viruses, and providing an entry point to psychosocial and medical
services. Unlike a study conducted in Montreal a decade ago to determine whether people who inject drugs
would use a supervised injecting facility if it were to be created (Green et al 13th IHRA conference Slovenia
March 2002), this qualitative study gathered views on current functioning of the well-known Vancouver SIF
‘Insite’. Two major concerns voiced were the prohibition on sharing drugs, a prohibition that holds in most
SIFs as it is deemed to constitute a form of trafficking, and a prohibition on assisted injecting. Individuals
who require assistance to inject are by definition dependent on another person for their safe injection. Some
SIFs acknowledge this vulnerability and are able to accommodate such individuals and their injectors. In
other countries, some modification to the legal framework may be required to allow these individuals to
benefit from this harm reduction service.
11
12. Stigma
Effect of a Community Popular Opinion Leader HIV/STI Intervention on Stigma in Urban, Coastal
Peru
Young SD, Konda K, Caceres C, Galea J, Sung-Jae L, Salazar X, Coates T. AIDS Behav. 2010 Oct 16. [Epub
ahead of print]
Evaluating interventions that reduce HIV stigma may help to craft effective stigma-reduction programs. This
study evaluates the effects of a community popular opinion leader HIV/STI (sexually transmitted
infection) intervention on stigma in urban, coastal Peru. Mixed effects modelling was used to analyze data
on 3,049 participants from the Peru site of the NIHM collaborative trial. Analyses looked at differences
between the comparison and intervention groups on a stigma index from baseline to 12- and 24-month
follow-up. Sub-analyses were conducted on heterosexual-identified men (esquineros), homosexual-
identified men (homosexuales), and socially marginalized women (movidas). Compared to participants
in the comparison group, intervention participants reported lower levels of stigma at 12- and 24-month
follow-up. Similar results were found within esquineros and homosexuales. No significant differences
were found within movidas. Findings suggest that interventions designed to normalize HIV prevention
behaviours and HIV communication can reduce HIV-related stigma and change community norms.
Editors’ note: Community popular opinion leaders are people who live among their peers and are well
respected by others. This large NIMH trial (National Institute of Mental Health Collaborative HIV/STD
Prevention Trial), based on the theory of diffusion of innovation, recruited popular, well-respected individuals
in 3 coastal cities of Peru to talk about HIV prevention during casual conversations with their peers. The
primary outcomes of interest were HIV testing uptake and decreased sexual risk. Interestingly, though the
intervention was designed to normalize HIV prevention behaviours, it had a measurable effects on stigma.
Qualitative studies are underway now to determine how peer-led casual conversations could have had the
effect on stigma that they did for men but not for women. Clearly social norms, perceptions, and stigma are
all interlinked and vary by culture and geography. More research on effective stigma reduction strategies is
needed in different contexts around the world to increase HIV testing uptake, stimulate adoption and
maintenance of safer sex behaviours, and encourage acceptance of people living with HIV and at risk of HIV
acquisition.
13. Care and support

Improving the Health and Mental Health of People Living With HIV/AIDS: 12-Month Assessment of a
Behavioral Intervention in Thailand
Li L, Lee SJ, Jiraphongsa C, Khumtong S, Iamsirithaworn S, Thammawijaya P, Rotheram-Borus MJ. Am J
Public Health. 2010 Oct 21. [Epub ahead of print]
Li and colleagues examined findings from a randomized controlled intervention trial designed to improve the
quality of life of people living with HIV in Thailand. A total of 507 people living with HIV were recruited from 4
district hospitals in northern and northeastern Thailand and were randomized to an intervention group
(n=260) or a standard care group (n=247). Computer-assisted personal interviews were administered
at baseline and at 6 and 12 months. At baseline, the characteristics of participants in the intervention and
standard care conditions were comparable. The mixed-effects models used to assess the impact of the
intervention revealed significant improvements in general health (B=2.51; P=.001) and mental health
(B=1.57; P=.02) among participants in the intervention condition over 12 months and declines among
those in the standard care condition. The authors’ results demonstrate that a behavioural intervention
was successful in improving the quality of life of people living with HIV. Such interventions must be
performed in a systematic, collaborative manner to ensure their cultural relevance, sustainability, and
overall success.
12
Editors’ note: The cognitive-based intervention for this trial was informed by pragmatic aspects of Buddhist
thought that emphasise personal responsibility, personal betterment, and change in life; by the lived
experience of shame and guilt among Thai people living with HIV; and by the family orientation of Thai
society. The four modules delivered over 13 weeks were healthy mind, healthy body, parenting and family
relationships, and social and community integration. The trial found a significant improvement in both
general health and mental health of participants in the intervention arm over a period of 12 months. Those
with improved general health were less likely to be depressed or have internalized shame, and were more
likely to report positively about family functioning. A significant association was found between mental health
and family functioning. The intervention did not have an effect on the physical health of study participants,
all of whom were receiving care in district hospitals throughout the study. Two conclusions are that adapting
initiatives to the sociocultural context is essential to increasing their potential for impact and that integrating
social and psychological components into HIV programmes can improve both individual and family well-
being.
14. Epidemiology
Modelling HIV epidemics in the antiretroviral era: the UNAIDS estimation and projection package
2009
Brown T, Bao L, Raftery AE, Salomon JA, Baggaley RF, Stover J, Gerland P., Sex Transm Infect. 2010 Oct 6.
[Epub ahead of print]
The UNAIDS Estimation and Projection Package (EPP) is a tool for country-level estimation and short-term
projection of HIV epidemics based on fitting observed HIV surveillance data on prevalence. This paper
describes the adaptations made in EPP 2009, the latest version of this tool, as new issues have arisen in
the global response, in particular the global expansion of antiretroviral therapy. Results By December 2008
over 4 million people globally were receiving antiretroviral therapy, substantially improving their survival.
EPP 2009 required modifications to correctly adjust for the effects of antiretroviral therapy on incidence
and the resulting increases in HIV prevalence in populations with high ART coverage. Because
changing incidence is a better indicator of program impact, the 2009 series of UNAIDS tools also
focuses on calculating incidence alongside prevalence. Other changes made in EPP 2009 include: an
improved procedure, incremental mixture importance sampling, for efficiently generating more accurate
uncertainty estimates; provisions to vary the urban/rural population ratios in generalised epidemics over
time; introduction of a modified epidemic model that accommodates behaviour change in low incidence
settings; and improved procedures for calibrating models. This paper describes these changes in detail,
and discusses anticipated future changes in the next version of EPP.
Editors’ notes: Getting ahead of the epidemic means knowing where it is and where it is going. For the
UNAIDS Estimation and Projection Package (EPP) to model national epidemics effectively to inform policy
and programming it must incorporate changes as the epidemic evolves and as our understanding of what
influences its evolution increases. The modifications described here reflect factors such as the increasing
numbers of people on antiretroviral therapy around the world – 5.2 million at last count. On treatment,
people are living longer with HIV and that means that HIV prevalence will tend to increase. But antiretroviral
therapy decreases viral load with the result that the infectiousness of individuals decreases and HIV
incidence will tend to decrease. Among the changes in EPP therefore are not only the numbers of people on
antiretroviral therapy in a country but also how many are on first-line versus second line regimens, the CD4
eligibility criterion that the country has adopted, the HIV progression rate in the absence of treatment (11
year survival versus a fast pattern of 9 years), and the distribution of antiretroviral therapy among defined
13
sub-populations. Further, the 2009 EPP allows for changing urban/rural proportions over time. The shift to a
focus on HIV incidence will be much appreciated by programme managers and policy makers who need to
know the effects of current programming on the trajectory of their epidemic so that they can make timely
changes.
15. Treatment
Profound Depletion of HIV-1 Transcription in Patients Initiating Antiretroviral Therapy during Acute
Infection
Schmid A, Gianella S, von Wyl V, Metzner KJ, Scherrer AU, Niederöst B, Althaus CF, Rieder P, Grube C, Joos B,
Weber R, Fischer M, Günthard HF. PLoS One. 2010 Oct 12;5(10). pii: e13310.
Although combination antiretroviral therapy initiated in the acute phase of HIV-1 infection may prevent
expansion of the latent reservoir, its benefits remain controversial. In the current study, HIV-1 RNA
transcription patterns in peripheral blood mononuclear cells (PBMC) were monitored during acute
antiretroviral therapy to assess the effect of early treatment on cellular viral reservoirs. Acutely HIV-1
infected patients (n = 24) were treated within 3-15 weeks after infection. Patients elected to cease
treatment after ≥1 year of therapy. HIV-1 DNA (vDNA), HIV-1 RNA species expressed both in latently and
productively infected cells, unspliced (UsRNA), multiply spliced (MsRNA-tatrev; MsRNA-nef), and PBMC-
associated extracellular virion RNA (vRex), expressed specifically by productively infected cells, were
quantified in PBMC by patient matched real-time PCR prior, during and post antiretroviral therapy. In a
matched control-group of patients on successful antiretroviral therapy started during chronic
infection (n = 15), UsRNA in PBMC and vDNA were measured cross-sectionally. In contrast to previous
reports, PBMC-associated HIV-1 RNAs declined to predominantly undetectable levels on antiretroviral
therapy. After antiretroviral therapy cessation, UsRNA, vRex, and MsRNA-tatrev rebounded to levels not
significantly different to those at baseline (p>0.1). In contrast, MsRNA-nef remained significantly lower as
compared to pretreatment (p = 0.015). UsRNA expressed at the highest levels of all viral RNAs, was
detectable on antiretroviral therapy in 42% of patients with antiretroviral therapy initiated during acute
infection as opposed to 87% of patients on antiretroviral therapy initiated during chronic infection (Fisher's
exact test; p = 0.008). Accordingly, UsRNA levels were 105-fold lower in the acute as compared to
the chronic group. Early intervention resulted in profound depletion of PBMC expressing HIV-1 RNA. This
is contrary to chronically infected patients who predominantly showed continuous UsRNA expression on
antiretroviral therapy. Thus, antiretroviral treatment initiated during the acute phase of infection
prevented establishment or expansion of long-lived transcriptionally active viral cellular reservoirs
in peripheral blood.
Editors’ note: This study of antiretroviral treatment in 24 acutely-infected individuals contributes tantalizing
findings to a small but growing body of literature. Antiretroviral treatment does not eradicate HIV from the
body or induce safe treatment-free periods – once you start you are on it for life. This study suggests that it
may be possible to reduce the latent reservoir of HIV during early treatment. Antiretroviral therapy in acute
infection appeared to have led to the clearance of long-lived cells harbouring latent proviruses that can be
transcriptionally active, meaning that they were in waiting for a chance to pounce. Larger studies have
included the QUEST study, the CASCADE study, the SETPOINT trial, and other studies that have
attempted to answer the question of whether starting antiretroviral treatment during acute HIV infection is
worth the drug toxicity, resistance, pill burden, and quality of life. We need proof of concept studies to
determine whether the ‘hit early and hard’ adage of Paul Ehrlich for the treatment of infectious diseases
really would work to limit HIV’s population size, toxicity, and potential to escape immunological and
chemotherapeutic/medical control.
14
16. Financing
Financing of HIV/AIDS programme scale-up in low-income and middle-income countries, 2009-31
Hecht R, Stover J, Bollinger L, Muhib F, Case K, de Ferranti D., Lancet. 2010 Oct 9;376(9748):1254-60.
As the global HIV pandemic nears the end of its third decade, the challenges of efficient mobilisation of
funds and management of resources are increasingly prominent. The aids2031 project modelled long-term
funding needs for HIV in developing countries with a range of scenarios and substantial variation in
costs: ranging from US$397 to $722 billion globally between 2009 and 2031, depending on policy
choices adopted by governments and donors. Hecht and colleagues examine what these figures mean for
individual developing countries, and estimate the proportion of HIV funding that they and donors will provide.
Scenarios for expanded HIV prevention, treatment, and mitigation were analysed for 15 representative
countries. The authors suggest that countries will move in increasingly divergent directions over the next 20
years; middle-income countries with a low burden of HIV will gradually be able to take on the modest
costs of their AIDS response, whereas low-income countries with a high burden of disease will
remain reliant upon external support for their rapidly expanding costs. A small but important group of
middle-income countries with a high prevalence of HIV (eg, South Africa) form a third category, in which
rapid scale-up in the short term, matched by outside funds, could be phased down within 10 years
assuming strategic investments are made for prevention and efficiency gains are made in treatment.
Editors’ note: This article about key long-term financing issues for low- and middle-income countries and
their external funder partners makes for sobering reading. It challenges us to consider four scenarios from
now to 2031 based on assumptions about political will, available resources, and strategic approaches. They
are ‘current trends’, ‘rapid scale-up’, ‘hard choices’, and ‘structural change’. ‘Rapid scale-up’ would prevent
7 million more deaths and 14 million more infections than ‘current trends’ but would require a ratcheting up
of resources to $35 billion per year in 2031 (compared with $24 billion that year for ‘current trends’). For
comparison, in 2009 $15.9 billion was spent on HIV in low- and middle-income countries. ‘Hard choices’
concentrates on proven cost-effective interventions and prioritises populations at higher risk of HIV
exposure, with the result that resource needs are the lowest ($18.5 billion in 2031) and 6 million deaths are
prevented compared with ‘current trends’. Although ‘hard choices’ achieves the most cost-effective results
for prevention, ‘structural change’ would have the greatest effect for reduction of future spread of HIV and
would cost $3 billion less per year by 2031 than ‘rapid scale-up’. Structural change would invest in strategies
to reduce gender-based violence and stigma and discrimination, modify employment practices to support
family integrity, and address other underlying social determinants of HIV. This article explores policy options
for countries and external development partners, while underscoring that this is no time to neglect
investment in research and development to generate game-changing prevention technologies and a cure.
17. Vaccines
AIDS vaccine for Asia Network (AVAN): expanding the regional role in developing HIV vaccines
Kent SJ, Cooper DA, Chhi Vun M, Shao Y, Zhang L, Ganguly N, Bela B, Tamashiro H, Ditangco R, Rerks-Ngarm
S, Pitisuttithum P, Van Kinh N, Bernstein A, Osmanov S; AIDS Vaccine for Asia Network investigators and
supporters. Collaborators: Chen Z, Esparza J, Excler JL, Flores J, Hankins C, Ibrahim F, Kaufman J, Kochhar S,
Mathieson B, Mehandale S, Nguyen VK, Ruxrungtham K, Sandström E, Truong XL, Yamamoto N, France T,
Teng T, Liang H, Xin X. PLoS Med. 2010 Sep 21;7(9):e1000331.
The HIV pandemic continues to spread and an AIDS vaccine is urgently needed. Regional alliances and
international collaborations can foster the development and evaluation of the next generation of HIV vaccine
candidates. The importance of coordinating and harmonizing efforts across regional alliances has become
abundantly clear. The authors and their collaborators recently formed the AIDS Vaccine for Asia Network
15
(AVAN) to help facilitate the development of a regional AIDS vaccine strategy that accelerates research
and development of an AIDS vaccine through government advocacy, improved coordination, and
harmonization of research; develops clinical trial and manufacturing capacity; supports ethical and
regulatory frameworks; and ensures community participation.
Editors’ note: Asia, home to over 60% of the world’s population, has 5 million people living with HIV and
more than 500 million at risk for HIV exposure in highly variable epidemics across to the region. Region-
specific challenges to creation of an efficacious HIV vaccine include the circulation of multiple HIV subtypes
and circulating recombinant forms (CRFs) occurring when gene swapping occurs in individuals infected with
two subtypes. Whereas India has predominantly subtype C, Thailand has CRF01_AE as does China which
also has CRF_07B´/C and B´. Diverse host genetics and disparate social, cultural, and political contexts are
the backdrop for a shift from blood borne to sexual transmission in many Asian epidemics. A major
challenge for HIV vaccine trials is the need for harmonization of regulatory and ethical frameworks across
the region. WHO, UNAIDS, and the Global HIV Vaccine Enterprise are working closely with AVAN as it
develops its regional HIV vaccine strategy in the run-up to AIDS Vaccine 2011. The annual vaccine
conference will be hosted by Thailand in Bangkok September 12-15, 2011.
18. Comorbidity
Human papillomavirus infection and cytologic abnormalities of the anus and cervix, among HIV-
infected women in the study to understand the natural history of HIV in the era of effective therapy
(the SUN study)
Kojic EM, Cu-Uvin S, Conley L, Bush T, Onyekwuluje J, Swan DC, Unger ER, Henry K, Hammer JH, Overton ET,
Darragh TM, Palefsky JM, Vellozzi C, Patel P, Brooks JT. Sex Transm Dis. 2010 Oct 14. [Epub ahead of print]
Human papillomavirus (HPV) infection of the cervix and related abnormal cervical cytology in HIV-infected
women has been well described. Little is known about anal HPV infection in HIV-infected women. The SUN
Study is a prospective cohort study of 700 HIV-infected patients including 167 women. At baseline,
patients completed a behavioural questionnaire and provided, among other samples, cervical and anal
swabs for HPV detection and genotyping and for cytologic examination. Here, Kojic and colleagues present
the available baseline data for 120 of the 167 women in the SUN study: median age: 38 years, 57% non-
Hispanic black, median CD4 cell count 444.5 cells/mm, of whom, 77% were taking antiretroviral
therapy. The prevalences in the anus and cervix of any HPV were 90% and 83%, respectively (P =
0.039), and of high-risk (HR) types 85% and 70%, respectively, (P = 0.001). There was no significant
difference in the prevalences of abnormal cytology between the anus and cervix: 38% and 33%,
respectively (P = 0.217). Although the presence of abnormal cervical cytology was associated with the
presence of abnormal anal cytology (relative risk: 1.7, P = 0.024), its sensitivity (52.5%) and positive
predictive value positive (45.6%) for identifying women with abnormal anal cytology were poor. A history of
anal sex was not associated with anal HPV infection or abnormal anal cytology. In this cohort of HIV-
infected women, anal HPV infection was more prevalent and diverse than cervical HPV infection. Anal
cytologic abnormalities were as prevalent as cervical cytologic abnormalities, and although abnormal
cervical cytology was predictive of abnormal anal cytology, results were not highly concordant. These data
support the need for studies of anal cytologic screening of HIV-infected women.
Editors’ note: Cervical cancer has always been a concern for women living with HIV, whether or not they
are on antiretroviral therapy, but now a watching brief on anal cancer in women is warranted. Although this
is a relatively small study (120 women living with HIV), the findings are striking: a higher likelihood of anal
16
HPV than cervical HPV, with a higher diversity of high- and low-risk types found at the anal site. The
proportion of women with anal HPV is higher than ever reported, possibly due to improvements in PCR
(polymerase chain reaction) methodologies. There was no association of anal HPV with self-reported anal
intercourse. Higher anal HPV prevalence than cervical HPV prevalence may possibly reflect previous
treatment for cervical HPV-related disease. Aside from the clear need for screening for anal dysplasia, there
are two conclusions of interest for prevention of anal cancer in women living with HIV. First, smoking
increased the number of HPV types found at both the anal and cervical sites – this is consistent with a study
of over 10,000 women that found a dose-dependent increased risk of HPV prevalence in smokers. Second,
none of the women had all 4 types targeted by the quadrivalent vaccine (6, 11, 16, and 18) in either cervix
or anus. Advice to women living with HIV: stop smoking or don’t start and get vaccinated for HPV.
19. Sexual transmission and concurrency

Concurrent sexual partnerships and primary HIV infection: a critical interaction
Eaton JW, Hallett TB, Garnett GP. AIDS Behav. 2010 Oct 2. [Epub ahead of print]
The combination of long-term concurrent sexual partnerships and high infectiousness early in HIV infection
has been suggested as a key driver of the extensive spread of HIV in general populations in sub-Saharan
Africa, but this has never been scientifically investigated. Eaton and colleagues use a mathematical model
to simulate HIV spreading on sexual networks with different amounts of concurrency. The models show that
if HIV infectiousness is constant over the duration of infection, the amount of concurrency has much less
influence on HIV spread compared to when infectiousness varies over three stages of infection with high
infectiousness in the first months. The proportion of transmissions during primary infection is sensitive
to the amount of concurrency and, in this model, is estimated to be between 16 and 28% in spreading
epidemics with increasing concurrency. The sensitivity of epidemic spread to the amount of concurrency
is greater than predicted by models that do not include primary HIV infection.
Editors’ note: Concurrent sexual partnerships are those that overlap in time – concurrency increases the
numbers of partners exposed to HIV infection for a given number of lifetime sexual partners. This modelling
exercise examined the influence of 11 different levels of concurrency and varied transmission probabilities
during three stages of HIV: primary infection (2.9 months), asymptomatic infection (8.4 years), and
symptomatic infection/AIDS (9.0 months), assuming that there is no transmission risk during the remaining
10 months before death. The result is that although primary infection amplifies the importance of concurrent
sexual partnerships substantially, this combo does not completely explain diverse epidemics in sub-Saharan
Africa. Small populations of people with a greater number of sexual partners and co-factors that increase
HIV transmission (e.g. herpes simplex infection) also contribute to accelerating HIV spread. Nonetheless,
the model suggests that reducing concurrency could play a crucial role in reducing HIV incidence.
That was HIV this week, signing off.
17
Editors’ notes on journal access
For readers in all countries:
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For employees of UNAIDS or WHO:

If you work for WHO or UNAIDS in Geneva, you can access a number of journals available from the WHO
library by going to the WHO intranet (click here). If you work for UNAIDS outside Geneva you can access the
WHO intranet through the following link: remote. When you have entered your UNAIDS username and
password, click on “intranet” – “WHO”. On the WHO intranet homepage, click on “information resources” -
“WHO library” – “online information resources” – “online journals (GIFT)” - “A to Z list” and you will see the list
of accessible journals.
18

Unaids Csa-Ro Hiv This Week 87 101223

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Unaids Csa-Ro Hiv This Week 87 101223

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HIV This Week: what scientific journals said

1. HIV Prevention 10. National responses

3. Blood transfusion risk

Estimate of the residual risk of transfusion-transmitted human immunodeficiency virus infection in

8. Basic science: HIV research

9. Universal access: paediatric formulations

10. National responses

11. Supervised injecting facilities

13. Care and support

19. Sexual transmission and concurrency

That was HIV this week, signing off.

For residents of low- and middle-income countries:

For employees of UNAIDS or WHO:

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