Kit Fairley (http://sti.bmj.com/content/87/Suppl_2/ii25.full)  in this journal offers an overview of the many ways in which information technology can be used in the area of STIs.  This is most obviously through the role of electronic medical records (EMR); but also through the possibility these offer for clinical decision support systems that can be used to generate prompts and reminders.  Information Technology (IT) has also opened up possibilities such as computer assisted self-interviewing (http://sti.bmj.com/content/86/4/310.abstract?sid=07f1ed96-1c3f-4a99-9da5-58f02157ea9e), provision of wider access to counselling services, facilitation of partner notification.  If Gaydos et al.  are on the right track (http://www.iwantthekit.org), IT may one day “completely change the way services are provided”.  A number of papers published by STIs have focussed on trialling short message system reminders for re-testing/re-screening.  These have been show to have some effectiveness in the area of Chlamydia screening (http://sti.bmj.com/content/89/1/11.abstract?sid=07f1ed96-1c3f-4a99-9da5-58f02157ea9e; http://sti.bmj.com/content/89/1/16.abstract?sid=07f1ed96-1c3f-4a99-9da5-58f02157ea9e; http://sti.bmj.com/content/87/Suppl_1/A258.3.abstract?sid=07f1ed96-1c3f-4a99-9da5-58f02157ea9e) and in the area of MSM HIV retesting achieved a fourfold increase in uptake (http://sti.bmj.com/content/87/3/229.abstract?sid=07f1ed96-1c3f-4a99-9da5-58f02157ea9e).

A recent randomized control (RCT) study from a USAID-funded paediatric referral clinic in Kenya (Were & Vreeman), however, points to one impressively fruitful application of IT to STIs which seems to have failed to attract the attention it deserves (http://pediatrics.aappublications.org/content/131/3/e789.abstract?sid=f4698a8a-9724-4227-8896-3a9f57f92729).  In limited resource settings the complex process of pediatric HIV follow-up seems particularly apt to benefit from EMRs that can generate prompts to clinicians – especially where such staff are less than adequately trained, or are subject to high rates of turn-over, or overwhelmed by patient demand.  The reminders generated through this clinical decision support system (CDSS) include PCR tests, CD4 tests, ARV reminders, as well as baseline chemistry & hematology studies, chest X-rays and malnutrition reminders.  The RCT study claims a nearly fourfold improvement in adherence to protocols overall – admittedly with some procedures (e.g. chest x-rays, laboratory tests other than ELISA) benefiting enormously more than others (e.g. initiation of ART ).  Of course, the effectiveness of such reminders, as the authors emphasize, ultimately depends on the quality of the input data informing the “summaries” from which reminders are generated.

The effectiveness of CDSS in this area seems less remarkable than the apparent absence of studies like that of Were & Vreeman.  The authors cite studies of the use of computer-based alerts and reminders for HIV care in the US, and a comparative study between 2 clinics of a system of computer-generated reminders for CD4 testing of adults.  But, “rigorously controlled trials of CDSS effectiveness in resource-limited settings could not be found”.  The authors conclude that pediatric HIV care in limited resource settings is one area where the application of technology has the potential dramatically to improve compliance with protocols.  Such a claim seems to warrant further investigation.

The World Health Organization (WHO) has issued its first ever guidelines on the prevention and treatment of HIV for populations of men who have sex with men (MSM) and transgender individuals (TG). The guidelines have been in preparation since the September 2008 WHO global consultation in Geneva. Both populations – MSM and TG – are known to suffer particular high incidence of HIV (globally, one in twenty for MSM).

The guidelines (21 in total) are intended specifically for policy-makers, health service providers and community leaders in low- and middle-income nations (who apparently requested them), though the WHO recommends they should also “be available” in high-income countries.

Where possible the approach aims to be “evidence-based”, with discussion of relevant findings and risk ratios given for each recommended intervention – even where (as in the majority of recommendations) the evidence base is small and low quality (often no “biological outcomes”), and the recommendation has to be given on the grounds that benefit will exceed harm. Still the discussion attached to individual recommendations (about 500 words on each) provides a short systematic review of the relevant literature, commenting on the nature of the evidence, the findings, the feasibility and acceptability of the intervention, likely benefits and risks.

What about the content of recommendations themselves? Anything surprising?

Two things in particular.

First, there is a strong insistence on the importance of the development of legal frameworks to protect human rights and protect minorities from stigma (and worse); also on the development of an inclusive approach in the provision of health care (e.g. inclusive of MSM and TG). This is very much in line with UNAIDS frameworks, and understandable where you remember there are 70 countries in which homosexuality is punishable by law (WHO is clearly venturing into a cultural mine-field here).

Second, consistent condom use is recommended over sero-sorting for MSM and TG, and male circumcision is not recommended as a specific intervention for HIV prevention.

Elsewhere, there are few surprises.

Provision of testing and counselling is recommended, as are behavioural interventions on an individual and community basis, including internet-based information, social marketing and sex venue-based outreach – all on the basis of rather low-grade evidence.

There are also recommendations covered by existing WHO guidance respecting: the provision of ART at CD4 count of <350; opioid substitution and the provision of clean needles for intravenous drug users; “catch-up” HBV vaccination. Testing and treatment for STIs is recommended as per existing WHO guidance (management algorithms are given). Recommendations also include periodic syphilis serological testing (moderate quality evidence), and periodic Gonorrhoea and Chlamydia testing with NAAT where available (low-quality evidence). However, periodic culture based testing for Gonorrhoea is not recommended.

A final section addresses developments in PrEP, but without giving any recommendations.  Rendez-vous 2015 for the next planned revision of the guidelines!

World Health Organization Report, Prevention and treatment of HIV and other sexually transmitted infections among men who have sex with men and transgender people: Recommendations for a public health approach, World Health Organization, Geneva 2011

http://whqlibdoc.who.int/publications/2011/9789241501750_eng.pdf

Almost thirty years exactly after the first official AIDS diagnosis on 1st June 1981, and 10 years since the landmark UN General Assembly Special Session on HIV/AIDS, member countries meet once again to review the global response to HIV AIDS at the UN General Assembly High-Level Meeting on HIV/ AIDS from 8–10 June in New York. Before the national representatives will be a declaration, formulated by UNAIDS (the Joint United Nations Programme on HIV/AIDS). Known as the “zero draft” (zero infections, zero discriminations, zero Aids related deaths), the declaration is publicly available (see below) and has already been widely discussed by member countries. The scale-up of provision envisaged by the declaration has serious cost implications, as well as implications in the realm of intellectual property rights (TRIPS) where these affect pharmaceutical products. Elements of the declaration are known to be strongly resisted by some developed countries. The recently published (2nd June) UNAIDS report AIDS at 30: Nations at the Crossroads (p.105) places a figure on the proposed scale-up of $22-23bn by 2015, as compared with the current $16bn – in other words a global increase of about a third in order to “decisively alter the course of the epidemic in the next decade”. The message coming out of the UNAIDS Report (published a week in advance of the conference) is that the world would be well advised to commit to the financial implications of placing global resourcing on a more rational and sustainable footing. The necessary up-scaling of global and national efforts is a rational investment and will pay off in the middle- to long-term.
Simultaneously with the UNAIDS report there appeared a health policy paper in the Lancet, Towards an improved investment approach for an effective response to HIV/AIDS. The latter is authored by Bernhard Schwartlaender (principal author) of UNAIDS and other researchers from UNAIDS and a wide range of other organizations “on behalf of the Investment Framework Study Group”. Irritatingly for the general medical reader, its natural constituency, the Lancet paper gives no account of the history of this group and fails to make, within the context of the paper itself, any explicit link to UNAIDS or other international organizations. (How, after all, are we to read a “health policy” paper without situating it in the context of contemporary “health policy” developments?) However, the UNAIDS Report (p.105) appears to refer to the framework proposed in the Lancet paper as “a 2011 investment framework proposed by UNAIDS and its partners”.

Towards an improved investment approach for an effective response to HIV/AIDS
The paper points to the shortcomings of the “prevailing commodity approach” which targets discrete interventions rather than overall results. It proposes to replace it with an “investment framework” incorporating a range of social as well as medical interventions synergizing with general development objectives. The first section of the paper describes the investment framework. The second examines the resource implications as these emerge from a modelling exercise based on the investment framework, estimating resource needs and returns on investment for 139 low- and middle-income countries.
The investment framework is characterized by a concern to give due weight to the social and behavioural aspect of programme activities – e.g. behavioural change especially in connection with “key populations” (e.g. men who have sex with men and intravenous drug users) and community approaches in support of HIV testing and ART adherence. In addition, the model factors in complementary strategies (“critical enablers”) – both in the area of wider social policies conducive to “rational HIV/AIDS responses”, such as stigma reduction and human rights advocacy, and in the more health specific area of incentives for programme participation or methods to improve ART adherence. Thirdly, the model factors in synergies with other development goals, such as the potential of HIV funding to act as a catalyst for the promotion of rational investment across various sectors.
Running the model based on this investment framework gives the figure of $22bn at which the authors predict resource needs will peak in 2015. Thereafter, these needs are expected to decline for three reasons: target rates for interventions will have been reached; efficiency gains will be achieved; and new infections will begin to decrease resulting in decreased need for services. The model puts figures on expenditure not only in the area of basic programme activities, but also in the area of critical enablers, and even development synergies. A case is made for the proposed framework in terms of return on the investment: the $46.5bn invested over the period 2011 – 2020 will, according to the authors, be offset by savings incurred from avoidance to treatment costs estimated at a conservative cost of $40bn.

AIDS at 30: Nations at the Crossroads.
Aspects of the proposed up-scaling of the global response, as set out in Chapter 3 of the Report, are in line with the approach already discussed in relation to the investment framework, and build, of course, on existing UNAIDS policies (see below: UNAIDS Strategy:2012-2015:Getting to Zero). In relation to resource implications, the Report actually refers to the investment framework (p.105) and the projections for resource needs given in the Lancet paper. The Report’s articulation of these issues could have been better organized. But the general tenor of what is proposed is captured in the slogan “sustainable outcomes”. The aspect of sustainability reflects the need for an upscale of global funding, and an increased domestic investment on the part of “high-burden” countries, consonant with their ownership of the programmes. (If current domestic investment by countries were in proportion to the disease burden and size of their health budgets, the Report tells us, investment in sub-Saharan Africa would be double what it is). The aspect of outcomes suggests a shift from an “outputs”- dominated mentality. It reflects the aspiration to a more holistic approach and “smarter metrics” which evaluate the true effectiveness of interventions, leading to investment of resources where they will bring most benefit. Ownership of programmes, their integration within the wider context of health and social policy and synergy with related development goals are consistently emphasised.
Chapters 1 and 2 of the Report offer an overview of the past decade. They chart the success of countries in meeting those targets, recording the gains in treatment access, and the reduction of vertical transmission, as well as difficulties encountered in such areas as reducing HIV stigmatization, targeting interventions at “key populations”, and communicating the safe-sex message to those at risk. Chapter 1 offers a global survey; chapter 2 provides a break-down by region (Africa; Asia and the Pacific; Eastern Europe and Central Asia; Latin American; the Caribbean; the Middle East and North Africa). Chapter 4 provides “score-cards” for individual countries in regard to: HIV incidence; ARVs to prevent new child infections; ART coverage; HIV progress indicators.

Bernhard Schwartlaeder et al., “Towards an improved investment approach for an effective response to HIV/AIDS”, The Lancet, published online, 3rd June 2011

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60702-2/abstract

AIDS at 30: Nations at the Crossroads, Joint United Nations Programme on HIV/AIDS, June 2011

http://www.unaids.org/en/resources/unaidspublications/2011/

Zero Draft, 28th April 2011

http://www.aidsactioneurope.org/fileadmin/files/5.News/5a.Announcements/hivaidszerodraftpdf.pdf

Complete HLM HIV/AIDS Zero Draft Compilation 19th May 2011 10:00pm

http://donttradeourlivesaway.files.wordpress.com/2011/05/complete-compilation-zero-draft-19th-may-2011-10pm-1.pdf

Getting to Zero: Strategy 2010-2015: Joint United Nations Policy on HIV/AIDS, 2010

http://www.unaids.org/en/media/unaids/contentassets/documents/unaidspublication/2010/JC2034_UNAIDS_Strategy_en.pdf

Immediate initiation of Anti-Retroviral Therapy (ART) on diagnosis with HIV produces a 96% reduction in transmission to a non-infected partner. This is the remarkable finding of a large, multi-national, randomized clinical trial, begun in April 2005 by the HIV Prevention Trials Network (HPTN), and enrolling 1,760 HIV sero-discordant couples at 13 sites across Africa, Asia and the Americas.
As a condition of a couple’s enrolment, the HIV infected partner was in every case required to have a CD4 count of between 350 and 550 cells/mm3. The enrolled couples were randomized to two groups. In the “immediate ART group” the HIV infected partner initiated ART straight away; in the “delayed ART group” the HIV infected partner began ART when their CD4 count fell below 250 cells/mm3, or developed an AIDS-related illness.
The immediate ART group saw only one transmission to partner, as compared with 27 transmissions in the delayed ART group. Thus early ART appears to have reduced sexual transmission of HIV to the uninfected partner. The authors also claim that the benefits of early ART initiation extended to the infected partner, with a statistically significant reduction in the incidence of extra-pulmonary tuberculosis (3 in the immediate ART group as against 17 cases in the delayed ART group).
The clear message is therefore that interventions should link prevention with care efforts, since early initiation of ART has a decisive impact on transmission as well as benefits for the infected individual.
This trial (HPTN 052) is one of a number undertaken by the HIV Prevention Trials Network (HPTN). Largely funded by the US National Institute for Allergy and Infections (NIAID), the network embraces trials that deploy partnerships between researchers and communities across the world. HPTN trials investigate various aspects of HIV transmission. HPTN 043 demonstrated the effectiveness of community mobilization in extending the coverage of HIV testing services. HPTN 065, currently underway in the US, is looking at the impact on HIV transmission of increased knowledge of HIV status and linkage to care.

http://www.nbc12.com/story/14633253/initiation-of-antiretroviral-treatment-protects-uninfected-sexual-partners-from-hiv-infection-hptn-study-052

http://www.hptn.org/index.htm

A recent study published in the Lancet seeks to give a statistical picture of HAART coverage in China and its impact on mortality from 2002 to 2009. It is based on a correlation of data from the Chinese national epidemiological database, which records positive HIV results, and a “treatment” database.
HIV affects an estimated 740,000 people living in China. The nature of the available data means that this study is restricted to the 145,000 individuals who are either “treatment eligible” because their CD4 count falls below a certain level (<350 cells/mm3 as from 2008; <200 prior to 2008), or reported as having AIDS or WHO stage 3 or 4 HIV/AIDS. Coverage here refers to coverage of this treatment eligible group.
Correlation of mortality with a range of risk factors reveals late diagnosis (as indicated by low CD4 count on diagnosis) and no HAART as by far the most significant predictors of mortality (adjusted hazard ratio of 7.92 for CD4 <50, 3.54 for CD4 50-199, 4.35 for no HAART). The study focuses on the correlation of mortality with HAART coverage, defined as proportion of person-years from treatment eligible date spent on HAART. The overall figures show a sharp increase in coverage (as defined above) between 2002 and 2009 from near 0% to 61.7%, and of a concomitant decline in mortality from 39.3 deaths per 100 person-years to 14.2 deaths.
Particularly interesting, however, is the picture which emerges from the stratification of the results by infection route (categorised as: blood/plasma transfusion; sexually infected; injecting drug user) – especially when these figures are set in the context of what this study tells us about central government interventions. A coverage of 80.2% in the blood/plasma transfusion group (as of 2009), concomitant with a mortality of 6.7 per 100 person-years, indicates the relative success of a raft of national government interventions directed at this population, including: wide-scale HIV screening in areas with large populations of former plasma donors; free antiretroviral treatment to patients with AIDS living in rural areas and to those in urban areas without insurance; free drugs to HIV-infected pregnant women; HIV testing of newborn babies. Coverage of 42.7% in injecting drug users and 61.7% in the sexually infected group (as of 2009), with concomitant mortality of 15.9 and 17.5 deaths per 100 person-years, evidently reflects the lower penetration of interventions into these groups.
The study provides statistical corroboration of the effectiveness of interventions in the blood/plasma donation group, and suggests the potential of HAART to improve outcomes among injecting drug users and those sexually infected, especially when offered before patients become severely immuno-suppressed.

Fujie Zhang et al., “Effect of earlier initiation of antiretroviral treatment and increased treatment coverage on HIV-related mortality in China: a national observational cohort study”, The Lancet, published online 19th May 2011

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(11)70097-4/fulltext

Far more needs to be done to diagnose incident Hepatitis C (HCV) in HIV-infected men in the era highly active anti-retroviral therapy (HAART).  This is the message coming out of a recent US long-term study (http://cid.oxfordjournals.org/content/early/2011/01/29/cid.ciq201.full).

Current US Public Health Service HIV guidelines endorse HCV testing only at initial HIV diagnosis – maybe because of low rates of HCV transmission in heterosexual couples.  But, according to the authors of this study, this does not respond to the importance of male to male transmission, and strong possibility, indicated by this study and others, that intravenous drug use is not the dominant means of transmission.  HCV in HIV-infected people is a serious cause of morbidity and mortality, but clinically silent until an advanced stage.  In order to be able to intervene at the acute stage where the disease is responsive to treatment, and to contain epidemiological spread, it is imperative, the authors argue, to develop new approaches to diagnosis and treatment.

Of the 1830 men engaged in the study (94% in HAART) 36 sero-converted, amounting to an incidence of .51 cases in 100 person years.  Sero-conversion was also associated with IDU history (25%) and poor HIV suppression.  This suggests nonparenteral transmission, and possibly a tendency to poor adherence to HAART, suggestive of risk-taking behaviour.

What would be the optimal interval of routine HCV anti-body surveillance for at risk HIV infected persons?  This remains to be determined – but our authors cite the recommendation of the New York State Department of Health AIDS Department, which is for annual serological testing.

Lynn E. Taylor, “Incident Hepatatis C Virus Infection among US HIV Infected men enrolled in Clinical Trials”, Clinical Infectious Diseases, March 2011

http://cid.oxfordjournals.org/content/early/2011/01/29/cid.ciq201.full