HIV This Week

Wodak A, McLeod L. The role of harm reduction in controlling HIV among injecting drug users. AIDS. 2008;Suppl 2:S81-92.

Injecting drug users now account for one in 10 new HIV infections world wide. Yet it has been known since the early 1990s that HIV among injecting drug users can be effectively, safely and cost-effectively controlled by the early and vigorous implementation of a comprehensive package of strategies known as 'harm reduction'. This concept means that decreasing drug-related harms is accorded an even higher priority than reduction of drug consumption. Strategies required involve: explicit and peer-based education about the risk of HIV from sharing injecting equipment; needle syringe programmes; drug treatment (including especially opiate substitution treatment), and community development. Many countries experiencing or threatened by an HIV epidemic among injecting drug users have now adopted harm reduction but often implementation has been too little and too late. Although coverage is slowly improving in many countries, HIV is still spreading faster among injecting drug users than harm reduction programmes while coverage in correctional centres lags far behind community settings. The scientific debate about harm reduction is now over. National and international support for harm reduction is growing while almost all the major UN organizations responsible for drug policy now support harm reduction. Only a small number of countries, led by the USA, are still vehemently opposed to harm reduction. Excessive reliance on drug law enforcement remains the major barrier to increased adoption of harm reduction. Sometimes zealous drug law enforcement undermines harm reduction. A more balanced approach to drug law enforcement is required with illicit drug use recognized primarily as a health and social problem.

Editor’s Note: With injecting drug use reported from 144 countries, of which 128 have detected HIV among injecting drug users, the pragmatic approach of harm reduction must be scalled-up deliberately and rapidly around the world. It is no longer conscionable to deny access to sterile needles and syringes and to substitution treatment for injecting drug uses in the face of the evidence of their effectiveness in reducing HIV infection. Promotion and protecting the human rights of injecting drug users underpin effective public health responses to stem the HIV epidemic among them. There is no time to lose.

Gowing L, Farrell M, Bornemann R, Sullivan L, Ali R. Substitution treatment of injecting opioid users for prevention of HIV infection. Cochrane Database Syst Rev. 2008;(2):CD004145.

Injecting drug users are vulnerable to infection with HIV and other blood borne viruses as a result of collective use of injecting equipment as well as sexual behaviour. Gowing and co-authors aimed to assess the effect of oral substitution treatment for opioid-dependent injecting drug users on rates of HIV infections,and high risk behaviours. They searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and PsycINFO to March 2007. They also searched reference lists of articles, reviews, and conference abstracts. Studies were required to consider the incidence of risk behaviours, or the incidence of HIV infection related to substitution treatment of opioid dependence. All types of original studies were considered. Two reviewers independently assessed studies for inclusion. One reviewer extracted data from included studies, assessed quality, and confirmed decisions by consulting with all other reviewers. The authors included thirty-three studies, involving 10,400 participants. The majority were not randomised controlled studies and there were problems of confounding and bias. The studies varied in several aspects limiting the extent of quantitative analysis. Studies consistently showed that oral substitution treatment for opioid-dependent injecting drug users was associated with statistically significant reductions in illicit opioid use, injecting use, and sharing of injecting equipment. It was also associated with reductions in the proportion of injecting drug users reporting multiple sex partners or exchanges of sex for drugs or money, but had little effect on condom use. It appears that the reductions in risk behaviours related to drug use do translate into reductions in cases of HIV infection. The authors conclude that oral substitution treatment for injecting opioid users reduces drug-related behaviours with a high risk of HIV transmission, but has less effect on sex-related risk behaviours. The lack of data from randomised controlled studies limits the strength of the evidence presented in this review.

Editor’s Note: This review assessing the effectiveness of oral substitution treatment in reducing injecting and sexual risk behaviours included studies of methadone, buprenorphine, LAAM (levo alpha acetyl methadol), codeine, and slow release morphine but not of the injectable preparations used in Switzerland, the Netherlands, the United Kingdom and Germany. Substitution treatment, a key pillar of harm reduction, reduces risk behaviours and HIV acquisition. It is high time to remove legal, policy, and other barriers to offering it to opioid dependent injecting drug users around the world.

Chenine A-L, Shai-Kobiler E, Steele LN, Ong H, Augostini P, et al. Acute Schistosoma mansoni Infection Increases Susceptibility to Systemic SHIV Clade C Infection in Rhesus Macaques after Mucosal Virus Exposure. PLoS Negl Trop Dis. 2008;2(7):e265

Individuals living in sub-Saharan Africa represent 10% of the world’s population but almost 2/3 of all people living with HIV. The disproportionate HIV-1 infection rates in this region may be linked to helminthic parasite infections that affect many individuals in the developing world. However, the hypothesis that parasite infection increases an individual’s susceptibility to HIV-1 has never been prospectively tested in a relevant in vivo model. Chenine and colleagues measured whether pre-existing infection of rhesus monkeys with a parasitic worm would facilitate systemic infection after mucosal AIDS virus exposure. Two groups of animals, one consisting of normal monkeys and the other harbouring Schistosoma mansoni, were challenged intra-rectally with decreasing doses of R5-tropic clade C simian-human immunodeficiency virus (SHIV-C). Systemic infection occurred in parasitized monkeys at viral doses that remained sub-infectious in normal hosts. In fact, the 50% animal infectious (AID50) SHIV-C dose was 17-fold lower in parasitized animals compared to controls (P = 0.001). Coinfected animals also had significantly higher peak viral RNA loads than controls (P = 0.001), as well as increased viral replication in CD4+ central memory cells (P = 0.03). These data provide the first direct evidence that acute schistosomiasis significantly increases the risk of de novo HIV acquisition, and the magnitude of the effect suggests that control of helminth infections may be a useful public health intervention to help decrease the spread of HIV-1.

Editors’ note: The possibility that helminth infections could be a risk factor for increased susceptibility to HIV infection among people living in areas endemic for these parasites has been raised for years. Macaques self cure their schistosomiasis 20 to 25 weeks after exposure to cercariae which limits the application of these findings to the acute phase of schistosomiasis. However, treatment of helminth infections is inexpensive, safe, and easily administered to communities. Important in its own sake, treatment of helminth infections in endemic areas should be further studied for its possible role in HIV prevention.

Mantell JE, Stein ZA, Susser I. Women in the Time of AIDS: Barriers, Bargains, and Benefits. AIDS Educ Prev. 2008;(2):91-106.

Mantell and colleagues comment here on the implications of new HIV prevention technologies (physical and chemical barriers) for women’s health and women’s rights. Four relevant themes are selected that have emerged in the social and behavioural science literature: structural factors (global and national) limiting the availability of female condoms, control and empowerment with female-initiated HIV prevention technologies, covert use of female-initiated HIV prevention technologies, and male partners as part of the bargain for barriers. There is now a rich and diverse literature on all of these issues, relevant and informative, which the authors draw together in this commentary. Discussion of these themes suggests guidelines for policy, research, and action. First, the misconceptions, biases, and prejudices of global and national leaders, including donors, necessitate that we persevere in presenting data to them and engaging them in discussion. Second, we need to support women within their local social contexts to negotiate for their rights, balancing pragmatic approaches to their partners in their initiation of protection, and applying according to each situation as appropriate, a continuum from discretion and clandestine use to deception. Third, men have to be brought in as active participants, and their positive and negative experiences and interests inserted into practices and policies.

Editor’s Note: This thoughtful article underscores women’s need for different HIV prevention methods at different life stages and with different partners. Subsidizing and scaling up female condom programming to overcome access and supply constraints and further trials of cervical barrier methods are urgently needed to make an array of female-initiated protection methods to choose from for all women a reality.

Hoffman S, Cooper D, Ramjee G, Higgins JA, Mantell JE. Microbicide acceptability: insights for future directions from providers and policy makers. AIDS Educ Prev . 2008;20(2):188-202 .

To help fill the gap concerning health care providers’ and policy makers’ knowledge of and views concerning microbicides, Hoffman and colleagues compared data from one U.S. study and two South African studies that explored these issues. Frontline providers in South Africa were enthusiastic about any method that would have the potential to slow the HIV epidemic, whereas providers in New York City and policy makers in South Africa balanced their enthusiasm with more concerns. Across all studies, participants wanted timely and accurate scientific information, and they raised issues about safety, « messiness,», and cost. Many had difficulty understanding that promoting a partially effective method can reduce risk if a client uses it more often than a highly effective method. Microbicide advocates need to effectively communicate to providers the evidence-based findings from microbicide trials and find approaches to introduce concepts such as « harm reduction » and « prevention equation » perspectives in client counselling. Developing these approaches will maximize the positive influence that providers can exert on user acceptability of microbicides once they become available.

Editor’s Note: Discussions of partial protection and the prevention equation in relation to microbocides have resonance for other prevention methods, currently available and under investigation. Health care providers skilled in explaining these concepts are key to the adoption of combination prevention for better protection.

Rosen S, Fox MP, Gill CJ. Patient retention in antiretroviral therapy programs in sub-Saharan Africa: a systematic review. PLoS Med. 2007;4(10):e298.

Long-term retention of patients in Africa's rapidly expanding antiretroviral therapy programmes for HIV is essential for these programmes' success but has received relatively little attention. In this paper Rosen and colleagues present a systematic review of patient retention in antiretroviral therapy programmes in sub-Saharan Africa. They searched Medline, other literature databases, conference abstracts, publications archives, and the "grey literature" (project reports available online) between 2000 and 2007 for reports on the proportion of adult patients retained (i.e., remaining in care and on antiretroviral therapy) after 6 months or longer in sub-Saharan African, non-research antiretroviral therapy programs, with and without donor support. Estimated retention rates at 6, 12, and 24 months were calculated and plotted for each program. Retention was also estimated using Kaplan-Meier curves. In sensitivity analyses the authors considered best-case, worst-case, and midpoint scenarios for retention at 2 years; the best-case scenario assumed no further attrition beyond that reported, while the worst-case scenario assumed that attrition would continue in a linear fashion. The authors reviewed 32 publications reporting on 33 patient cohorts (74,192 patients, 13 countries). For all studies, the weighted average follow-up period reported was 9.9 months, after which 77.5% of patients were retained. Loss to follow-up and death accounted for 56% and 40% of attrition, respectively. Weighted mean retention rates as reported were 79.1%, 75.0% and 61.6% at 6, 12, and 24 months, respectively. Of those reporting 24 months of follow-up, the best program retained 85% of patients and the worst retained 46%. Attrition was higher in studies with shorter reporting periods, leading to monthly weighted mean attrition rates of 3.3%/month, 1.9%/month, and 1.6%/month for studies reporting to 6, 12, and 24 months, respectively, and suggesting that overall patient retention may be overestimated in the published reports. In sensitivity analyses, estimated retention rates ranged from 24% in the worse case to 77% in the best case at the end of 2 years, with a plausible midpoint scenario of 50%. Since the inception of large-scale antiretroviral therapy access early in this decade, antiretroviral therapy programs in Africa have retained about 60% of their patients at the end of 2 years. Loss to follow-up was the major cause of attrition, followed by death. Better patient tracing procedures, better understanding of loss to follow-up, and earlier initiation of antiretroviral therapy to reduce mortality are needed if retention is to be improved. Retention varies widely across programmes, and programmes that have achieved higher retention rates can serve as models for future improvements.

Editors’ note: An estimated half of people starting antiretroviral treatment in Africa in programmes that publish their results are no longer receiving treatment after two years. Starting treatment earlier to prevent mortality and concerted efforts to discover and remedy the conditions that lead people to drop out of programmes are obvious first steps. Sharing what works in patient monitoring and tracing, as well as in overcoming transport, nutritional, financial, and other barriers, is urgently needed.

Toure S, Kouadio B, Seyler C, Traore M, Dakoury-Dogbo N, Duvignac J, Diakite N, Karcher S, Grundmann C, Marlink R, Dabis F, Anglaret X; Aconda Study Group. Rapid scaling-up of antiretroviral therapy in 10,000 adults in Côte d’Ivoire: 2-year outcomes and determinants. AIDS. 2008;22(7):873-82.

Toure and colleagues aimed to assess the rates and determinants of mortality, loss to follow-up, and immunological failure in a nongovernmental organization-implemented program of access to antiretroviral treatment in Côte d’Ivoire. In each new treatment center, professionals were trained in HIV care, and a computerized data system was implemented. Individual patient and programme level determinants of survival, loss to follow-u,p and immunological failure were assessed by multivariate analysis. Between May 2004 and February 2007, 10,211 patients started antiretroviral treatment in 19 clinics (median pre-antiretroviral treatment CD4 cell count, 123 cells/microl; initial regimen zidovudine-lamivudine-efavirenz, 20%; stavudine-lamivudine-efavirenz, 22%; stavudine-lamivudine-nevirapine, 52%). At 18 months on antiretroviral treatment, the median gain in CD4 cell count was +202 cells/microlitre, the probability of death was 0.15, and the probability of being loss to follow-up was 0.21. In addition to the commonly reported determinants of impaired outcomes (low CD4 cell count, low BMI, low haemoglobin, advanced clinical stage, old age and poor adherence), two factors were also shown to independently jeopardize prognosis: male sex (men vs. women: hazard ratio = 1.52 for death, 1.27 for loss to follow-up, 1.31 for immunological failure); and attending a recently opened clinic (inexperienced vs. experienced centers: hazard ratio = 1.40 for death, 1.58 for loss to follow-up). None of the three outcomes was associated with the drug regimen. In this rapidly scaling-up program, survival and immune reconstitution were good; women and patients followed up in centers with longer experience had better outcomes; and outcomes were similar in zidovudine/stavudine-based regimens and in efavirenz/nevirapine-based regimens. Decreasing the rate of loss to follow-up should now be the top priority in antiretroviral treatment rollout.

Editors’ note: An easy-to-manage computerized data monitoring system in 10 mostly primary health care units provided real-time indicators of numbers of patients in care and their treatment progress. Male sex was associated with immunological failure, mortality, and higher rates of programme withdrawal, suggesting that these are interlinked. Experienced centres should be twinned with new treatment centres for assistance in monitoring and improving the economical, managerial, logistical, and organizational characteristics that influence patient outcomes.