Articles tagged as "Issue #38 - October 14, 2007"

HIV This Week issue #38

Welcome to the thirty-eighth issue of HIV This Week!  In this issue, we cover research ethics (can and should adolescents in South Africa be the subjects of HIV vaccine trials and what would it take?; ever heard of the CIOMS Guidelines on Ethics of Clinical Trials – now you have!), stigmatisation (perceived stigma from health care providers turns people away from care in Los Angeles County), basic science (chemokine receptor genetic polymorphisms may be important for disease progression and not just for susceptibility to HIV in the first place), injecting drug use (public injecting in Vancouver – schedules at the supervised injection facility may be a contributing factor), HIV testing (rural community-based VCT in Chiang Mai Province, northern Thailand; increased sexual risk after a negative HIV result in Manicaland, Zimbabwe), sexual transmission and behaviour (HIV risk and protective factors in uncircumcised young men in Kisumu, Kenya; modelling shows not only that serosorting may not protect, it can potentially increase HIV transmission), pre-exposure prophylaxis (modelling the impact before any trial results – an interesting exercise), treatment (genotypic drug resistance mutations in Ivory Coast – time to think second line drug prices; quality of life among rural Ugandans on antiretroviral therapy; CD4 cell count testing and improved prognosis in asymptomatic HIV patients in rural Rakai district, Uganda; treatment interruptions and other causes of disease progression among injecting drug users on antiretroviral treatment in Baltimore; survival benefit after changes in the AIDS case definition to CD4 count below 350 cells/mm in Sao Paulo State, Brasil), microbicides (an overview of the past, present and future of the search for an effective anti-HIV microbicide).

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Cate Hankins

Tania Lemay

Chief Scientific AdviserInterim Research Officer

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Ethics in research

Slack C, Strode A, Fleischer T, Gray G, Ranchod C. Enrolling adolescents in HIV vaccine trials: Reflections on legal complexities from South Africa. BMC Med Ethics 2007;8:5.

Photo credit: UNAIDS/G.PirozziSouth Africa is likely to be the first country in the world to host an adolescent HIV vaccine trial. Adolescents may be enrolled in late 2007. In the development and review of adolescent HIV vaccine trial protocols there are many complexities to consider, and much work to be done if these important trials are to become a reality. This article sets out essential requirements for the lawful conduct of adolescent research in South Africa including compliance with consent requirements, child protection laws, and processes for the ethical and regulatory approval of research.  This article outlines likely complexities for researchers and research ethics committees, including determining that trial interventions meet current risk standards for child research. Explicit recommendations are made for role-players in other jurisdictions who may also be planning such trials. This article concludes with concrete steps for implementing these important trials in South Africa and other jurisdictions, including planning for consent processes; delineating privacy rights; compiling information necessary for ethics committees to assess risks to child participants; training trial site staff to recognize when disclosures trigger a mandatory reporting response; networking among relevant ethics committees; and lobbying the National Regulatory Authority for guidance.

Editors’ note: The reflections in this article have relevance beyond HIV vaccine trials to any trials involving adolescents. They have an evolving capacity to understand and consent to experimental products and interventions. In the case of HIV, enrolling adolescents in trials of novel biomedical HIV prevention products is particularly important in high incidence settings where adolescents are at very high risk of HIV exposure. They would be the primary beneficiaries for any public health programme involving a successful biomedical prevention product.


Macrae DJ. The Council for International Organizations and Medical Sciences (CIOMS) Guidelines on Ethics of Clinical Trials. Proc Am Thorac Soc 2007;4:176-9.

Numerous bodies from many countries, including governments, government regulatory departments, research organizations, medical professional bodies, and health care providers, have issued guidance or legislation on the ethical conduct of clinical trials. It is possible to trace the development of current guidelines back to the post-World War II Nuremburg war crimes trials, more specifically the « Doctors’ Trial. » From that trial emerged the Nuremburg Code, which set out basic principles to be observed when conducting research involving human subjects and which subsequently formed the basis for comprehensive international guidelines on medical research, such as the Declaration of Helsinki. Most recently, the Council for International Organizations and Medical Sciences (CIOMS) produced detailed guidelines (originally published in 1993 and updated in 2002) on the implementation of the principles outlined in the Declaration of Helsinki. The CIOMS guidelines set in an appropriate context the challenges of present-day clinical research, by addressing complex issues including HIV research, availability of study treatments after a study ends, women as research subjects, safeguarding confidentiality, compensation for adverse events, as well guidelines on consent.

Editors’ note: UNAIDS and WHO have just completed updating of the popular 2000 UNAIDS guidance document Ethical considerations in HIV preventive vaccine research with the assistance of an expert panel composed of members from Australia, Brazil, Great Britain, India, Israel, Nigeria, South Africa, Switzerland, Thailand and the USA. Entitled Ethical considerations in biomedical HIV prevention trials: UNAIDS/WHO guidance document, it is consistent with CIOMS and other international research ethics guidelines. Containing 19 guidance points, it will be translated initially into French, Portuguese, Spanish and Russian.

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Stigmatisation

Janni J. Kinsler, Mitchell D. Wong, Jennifer N. Sayles, Cynthia Davis, William E. Cunningham. The Effect of Perceived Stigma from a Health Care Provider on Access to Care Among a Low-Income HIV-Positive Population. AIDS Patient Care and STDs 2007, 21(8): 584-592.

Perceived stigma in clinical settings may discourage HIV-infected individuals from accessing needed health care services. Having good access to care is imperative for maintaining the health, well being, and quality of life of persons living with HIV. The purpose of this prospective study, which took place from January 2004 through June 2006, was to evaluate the relationship between perceived stigma from a health care provider and access to care among 223 low income, HIV-infected individuals in Los Angeles County. Approximately one fourth of the sample reported perceived stigma from a health care provider at baseline, and about one fifth reported provider stigma at follow up. We also found that access to care among this population was low, as more than half of the respondents reported difficulty accessing care at baseline and follow up. Perceived stigma was found to be associated with low access to care both at baseline (odds ratio [OR] = 3.29; 95% confidence interval [CI] = 1.55, 7.01) and 6-month follow up (2.85; 95% CI = 1.06, 7.65), even after controlling for sociodemographic characteristics and most recent CD4 count. These findings are of particular importance because lack of access or delayed access to care may result in clinical presentation at more advanced stages of HIV disease. Interventions are needed to reduce perceived stigma in the health care setting. Educational programs and modelling of nonstigmatizing behaviour can teach health care providers to provide unbiased care.

Editors’ note: Training and continuing education programmes for doctors, nurses, orderlies, assistants and other health care providers should address stigma – exploring provider attitudes and identifying behaviours which can convey stigma inadvertently. Patients themselves may feel vulnerable to disapproval and readily perceive stigma. Health care providers need to learn ways to express acceptance and set patients at ease so that they will freely access services.

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Basic Science

Reiche EM, Bonametti AM, Voltarelli JC, Morimoto HK, Watanabe MA. Genetic polymorphisms in the chemokine and chemokine receptors: impact on clinical course and therapy of the human immunodeficiency virus type 1 infection (HIV-1). Curr Med Chem. 2007;14(12):1325-34.

The natural history and pathogenic processes of infection by the human immunodeficiency virus type 1 (HIV-1) are complex, variable, and dependent upon a multitude of viral and host factors and their interactions. The CCR5-Delta32 allele remains the most important genetic factor known to be associated with host resistance to the HIV-1 infection. However, other mutations in the CCR5, CCR2, CX(3)CR1, CXCL12 (SDF1), and CCL5 (RANTES) genes have been identified and associated with host resistance and/or susceptibility to HIV-1 infection and disease progression. Some studies have also suggested that chemokine receptor gene polymorphisms may affect response to potent antiretroviral therapy. This article reviews the polymorphisms already described in the mutant chemokine receptors or ligands and their impact on the host susceptibility to HIV-1 infection and on the clinical course of the disease, as well as the development of new anti-HIV therapies that takes into account these potential targets in the host. These genetic polymorphisms could be used as genetic markers to detect individuals at higher risk of developing either a faster disease progression or therapeutic failure. Once these individuals are identified, therapeutic strategies based on either different, more aggressive drugs or combinations of drugs can be used, either alone or in combination with shorter intervals for therapeutic monitoring. Pharmaco-genetics is very likely to underlie future therapies for HIV-1 infection, and current patients with multi-resistance to the existing antiretroviral agents could also benefit from this approach. These developments also underscore the importance of continuing the investigation of new therapies targeted to the host in order to inhibit the HIV-1 entry into the host cells.

Editors’ note: Detecting genetic polymorphisms and determining their influence on HIV disease progression place emphasis on host characteristics rather than solely on viral resistance. It could lead eventually to the tailoring of the timing and composition of antiretroviral therapy for individual patients, as well as different monitoring frequencies both before and after antiretroviral initiation based on patient genetic profiles.

Basic science
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Injecting Drug Use

McKnight I, Maas B, Wood E, Tyndall MW, Small W, Lai C, Montaner JS, Kerr T. Factors associated with public injecting among users of Vancouver’s supervised injection facility. Am J Drug Alcohol Abuse 2007;33:319-25.

McKnight and colleagues evaluated factors associated with public drug injection among a cohort of injection drug users (SEOSI Scientific Evaluation of Supervised Injecting cohort study) originally recruited from within Vancouver’s supervised injecting facility. The authors used univariate statistics and logistic regression to examine factors associated with public drug injection among SEOSI participants. Between June 2004 and July 2005, 714 IDU were followed up as part of SEOSI. In multivariate analyses, factors associated with public drug injection included homelessness (adjusted odds ratio (aOR) = 3.10; p < .001), syringe lending (aOR = 5.39; p < .001), requiring help injecting (aOR = 1.60; p = .05), and reporting that wait times affected frequency of supervised injecting facility use (aOR = 3.26; p < .001). Persistent public injection was independently associated with elevated HIV risk behaviours, as well as programmatic factors that limit supervised injecting facility use. Supervised injecting facility programme expansion may further help to reduce persistent risk behaviours and the community concerns related to public injection drug use.

Editors’ note: Public injecting carries a much higher risk of HIV exposure because it is generally furtive, rushed, and undertaken under conditions of poor lighting with whatever equipment is available. As well, discarded injecting equipment may pose risks of accidental needle stick injuries to the community. This study determined several variables independently linked to public injecting, including one that is under the control of programme planners – waiting times at the supervised injecting facility.

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HIV testing

Kawichai S, Celentano DD, Chariyalertsak S, Visrutaratna S, Short O, Ruangyuttikarn C, Chariyalertsak C, Genberg B, Beyrer C. Community-based Voluntary Counseling and Testing Services in Rural Communities of Chiang Mai Province, Northern Thailand. AIDS Behav 2007 Sep;11(5):770-7

Between September, 2002 to May, 2003, Kawichai and colleagues implemented community-based HIV Voluntary Counselling and Testing (VCT) services in four rural areas of Chiang Mai Province. The services included providing AIDS education and free mobile VCT using rapid testing with same day results. Overall, 427 villagers came for VCT (testers) and consented to be interviewed. HIV prevalence among testers was 4.9%, range from 1.1 to 8.4% by area. ‘It is free’ and/or ‘convenient’ were the most frequently cited factors that motivated them to get tested (72%) from our mobile VCT. Rural residents came for VCT when logistical barriers were removed.  HIV prevalence among testers in some areas was high. Without extending HIV prevention efforts to population segments with less access to health care, the HIV problem in Thailand may re-emerge. Convenient and low-cost VCT may prove crucial for containing this HIV epidemic.

Editors’ note: Rural community-based HIV testing and counselling services can have good uptake it they are free, confidential and convenient. It is important to collect, analyse and publish data on the comparative costs of mobile testing services, including the home-based testing being carried out in Uganda and Kenya, to have a better idea of their relative merit.


Sherr L, Lopman B, Kakowa M, Dube S, Chawira G, Nyamukapa C, Oberzaucher N, Cremin I, Gregson S. Voluntary counselling and testing: uptake, impact on sexual behaviour, and HIV incidence in a rural Zimbabwean cohort. AIDS 2007;21:851-60.

The objectives of this study were to examine the determinants of uptake of voluntary counselling and testing (VCT) services, to assess changes in sexual risk behaviour following VCT, and to compare HIV incidence amongst testers and non-testers. This was a prospective population-based cohort study of adult men and women in the Manicaland province of eastern Zimbabwe. Demographic, socioeconomic, sexual behaviour and VCT utilization data were collected at baseline (1998-2000) and follow-up (3 years later). HIV status was determined by HIV-1 antibody detection. In addition to services provided by the government and non-governmental organizations, a mobile VCT clinic was available at study sites. Lifetime uptake of VCT increased from under 6% to 11% at follow-up. Age, increasing education and knowledge of HIV were associated with VCT uptake. Women who took a test were more likely to be HIV positive and to have greater HIV knowledge and fewer total lifetime partners. After controlling for demographic characteristics, sexual behaviour was not independently associated with VCT uptake. Women who tested positive reported increased consistent condom use in their regular partnerships. However, individuals who tested negative were more likely to adopt more risky behaviours in terms of numbers of partnerships in the last month, the last year and in concurrent partnerships. HIV incidence during follow-up did not differ between testers and non-testers. Motivation for VCT uptake was driven by knowledge and education rather than sexual risk. Increased sexual risk following receipt of a negative result may be a serious unintended consequence of VCT. It should be minimized with appropriate pre- and post-test counselling.

Editors’ note: These findings have been the subject of much discussion since they appeared. They suggest that sexual risk is not a strong motivator of decisions to get tested for HIV in this area of Zimbabwe and that there is a tendency to increase the number of sexual partners for those who do decide to get tested and are found negative. This has been seen in other settings in which people appear to interpret an HIV-negative result as evidence of some invulnerability. Community testing literacy programmes to accompany any offer of services are key to changing social norms around sexual behaviour, with access to HIV testing and counselling being the entry point to discussions in communities about the need for change and how to foster it.

HIV testing
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Sexual transmission and behaviour

Mattson CL, Bailey RC, Agot K, Ndinya-Achola JO, Moses S. A nested case-control study of sexual practices and risk factors for prevalent HIV-1 infection among young men in Kisumu, Kenya. Sex Transm Dis 2007 Oct;34(10):731-6.

Mattson and colleagues’ objectives were to investigate sexual practices and risk factors for prevalent HIV infection among young men in Kisumu, Kenya. The goal of this study was to identify behaviours associated with HIV in Kisumu to maximize the effectiveness of future prevention programs. In this study, lifetime sexual histories were collected from a nested sample of 1337 uncircumcised participants within the context of a randomized controlled trial of male circumcision to reduce HIV incidence. The results showed that sixty-five men (5%) tested positive for HIV. Multiple logistic regression revealed the following independent predictors of HIV: older age, less education, being married, being Catholic, >4 lifetime sex partners, prior treatment for an STI, sex during partner’s menstruation, ever practicing bloodletting, and receipt of a medical injection in the last 6 months. Prior HIV testing and post-coital cleansing were protective. In conclusion, this analysis confirms the importance of established risk factors for HIV and identifies practices that warrant further investigation.

Editors’ note: Some things can’t be changed, other things can, and yet other things could. If all uncircumcised men reduced their numbers of sexual partners, avoided sex during menstruation, used condoms correctly and consistently, and had ready access to water and used it after sex (does it help?), HIV transmission from women to men would fall. Adding ‘know your status’ campaigns along with male circumcision in hyperendemic areas would reduce risk for young men even further.


Butler DM, Smith DM. Serosorting can potentially increase HIV transmissions. AIDS 2007;21:1218-20.

The effectiveness of a serosorting strategy for HIV prevention depends on the accuracy of individuals’ serostatus disclosures. Butler and Smith modelled the risks of sexual transmission of HIV under various circumstances differing by the type of disclosures made. Accounting for rates of unrecognized HIV infection, treatment status and differences in infectivity by stage of infection, they found that serosorting can increase the transmission risk for some groups.

Editors’ note: Although serosorting sounds like a common sense HIV prevention strategy, it has not been proven to be effective. Partner turnover and concurrent partnerships increase the risk of undiagnosed primary HIV infection. Better strategies are to avoid penetration, reduce the number of partners and use condoms correctly and consistently each time.

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Pre-exposure prophylaxis

Abbas UL, Anderson RM, Mellors JW. Potential Impact of Antiretroviral Chemoprophylaxis on HIV-1 Transmission in Resource-Limited Settings. PLoS ONE 2007 Sep 19;2(9):e875.

The potential impact of pre-exposure chemoprophylaxis (PrEP) on heterosexual transmission of HIV-1 infection in resource-limited settings is uncertain. A deterministic mathematical model was used to simulate the effects of antiretroviral PrEP on an HIV-1 epidemic in sub-Saharan Africa under different scenarios (optimistic, neutral and pessimistic) both with and without sexual disinhibition (risk compensation). Sensitivity analyses were used to evaluate the effect of uncertainty in input parameters on model output and included calculation of partial rank correlations and standardized rank regressions. In the scenario without sexual disinhibition (risk compensation) after PrEP initiation, key parameters influencing infections prevented were effectiveness of PrEP (partial rank correlation coefficient (PRCC) = 0.94), PrEP discontinuation rate (PRCC = -0.94), level of coverage (PRCC = 0.92), and time to achieve target coverage (PRCC = -0.82). In the scenario with sexual disinhibition (risk compensation), PrEP effectiveness and the extent of sexual disinhibition (risk compensation) had the greatest impact on prevention. An optimistic scenario of PrEP with 90% effectiveness and 75% coverage of the general population predicted a 74% decline in cumulative HIV-1 infections after 10 years, and a 28.8% decline with PrEP targeted to the groups at highest risk of HIV exposure (16% of the population). Even with a 100% increase in at-risk behaviour from sexual disinhibition (risk compensation), a beneficial effect (23.4%-62.7% decrease in infections) was seen with 90% effective PrEP across a broad range of coverage (25%-75%). Similar disinhibition (risk compensation) led to a rise in infections with lower effectiveness of PrEP (</=50%). Mathematical modelling supports the potential public health benefit of PrEP. Approximately 2.7 to 3.2 million new HIV-1 infections could be averted in southern sub-Saharan Africa over 10 years by targeting PrEP (having 90% effectiveness) to those at highest behavioural risk and by preventing sexual disinhibition (risk compensation). This benefit could be lost, however, by sexual disinhibition (risk compensation) and by high PrEP discontinuation, especially with lower PrEP effectiveness (</=50%).

Editors’ note: There are five phase III trials of pre-exposure prophylaxis (PrEP), using tenofovir disoproxil fumarate (TDF) or Tenofovir (TDF)/emtricitabine (FTC) or both, that are either in the field or due to start within the next few months. The study populations include discordant couples, men who have sex with men, women at higher risk of HIV exposure, injecting drug users and young heterosexuals. Attempting to model population level PrEP impact in the absence of trial results is hazardous. A clear message from this exercise however is that risk compensation, where people increase their risk behaviour because they perceive themselves to be less at risk, could counterbalance any benefit – a concern for any new addition to the prevention menu.

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Treatment

Seyler C, Adje-Toure C, Messou E, Dakoury-Dogbo N, Rouet F, Gabillard D, Nolan M, Toure S, Anglaret X. Impact of genotypic drug resistance mutations on clinical and immunological outcomes in HIV-infected adults on HAART in West Africa. AIDS 2007;21:1157-1164.

 

Seyler and colleagues’ objectives were to analyse the association between the presence of resistance mutations and treatment outcomes. The impact of HIV-1 drug resistance mutations in African adults on HAART (highly active antiretroviral treatment) has so far never been reported. In 2004 in Abidjan, Cote d’Ivoire, 106 adults on HAART had plasma viral load measurements. Patients with detectable viral loads had resistance genotypic tests. Patients were followed until 2006. Main outcomes were serious morbidity and immunological failure (CD4 cell count < 200 cells/mul). The results showed that at study entry, the median previous time on HAART was 37 months and the median CD4 cell count was 266 cells/mul; 58% of patients had undetectable viral loads, 20% had detectable viral loads with no major resistance mutations, and 22% had detectable viral loads with one or more major mutations. The median change in CD4 cell count between study entry and study termination was +129 cells/mul in patients with undetectable viral loads, +51 cells/mul in those with detectable viral loads with no mutations and +3 cells/mul in those with detectable viral loads with resistance mutations. Compared with patients with undetectable viral loads, those with detectable viral loads with resistance mutations had adjusted hazard ratios of immunological failure of 4.32 (95%CI 1.38-13.57, P = 0.01). One patient died. The 18-month probability of remaining free of morbidity was 0.79 in patients with undetectable viral loads and 0.69 in those with resistance mutations (P = 0.19). The authors conclude that in this setting with restricted access to second-line HAART, patients with major resistance mutations had higher rates of immunological failure, but most maintained stable CD4 cell counts and stayed alive for at least 20 months.

Editors’ note: Detectable viral loads are more likely in any setting to be associated with an increased likelihood of morbidity and immunological failure over time. This Ivory Coast study of 106 patients who had already been on antiretroviral therapy for a median of 3 years likely had too few subjects and too short a period of follow-up to demonstrate differences in morbidity among those who had detectable viral loads versus those that didn’t, let alone to demonstrate differences by whether they had resistance mutations or not. In any case, drug resistance testing in the absence of second line therapy would put the cart before the horse. Bringing down the cost of second line drugs to make them more accessible is a clear priority.


Stangl AL, Wamai N, Mermin J, Awor AC, Bunnell RE. Trends and predictors of quality of life among HIV-infected adults taking highly active antiretroviral therapy in rural Uganda. AIDS Care 2007;19:626-36.

Stangl and colleagues examined trends and predictors of quality of life (QOL) over 12 months among a prospective cohort of 947 HIV-1-infected adults initiating highly active antiretroviral therapy (HAART) between May 2003 and May 2004 in rural Uganda.  Participants provided clinical, demographic and psychosocial data at baseline and every three months thereafter. Outcome measures included physical and mental health summary scores based on the Medical Outcomes Study-HIV Health Survey (MOS-HIV). Generalised estimating equations were used to assess magnitude of change in summary scores and factors associated with QOL. Of 710 women and 237 men enrolled, the mean age was 38.7 years and mean baseline CD4 cell count was 124.1 cells/microL. At enrolment, physical and mental health summary scores were 39.2 and 40, respectively. By 12 months of HAART, scores increased by 11.2 points (p <0.001) and 7.4 points (p <0.001), respectively. For both scores, most gains were achieved by the third month of therapy. While several clinical, psychosocial and socio-demographic factors predicted quality of life at HAART initiation, financial dependence on others was the only remaining predictor after controlling for time on HAART. Interventions to enhance the economic and employment opportunities of patients taking HAART in rural Africa may help maximise gains in QOL.

Editors’ note: As people’s quality of life improves after initiating antiretroviral treatment, their capacity to return to work and contribute to family and community life increases. Treatment programmes should help patients anticipate this shift and plan for reintegration into productive activities – for their own and the community’s benefit.


Kagaayi J, Makumbi F, Nakigozi G, Wawer MJ, Gray RH, Serwadda D, Reynolds SJ. WHO HIV clinical staging or CD4 cell counts for antiretroviral therapy eligibility assessment? An evaluation in rural Rakai district, Uganda. AIDS 2007;21:1208-1210.

The ability of WHO clinical staging to predict CD4 cell counts of 200 cells/mul or less was evaluated among 1221 patients screened for antiretroviral therapy (ART). Sensitivity was 51% and specificity was 88%. The positive predictive value was 64% and the negative predictive value was 81%. Clinical criteria missed half the patients with CD4 cell counts of 200 cells/mul or less, highlighting the importance of CD4 cell measurements for the scale-up of ART provision in resource-limited settings.

Editors’ note: People with symptoms and signs indicative of HIV disease who test HIV-positive are eligible for antiretroviral treatment in the absence of CD4 count testing. This study highlights the importance of CD4 count testing for those who are asymptomatic and HIV-positive. Waiting for them to develop disease misses an important window of opportunity to improve their long-term survival.


Mehta SH, Lucas G, Astemborski J, Kirk GD, Vlahov D, Galai N. Early immunologic and virologic responses to highly active antiretroviral therapy and subsequent disease progression among HIV-infected injection drug users. AIDS Care 2007;19:637-45.

Mehta and colleagues examined the prevalence and prognostic value of early responses to highly active antiretroviral therapy (HAART) among community-based injection drug users (IDUs) in Baltimore. Virologic (HIV RNA <1000 copies/ml) and immunologic (CD4 >500 cells/ul or increase of 50 cells/ul from the pre-HAART level) responses were examined in the 1st year of HAART initiation. Cox regression was used to examine the effect of early response on progression to new AIDS diagnosis or AIDS-related death. Among 258 HAART initiators, 75(29%) had no response, 53(21%) had a virologic response only, 38(15%) had an immunologic response only and 92(36%) had a combined immunologic and virologic response in the first year of therapy. Poorer responses were observed in those who were older, had been recently incarcerated, reported injecting drugs, had not had a recent outpatient visit and had some treatment interruption within the 1st year of HAART. In multiple Cox regression analysis, the risk of progression was lower in those with combined virologic and immunologic response than in non-responders, (relative hazard [RH], 0.32; 95% confidence interval [CI], 0.17-0.60). Those with discordant responses had reduced risk of progression compared to non-responders but experienced faster progression than those with a combined response, although none of these differences was statistically significant. Early discordant and non response to HAART was common, often occurred in the setting of injection drug use and treatment interruption and was associated with poorer survival. Interventions to reduce treatment interruptions and to provide continuity of HIV care during incarceration among IDUs are needed to improve responses and subsequent survival.

Editors’ note: Transitions between the community and the prison and then between the prison and the community are critical for ensuring that people taking antiretroviral medications who are being incarcerated or who are being released continue to take their medications without interruption. Public health and correctional authorities should examine the circumstances around incarceration and release in order to design interventions aimed at ensuring treatment continuity – for HIV and for other chronic conditions.


Kilsztajn S, Lopes ES, do Carmo MS, Rocha PA. Improvement in Survival Among Symptomatic AIDS Patients by Exposure Category in Sao Paulo. J Acquir Immune Defic Syndr 2007 Jul 1;45(3):342-7.

 

This study assesses AIDS survival time per AIDS-case definition and exposure category in Sao Paulo State, Brazil during the periods 1992 to 1995 and 1998 to 2001. Kilsztajn andd colleagues employed case-fatality rate per AIDS case, Cox proportional hazards analysis, and Kaplan-Meier survival time. Their results showed that the case-fatality rate per AIDS case in 1998 to 2001 was 37.6% for symptomatic (Centers for Disease Control and Prevention/modified and/or Paho/Caracas) and 9.7% for the Brazilian asymptomatic CD4 count <350 cells/mmAIDS-case definitions. Heterosexual/female patients were diagnosed earlier and presented the lowest case-fatality rate, followed by homosexual/male patients, heterosexual/male patients, and injecting drug users. In the multivariate Cox proportional hazards model, the period of diagnosis (hazard ratio = 2.66; 95% confidence interval [CI]: 2.58 to 2.74) and AIDS-case definition (hazard ratio = 4.48; 95% CI: 4.53 to 5.16) were strong predictors of survival. For the total AIDS cases, excluding death definition and undetermined exposure category, the estimated first quarter survival time improved from 4 months in 1992 to 1995 to 50 months in 1998 to 2001. Considering only the symptomatic AIDS-case definition, however, the improvement was from 4 months in the period 1992 to 1995 to 14 months in the period 1998 to 2001. The authors conclude that the survival improvement in Sao Paulo State was attributable to the introduction of anti-retroviral therapy with free universal access in 1996 and to earlier diagnosis associated with the introduction in 1998 of the Brazilian asymptomatic CD4 count <350 cells/mm AIDS-case definition with superior sensitivity compared with the symptomatic AIDS-case definitions.

Editors’ note: This study demonstrates on a population level the striking benefits of early diagnosis among asymptomatic patients and a higher CD4 count threshold at treatment initiation in a universal access programme.

Treatment
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Microbicides

Nuttall J, Romano J, Douville K, Galbreath C, Nel A, Heyward W, Mitchnick M, Walker S, Rosenberg Z. The Future of HIV Prevention: Prospects for an Effective Anti-HIV Microbicide. Infect Dis Clin North Am 2007;21:219-39.

Topical microbicides are self-administered products for prevention of HIV transmission, and they present one of the most promising strategies for combating the HIV epidemic. The development of microbicides is a long and complicated process, with many hurdles that are unique to this class of product, including challenges in product design, in the conduct and design of clinical trials, and in obtaining licensure of a new class of products intended for use almost exclusively in developing countries. Once they have been registered, there are additional challenges to the marketing and distribution of microbicides. An overview of the types of microbicide currently in development, and a summary of the issues and the approaches being taken to address them, are provided.

Editors’ note: This is a good overview article on microbicide development in a publication that includes similar overviews of male circumcision, control of sexually transmitted infections, vaccines and HIV epidemiology.

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