HIV This Week

Kalichman SC, Simbayi LC, Vermaak R, Cain D, Jooste S, Peltzer K, Habilis D. HIV/AIDS risk reduction counseling for alcohol using sexually transmitted infections clinic patients in Cape Town, South Africa. J Acquir Immune Defic Syndr 2007 Feb 22; [Epub ahead of print]

HIV is ravaging southern Africa, and HIV transmission risk behaviours are facilitated by alcohol use in sexual contexts. There are no known interventions that directly target HIV risk behaviour among people who drink and are at risk for HIV in Africa. Kalichman and colleagues test a behavioural risk reduction counselling intervention for use in sexually transmitted infection (STI) clinics in southern Africa. A randomized intervention trial was conducted with 143 STI clinic patients in Cape Town, South Africa. Participants received an experimental 60-minute HIV and alcohol risk reduction behavioural skills intervention or a control 20-minute HIV education condition. Participants were followed for 3 and 6 months after the intervention, with 73% retention. Overall, the experimental intervention demonstrated more than a 25% increase in condom use and a 65% reduction in unprotected intercourse over the 6-month follow-up period, with risk reduction significantly greater for the experimental condition than for the control condition at both follow-ups. Alcohol use in sexual contexts [F(1,94) = 6.2; P < 0.05] and expectancies that alcohol enhances sexual experiences [F(1,94) = 8.3; P < 0.01] were also significantly lower for the experimental condition at the 3-month follow-up. The authors conclude that an HIV prevention counselling intervention reduced HIV transmission risks for up to 6 months in this STI clinic population. Effects may be sustained with structural interventions to reduce alcohol use in sexual contexts and support risk reduction behaviour changes over the long-term.

Editors’ note : Alcohol can have a major mediating effect on sexual behaviour – ‘disinhibition’ is the correct term to use for one of alcohol’s effects. Alcohol may explain some of the discordance observed in alcohol drinking populations between knowledge and behaviour. A combination of risk reduction skills development and structural interventions to address the environmental context holds promise, just as it has done so with making excessive drinking and driving unacceptable.

Repik A, Richards KH, Clapham PR. The promise of CCR5 antagonists as new therapies for HIV. Curr Opin Investig Drugs 2007;8:130-9.

The chemokine receptors CCR5 and CXCR4 were identified as HIV-1 co-receptors in 1996. Since then, a range of agents that bind these receptors and potently block HIV-1 infection have been described, including monoclonal antibodies, peptides and modified chemokines. However, small organic molecules that bind CCR5 are currently the most promising of the co-receptor antagonists for the potential treatment of HIV. These agents are now in advanced stages of clinical development and should soon augment current therapies, as well as being candidates for inclusion in microbicides. Unlike existing drugs that target HIV proteins (e.g., reverse transcriptase and protease), co-receptor antagonists bind receptors encoded by the host. As a consequence, blockade of these receptors may result in immunosuppressive effects or other disorders. Furthermore, co-receptor inhibitors may also be more toxic than currently available HIV therapies, and it is not yet clear whether they will become candidates for first-line therapy. Nonetheless, safer, less toxic versions of such inhibitors may be achievable in the future. The use of CCR5 inhibitors as a second-line treatment increases the possibility that these reagents will select for more pathogenic CXCR4-using variants. The development of effective CXCR4 antagonists for dual treatment would be beneficial; however, whether long-term treatment with antagonists of the widely expressed CXCR4 receptor is feasible without toxicity is unknown. This review discusses the current status of CCR5 antagonists, their modes of action and their development for therapeutic use.

Editors’ note : This review highlights the challenges of finding treatments that will both block HIV’s use of the immune system and allows the immune system to continue functioning. At the conference in February on Retroviruses and Opportunistic Infections in Los Angeles, promising short term (24 weeks) results comparing the addition of a CCR5 inhibitor to a background regimen alone showed more patients achieved undetectable virus and toxicity was not higher. More trials are needed to confirm these findings and assess the durability of both the effects on viral load and low toxicity.

Krakovska O, Wahl LM. Optimal drug treatment regimens for HIV depend on adherence. J Theor Biol 2007 Jan 23; [Epub ahead of print]

 Drug therapies aimed at suppressing the human immunodeficiency virus (HIV) are highly effective, often reducing the viral load to below the limits of detection for years. Adherence to such antiviral regimens, however, is typically far from ideal. Krakovska and Wahl have previously developed a model that predicts optimal treatment regimens by weighing drug toxicity against CD4(+) T-cell counts, including the probability that drug resistance will emerge. The authors use this model to investigate the influence of adherence on therapy benefit. For a drug with a given half-life, the authors compare the effects of varying the dose amount and dose interval for different rates of adherence, and compute the optimal dose regimen for adherence between 65% and 95%. Their results suggest that for optimal treatment benefit, drug regimens should be adjusted for poor adherence, usually by increasing the dose amount and leaving the dose interval fixed. The authors also find that the benefit of therapy can be surprisingly robust to poor adherence, as long as the dose interval and dose amount are chosen accordingly.  

Editors’ note : This is an interesting conclusion from a theoretical modelling study but whether it could have practical application in clinical practice to reduce the risk of viral resistance to antiretroviral drugs and improve treatment responses without increasing toxicity remains to be determined.

Ramchandani SR, Mehta SH, Saple DG, Vaidya SB, Pandey VP, Vadrevu R, Rajasekaran S, Bhatia V, Chowdhary A, Bollinger RC, Gupta A. Knowledge, attitudes, and practices of antiretroviral therapy among HIV-infected adults attending private and public clinics in India. AIDS Patient Care STDS 2007;21:129-42.

India has approximately 5.2 million persons infected with HIV. Although antiretroviral therapy (ART) is being widely introduced in public clinics, many HIV-infected persons still seek care via the private sector. A cross-sectional survey was conducted in 2004 at six public and private sites to characterize the knowledge, attitudes, and practices (KAP) of ART among patients with HIV receiving care in India. Of 1667 persons surveyed, 609 (36%) had heard of ART and 19% of these persons reported that ART could cure HIV. Twenty-four percent reported that they were currently taking ART, with 18% of these patients not actually on ART according to their provider. Major barriers to taking ART were cost (33%), lack of knowledge of ART (41%), and deferral by physician (30%). More than half of all public and private patients had not heard of CD4 (57%) or viral load testing (80%), and even fewer had received these tests (32% and 11%, respectively). Private clinic attendees were almost 4 times more likely to be on ART (35% versus 9%, p < 0.0001), more likely to be male, have a higher education, be partnered, have a higher income, and have had a CD4 or viral load (p < 0.0001). Overall, low levels of ART knowledge and access were observed among HIV infected patients, with access to ART being particularly low among patients attending public clinics. Ramchandani and colleagues conclude that in order to make widespread dissemination of ART effective in India, further educational and programmatic efforts are likely needed to optimize access, treatment awareness, and compliance among patients with HIV.

Editors’ note : Treatment literacy programmes for individuals, families and communities have been shown to be important elsewhere in creating demand and supporting adherence but this study suggests that health care providers need more training in patient education techniques and that financial barriers need to be examined and reduced.

Hillis SD, Rakhmanova A, Vinogradova E, Voronin E, Yakovlev A, Khaldeeva N, Akatova N, Samarskaya M, Volkova G, Kissin D, Jamieson DJ, Glynn MK, Robinson J, Miller WC. Rapid HIV testing, pregnancy, antiretroviral prophylaxis and infant abandonment in St Petersburg. Int J STD AIDS 2007;18:120-2.

In St Petersburg, Russia, a rapid HIV-testing programme was implemented in April 2004 for high-risk women giving birth. Among 670 women without prenatal care who received rapid HIV testing, 6.4% (43) had positive results. Among HIV-positive mothers, receipt of intrapartum antiretroviral prophylaxis increased significantly compared to pre-programme levels (76 versus 41%). Additionally, infant abandonment increased significantly (50% versus 26%), and was 10 times greater in women with unintended versus intended pregnancies (73% versus 7%).

Editors’ note : This study highlights the advantages and disadvantages of rapid HIV testing. Although knowledge of serostatus is required for uptake of antiretroviral prophylaxis to reduce mother-to-child transmission, the HIV testing process may not adequately prepare the pregnant mother to receive her HIV diagnosis and can lead to increased infant abandonment. Supportive counselling and services are critical to helping women understand their HIV diagnosis, the probability of transmission to their infant and future perspectives for themselves and their babies.

Magoni M, Okong P, Bassani L, Kituka Namaganda P, Onyango S, Giuliano M. Implementation of a programme for the prevention of mother-to-child transmission of HIV in a Ugandan hospital over five years: challenges, improvements and lessons learned. Int J STD AIDS 2007;18:109-13.

To identify factors that may limit acceptance of HIV testing and enrolment in the programmes for the prevention of mother-to-child-transmission of HIV, Magoin and colleauges retrospectively assessed the performance of the service at St Francis Hospital, Nsambya in Kampala. Over five years, a total of 26,556 pregnant women were offered voluntary counselling and confidential HIV testing and, if HIV positive, enrolment in the programme. Acceptance of the HIV test increased in the last two years (from 72.7% in 2001-2002 to 79.9% in 2003-2004). Enrolment in the programme increased over time and was greater among older (64% in women older than 30 years and 44.8% in those aged less than 20 years) and highly educated women. HIV prevalence was associated with age and inversely associated with the level of education. The need for specific personnel for counselling, male partners’ involvement and availability of antiretroviral drugs for those who needed treatment were identified as factors possibly affecting implementation.

Editors’ note : This one hospital has implemented and sustained a large prevention of mother-to-child transmission programme which demonstrates increasing acceptance of prenatal HIV testing over time. There is no doubt that the quality of counselling, the extent of male partners’ involvement and availability of treatment are important factors influencing women’s decisions to accept HIV testing during pregnancy.

Brewer DD, Potterat JJ, Roberts JM Jr, Brody S. Male and female circumcision associated with prevalent HIV infection in virgins and adolescents in Kenya, Lesotho, and Tanzania. Ann Epidemiol 2007;17:217-226.

Brewer and colleagues state that a remarkable proportion of self-reported virgins and adolescents in eastern and southern Africa are infected with HIV, yet non-sexual routes of transmission have not been systematically investigated in such persons. Many observers in this region have recognized the potential for HIV transmission through unhygienic circumcision procedures. The authors assessed the relation between male and female circumcision (genital cutting) and prevalent HIV infection in Kenyan, Lesothoan, and Tanzanian virgins and adolescents. They analyzed data from recent cross-sectional national probability sample surveys of adolescents and adults in households, focusing on populations in which circumcision was common and usually occurred in puberty or later. Circumcised male and female virgins were substantially more likely to be HIV infected than uncircumcised virgins (Kenyan females: 3.2% vs. 1.4%, odds ratio [OR] = 2.38; Kenyan males: 1.8% vs. 0%, OR undefined; Lesothoan males: 6.1% vs. 1.9%, OR 3.36; Tanzanian males: 2.9% vs. 1.0%, OR 2.99; weighted mean phi correlation = 0.07, 95% confidence interval, 0.03 to 0.11). Among adolescents, regardless of sexual experience, circumcision was just as strongly associated with prevalent HIV infection. However, uncircumcised adults were more likely to be HIV positive than circumcised adults. Self-reported sexual experience was independently related to HIV infection in adolescent Kenyan females, but was unrelated to HIV infection in adolescent Kenyan, Lesothoan, and Tanzanian males. The authors conclude that HIV transmission may occur through circumcision-related blood exposures in eastern and southern Africa.

Editors’ note : Given that uncircumcised adults were more likely to be HIV positive than circumcised adults, while uncircumcised adolescents were not when compared to their circumcised age equals, contaminated circumcision equipment is clearly the likely explanation. This highlights the continued need for regulation, legislation, supervision and monitoring of traditional and medical circumcision settings.