HIV This Week

Lunzen J, Glaunsinger T, Stahmer I, Baehr V, Baum C, Schilz A, Kuehlcke K, Naundorf S, Martinius H, Hermann F, Giroglou T, Newrzela S, Muller I, Brauer F, Brandenburg G, Alexandrov A, von Laer D. Transfer of autologous gene-modified T cells in HIV-infected patients with advanced immunodeficiency and drug-resistant virus. Mol Ther 2007;15:1024-33.

Drug toxicity and viral resistance limit the long-term efficacy of antiviral drug treatment for human immunodeficiency virus (HIV) infection. Thus, alternative therapies need to be explored. Lunzen and colleagues tested the infusion of T lymphocytes transduced with a retroviral vector (M87o) that expresses an HIV entry-inhibitory peptide (maC46). Gene-modified autologous T cells were infused into ten HIV-infected patients with advanced disease and multidrug-resistant virus during antiretroviral combination therapy. T-cell infusions were tolerated well, with no severe side effects. A significant increase of CD4 counts was observed after infusion. At the end of the 1-year follow-up, the CD4 counts of all patients were still around or above baseline. Gene-modified cells could be detected in peripheral blood, lymph nodes, and bone marrow throughout the 1-year follow-up, and marking levels correlated with the cell dose. No significant changes of viral load were observed during the first 4 months. Four of the seven patients who changed their antiviral drug regimen thereafter responded with a significant decline in plasma viral load. In conclusion, the transfer of gene-modified cells was safe, led to sustained levels of gene marking, and may improve immune competence in HIV-infected patients with advanced disease and multidrug-resistant virus.

Editors’ note: Gene therapy is a new frontier in HIV treatment just as it is in the treatment of cancer and inherited genetic disorders. In this case, infusing patients’ T-cells which have been modified to inhibit HIV entry was found to be safe in ten people so it is likely that a larger study will now be conducted to look more closely at the extent and significance of the immunological effects.

Mehta S, Fawzi W. Effects of vitamins, including vitamin A, on HIV/AIDS patients. Vitam Horm 2007;75:355-83.

An estimated 25 million lives have been lost to acquired immune-deficiency syndrome (AIDS) since the immunodeficiency syndrome was first described in 1981. The progress made in the field of treatment in the form of antiretroviral therapy (ART) for HIV disease/AIDS has prolonged as well as improved the quality of life of HIV-infected individuals. However, access to such treatment remains a major concern in most parts of the world, especially in the developing countries. Hence, there is a constant need to find low-cost interventions to complement the role of ART in prevention of HIV infection and slowing clinical disease progression. Nutritional interventions, particularly vitamin supplementation, have the potential to be a low-cost method for being such an intervention by virtue of their modulation of the immune system. Among all the vitamins, the role of vitamin A has been studied most extensively; most observational studies have found that low vitamin A levels are associated with increased risk of transmission of HIV from mother to child. This finding has not been supported by large randomized trials of vitamin A supplementation; on the contrary, these trials have found that vitamin A supplementation increases the risk of mother-to-child transmission (MTCT). There are a number of potential mechanisms that might explain these contradictory findings. One is the issue of reverse causality in observational studies-for instance, advanced HIV disease may suppress release of vitamin A from the liver. This would lead to low levels of vitamin A in the plasma despite the body having enough vitamin A liver stores. Further, advanced HIV disease is likely to increase the risk of MTCT, and hence it would appear that low serum vitamin A levels are associated with increased MTCT. The HIV genome also has a retinoic acid receptor element: Hence, vitamin A may increase HIV replication via interacting with this element, thus increasing risk of MTCT. Finally, vitamin A is known to increase lymphoid cell differentiation, which leads to an increase in CCR5 receptors. These receptors are essential for attachment of HIV to the lymphocytes and therefore, an increase in their number is likely to increase HIV replication. Vitamin A supplementation in HIV-infected children, on the other hand, has been associated with protective effects against mortality and morbidity, similar to that seen in HIV-negative children. The risk for lower respiratory tract infection and severe watery diarrhoea has been shown to be lower in HIV-infected children supplemented with vitamin A. All-cause mortality and AIDS-related deaths have also been found to be lower in vitamin A-supplemented HIV-infected children. The benefits of multivitamin supplementation, particularly vitamins B, C, and E, have been more consistent across studies. Multivitamin supplementation in HIV-infected pregnant mothers has been shown to reduce the incidence of adverse pregnancy outcomes such as foetal loss and low birth weight. It also has been shown to decrease rates of MTCT among women who have poor nutritional or immunologic status. Further, multivitamin supplementation reduces the rate of HIV disease progression among patients in early stage of disease, thus delaying the need for ART by prolonging the pre-ART stage. In brief, there is no evidence to recommend vitamin A supplementation of HIV-infected pregnant women; however, periodic vitamin A supplementation of HIV-infected infants and children is beneficial in reducing all-cause mortality and morbidity and is recommended. Similarly, multivitamin supplementation of people infected with HIV, particularly pregnant women, is strongly suggested.

Editors’ note: It has taken quite some time to tease out the role of vitamin A deficiency and whether supplementation is useful and if so, for whom. Although vitamin A deficiency does not appear to increase the risk of HIV transmission, it should be treated and prevented in people living with HIV of all ages on general health grounds.

Bongaarts J. Late marriage and the HIV epidemic in sub-Saharan Africa. Popul Stud (Camb) 2007;61:73-83.

The causes of large variation in the sizes of HIV epidemics among countries in sub-Saharan Africa are not well understood. Here Bongaart assesses the potential roles of late age at marriage and a long period of premarital sexual activity as population risk factors, using ecological data from 33 sub-Saharan African countries and with individual-level data from Demographic and Health Surveys (DHS) in Kenya and Ghana in 2003. The ecological analysis finds a significant positive correlation between HIV prevalence and median age at first marriage, and between HIV prevalence and interval between first sexual intercourse and first marriage. The individual-level analysis shows that HIV infection per year of exposure is higher before than after first marriage. These findings support the hypothesis of a link between a high average age at marriage and a long period of premarital intercourse during which partner changes are relatively common and facilitate the spread of HIV.

Editors’ note: This ecological association makes common sense overall, particularly for young men and increasingly for young women. However, in societies in which adolescent marriage – a human rights concern - is common, HIV prevalence can be higher among married adolescent girls than among unmarried sexually active girls of the same age. This can be the result of the broader age gap between spouses versus between girlfriend-boyfriends, with implications for pre-marital HIV risk in the husband, and difficulties in negotiating condom use within marriage. Marriage cannot automatically be assumed to be either risky or protective – it is the behaviours that make the difference when HIV is looking for opportunities.

Porto MP. Fighting AIDS among adolescent women: effects of a public communication campaign in Brazil. J Health Commun 2007;12:121-32.

In 2003, Brazil’s Ministry of Health launched a national campaign aimed at promoting the use of condoms by adolescent women. The Carnival Campaign was broadcast on television and radio between February 16 and March 3 and targeted young women, between 13 and 19 years of age, a social group that previously had registered a growth in the number of cases of AIDS and other sexually transmitted diseases (STDs). The Ministry hired Kelly Key, a Brazilian pop singer, to deliver the campaign messages. One of the objectives was to empower the girls and encourage them not to be ashamed to buy condoms and to demand that their partners use them. The article presents the results of a national survey conducted with 1,006 adolescent women, which was sponsored by the Ministry of Health. The results show that campaign materials reached the main target public and that they were very positively received. Moreover, the survey data show that the Carnival Campaign had important effects, generating discussions in the adolescents’ social environments and reinforcing a social norm that favours the participation of women in the purchase and use of condoms.

Editors’ note: Social change communication to create and reinforce new social norms for HIV prevention can use strategies like this one which open up space for discussion, negotiation and safer behaviour. Although a well known woman artist influenced and empowered adolescent girls, the fact that the campaign messages were carried on television and radio meant that it was likely that considerable numbers of men and boys would also have seen and heard the messages, enhancing the probability that they will react favourably. The next step is to change social norms about what it means to be a real man so that men and boys will act favourably from the start.

Boer H, Mashamba MT. Gender power imbalance and differential psychosocial correlates of intended condom use among male and female adolescents from Venda, South Africa. Br J Health Psychol 2007;12:51-63.

In South Africa, a gender power imbalance exists which may prevent women from negotiating safe sexual encounters. In this study Boer and colleagues tested which constructs from Protection Motivation Theory (PMT) and the Theory of Planned Behaviour (TPB) and their circumstances were most related to condom use intention. The authors hypothesized that in a situation of gender power imbalance, self-efficacy would be a more salient correlate of intended condom use for females, while for males’ attitude to condoms and subjective norm would be more important. This study employed a cross-sectional questionnaire design. Male participants (N=94) and female participants (N=101) from Venda, South Africa completed standard, multi-item, reliable measures of Theory of Planned Behaviour constructs (condom-related attitude, subjective norm, perceived behavioural control, intention) and Protection Motivation Theory constructs (vulnerability, severity, fear, response-efficacy, self-efficacy) and reported their past condom use behaviour. Regression analysis indicated that among males, attitude to condoms and subjective norm were significantly related to intended condom use. Among females, attitude to condoms and self-efficacy were significantly related to intended condom use. The findings indicate that in a situation of gender power imbalance, psychosocial correlates of intended condom use differ for males and females. Gender-specific analysis of determinants of condom use may be more appropriate in a situation of gender power imbalance.

Editors’ note: The authors’ hypothesis was confirmed: perceived norm is most important for men while for women their level of confidence to propose or insist on condom use is most related to intentions to use condoms. Now if we can increase women’s confidence and create the social norms such that men expect that condoms will be used, we may get high condom use levels yet!

Schulte J, Dominguez K, Sukalac T, Bohannon B, Fowler MG; Pediatric Spectrum of HIV Disease Consortium. Declines in low birth weight and preterm birth among infants who were born to HIV-infected women during an era of increased use of maternal antiretroviral drugs: Pediatric Spectrum of HIV Disease, 1989-2004. Pediatrics 2007;119:e900-6.

Schulte and colleagues’ goal was to determine trends in low birth weight and preterm birth among US infants born to HIV-infected women. The authors used data from the longitudinal Pediatric Spectrum of HIV Disease, a large HIV cohort, to assess trends in low birth weight and preterm birth from 1989 to 2004 among 11,321 study infants. Among women with prenatal care, the authors also assessed risk factors, including maternal antiretroviral therapy during pregnancy, that were predictive of low birth weight and preterm birth using univariate and multivariate logistic regression models. Overall, 11,231 of 14,464 infants who were enrolled in Pediatric Spectrum of HIV Disease were tested during the neonatal period. From 1989 to 2004, testing increased from 32% to 97%. The proportion of HIV-exposed infants who had low birth weight decreased from 35% to 21% and occurred in all racial/ethnic groups. Prevalence of preterm birth decreased from 35% to 22% and occurred in all groups. Any maternal antiretroviral therapy use increased from 2% to 84%. Among 8793 women who had prenatal care, low birth weight was associated with a history of illicit maternal drug use, unknown maternal HIV status before delivery, symptomatic maternal HIV disease, black race, Hispanic ethnicity, and infant HIV infection. Antiretroviral therapy or lack of it was not associated with low birth weight. Among women with prenatal care, preterm birth was associated with a history of illicit maternal drug use, symptomatic maternal HIV disease, no antiretroviral therapy, receipt of a 3-drug highly active antiretroviral therapy regimen with protease inhibitors, black race, and infant HIV infection. The authors conclude that the proportion of infants who had low birth weight or were born preterm declined during an era of increased maternal antiretroviral therapies. These Pediatric Spectrum of HIV Disease trends differ from the overall increases in both outcomes among the US population.

Editors’ note: It is quite striking that preterm births and low birth weight are on the rise in the USA overall and yet pregnancy outcomes for women living with HIV in all racial/ethnic groups improved from 1999 to 2004. Since antiretroviral therapy or lack of it was not associated with low birth weight, perhaps it was antenatal care itself that turned the tide for infants born to HIV-infected mothers in the US.

Hutchinson GA, Jameson EM. Prevalence and risk factors for HIV infection in pregnant women in north Trinidad. West Indian Med J 2006;55:346-50.

The prevalence of HIV infection in the Caribbean is reported to be second only to sub Saharan Africa. HIV in pregnancy has become an increasingly important focus of attention in HIV research because of its role in contributing to spread of the infection. This study sought to establish the prevalence and risk factors associated with HIV infection among antenatal women in the northwest region of Trinidad. Using a cross-sectional survey design, interviews were conducted with each new pregnant attendee to the antenatal clinics in the county of St George West over a six-month period after informed consent was obtained. These women were all offered routine HIV testing in their antenatal assessment. Their HIV results were confirmed through the island’s HIV monitoring facility. The interviews included questions on demographics, known risk factors for HIV infection, mental health history and related information on their partners. Women who had refused testing were also asked to give reasons for this. There were a total of 541 women attending the clinic for the first time during the six-month period seven of them refused testing. Of the remaining 534 women, 37 were HIV positive (6.8%). Fourteen of the HIV positive women (37.8%) admitted to knowing of their status prior to becoming pregnant. Risk factors significantly associated with positive HIV status were early age of first sexual intercourse, a history of sexually transmitted disease, mental health problems and homelessness. Regression analysis established a history of sexually transmitted disease as the only independent predictor of HIV infection in this sample. These findings reveal a high rate of HIV infection among pregnant women in northwest Trinidad and suggest that having a history of sexually transmitted disease is a key determinant of this. Prevention efforts must therefore be targeted at identifying the factors which influence this and these include early sexual activity and the experience of childhood sexual abuse.  

Editors’ note: Although a history of sexually transmitted disease was the only independent predictor of HIV infection among pregnant women in north-west Trinidad, sexually transmitted infections are themselves associated with broader problems which must be addressed on the grounds of human rights (child sexual abuse) and psychosocial health (homelessness and mental health problems). Delaying onset of sexual debut would go a long way to reducing risk for Trinidadian adolescents and young women.

Nyika A. Ethical and regulatory issues surrounding African traditional medicine in the context of HIV/AIDS. Developing World Bioeth 2007;7:25-34.

It has been estimated that more than 80% of people in Africa use traditional medicine. With the HIV epidemic claiming many lives in Africa, the majority of people affected rely on traditional medicine mainly because it is relatively affordable and available to the poor populations who cannot afford orthodox medicine. Whereas orthodox medicine is practiced under stringent regulations and ethical guidelines emanating from The Nuremburg Code,(1) African traditional medicine seems to be exempt from such scrutiny. Although recently there have been calls for traditional medicine to be incorporated into the health care system, less emphasis has been placed on ethical and regulatory issues. In this paper, an overview of the use of African traditional medicine in general, and for HIV in particular, is given, followed by a look at: (i) the relative laxity in the application of ethical standards and regulatory requirements with regards to traditional medicine; (ii) the importance of research on traditional medicine in order to improve and demystify its therapeutic qualities; (iii) the need to tailor-make intellectual property laws to protect traditional knowledge and biodiversity. A framework of partnerships involving traditional healers’ associations, scientists, policy makers, patients, community leaders, members of the communities, and funding organizations is suggested as a possible method to tackle these issues. It is hoped that this paper will stimulate objective and constructive debate that could enhance the protection of patients’ welfare.

Editors’ note : The pragmatic approach suggested here fits with the perspectives of the UNAIDS’ best practice publication from November 2006: Collaborating with Traditional Healers for HIV Prevention and Care in sub-Saharan Africa: suggestions for Programme Managers and Field Workers which will shortly be available in the new 16 page Highlights version.