HIV This Week

Welcome to the forty-fourth issue of HIV This Week!  In this issue, we cover basic science (how we could stop helping HIV do its dirty work), economics (one additional year of education reduces the hazard of HIV acquisition by 7% in rural KwaZulu Natal; HIV is out of step: wealth and higher HIV prevalence in eight countries in sub-Saharan Africa), prevention (futility in biomedical HIV prevention trials: what happened to the SAVVY vaginal gel (C31G) randomised controlled trial in Nigeria; putting the spotlight on HIV-1-discordant couples in mature epidemics), male circumcision (from Rakai, Uganda: what you have always wanted to know about sexual satisfaction and function), reproductive health (high HPV 16 and 18 levels in HIV positive and negative women in Lusaka; cervical cancer screening as part of comprehensive care for women living with HIV on antiretroviral drugs; conceiving naturally and more safely: how can serodiscordant couples do it?), infant feeding (from Botswana: time to reconsider early weaning?), drug development (what’s on for the next 25 years?), prevention of mother-to-child transmission (encouraging trends from Barbados), treatment (bad partners: Hepatitis C and HIV; finger-prick blood samples for CD4 cell counts), resources/impact/development (profits and equitable access: the role of voluntary licensing agreements; the cost-effectiveness of applying developed world antiretroviral therapy guidelines in South Africa), and epidemiology (no single gold standard: reconciling population and antenatal-based HIV prevalence estimates).

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Brass AL, Dykxhoorn DM, Benita Y, Yan N, Engelman A, Xavier RJ, Lieberman J, Elledge SJ. Identification of Host Proteins Required for HIV Infection Through a Functional Genomic Screen. Science. 2008 Jan 10 [Epub ahead of print]

Photo credit: Boehringer-Ingelheim

HIV-1 exploits multiple host proteins during infection. Brass and colleagues performed a large-scale small interfering RNA (siRNA) screen to identify host factors required by HIV-1 and identified over 250 HIV-dependency factors (HDFs). These proteins participate in  a broad array of cellular functions and implicate new pathways in the viral life  cycle. Further analysis revealed previously unknown roles for retrograde Golgi transport proteins (Rab6 and Vps53) in viral entry, a karyopherin (TNPO3) in viral integration, and the Mediator complex (Med28) in viral transcription. Transcriptional analysis revealed that HDF genes were enriched for high expression in immune cells suggesting that viruses evolve in host cells that optimally perform the functions required for their life cycle. This effort illustrates the power with which RNA interference and forward genetics can be used to expose the dependencies of human pathogens such as HIV, and in so doing identify potential targets for therapy.

Editors’ note: A small virus, HIV-1 has nine genes that code only 15 proteins and yet has a complex life cycle. This elegant research began with the premise that HIV-1 must depend on host factors and found that 273 human proteins help HIV to infect cells, enter the nucleus, integrate into the human chromosome, and make copies of itself. These host-dependency factors could make excellent targets for drugs in much the same way that CCR5 inhibitors prevent viral docking for cell entry. However, we humans need these proteins too, so determining which ones we can get by without is the challenging path of research inquiry this work has opened up.

Bärnighausen T, Hosegood V, Timaeus IM, Newell ML. The socioeconomic determinants of HIV incidence: evidence from a longitudinal, population-based study in rural South Africa. AIDS. 2007 Nov;21 Suppl 7:S29-38.

Knowledge of the effect of socioeconomic status on HIV infection in Africa stems largely from cross-sectional studies. Cross-sectional studies suffer from two important limitations: two-way causality between socioeconomic status and HIV serostatus and simultaneous effects of socioeconomic status on HIV incidence and HIV-positive survival time. Both problems are avoided in longitudinal cohort studies. Bärnighausen and colleagues  used data from a longitudinal HIV surveillance and a linked demographic surveillance in a poor rural community in KwaZulu-Natal, South Africa, to investigate the effect of three measures of socioeconomic status on HIV incidence: educational attainment, household wealth categories (based on a ranking of households on an assets index scale) and per capita household expenditure. Their sample comprised of 3325 individuals who tested HIV-negative at baseline and either HIV-negative or -positive on a second test (on average 1.3 years later). In multivariable survival analysis, one additional year of education reduced the hazard of acquiring HIV by 7% (P = 0.017) net of sex, age, wealth, household expenditure, rural vs. urban/periurban residence, migration status and partnership status. Holding other factors equal, members of households that fell into the middle 40% of relative wealth had a 72% higher hazard of HIV acquisition than members of the 40% poorest households (P = 0.012). Per capita household expenditure did not significantly affect HIV incidence (P = 0.669). The authors conclude that although poverty reduction is important for obvious reasons, it may not be as effective as anticipated in reducing the spread of HIV in rural South Africa. In contrast, their results suggest that increasing educational attainment in the general population may lower HIV incidence.

Editors’ note: In early stages of the epidemic, higher education may increase HIV risk due, in part, to higher numbers of sexual partners. As HIV epidemics mature, the highly educated may adopt risk-reducing behaviours more quickly, possibly because they are more empowered to negotiate safer sex. This longitidinal study in a poor South Africa community provides strong support for structural interventions to keep children in school, with each additional year reducing HIV risk. The higher HIV prevalence seen among members of households falling in the middle 40% of relative wealth underscores findings from other studies suggesting that the relationship between HIV and poverty/wealth is complex.

Mishra V, Assche SB, Greener R, Vaessen M, Hong R, Ghys PD, Boerma JT, Van Assche A, Khan S, Rutstein S.  HIV infection does not disproportionately affect the poorer in sub-Saharan. Africa AIDS. 2007 Nov;21 Suppl 7:S17-28.

Wealthier populations do better than poorer ones on most measures of health status, including nutrition, morbidity and mortality, and healthcare utilization. This study examines the association between household wealth status and HIV serostatus to identify what characteristics and behaviours are associated with HIV infection, and the role of confounding factors such as place of residence and other risk factors. Data are from eight national surveys in sub-Saharan Africa (Kenya, Ghana, Burkina Faso, Cameroon, Tanzania, Lesotho, Malawi, and Uganda) conducted during 2003-2005. Dried blood spot samples were collected and tested for HIV, following internationally accepted ethical standards and laboratory procedures. The association between household wealth (measured by an index based on household ownership of durable assets and other amenities) and HIV serostatus is examined using both descriptive and multivariate statistical methods. In all eight countries, adults in the wealthiest quintiles have a higher prevalence of HIV than those in the poorer quintiles. Prevalence increases monotonically with wealth in most cases. Similarly for cohabiting couples, the likelihood that one or both partners is HIV infected increases with wealth. The positive association between wealth and HIV prevalence is only partly explained by an association of wealth with other underlying factors, such as place of residence and education, and by differences in sexual behaviour, such as multiple sex partners, condom use, and male circumcision. Mishra and colleagues conclude that in sub-Saharan Africa, HIV prevalence does not exhibit the same pattern of association with poverty as most other diseases. HIV programmes should also focus on the wealthier segments of the population.

Editors’ note: HIV clearly disproportionately affects the poor in sub-Saharan Africa when they do become infected; however, the poor appear to be at lower risk of HIV infection in the first place. This eight country study found that wealth, defined as higher household economic status, is associated with higher HIV prevalence among adult men and women. Qualitative research is needed to better understand why wealthier people who tend to be more educated, have a greater knowledge of HIV prevention methods, access health care, and use condoms more, still have higher HIV prevalence. Higher mobility and concurrent partnerships may be creating risky sexual networks for the virus to travel.

Feldblum PJ, Adeiga A, Bakare R, Wevill S, Lendvay A, Obadaki F, Olayemi MO, Wang L, Nanda K, Rountree W. SAVVY Vaginal Gel (C31G) for Prevention of HIV Infection: A Randomized Controlled Trial in Nigeria. PLoS ONE. 2008 Jan 23;3(1):e1474.

The objective of this trial was to determine the effectiveness of 1.0% C31G (SAVVY) in preventing male-to-female vaginal transmission of HIV infection among women at high risk. This was a Phase 3, double-blind, randomized, placebo-controlled trial. Participants made up to 12 monthly follow-up visits for HIV testing, adverse event reporting, and study product supply. The study was conducted between September 2004 and December 2006 in Lagos and Ibadan, Nigeria, where Feldblum and colleagues enrolled 2153 HIV-negative women at high risk of HIV infection. Participants were randomized on a one to one ratio to SAVVY or placebo. The effectiveness endpoint was incidence of HIV infection as indicated by detection of HIV antibodies in oral mucosal transudate (rapid test) or blood (ELISA), and confirmed by Western blot or PCR testing. The authors observed 33 seroconversions (21 in the SAVVY group, 12 in the placebo group). The Kaplan-Meier estimates of the cumulative probability of HIV infection at 12 months were 0.028 in the SAVVY group and 0.015 in the placebo group (2-sided p-value for the log-rank test of treatment effect 0.121). The point estimate of the hazard ratio was 1.7 for SAVVY versus placebo (95% confidence interval 0.9,3.5). Because of lower-than-expected HIV incidence, Feldblum et al did not observe the required number of HIV infections (66) for adequate power to detect an effect of SAVVY. Follow-up frequencies of adverse events, reproductive tract adverse events, abnormal pelvic examination findings, chlamydial infections and vaginal infections were similar in the study arms. No serious adverse event was attributable to SAVVY use. SAVVY did not reduce the incidence of HIV infection. Although the hazard ratio was higher in the SAVVY than the placebo group, we cannot conclude that there was a harmful treatment effect of SAVVY. TRIAL REGISTRATION: ClinicalTrials.gov NCT00130078.

Editors’ note: The lower than expected HIV incidence seen in this trial, as in the SAVVY trial in Ghana, led this study’s Data Monitoring Committee to recommend the trial be stopped. An additional 1980 participants would have been required to reach the level of 66 infections required for study power. The low incidence may in part be the result of rigorous responses to trial risk reduction measures because gel was reportedly used alone (without a condom) in only 9% of coital acts. Those who used gel tended also to use condoms. Research funders and researchers need to anticipate that trial participants will respond to risk reduction counselling and therefore plan for larger study populations in order to achieve convincing results whether these are positive or negative.

Guthrie BL, de Bruyn G, Farquhar C. HIV-1-discordant couples in sub-Saharan Africa: explanations and implications for high rates of discordancy. Curr HIV Res 2007;5:416-29.

In sub-Saharan Africa, approximately 1 in 2 HIV-1-infected persons living in a couple have a serodiscordant partner. Recent data suggest a large proportion of new HIV-1 infections in mature epidemics occur within discordant couples, making discordancy a major contributor to the spread of HIV in Africa. What accounts for high rates of HIV-1 discordance and why some individuals remain uninfected despite repeated sexual exposure to HIV-1 is unknown. Studying HIV-1-discordant couples may contribute to understanding correlates of HIV-1 immunity and acute infection. Additionally, HIV-1-discordant couples are an important population for prevention efforts. Consequently, HIV-1-discordant couples are increasingly viewed as a valuable source of participants for HIV vaccine and prevention trials. This review summarizes and critiques existing data on HIV-1-discordant couples in developing countries, including an analysis of transmission rates within discordant couples, description of biological and behavioral characteristics important in planning HIV-1 vaccine and prevention trials, and challenges faced when carrying out such studies. 

Editors’ note: Although discordant heterosexual couples are part of the general population, HIV prevention strategies addressing them need to be tailored and focussed. Discordancy is not recognized until HIV testing is undertaken, highlighting the importance of community-based HIV testing; partner testing in antenatal programmes, regardless of the pregnant woman’s test result; know your status campaigns; and provider-initiated HIV testing in clinical settings.

Kigozi G, Watya S, Polis CB, Buwembo D, Kiggundu V, Wawer MJ, Serwadda D, Nalugoda F, Kiwanuka N, Bacon MC, Ssempijja V, Makumbi F, Gray RH. The effect of male circumcision on sexual satisfaction and function, results from a randomized trial of male circumcision for human immunodeficiency virus prevention, Rakai, Uganda. BJU Int. 2008 Jan;101(1):65-70.

Kigozi and colleagues investigate the relationship between adult male circumcision and sexual satisfaction and function in men, as observational studies on the effect of adult male circumcision on sexual satisfaction show conflicting results. They investigated self-reported sexual satisfaction and function among men enrolled in a randomized trial of male circumcision for human immunodeficiency virus (HIV) prevention conducted in Rakai, Uganda. In all, 4456 sexually experienced HIV-negative males aged 15-49 years were enrolled; 2210 were randomized to receive immediate circumcision (intervention arm) and 2246 to circumcision delayed for 24 months (control arm). Men were followed up at 6, 12 and 24 months, and information on sexual desire, satisfaction and erectile dysfunction was collected. These variables were compared between the study arms and over time within the study arms, using chi-square or Fisher’s exact tests. The trial registration number is NCT00425984. There were no differences between the study arms at enrollment and problems with sexual satisfaction and function were reported by <2% of participants in both study arms at all time points. At 6 months, no difficulty with penetration was reported by 98.6% of circumcised men and 99.4% of controls (P = 0.02), and no pain on intercourse was reported by 99.4% circumcised and 98.8% of uncircumcised men (P = 0.05). There were no differences between the study arms in penetration or dyspareunia at later visits. Sexual satisfaction increased from 98.0% at enrollment to 99.9% at 2 years among the controls (P < 0.001), but there was no trend in satisfaction among circumcised men (enrollment 98.5%, 2 years 98.4%, P = 0.8). The authors conclude that adult male circumcision does not adversely affect sexual satisfaction or clinically significant function in men.

Editors’ note: Previous studies of the effect of male circumcision on sexual pleasure and function have been small, observational, short-term studies of highly selected populations. This large trial found no differences between uncircumcised men and men who became circumcised, in sexual desire, ability to achieve or maintain an erection, normal ejaculation and sexual satisfaction over a 2-year period. Public health messaging strategies need to incorporate discussions of sexual pleasure to minimize both fears of loss of sexual function or pleasure and false expectations that male circumcision will enhance these.

Ng’andwe C, Lowe JJ, Richards PJ, Hause L, Wood C, Angeletti PC. The distribution of sexually transmitted Human Papillomaviruses in HIV positive and negative patients in Zambia, Africa. BMC Infect Dis 2007;7:77. http://www.biomedcentral.com/content/pdf/1471-2334-7-77.pdf.

Human Papillomaviruses (HPV) are double-stranded DNA viruses, considered to be the primary etiological agents in cervical intraepithelial neoplasias and cancers. Approximately 15-20 of the 40 mucosal HPVs confer a high-risk of progression of lesions to invasive cancer. In this study, Ng’anwe and colleagues investigated the prevalence of sexually transmitted HPVs in Human Immunodeficiency Virus (HIV) positive and negative patients in Zambia, Africa. The rate of high-risk HPV genotypes worldwide varies within each country. Thus, we sought to investigate the rates of HPV infection in sub-Saharan Africa and the potential role of HIV in affecting the HPV genotype distribution. This retrospective cross-sectional study reports findings on the association and effects of HIV on HPV infections in an existing cohort of patients at University Teaching Hospital (UTH) Lusaka, Zambia. The objective of this study was to assess HPV prevalence, genotype distribution and to identify co-factors that influence HPV infection. Polymerase chain reaction (PCR) with two standard consensus primer sets (CpI/II and GP5+/6+) was used to test for the presence of HPV DNA. Primers specific for b-actin were used to monitor DNA quality. Vaginal lavage samples collected between 1998-1999 from total of 70 women from a larger cohort that were analyzed for HIV and human herpesvirus infection. Seventy of the samples yielded usable DNA. HIV status was determined by two rapid assays, Capillus and Determine. The incidence of HIV and HPV infections and HPV genotype distributions were calculated and statistical significance was determined by Chi-Squared test. Ng’andwe and colleagues determined that most common HPV genotypes detected among these Zambian patients were types 16 and 18 (21.6% each), which is approximately three-fold greater than the rates for HPV16, and ten-fold greater than the rates for HPV18 in the United States. The worldwide prevalence of HPV16 is approximately 14% and HPV18 is 5%. The overall ratio of high-risk  to low-risk  HPVs in the patient cohort was 69% and 31% respectively; essentially identical to that for the HR and LR distributions worldwide. However, we discovered that HIV positive patients were two-times as likely to have an high risk HPV as HIV negative individuals, while the distribution of low risk HPVs was unaffected by HIV status. Interestingly, we observed a nine-fold increase in HPV18 infection frequency in HIV positive versus HIV negative individuals. The rate of oncogenic HPVs (type 16 and 18) in Zambia was much higher than in the U.S., potentially providing an explanation for the high-rates of cervical cancer in Zambia. Surprisingly, we discovered a strong association between positive HIV status and the prevalence of high risk HPVs, and specifically HPV18.

Editors’ note: Although the sample size is small, the findings are striking and provide justification for the introduction of a public health HPV vaccine programme in Zambia where the immunosuppressive effects of HIV infection may be contributing to the surprising levels of high risk HPV 16 and 18. Public sector prices for low-and middle- income countries for the quadrivalent recombinant vaccine against HPV 6, 11, 16, 18 (Merck’s GARDASIL) and the bivalent recombinant vaccine against HPV 16, 18 (Glaxo Smith Kline’s CERVARIX) are urgently needed. For example, GARDASIL, which is being rolled out in some industrial countries now, costs an estimated $360 for the three dose series.

Franceschi S, Jaffe H. Cervical cancer screening of women living with HIV infection: a must in the era of antiretroviral therapy. Clin Infect Dis 2007;45:510-3.

Women living with human immunodeficiency virus (HIV) infection have a much higher risk of human papillomavirus infection and cervical cancer than do HIV-negative women. Before the introduction of antiretroviral therapy, the lack of cervical cancer screening among HIV-positive women probably had little influence on their life expectancies because of the high competing mortality associated with other causes, but the situation is changing rapidly everywhere. In sub-Saharan Africa, for instance, approximately 400,000 HIV-positive women were receiving antiretroviral therapy in 2005. Funds given to antiretroviral therapy programs in low-resource countries not only support the purchase of drugs, but they also support the development of clinical infrastructures and laboratories. Because women who receive antiretroviral therapy are observed regularly, they can also receive the continuity of care needed for cervical screening. Therefore, the real opportunity to prevent cervical cancer in HIV-positive women in low-resource countries should not be missed, especially as new, inexpensive screening methods (e.g., rapid human papillomavirus tests) are under evaluation.

Editors’ note: Until universal HPV vaccination strategies are in place, preventing avoidable deaths due to cervical cancer relies on early diagnosis. Comprehensive care for women living with HIV includes regular cervical screening to detect and treat the HPV-induced cervical lesions that can lead to carcinoma of the cervix, an AIDS-defining disease.

Barreiro P, Castilla JA, Labarga P, Soriano V. Is natural conception a valid option for HIV-serodiscordant couples? Hum Reprod 2007 Sep;22(9):2353-8.

The remarkable reduction in HIV-related morbidity and mortality as a consequence of the widespread use of highly active antiretroviral therapy (HAART) has led to a growing number of HIV-positive persons and their partners requesting counselling regarding the chances of reproduction. A thoughtful medical evaluation of the couple, which should entail HIV status, screening for genital infections and fertile potential, is needed before considering any reproductive attempt. Given that both sexual and perinatal transmission of HIV is directly correlated with the level of viral replication, being almost negligible in patients with undetectable viremia, HAART should be given to the infected partner to minimize the risk of transmission. Assisted reproduction after ’sperm washing’ may further reduce the chances of infection, although this is not within reach or desire for a significant number of HIV-serodiscordant couples. From our perspective, natural conception could now be considered a possible alternative for HIV-serodiscordant couples, as long as complete suppression of viremia with HAART is achieved in the HIV-positive partner. The objective of this paper is to propose a protocol that may minimize risks in HIV-discordant couples that have opted for natural conception.

Editors’ note: Reproductive counselling of male-positive, female-negative sero-discordant couples desiring a pregnancy focuses on ways of reducing the risk of sexual transmission while fulfilling personal reproductive goals. Although not mentioned by this Spanish team, some HIV-negative women are using antiretroviral prophylaxis in the hopes of reducing risk even further, although the safety and efficacy of doing so is unknown.

Shapiro RL, Lockman S, Kim S, Smeaton L, Rahkola JT, Thior I, Wester C, Moffat C, Arimi P, Ndase P, Asmelash A, Stevens L, Montano M, Makhema J, Essex M, Janoff EN. Infant morbidity, mortality, and breast milk immunologic profiles among breast-feeding HIV-infected and HIV-uninfected women in Botswana. J Infect Dis 2007; 196:562-9.

Infants of human immunodeficiency virus (HIV)-positive women have high mortality, but the immunologic integrity and protection afforded by the breast milk of HIV-positive women is unknown. Shapiro and colleagues determined morbidity and mortality by 24 months among breast-fed infants of 588 HIV-positive and 137 HIV-negative women followed-up in a clinical trial in Botswana. A matched case-control study compared clinical, behavioral, and breast milk immunologic parameters among 120 HIV-positive women by infant outcome. Breast milk factors were also compared between HIV-positive and HIV-negative women. Twenty-four-month mortality was 29.5% among HIV-positive infants, 6.7% among HIV-exposed uninfected infants, and 1.6% among HIV-unexposed infants. No differences were detected in breast milk immunologic profiles of HIV-positive women whose infants were either ill or well. Discontinuation of breast-feeding was the strongest predictor of illness (P<.001). Levels in breast milk of pathogen-specific immunoglobulin (Ig) G and IgA to Haemophilus influenzae, Campylobacter jejuni, Helicobacter pylori, Streptococcus pneumoniae, and innate immune factors were not lower among HIV-positive women than among HIV-negative women. Mortality was higher among HIV-positive and HIV-exposed infants than among HIV-unexposed infants. However, the immunologic profiles of breast milk among HIV-positive women were intact, and discontinuation of breast-feeding was the primary risk for infant morbidity. Thus, the breast milk of HIV-positive women may confer protection against common infant pathogens.

Editors’ note: This first analysis comparing breast milk immunological profiles among HIV-positive and HIV-negative women did not detect in any differences in immunoglobin levels or other immune factors. Current recommendations are for exclusive breastfeeding by mothers with HIV infection, when breast-milk substitutes are unsafe or not feasible, and early weaning around 6 months of age. In this study, infants exposed to HIV were weaned at 5 to 6 months of age, whereas 9 months was the average for the HIV-unexposed group. Given the higher mortality at 6 and 24 months in the early weaning group, further study is required to find the right balance between risk of HIV transmission and risk of mortality from childhood illness.

Flexner C. HIV drug development: the next 25 years. Nat Rev Drug Discov. 2007 Dec;6(12):959-66.

The development of drugs for HIV infection began soon after the virus was discovered 25 years ago. Since then, progress has been substantial, but numerous uncertainties persist about the best way to manage this disease. Flexner reviews the current treatment options, considers novel mechanisms that can be exploited for existing drug targets, and explores the potential of novel targets. With a view to the next quarter century, he considers whether drug resistance can be avoided, which drug classes will be favoured over others, which strategies are most likely to succeed, and the potential impact of pharmacogenomics and individualized therapy.

Editors’ note: Despite the fact that 23 antiretroviral drugs are now approved, better tolerated, more convenient, and less expensive regimens are needed. Combination chemotherapy for chronic HIV treatment is based on prevention of resistance rather than pharmacological synergy. New drug classes with either high genetic barriers to resistance or that block human proteins needed by the virus are needed as are drugs that can be produced cheaply in recombinant bacteria or plants. With 33 million people living with HIV and 2.5 million new infections added each year, demand for treatment will continue to rise, giving impetus for continued research and development.

Kumar A, St White H, Carter AO. Trends in the uptake of antenatal voluntary counselling and testing for HIV andHIV prevalence among childbearing women in Barbados, 1993-2004: evidence to gauge the effectiveness of HIV prevention measures. West Indian Med J. 2007 Jan;56(1):60-5.

Kumar and colleagues describe the long term trends in the uptake of antenatal voluntary counselling and testing (VCT) for Human Immunodeficiency Virus (HIV) and in the HIV prevalence among pregnant women. These data were used to gauge the impact of the National Acquired Immunodeficiency Syndrome (AIDS) Intervention Programme on preventing mother-to-child transmission (PMTCT) in Barbados. They conducted a population based study. Data for this report were drawn from the HIV Surveillance Programme for the mother-to-child transmission of HIV. The study population comprised all pregnant women who attended the various antenatal care clinics throughout Barbados during the period between 1993 and 2004. The uptake of the VCT for HIV among the pregnant women in Barbados has increased from 39.9% in 1993 to over 89.7% in 2004 (p < 0.0001). Mean annual HIV prevalence decreased from 10.5 per thousand women screened in 1993-1996 to 8.2 during 2001-2004 (p =0.121). Mean annual incidence rate of newly diagnosed HIV infection among the pregnant women declined from 8.8 per thousand women screened during 1993-1996 to 4.5 per thousand pregnant women screened during 2001-2004 (p = 0.004). Mean annual incidence rate of newly diagnosed HIV infection among the pregnant women aged less than 25 years during the corresponding period declined from 10.2 per thousand women aged less than 25 years screened to 4.8 per thousand women screened (p = 0.003). There has been a significant decline in the prevalence and incidence of HIV since the late-1990s. Although new infections are still occurring, the numbers are small. The decline may partly be explained by the impact of PMTCT and the general preventive measures on the spread of HIV among this population.

Editors’ note: The increase in HIV testing uptake in pregnancy from 40% to 90% over a 10-year period is striking. HIV prevalence remains high at 8% but newly diagnosed HIV infections have almost halved overall. The greater fall in incidence among women less than 25 years of age suggests that overall prevention efforts have found fertile ground among young people.

Pellicano R, Fagoonee S, Repici A, Rizzetto M. Hepatitis C virus and human immunodeficiency virus: a dangerous dealing. Panminerva Med 2007;49:79-82.

It is estimated that, in the United States and Europe, 15-30% of people with human immunodeficiency virus (HIV) are coinfected with hepatitis C virus (HCV). Among these patients, approximately 80% are injecting drug users (IDU), 71% are hemophiliacs, and around 20% are homosexual/bi-sexual men. HIV infection accelerates the natural history of HCV infection. On the contrary, highly active antiretroviral therapy reduces the rate of mortality due to liver disease by immune restoration. Since having HIV implies being at risk also for HCV as both infections can be acquired in similar ways, all individuals with the former should be screened for the latter. Loss of antibodies against HCV in HIV-seropositive IDU has been shown. Thus, quantitative tests determining HCV-RNA levels in blood are currently being employed for diagnosis confirmation in case of an obvious ”risk group”. Since HIV can progress more rapidly than HCV, it may be preferable to treat HIV first. The 2007 recommendations from HCV-HIV International Panel indicate current treatment of HCV in coinfected patients with pegylated formulation of interferon at standard doses plus weight based ribavirin. The treatment duration should be evaluated on the basis of HCV genotype. Liver transplantation is a most debated issue when dealing with HCV/HIV coinfected subjects. Mortality among HIV-positive liver transplant recipients is similar to that of age and race-matched HIV-negative controls. The present concise review attempts to highlight the current clinical situation on HIV/HCV coinfection.

Editors’ note: HIV/HCV co-infection is not uncommon in high-income countries and complicates decisions about treatment sequencing. Screening to detect hepatitis C infection in people living with HIV is therefore important in settings in which interferon/ribavirin combination therapy can be initiated. Sterile needles and syringes to prevent HCV transmission as well as HIV infection should be available in all clinical settings and should be provided as a harm reduction strategy to injecting drug users everywhere. 

Maclennan CA, van Oosterhout JJ, White SA, Drayson MT, Zijlstra EE, Molyneux ME. Finger-prick blood samples can be used interchangeably with venous samples for CD4 cell counting indicating their potential for use in CD4 rapid tests. AIDS 2007;21:1643-1645.

The objective of this study was to investigate the utility of finger-prick blood samples for CD4 cell counting. Maclennan and colleagues estimated agreement between CD4 cell counts in paired finger-prick and venous samples from 110 HIV-positive adults from Malawi. Bias was 6.6 cells/mul (limits of agreement -50.7 and 63.7 cells/mul) for absolute counts and 0.71% (limits of agreement -2.07 and 3.48%) for %CD4/lymphocyte suggesting that finger-prick blood samples can be used interchangeably with venous samples for CD4 cell counting.

Editors’ note: Clinical staging does not always correspond to the degree of immunosuppression measured by CD4 counts. Rapid CD4 cell count tests are under development and could be performed on finger-prick blood samples which do not require a trained phlebotomist. This study found excellent agreement between finger-prick and venous blood samples for CD4 lymphocyte counts when adequate blood flow from the finger occurred without squeezing, which can lead to dilution by tissue fluid. Finger-prick sampling is already used for rapid HIV tests and malaria parasite slides and may be more acceptable to patients than venipuncture.

Dionisio D  , Khanna AK, Nicolaou S , Raghavan V, Juneja S, Sengupta A,   Messeri D. For-profit policies and equitable access to antiretroviral drugs in resource-limited countries. Future HIV Therapy January 2008, Vol. 2, No. 1, Pages 25-36.

Unaffordable prices continue to obstruct access to antiretroviral drugs in income-constrained countries. This article explores the fitness of a multi-pronged, incentive-bound, WHO-mediated voluntary license strategy for attuning research, innovation, profit and equitable access to antiretrovirals in under-served markets. The potential of the model was investigated by examining: the predictable effect on current regulatory practices (trade-related aspects of intellectual property rights [TRIPS] and TRIPS-plus measures); the expected benefits, either in terms of equity or safeguarding of the generic and brand name manufacturer’s interests; the interplay dynamics with drug trading policies of deeply concerned countries (China, India, countries in the EU, USA, Brazil, South Africa and Thailand); and the suitability for helping plants for generic antiretrovirals, including home plants in Sub-Saharan Africa, undertake research and development partnerships encompassing innovation, technological catch-up, exploitation of TRIPS flexibilities, as well as raised marketing power and an increase in domestic employment. The explored strategy, although far from being the ideal solution, looks like it would be reliable to help expand equitable and sustainable access to appropriate antiretrovirals in resource-limited populations, as long as it entwines with the WHO’s brokerage. It should also boost know-how, technology transfer, innovation, research and development, as well as national industry plant development and penetration of the wealthy and under-served markets by generic drug enterprises.

Editors’ note: The advantage and dynamics of voluntary licensing agreements between multinational brand-name corporations and generic manufacturers are described in this paper which provides specific examples [Bristol-Myers Squibb and Aspen Pharmacare (sub-Saharan Africa) and Emcure (India); Tibotec Pharmaceuticals and Aspen Pharmacare (sub-Saharan Africa); Roche and Addis Pharmaceutical Factory (Ethiopia) and Varichem Pharmaceuticals (Zimbabwe)]. The authors argue that WHO should play a brokering role in this confluence of interest to secure low priced drugs and expanded access to antiretroviral medications through voluntary licensing agreements.

Vijayaraghavan A, Efrusy MB, Mazonson PD, Ebrahim O, Sanne IM, Santas CC. Cost-effectiveness of alternative strategies for initiating and monitoring Highly Active Antiretroviral Therapy in the developing world. J Acquir Immune Defic Syndr 2007 Sep 1;46(1):91-100.

The objective was to determine the cost-effectiveness of initiating and monitoring highly active antiretroviral therapy (HAART) in developing countries according to developing world versus developed world guidelines. The design was a Lifetime Markov model incorporating costs, quality of life, survival, and transmission to sexual contacts. Vijayaraghavan and colleagues evaluated treating patients with HIV in South Africa according to World Health Organization (WHO) ”3 by 5” guidelines (treat CD4 counts </=200 cells/mm3 patients with AIDS, and monitor CD4 cell counts every 6 months) versus modified WHO guidelines that incorporate the following key differences from developed world guidelines: treat CD4 counts </=350 cells/mm3 viral loads >100,000 copies/mL, and monitor CD4 cell counts and viral load every 3 months. Incorporating transmission to partners (excluding indirect costs), treating patients according to developed versus developing world guidelines increased costs by US $11,867 and increased life expectancy by 3.00 quality-adjusted life-years (QALYs), for an incremental cost-effectiveness of $3956 per QALY. Including indirect costs, over the duration of the model, there are net cost savings to the economy of $39.4 billion, with increased direct medical costs of $60.5 billion offset by indirect cost savings of $99.9 billion. Treating patients with HIV according to developed versus developing world guidelines is highly cost-effective and may result in substantial long-term savings.

Editors’ note: This unusual study compares the health and economic impacts of implementing treatment guidelines for the developed world (US Department of Health and Human Services) versus guidelines for the developing world (WHO) in South Africa. Initiating treatment at a higher CD4 cell count and using viral load tests to identify treatment failure more quickly so that regimens can be switched have both survival and quality of life benefits. That this modelling predicted a net savings to the economy of $39 billion over the next 38 years is perhaps surprising. It emphasizes the importance of indirect cost savings (primarily resulting from socially and economically productive years of life saved for index patients and their sexual partners) in countering direct medical costs, which are themselves staggering.

Rice BD, Batzing-Feigenbaum J, Hosegood V, Tanser F, Hill C, Barnighausen T, Herbst K, Welz T, Newell ML. Population and antenatal-based HIV prevalence estimates in a high contracepting female population in rural South Africa. BMC Public Health 2007;7:160.
http://www.biomedcentral.com/content/pdf/1471-2458-7-160.pdf

The objective was to present and compare population-based and antenatal-care (ANC) sentinel surveillance HIV prevalence estimates among women in a rural South African population where both provision of ANC services and family planning is prevalent and fertility is declining. With a need, in such settings, to understand how to appropriately adjust ANC sentinel surveillance estimates to represent HIV prevalence in general populations, and with evidence of possible biases inherent to both surveillance systems, Rice and colleagues explore differences between the two systems. There is particular emphasis on unrepresentative selection of ANC clinics and unrepresentative testing in the population. HIV sero-prevalence amongst blood samples collected from women consenting to test during the 2005 annual longitudinal population-based serological survey was compared to anonymous unlinked HIV sero-prevalence amongst women attending antenatal care (ANC) first visits in six clinics (January to May 2005). Both surveillance systems were conducted as part of the Africa Centre Demographic Information System. Population-based HIV prevalence estimates for all women (25.2%) and pregnant women (23.7%) were significantly lower than that for ANC attendees (37.7%). A large proportion of women attending urban or peri-urban clinics would be predicted to be resident within rural areas. Although overall estimates remained significantly different, presenting and standardising estimates by age and location (clinic for ANC-based estimates and individual-residence for population-based estimates) made some group-specific estimates from the two surveillance systems more predictive of one another. It is likely that where ANC coverage and contraceptive use is widespread and fertility is low, population-based surveillance under-estimates HIV prevalence due to unrepresentative testing by age, residence and also probably by HIV status, and that ANC sentinel surveillance over-estimates prevalence due to selection bias in terms of age of sexual debut and contraceptive use. The results presented highlight the importance of accounting for unrepresentative testing, particularly by individual residence and age, through system design and statistical analyses.

Editors’ note: Triangulation of data from different sources is a cornerstone in the process of refining HIV prevalence estimates. This article details the thinking processes required to identify possible biases inherent to both surveillance systems, the adjustments required, and the pitfalls of considering population-based estimates to be the gold standard.