Initial lessons from public-private partnerships in drug and vaccine development.

In recent years, venture capital approaches have delivered impressive results in identifying and funding promising health discoveries and bringing them to market. This success has inspired public sector experiments with "social venture capital" approaches to address the dearth of affordable treatment and prevention for diseases of the developing world. Employing the same focus on well-defined and measurable objectives, and the same type of connections to pool and deploy resources as their for-profit counterparts, social venture capitalists seek to use the tools and incentives of capitalism to solve one of its biggest failures: the lack of drugs and vaccines for diseases endemic to low-income populations. As part of a larger trend of partnerships emerging in health product donation and distribution, public-private partnerships for pharmaceutical development have led research and development (R&D) efforts to generate more accessible and efficacious products for diseases such as malaria, tuberculosis, and AIDS. In this article, three R&D-focused partnerships are explored: the International AIDS Vaccine Initiative; the Medicines for Malaria Venture; and the newly formed Global Alliance for TB Drug Development. The article highlights key elements essential to the success of these ventures.

An AIDS vaccine for all the world. Interview by Matthew O'Rourke.

AIDS: Dr. Seth Berkley, president of the International AIDS Vaccine Initiative (IAVI) is interviewed by the editor of AIDS Clinical Care on the current state of vaccine development and the prospects for those vaccines. IAVI was recently awarded a $25-million grant by Bill and Melinda Gates. IAVI's strategies are outlined, and the complexity of developing a vaccine which is effective against a rapidly mutating virus is discussed.^ieng

A randomized, community trial of intensive sexually transmitted disease control for AIDS prevention, Rakai, Uganda.

OBJECTIVE: To describe the design and first-round survey results of a trial of intensive sexually transmitted disease (STD) control to reduce HIV-1 incidence. STUDY DESIGN: Randomized, controlled, community-based trial in Rakai District, Uganda. METHODS: In this ongoing study, 56 communities were grouped into 10 clusters designed to encompass social/sexual networks; clusters within blocks were randomly assigned to the intervention or control arm. Every 10 months, all consenting resident adults aged 15-59 years are visited in the home for interview and sample collection (serological sample, urine, and, in the case of women, self-administered vaginal swabs). Sera are tested for HIV-1, syphilis, gonorrhea, chlamydia, trichomonas and bacterial vaginosis. Following interview, all consenting adults are offered directly observed, single oral dose treatment (STD treatment in the intervention arm, anthelminthic and iron-folate in the control arm). Treatment is administered irrespective of symptoms or laboratory testing (mass treatment strategy). Both arms receive identical health education, condom and serological counseling services. RESULTS: In the first home visit round, the study enrolled 5834 intervention and 5784 control arm subjects. Compliance with interview, sample collection and treatment was high in both arms (over 90%). Study arm populations were comparable with respect to sociodemographic and behavioral characteristics, and baseline HIV and STD rates. The latter were high: 16.9% of all subjects were HIV-positive, 10.0% had syphilis, and 23.8% of women had trichomonas and 50.9% had bacterial vaginosis. CONCLUSIONS: Testing the effects of STD control on AIDS prevention is feasible in this Ugandan setting.

PIP: An ongoing (1994-98) randomized, community-based trial in Uganda's Rakai District is assessing the assumption that intensive sexually transmitted disease (STD) control efforts result in marked declines in HIV/AIDS prevalence. Described, in this article, are the project design and findings of the first-round baseline survey. 56 communities were grouped into 10 clusters designed to encompass social/sexual networks and clusters within blocks were randomly assigned to the intervention or control arm. All consenting permanent residents of the district are visited in their homes at 10-month intervals where they are administered extensive questionnaires, provide urine and vaginal swab samples, and are offered mass treatment regardless of symptoms or laboratory testing (single oral dose STD treatment in the intervention arm and anthelmintics and iron folate in the control arm). Both groups receive identical health education, condom promotion, and serologic counseling services. In the first round of home visits, 5834 intervention and 5784 control arm subjects were enrolled, representing about 90% of eligible adults. The groups were comparable in terms of sociodemographic and behavioral characteristics and baseline rates of HIV and STDs. 16.9% of subjects were HIV-positive, 10.0% had syphilis, 23.8% of women had trichomonas, and 50.9% had bacterial vaginosis. Detailed STD assessment is expected not only to document the relationship between STD control and HIV, but also to identify which STDs confer the greatest population attributable risk for HIV transmission, facilitating targeted control efforts in the future.

Global prevalence and incidence estimates of selected curable STDs.

OBJECTIVES: To update the WHO global and regional estimates of the prevalence and incidence of syphilis, gonorrhoea, chlamydia, and trichomoniasis. METHODS: Prevalence estimates for syphilis, gonorrhoea, chlamydia, and trichomoniasis were generated for each of the nine UN regions for males and females between the ages of 15 and 49 in 1995 based on an extensive review of the published and unpublished medical literature since 1985. Incidence estimates were based on the prevalence figures and adjusted to take into account the estimated average duration of infection for each disease in a particular region. The latter was assumed to depend upon a number of factors including the duration of infection in the absence of treatment, the proportion of individuals who develop symptoms, the proportion of individuals treated, and the appropriateness of treatment. RESULTS: In 1995 there were over 333 million cases of the four major curable STDs in adults between the ages of 15 and 49--12 million cases of syphilis, 62 million cases of gonorrhoea, 89 million cases of chlamydia, and 170 million cases of trichomoniasis. Geographically, the vast majority of these cases were in the developing world reflecting the global population distribution. CONCLUSIONS: STDs are among the most common causes of illness in the world. Estimates of the global prevalence and incidence of these infections are limited by quantity and quality of data available from the different regions of the world. Improving global STD estimates will require more well designed epidemiological studies on the prevalence and duration of infection.

The International AIDS Vaccine Initiative.

AIDS: According to researchers, the development of a safe and inexpensive HIV vaccine is the only hope of taming the global AIDS epidemic. More than 20 vaccines devised to cure viral infections in humans exist; however, the development of an HIV vaccine has proved to be problematic on numerous fronts. One difficulty relates to the fact that HIV is a complex retrovirus that provides researchers with no perfect animal models for study. Also, as the AIDS epidemic has spread, many research dollars have been drawn from vaccine development and devoted to devising better treatments for the disease. The International AIDS Vaccine Initiative (IAVI) is refocusing the vaccine-development effort using a push-pull strategy. As a push measure, the organization resolves to advocate the vaccine development cause around the globe, urging activists, scientists, government officials, corporate leaders, and sources of funding to rally around the cause. As a pull measure, the IAVI hopes to foster the creation of incentives for pharmaceutical companies working on vaccine research. The incentives could include legislation to alleviate drug makers' regulatory and liability problems, and a vaccine purchase fund to ensure vaccine sales in impoverished parts of the world. The IAVI hopes its efforts will combine the resources of industry, researchers, and government, and lead to the speedy development and implementation of an effective HIV vaccine.^ieng

International aspects of the AIDS/HIV epidemic.

This review provides the reader with pertinent information on the epidemiology, prevention, and new technologies of the ongoing HIV pandemic. These aspects are key to international policy discussions surrounding the public health response to the international spread of HIV. Our understanding of the impact of AIDS on other diseases is evolving, as is our insight into the demographic and economic effects of the epidemic on the global community. Observations on the success of certain prevention strategies allow rational allocation of resources in newly affected epidemic areas. Information on the origin and nature of HIV transmission exemplifies the phenomenon of global emerging infections. As world populations are brought closer together through transportation, communication, trade, and commerce, insight into emerging infections of epidemic potential becomes increasingly important to the practitioner of public health. Although important, legal and social aspects of the epidemic will not be emphasized here. The epidemics of HIV/AIDS in the United States and Europe are not reviewed here. The global pandemic has recently been described in an overview in this publication to which the reader is also referred.

Incidence of HIV-1 infection in a rural region of Uganda.

OBJECTIVE: To determine the incidence of infection with HIV-1 and the risk factors associated with seroconversion in three geographical strata of a rural Ugandan district. DESIGN: Serological, sociodemographic, and behavioural surveys of everyone aged 13 or more in 21 randomly selected communities at baseline and one year later. SETTING: Rural population of Rakai district, southwestern Uganda, residing in main road trading centres, secondary trading villages, and agricultural villages. SUBJECTS: In 1989, 1292 adults provided a blood sample and interview data; one year later, 778 survivors (77%) who had been seronegative at baseline provided follow up data. MAIN OUTCOME MEASURES: Incidence of HIV infection in relation to individual characteristics and risk factors, including place of residence. RESULTS: Incidence of HIV infection in all adults was 2.1/100 person years of observation (SE 0.5 (95% confidence interval 1.1 to 3.1)); in people aged 15-39 the incidence was 3.2/100 person years. Incidence was highest in men and women aged 20-24 (9.2/100 person years (3.9) and 6.8/100 person years (2.9) respectively). Risk factors significantly associated with seroconversion were age 24 and under and two or more sexual partners. Between the surveys the proportion of all respondents reporting high risk behaviour (two or more partners) significantly increased from 8.9% to 12.3%. CONCLUSIONS: Despite preventive programmes and substantial knowledge about AIDS the incidence of HIV infection remains high in this rural population. Prevention aimed at vulnerable rural communities is urgently needed to contain the HIV epidemic.

PIP: In 1990, researchers followed up on as many of the 1292 adults they surveyed in 1989 as they who lived in rural Rakai district in southwestern Uganda to determine HIV-1 incidence and the risk factors associated with seroconversion. They were only able to follow up on 774 of the 1037 adults who were HIV-1 seronegative in 1989. In 1989, knowledge about AIDS and about sexual intercourse as a mode of HIV transmission was high (94% and 86%, respectively). The 1989 HIV-1 seroprevalence rate ranged from 38.5% in trading centers to 8.6% in agricultural villages off main and secondary roads. 21 (2.7%) had seroconverted (incidence = 2.1/100 person years). Since the researchers oversampled in trading centers, they estimated the weighted seroincidence to be 1.9%. HIV-1 seroconversion peaked in the 20-24 year old age group with it being greater in men than in women (9.2% vs. 6.8%). The most significant risk factor for seroconversion was number of sexual partners (8.3% for 2 or more partners vs. 2.5% for 0-1 partners; rate ratio = 3.4; p .01 for trend). The risk of seroconversion for someone with just 1 sexual partner was high (2.8%), reflecting the high HIV-1 seroprevalence in Rakai district. The percentage of subjects with at least 2 sexual partners rose from 8.9% in 1989 to 12.3% in 1990. Seroconversion was not associated with injections. No one had had a blood transfusion. Attendance at a 1989 AIDS education rally did not affect HIV seroconversion. In fact, it was greater among people attending the rally (3.5% vs. 2.1%). Logistic regression revealed that age and numbers of partners were the only significant factors affecting seroconversion (odds ration [OR] for 15-24 years compared to 25-39 years was 3.9 and OR for 2 or more sexual partners was 6.5). These findings indicated that existing HIV/AIDS education programs do not reduce HIV transmission and that better strategies are needed.

Parenteral transmission of HIV in Africa.

PIP: HIV is known to be transmitted sexually, perinatally, and parenterally. Parenteral transmission is defined as that which occurs outside of the alimentary tract, such as in subcutaneous, intravenous, intramuscular, and intrasternal injections. The relative percentage of HIV infection caused by each of these routes depends upon the prevalence of infection among particular groups of the population and on their shared behaviors. Although heterosexual transmission is the primary mode of HIV infection in Africa, health care providers and traditional healers both in and out of the health care setting in Africa administer a large number of injections. As such, parenteral transmission could be contributing significantly to HIV infection in the region. This paper reviews what is known about the parenteral transmission of HIV in Africa. The biology of parenteral transmission in blood and in interstitial fluid is described, then sections follow on HIV transmission by injection, occupational transmission, transmission by scarification, and transmission by immunization. Available data suggest that while HIV may be occasionally transmitted in Africa through injections, it is most likely not a major route of infection in the region. Sterilizing needles and syringes, and using injections as last resort therapy will greatly reduce the risk of parenteral HIV transmission.^ieng

AIDS and HIV infection in Uganda--are more women infected than men?

In countries in sub-Saharan Africa, HIV is transmitted primarily heterosexually. HIV infection and AIDS in women not only affects women's health but also has implications for the other members of society. Maternal infection is the source of most childhood HIV infection in Africa and maternal health is a strong predictor of child survival. In Uganda, a review of passive AIDS surveillance has shown almost equal numbers of clinical cases reported in men and women. However, in three population-based HIV serosurveys, women were consistently found to have a higher infection rate (approximately 1.4 times) than men. In addition, both AIDS case surveillance and seroprevalence studies demonstrate an earlier age of presentation and mean age of infection in women. The higher rate of HIV infection in women suggests either differential rates of transmission between women and men, higher rates of female sexual exposure to infected men, or longer survival among HIV-infected women compared with men. Although further studies are required to illuminate both the biology and the epidemiology of heterosexual HIV transmission in Africa, these findings of earlier and higher infection rates in women have important implications for women's health and child survival in Uganda and indicate the need for specially targeted interventions to reduce transmission in this group.

AIDS in Sub-Saharan Africa: an overview.

PIP: This article discusses the spread of AIDS in sub-Saharan Africa, a region where more than 1/2 of all HIV-infected people live. Of the estimated 8-10 million HIV-infected people worldwide, more than 5 million live in sub-Saharan Africa. Studies indicate that this region holds more than 75% of the world's HIV-infected women and 90% of the world's HIV-infected infants. Moreover, national surveys in sub-Saharan countries show that initial reports claiming that the AIDS pandemic was limited to urban areas were wrong, since rural areas have also suffered greatly from the disease. In developed countries, approximately 50% of HIV-infected people develop AIDS with 10 years. But researchers believe that in Africa the time between exposure to HIV and the manifestation of AIDS, as well as the time between the manifestation of AIDS and death, is shorter than in developed countries. While changes in the behavior among homosexuals and the virtual end of transmission via blood transfusion have led to a decline in rate of new infections in developed countries, Africa and the rest of the developing world continues to see an increase in the rate of infections. In sub-Sahara Africa, heterosexual transmission is the most common means of infection. Mother-to-child infections have also contributed to the spread of the disease. Researchers have also noted significant differences among the clinical illnesses of AIDS patients in Africa and the developed world. And unlike the developed world, Africa has had difficulties with the diagnosis and surveillance of the disease. In the coming years, the effects of AIDS will become even more pronounced in the region, as countries grapple with how to care of AIDS patients and provide for AIDS-related orphans.^ieng

The association of genital ulcer disease and HIV infection at a dermatology-STD clinic in Uganda.

At Mulago Hospital in Kampala, Uganda, 270 consecutive patients at the dermatology and sexually transmitted disease (STD) clinic were enrolled in a study to evaluate the association of clinical STD syndromes and human immunodeficiency virus (HIV) infection. Female patients became sexually active earlier than male patients and were younger at marriage. Persons with a history of an STD during the preceding 5 years were more likely to be HIV infected (43%) than those without such a history (26%; OR 2.08, 95% C.I. 1.17, 3.73). Examination at the time of the visit demonstrated an association between genital ulcers and HIV infection in male and female patients (OR 2.21, 95% C.I. 1.08, 4.53, and OR 8.54, 95% C.I. 1.45, 87.55, respectively) but no association between HIV and urethritis or vaginal discharge. The etiologic fraction for HIV infection of genital ulcers was 0.218. Men with a history of contact with prostitutes were more likely to be HIV infected than those without contact (50% versus 28%, p less than 0.05), but once controlled for STDs, this relationship was no longer significant. This study confirms other studies from East Africa that have shown a relationship between genital ulcers and HIV infection. This finding, in the presence of no association between other STD syndromes and HIV infection, suggests that genital ulcers may be truly associated with HIV infection rather than a marker of high-risk activities.