Heterosexual Epidemics Research Articles

Potential impact of HIV among IDUs on heterosexual transmission in Asian settings: scenarios from the Asian Epidemic Model

Introduction: An important public health question is the degree to which HIV epidemics among injecting drug users (IDUs) can contribute to more generalised spread of the virus heterosexually among non-IDUs. Mathematical models can be of use in understanding the complexities of such epidemiological problems. Methods: In this paper, the Asian Epidemic Model (AEM) is used to explore different scenarios for potential HIV transmission by IDUs to non-injecting sexual partners and beyond. The model is applied to a ‘general Asian’ setting, in which (1) there is the potential for sex work to drive a self-sustaining heterosexual epidemic, and (2) the vast majority of IDUs are male and do not engage in sex work themselves, but a substantial minority of the IDUs do purchase sexual services from sex workers. Within such a setting, three different scenarios are modeled, and within each scenario, the level of HIV prevalence among IDUs is varied, to see the impact of preventing HIV among IDUs at different stages. Results: The number of HIV infections attributable to IDUs over a 15-year period was greatest when the epidemic among IDUs started in advance of a generalised heterosexual epidemic, with a 171% increase in infections if the IDU prevalence was not kept under control. Once a heterosexual epidemic was underway, controlling HIV prevalence among IDUs still resulted in a meaningful reduction in infections (23%), including among non-IDUs. Once the heterosexual epidemic started to decline, the relative proportion of infections attributable to IDUs increased, creating a situation for IDUs to feed into new epidemics. Discussion: In the early stages of a heterosexual epidemic, maintaining HIV prevalence at low levels among IDUs can buy critical time to address the potential for rapid heterosexual transmission. In more advanced heterosexual epidemics, preventing HIV among IDUs can still avert a substantial number of infections.

Can HIV epidemics among IDUs ‘trigger’ a generalised epidemic?

Both Grassly et al. (2003) and Saidel et al. (2003) investigate the effect of injecting drug use (IDU) on the risk of a generalised heterosexual HIV epidemic, using modelling techniques. The difference in results is startling. While Grassly et al. find almost no effect of spread among IDUs on subsequent widespread heterosexual epidemics, Saidel et al. predict very large effects in diverse epidemic settings. We will discuss the main findings of both papers and possible reasons for the seemingly different results as well as policy implications, including the potential for using sexually transmitted infections (STIs) as an indirect indicator for the risk of generalised HIV epidemics (Lowndes et al., 2003). On the basis of the scarce available data about sexual and drug injecting behaviours in Russia, Grassly et al. investigate the risk for HIV/AIDS to expand beyond the traditional risk groups of injecting drug users and highly active sexual core groups into larger parts of the population. They discuss the possibility of a generalised epidemic in Russia, India and China, that is an epidemic that encompasses more than 1% of the adult population (UNAIDS/WHO, 2001). From their results, the authors conclude that the occurrence of a generalised epidemic cannot be ruled out. A lower bound of projected prevalence, as reflected by the 2.5th percentile, is already a staggering 5% of the adult population with HIV infection after 10 years, with the median and maximum prevalence reaching an almost unthinkable 60 and 80%, respectively. Although these projections may be seriously affected by the lack of data, they should be taken as very alarming indications of a possible worst case scenario. Less dependent on data availability than their actual prevalence estimates, and thus more reliable, are results from the sensitivity analyses. These show which parameters contribute most to the spread of HIV, and how the importance of those parameters changes with the course of the epidemic. In line with recent epidemiological data (Kral et al., 2001; Strathdee et al., 2001) and with previous modelling work (Blower, Hartel, Dowlatabadi, Anderson, & May, 1991), sexual transmission appears to gain importance in IDUs after initial rapid injection-related spread. However, the effect of epidemics in IDUs on the risk of a generalised heterosexual epidemic seems very small. In Grassly et al., mean rate of partner change explains 36 /40.9% of the variance in all-adult prevalence after 5 years, STI recovery/treatment explains 6.7 /10.9%, mixing between different sexual activity groups up to 3.9%, while needle sharing and the rate of acquiring new sharing partners among IDUs are in the range of 0.03 /1%. Moreover, random mixing between IDUs and non-IDUs has almost no effect on reaching the threshold of 5% total prevalence, as compared to random mixing of all adults, and it has only a slight effect on reaching the 0.1% total prevalence threshold, given high rates of needle sharing. These small effects occur in spite of a very high upper limit for the proportion of IDUs in the model: 10% of the adult population. Although it is stated that needle sharing remains important, the results seem to suggest a very small effect of epidemics among IDUs on the risk of generalised heterosexual spread. Saidel et al. take a different approach, focusing on the effect of IDU epidemics on the spread in sex workers and their clients, a main core group for sexual transmission. In the Asian settings described by their model there is extensive mixing between sex workers and IDUs so that the first effects of high prevalence in IDUs may indeed be expected among sex workers and clients. They use a similar compartmental model, with an IDU component and a heterosexual component, the latter describing spread due to commercial sex, casual sex and sex between spouses. To better understand the effect of * Corresponding author. E-mail address: lucas.wiessing@emcdda.eu.int (L. Wiessing). International Journal of Drug Policy 14 (2003) 99 /102

Varga, Christine A. South African young people's sexual dynamics: Implications for behavioural responses to HIV/AIDS. Resistance to behavioural change to reduce HIV/AIDS infection in predominantly heterosexual epidemics in third world countries, 1999. Canberra: Health Transition Centre, 13-34

Varga, Christine A. South African young people's sexual dynamics: Implications for behavioural responses to HIV/AIDS. Resistance to behavioural change to reduce HIV/AIDS infection in predominantly heterosexual epidemics in third world countries, 1999. Canberra: Health Transition Centre, 13-34

A distinctive clade B HIV type 1 is heterosexually transmitted in Trinidad and Tobago.

HIV-1 transmission worldwide is predominantly associated with heterosexual activity, and non-clade B viruses account for the most spread. The HIV-1 epidemic in Trinidad/Tobago and the Caribbean shares many features with such heterosexual epidemics, including a prominent role for coincident sexually transmitted diseases. This study evaluates the molecular epidemiology of HIV-1 in Trinidad/Tobago during a period when abrupt transition from homosexual to heterosexual transmission occurred in the absence of injecting drug use, concomitant with a rapid rise in HIV-1 prevalence in the heterosexual population. Of 31 viral isolates studied during 1987-1995, all cluster with subtype B reference strains. In the analysis of full env genes from 22 early seroconverters, the Trinidad isolates constitute a significant subcluster within the B subtype. The Trinidad V3 consensus sequence differs by a single amino acid from the prototype B V3 consensus and demonstrates stability over the decade of this study. In the majority of isolates, the V3 loop of env contains a signature threonine deletion that marks the lineage of the Trinidad HIV-1 clade B epidemic from pre-1984. No phenotypic features, including syncitium induction, neutralization profiles, and chemokine receptor usage, distinguish this virus population from other subtype B viruses. Thus, although the subtype B HIV-1 viruses being transmitted in Trinidad are genetically distinguishable from other subtype B viruses, this is probably the result of a strong founder effect in a geographically circumscribed population rather than genetic selection for heterosexual transmission. These results demonstrate that canonical clade B HIV-1 can generate a typical heterosexual epidemic.

An association between HIV-1 subtypes and mode of transmission in Cape Town, South Africa.

To determine HIV-1 env and gag subtypes in male homosexual and heterosexual populations in Cape Town, South Africa. DNA was isolated from blood originating from 61 patients attending local clinics. Samples were divided according to presumed mode of transmission: male homosexual (n = 26), heterosexual/vertical (n = 32), blood transfusion (n = 1) and unknown (n = 2). Proviral HIV-1 DNA was subtyped by heteroduplex mobility assay (HMA) based on the 799 base-pair V3-V5 region of the env gene (n = 47) or by sequence analysis of the p17 region of the gag gene (n = 33), or both. For HMA, reference plasmids were constructed containing the V1-V5 env region sequences (1.2-kb) representative of local subtypes. Subtype designation of reference subtypes was confirmed by sequence analysis of the V3-loop region. Analysis of the partial gag sequences and HMA of the V3-V5 env region identified three subtypes: B, C and D. A fourth env subtype, subtype E, was also identified by HMA. Subtypes were found to segregate according to mode of transmission, with subtype B viruses found in 96% (25 out of 26) of the male homosexual group and subtype C viruses found in 81% (26 out of 32) of the heterosexual/vertical transmission group. Subtype B viruses were also found in four heterosexual patients, one patient infected by blood transfusion and in two patients with unknown mode of transmission. Subtype D viruses were found in one male homosexual patient and one heterosexual patient. A subtype E virus was identified in a heterosexual patient. No discrepancy was found in subtype designation in samples analysed in both between the gag and env regions (n = 19). Subtype B viruses were associated with male homosexual transmission and subtype C viruses with heterosexual transmission, suggesting two independent epidemics. This data may have implications in the selection of appropriate vaccines for different risk groups in the country.

Assessing HIV vaccine effects.

It is unlikely that human immunodeficiency virus (HIV) vaccines will create impenetrable barriers to infection. When the barriers to infection are broken, however, vaccine effects on the progression of infection to disease and on the contagiousness of infection could be considerable. The usual outcomes of vaccine trials are either infection or disease. The authors argue that for HIV vaccines, the alternative outcome of contagiousness may be more important. Because of the long incubation period to acquired immunodeficiency syndrome (AIDS), a vaccine trial with AIDS as the outcome would be a long and costly undertaking. Because contagiousness is concentrated into the period of primary infection, vaccine trials assessing contagiousness would not take as long. An approach to assessing vaccine effects on the contagiousness of primary infection while simultaneously assessing protection against infection is presented. It involves randomizing vaccination of couples in whom both individuals are uninfected and one or both have a risk of infection outside the couple. In such a study, the vaccine effect on susceptibility to infection can be estimated from the proportions of vaccinated and unvaccinated couples in whom neither partner is infected. Estimation of the contagiousness effect also uses information on the frequency with which both partners are infected. In areas of the world where heterosexual epidemics are emerging within the context of concurrent partnerships, the randomization of vaccination of couples could increase the efficiency and decrease the costs of vaccine trials.