HIV This Week

Concurrency revisited: increasing and compelling epidemiological evidence

Mah TL, Shelton JD. J Int AIDS Soc. 2011 Jun 20;14:33.

Multiple sexual partnerships must necessarily lie at the root of a sexually transmitted epidemic. However, that overlapping or concurrent partnerships have played a pivotal role in the generalised epidemics of sub-Saharan Africa has been challenged. Much of the original proposition that concurrent partnerships play such a role focused on modelling, self-reported sexual behaviour data, and ethnographic data. While each of these has definite merit, each also has had methodological limitations. Actually, more recent cross-national sexual behaviour data and improved modelling have strengthened these lines of evidence. However, heretofore the epidemiologic evidence has not been systematically brought to bear. Though assessing the epidemiologic evidence regarding concurrency has its challenges, a careful examination, especially of those studies that have assessed HIV incidence, clearly indicates a key role for concurrency. Such evidence includes: 1) the early and dramatic rise of HIV infection in generalised epidemics that can only arise from transmission through rapid sequential acute infections and thereby concurrency; 2) clear evidence from incidence studies that a major portion of transmission in the population occurs via concurrency both for concordant negative and discordant couples; 3) elevation in risk associated with partner's multiple partnering; 4) declines in HIV associated with declines in concurrency; 5) bursts and clustering of incident infections that indicate concurrency and acute infection play a key role in the propagation of epidemics; and 6) a lack of other plausible explanations, including serial monogamy and non-sexual transmission. While other factors, such as sexually transmitted infections, other infectious diseases, biological factors and HIV sub-type, likely play a role in enhancing transmission, it appears most plausible that these would amplify the role of concurrency rather than alter it. Additionally, critics of concurrency have not proposed plausible alternative explanations for why the explosive generalised epidemics occurred. Specific behaviour change messaging bringing the concepts of multiple partnering and concurrency together appears salient and valid in promoting safer individual behaviour and positive social norms.

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Editor’s note: It is unclear why there have been and continue to be arguments overall the role of sexual partnership concurrency. Effective HIV prevention messages from the beginning of the response have highlighted ideas such as ‘when you sleep with a person you are sleeping with every person they have ever had sex with’. Modelling has suggested that primary infection amplifies the importance of concurrent sexual partnerships substantially, but concurrency and primary infection do not completely explain diverse epidemics in sub-Saharan Africa (see Eaton, HIV This Week Issue 87). Although primary infection can be important in fuelling ongoing transmission (see Powers, HIV This Week, Issue 93), the level of transmission seen in the HPTN 052 study when CD4 counts were 350-550 cells/ul suggests that the bulk of transmission is not acute infection related. Furthermore, transmission related to acute infection does not explain the doubling times seen in the southern Africa epidemics. Emphasising the role of sexual networking in spreading HIV infection can help people understand how their own risk is influenced by others beyond their immediate sexual partner but helping people to learn their HIV status and tailor their prevention response may have a bigger impact on decelerating HIV incidence than a focus on the role of concurrency alone

The role of acute and early HIV infection in the spread of HIV and implications for transmission prevention strategies in Lilongwe, Malawi: a modelling study

Powers KA, Ghani AC, Miller WC, Hoffman IF, Pettifor AE, Kamanga G, Martinson FE, Cohen MS. Lancet. Vol. 378 No. 9787 pp 256-268.

HIV transmission risk is higher during acute and early HIV infection than it is during chronic infection, but the contribution of early infection to the spread of HIV is controversial. Powers and colleagues estimated the contribution of early infection to HIV incidence in Lilongwe, Malawi, and predict the future effect of hypothetical prevention interventions targeted at early infection only, chronic infection only, or both stages. The authors developed a deterministic mathematical model describing heterosexual HIV transmission, informed by detailed behavioural and viral-load data collected in Lilongwe. They included sexual contact within and outside of steady pairs and divided the infectious period into intervals to allow for changes in transmissibility by infection stage. The authors used a Bayesian melding approach to fit the model to HIV prevalence data collected between 1987 and 2005 at Lilongwe antenatal clinics. They assessed interventions that reduced the per-contact transmission probability to 0·00003 in people receiving them, and varied the proportion of individuals receiving the intervention in each stage. Powers and colleagues estimated that 38·4% (95% credible interval 18·6-52·3) of HIV transmissions in Lilongwe are attributable to sexual contact with individuals with early infection. Interventions targeted at only early infection substantially reduced HIV prevalence, but did not lead to elimination, even with 100% coverage. Interventions targeted at only chronic infections also reduced HIV prevalence, but coverage levels of 95-99% were needed for the elimination of HIV. In scenarios with less than 95% coverage of interventions targeted at chronic infections, additional interventions reaching 25-75% of individuals with early infection reduced HIV prevalence substantially. The authors results suggest that early infection plays an important part in HIV transmission in this sub-Saharan African setting. Without near-complete coverage, interventions during chronic infection will probably have incomplete effectiveness unless complemented by strategies targeting individuals with early HIV infection.

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Editor’s note: Acute infection is the period between the time that people acquire HIV and the time that antibodies can be detected—people are highly infectious then and rarely know that they have HIV infection. Not only are viral loads extremely high due to the speed of viral replication but the virus itself is more infectious as it diverges from the founder virus or viruses that caused infection in the first place. The exact contribution of acute infection to ongoing HIV transmission is unknown but many have believed that it plays a lesser role in mature epidemics. This elegant mathematical modelling work using data (sexual behaviour, viral load, HIV prevalence) from Lilongwe, Malawi found that 38% of HIV transmission there (95%CI:19-52) was the result of sexual contact with people in early HIV infection, a period lasting about 5 months. Although the levels of long-term partner concurrency, sporadic concurrency, or rapid succession sequential monogamy are reportedly low (14% overall) in Lilongwe, short gaps (e.g. 11 days) between partners are likely an important contributor to HIV transmission dynamics. Testing the potential impact of various HIV prevention strategies, the model revealed that antiretroviral ‘treatment for prevention’ focused on people with chronic HIV infection would not eliminate HIV transmission. Combination prevention (behavioural, biomedical, and structural), which includes strategies to reduce vulnerability and to empower people to learn their HIV status and take steps to prevent acquiring or transmitting HIV infection, must also include innovative approaches to reducing the impact of acute infection if we are to get on top of the epidemic.

A surprising prevention success: why did the HIV epidemic decline in Zimbabwe?

Halperin DT, Mugurungi O, Hallett TB, Muchini B, Campbell B, Magure T, Benedikt C, Gregson S. PLoS Med. 2011 Feb 8;8(2):e1000414.

There is growing recognition that primary prevention, including behaviour change, must be central in the fight against AIDS. The earlier successes in Thailand and Uganda may not be fully relevant to the severely affected countries of southern Africa. Halperin and authors conducted an extensive multi-disciplinary synthesis of the available data on the causes of the remarkable HIV decline that has occurred in Zimbabwe (29% estimated adult prevalence in 1997 to 16% in 2007), in the context of severe social, political, and economic disruption. The behavioural changes associated with HIV reduction—mainly reductions in extramarital, commercial, and casual sexual relations, and associated reductions in partner concurrency—appear to have been stimulated primarily by increased awareness of AIDS deaths and secondarily by the country's economic deterioration. These changes were probably aided by prevention programmes utilizing both mass media and church-based, workplace-based, and other inter-personal communication activities. Focusing on partner reduction, in addition to promoting condom use for casual sex and other evidence-based approaches, is crucial for developing more effective prevention programmes, especially in regions with generalized HIV epidemics.

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Editors’ note: These authors take up the challenge of trying to explain the findings published last year on the prevalence and incidence declines in Zimbabwe by Gregson et al (covered in Issue 83 of HIV This Week http://hivthisweek.unaids.org/post/epidemiology-2). They synthesise data from a number of sources and their hypotheses do seem explanatory. HIV incidence peaked in Zimbabwe in 1991 while HIV prevalence peaked in 1997. HIV incidence declined initially after 1991, as a result of saturation of sub-populations of people at higher risk of HIV exposure, and then the pace of the decline accelerated after 1999. Reported condom use increased steadily during the 1990s reaching a level of 59% in non-marital sexual encounters by 1994 and the consistency of condom use improved among women in casual partnerships. AIDS deaths increased dramatically during the mid- to-late 1990s and the government policy of home-based care brought AIDS mortality into the lived experiences of Zimbabweans across the country. Focus groups and interviews repeatedly underscore the role that mortality played in reducing casual sex and other multiple sexual partnerships. The severe economic declines of the last 1990s and early 2000s amplified the trend to partner reduction as Zimbabwe’s gross domestic product (GDP) fell 40%, average real earnings declined 90%, and men’s ability to purchase sexual services or maintain multiple partnerships fell. The lessons for other countries in southern Africa are unclear since one would wish neither economic decline nor high AIDS mortality for them. However, Zimbabwe had high secondary education levels, particularly in urban men, which facilitated personal integration of AIDS awareness messages. More importantly, the national response saw broad-based community engagement strategies deployed that set the stage for influential interpersonal communication arising from within the population to change sexual norms.

Biological Factors that May Contribute to Regional and Racial Disparities in HIV Prevalence

Kaul R, Cohen CR, Chege D, Yi TJ, Tharao W, McKinnon LR, Remis R, Anzala O, Kimani J. Am J Reprod Immunol 2011 Mar;65(3):317-324

Despite tremendous regional and subregional disparities in HIV prevalence around the world, epidemiology consistently demonstrates that black communities have been disproportionately affected by the pandemic. There are many reasons for this, and a narrow focus on socio-behavioural causes may be seen as laying blame on affected communities or individuals. HIV sexual transmission is very inefficient, and a number of biological factors are critical in determining whether an unprotected sexual exposure to HIV results in productive infection. This review will focus on ways in which biology, rather than behaviour, may contribute to regional and racial differences in HIV epidemic spread. Specific areas of focus are viral factors, host genetics, and the impact of co-infections and host immunology. Considering biological causes for these racial disparities may help to destigmatize the issue and lead to new and more effective strategies for prevention.

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Editors’ note: Viral factors, host genetics, co-infections, and host immunology are all hypothesized to influence the two most important determinants of sexual HIV transmission—the level of HIV in genital/rectal secretions in the partner with HIV infection and the number and density of HIV-susceptible target cells in the mucosal lining of the penis, rectum, or female genital tract of the HIV-uninfected partner. The per-exposure risk of HIV transmission from men to women is almost 4-fold higher and that from women to men is 9-fold higher in low-income countries compared to high-income countries. Why is this the case? It is unclear whether virus clade affects patterns of HIV spread and geographic mapping is incomplete of genetic determinants, such as absence of the HIV co-receptor CCR5 on the cell surface created by homozygous CCR5-delta 32 deletion. However, the prevalence of co-infections may explain much of the geographical disparity in HIV. Treatments for tuberculosis, malaria, helminths, schistosomiasis, and filariasis have all been shown to reduce plasma viral load. Genital co-infections are known to increase both HIV transmission and susceptibility. Immune activation and inflammation are key host responses to invading pathogens and HIV replicates more efficiently in activated CD4 cells. Thus, rather than viral factors or host genetics, co-infections are the most likely biological explanation for geographical differences in HIV prevalence worldwide.